P2P [Phenylacetone] via aldol & Baeyer/Villiger

fan of zwitterion · Sun Feb 06, 2005 2:27 pm

Ok,

Bio and two dogs posted awhile back, what I think would be one of the most overlooked synthesis of Phenylacetone's

An acid catalysed Aldol Condensation, followed by a Baeyer/Villiger, peracid, eventully gives yield of P2P.

The literature is well documented, and verified by many former researchers.

MEK+Benzaldehyde--->MethylPhenylButanone

I vaguely remember Bio saying that is also could be achieved with Acetone and benzene, respectfully

1) An acid catalysed Aldol condensation of Benzaldehyde and Methyl Ethyl Ketone to give Methyl Phenyl Butenone ie C6H5CHO + CH3CH2COCH3 + dryHCL ---> C6H5CH=C(COCH3)CH3

2) The unsaturated ketone undergoes the Baeyer-Villiger oxidation with peroxy acids to give the enol ester of Phenyl propanone ie C6H5CH=C(COCH3)CH3 + RCO3H ----> C6H5CH=C(OCOCH3)CH3

3) The enol ester is then saponified with 10% NaOH solution to give Phenyl Propanone in about 35% yield based on the unsaturated ketone.
&--1050;&--1086;&--1085;&--1076;&--1077;&--1085;&--1089;&--1072;&--1094;&--1080;&--1103; Aldol.

200 gms Benzaldehyde &--1080; 300 gms Methyl Ethyl Ketone &--1089;&--1084;&--1077;&--1096;&--1080;&--1074;&--1072;&--1102;&--1090;&--1089;&--1103; &--1074; &--1083;&--1080;&--1090;&--1088;&--1086;&--1074;&--1086;&--1084; &--1093;&--1080;&--1084;&--1080;&--1095;&--1077;&--1089;&--1082;&--1086;&--1084; &--1089;&--1090;&--1072;&--1082;&--1072;&--1085;&--1077; &--1080; &--1086;&--1093;&--1083;&--1072;&--1078;&--1076;&--1072;&--1102;&--1090;&--1089;&--1103; &--1085;&--1080;&--1078;&--1077; 5C.&--1052;&--1077;&--1076;&--1083;&--1077;&--1085;&--1085;&--1086; &--1085;&--1072;&--1089;&--1099;&--1097;&--1072;&--1077;&--1084; &--1093;&--1083;&--1086;&--1088;&--1086;&--1074;&--1086;&--1076;&--1086;&--1088;&--1086;&--1076;&--1086;&--1084; &--1087;&--1086;&--1082;&--1072; &--1089;&--1084;&--1077;&--1089;&--1100; &--1085;&--1077; &--1091;&--1074;&--1077;&--1083;&--1080;&--1095;&--1080;&--1090;&--1089;&--1103; &--1074; &--1074;&--1077;&--1089;&--1077; &--1085;&--1072; 40 &--1075;. &--1042;&--1085;&--1072;&--1095;&--1072;&--1083;&--1077; &--1089;&--1084;&--1077;&--1089;&--1100; &--1087;&--1088;&--1086;&--1079;&--1088;&--1072;&--1095;&--1085;&--1072;&--1103; &--1087;&--1086;&--1090;&--1086;&--1084; &--1085;&--1072;&--1095;&--1080;&--1085;&--1072;&--1077;&--1090; &--1082;&--1088;&--1072;&--1089;&--1085;&--1077;&--1090;&--1100; &--1080; &--1089;&--1090;&--1072;&--1085;&--1086;&--1074;&--1080;&--1090;&--1089;&--1103; &--1084;&--1091;&--1090;&--1085;&--1086;&--1081; &--1085;&--1072;&--1089;&--1090;&--1086;&--1083;&--1100;&--1082;&--1086; &--1095;&--1090;&--1086; &--1085;&--1077;&--1074;&--1080;&--1076;&--1085;&--1086; &--1085;&--1072;&--1089;&--1082;&--1074;&--1086;&--1079;&--1100;. &--1057;&--1084;&--1077;&--1089;&--1100; &--1074;&--1099;&--1076;&--1077;&--1088;&--1078;&--1080;&--1074;&--1072;&--1077;&--1084; &--1085;&--1086;&--1095;&--1100; &--1080; &--1086;&--1085;&--1072; &--1089;&--1090;&--1072;&--1085;&--1086;&--1074;&--1080;&--1090;&--1089;&--1103; &--1082;&--1086;&--1088;&--1080;&--1095;&--1085;&--1077;&--1074;&--1086;&--1081;. &--1052;&--1086;&--1077;&--1084; &--1074;&--1086;&--1076;&--1086;&--1081; &--1080; &--1079;&--1072;&--1090;&--1077;&--1084; 10% &--1088;&--1072;&--1089;&--1090;&--1074;&--1086;&--1088;&--1086;&--1084; NaOH, &--1086;&--1088;&--1075;&--1072;&--1085;&--1080;&--1095;&--1077;&--1089;&--1082;&--1080;&--1081; &--1089;&--1083;&--1086;&--1081; &--1086;&--1090;&--1076;&--1077;&--1083;&--1103;&--1077;&--1084; &--1080; &--1076;&--1080;&--1089;&--1090;&--1080;&--1083;&--1083;&--1080;&--1088;&--1091;&--1077;&--1084;. &--1044;&--1080;&--1089;&--1090;&--1080;&--1083;&--1103;&--1090; &--1085;&--1072;&--1075;&--1088;&--1077;&--1074;&--1072;&--1077;&--1084; &--1087;&--1088;&--1080; 240C &--1085;&--1072;&--1095;&--1080;&--1085;&--1072;&--1077;&--1090; &--1086;&--1073;&--1088;&--1072;&--1079;&--1086;&--1074;&--1099;&--1074;&--1072;&--1090;&--1100;&--1089;&--1103; &--1078;&--1077;&--1083;&--1090;&--1086;&--1077; &--1084;&--1072;&--1089;&--1083;&--1086;, accross &--1080; &--1090;&--1077;&--1084;&--1087;&--1077;&--1088;&--1072;&--1090;&--1091;&--1088;&--1091; &--1087;&--1086;&--1089;&--1090;&--1077;&--1087;&--1077;&--1085;&--1085;&--1086; &--1087;&--1086;&--1074;&--1099;&--1096;&--1072;&--1077;&--1084; &--1076;&--1086; 260C. &--1052;&--1072;&--1089;&--1083;&--1086; &--1084;&--1086;&--1078;&--1085;&--1086; &--1082;&--1088;&--1077;&--1089;&--1090;&--1072;&--1083;&--1080;&--1079;&--1086;&--1074;&--1072;&--1090;&--1100; &--1074;&--1099;&--1076;&--1077;&--1088;&--1078;&--1080;&--1074;&--1072;&--1085;&--1080;&--1077;&--1084; &--1074; &--1084;&--1086;&--1088;&--1086;&--1079;&--1080;&--1083;&--1082;&--1077; &--1085;&--1072; &--1087;&--1088;&--1086;&--1090;&--1103;&--1078;&--1077;&--1085;&--1080;&--1080; &--1089;&--1091;&--1090;&--1086;&--1082;. &--1057;&--1072;&--1084;&--1072; &--1087;&--1086; &--1089;&--1077;&--1073;&--1077; &--1082;&--1088;&--1080;&--1089;&--1090;&--1072;&--1083;&--1080;&--1079;&--1072;&--1094;&--1080;&--1103; &--1085;&--1077; &--1087;&--1088;&--1086;&--1080;&--1079;&--1086;&--1081;&--1076;&--1077;&--1090;, &--1073;&--1077;&--1088;&--1077;&--1090;&--1077; &--1083;&--1086;&--1078;&--1082;&--1091; &--1083;&--1086;&--1078;&--1080;&--1090;&--1077; &--1074; &--1084;&--1086;&--1088;&--1086;&--1079;&--1080;&--1083;&--1082;&--1091; &--1082;&--1086;&--1075;&--1076;&--1072; &--1086;&--1085;&--1072; &--1073;&--1091;&--1076;&--1077;&--1090; &--1090;&--1086;&--1081; &--1078;&--1077; &--1090;&--1077;&--1084;&--1087;&--1077;&--1088;&--1072;&--1090;&--1091;&--1088;&--1099; &--1095;&--1090;&--1086; &--1080; &--1088;&--1072;&--1089;&--1090;&--1074;&--1086;&--1088; &--1086;&--1087;&--1091;&--1089;&--1082;&--1072;&--1077;&--1090;&--1077; &--1077;&--1077; &--1074; &--1085;&--1077;&--1075;&--1086; , &--1101;&--1090;&--1086; &--1074;&--1099;&--1079;&--1086;&--1074;&--1077;&--1090; &--1085;&--1072;&--1095;&--1072;&--1083;&--1100;&--1085;&--1091;&--1102; &--1082;&--1088;&--1077;&--1089;&--1090;&--1072;&--1083;&--1080;&--1079;&--1072;&--1094;&--1080;&--1102; &--1080; &--1087;&--1086;&--1090;&--1086;&--1084; &--1086;&--1085;&--1072; &--1087;&--1088;&--1086;&--1076;&--1086;&--1083;&--1078;&--1080;&--1090;&--1089;&--1103;. &--1055;&--1088;&--1086;&--1080;&--1089;&--1093;&--1086;&--1076;&--1080;&--1090; &--1087;&--1077;&--1088;&--1077;&--1093;&--1086;&--1076; &--1086;&--1090; &--1086;&--1088;&--1072;&--1085;&--1100;&--1078;&--1077;&--1074;&--1086;&--1075;&--1086; &--1084;&--1072;&--1089;&--1083;&--1072; &--1082; &--1082;&--1088;&--1080;&--1089;&--1090;&--1072;&--1083;&--1072;&--1084; &--1089;&--1077;&--1088;&--1085;&--1086;&--1075;&--1086; &--1094;&--1074;&--1077;&--1090;&--1072; &--1084;&--1072;&--1089;&--1089;&--1086;&--1081; 180 &--1075; Methyl Phenyl Butenone.

&--1054;&--1082;&--1080;&--1089;&--1083;&--1077;&--1085;&--1080;&--1077; Baeyer-Villiger.
The reaction of the above unsaturated ketone with peracetic acid was first done by Boesken reported in Rec. Trav. Chim. 55, 786 (1936). There is some discussion of this also in US patent 3980708. Also see Organic Reactions Vols 9 & 43 I think. By following the directions in US Patent 5670661 you will get about 35% ketone based on the weight of the unsaturated ketone used. In that patent it is suggested that by recycling a higher percentage can be achieved.

&--1042; &--1083;&--1080;&--1090;&--1088;&--1086;&--1074;&--1091;&--1102; &--1082;&--1086;&--1083;&--1073;&--1091; &--1076;&--1086;&--1073;&--1072;&--1074;&--1083;&--1103;&--1077;&--1084; 625 ml &--1083;&--1077;&--1076;&--1103;&--1085;&--1086;&--1081; &--1091;&--1082;&--1089;&--1091;&--1089;&--1085;&--1086;&--1081; &--1082;&--1080;&--1089;&--1083;&--1086;&--1090;&--1099; &--1080; 143 grms &--1053;&--1072;&--1090;&--1088;&--1080;&--1103; &--1087;&--1077;&--1088;&--1073;&--1086;&--1088;&--1072;&--1090;&--1072;. &--1050; &--1101;&--1090;&--1086;&--1084;&--1091; &--1076;&--1086;&--1073;&--1072;&--1074;&--1083;&--1103;&--1077;&--1084; 100 grms methyl phenyl butenone &--1089; &--1087;&--1086;&--1084;&--1077;&--1096;&--1080;&--1074;&--1072;&--1085;&--1080;&--1077;&--1084; &--1080; &--1085;&--1072;&--1075;&--1088;&--1077;&--1074;&--1072;&--1077;&--1084; &--1076;&--1086; 50C. &--1050;&--1086;&--1075;&--1076;&--1072; &--1073;&--1091;&--1076;&--1077;&--1090;&--1077; &--1085;&--1072;&--1075;&--1088;&--1077;&--1074;&--1072;&--1090;&--1100; &--1089;&--1090;&--1072;&--1088;&--1072;&--1081;&--1090;&--1077;&--1089;&--1100; &--1085;&--1077; &--1087;&--1077;&--1088;&--1077;&--1075;&--1088;&--1077;&--1090;&--1100;, &--1086;&--1076;&--1085;&--1072;&--1082;&--1086;, &--1077;&--1089;&--1083;&--1080; &--1089;&--1084;&--1077;&--1089;&--1100; &--1073;&--1091;&--1076;&--1077;&--1090; &--1089;&--1083;&--1080;&--1096;&--1082;&--1086;&--1084; &--1093;&--1086;&--1083;&--1086;&--1076;&--1085;&--1072;&--1103; &--1086;&--1085;&--1072; &--1085;&--1072;&--1095;&--1080;&--1085;&--1072;&--1077;&--1090; &--1079;&--1072;&--1090;&--1074;&--1077;&--1088;&--1076;&--1077;&--1074;&--1072;&--1090;&--1100;. &--1055;&--1086;&--1084;&--1077;&--1096;&--1080;&--1074;&--1072;&--1085;&--1080;&--1077; &--1080; &--1085;&--1072;&--1075;&--1088;&--1077;&--1074; &--1087;&--1088;&--1086;&--1076;&--1086;&--1083;&--1078;&--1072;&--1077;&--1084; &--1087;&--1088;&--1080;&--1073;&--1083;&--1080;&--1079;&--1080;&--1090;&--1077;&--1083;&--1100;&--1085;&--1086; 6 &--1095;&--1072;&--1089;&--1086;&--1074;. &--1055;&--1086;&--1089;&--1083;&--1077; &--1095;&--1077;&--1075;&--1086; &--1086;&--1093;&--1083;&--1072;&--1078;&--1076;&--1072;&--1077;&--1084; &--1074;&--1083;&--1080;&--1074;&--1072;&--1085;&--1080;&--1077;&--1084; &--1074; 1 &--1083;&--1080;&--1090;&--1088; H2O &--1080; &--1080;&--1079;&--1074;&--1083;&--1077;&--1082;&--1072;&--1077;&--1084; &--1089; &--1090;&--1086;&--1083;&--1091;&--1086;&--1083;&--1086;&--1084; &--1080;&--1083;&--1080; &--1076;&--1080;&--1093;&--1083;&--1086;&--1088;&--1084;&--1077;&--1090;&--1072;&--1085;&--1086;&--1084;. &--1056;&--1072;&--1089;&--1090;&--1074;&--1086;&--1088;&--1080;&--1090;&--1077;&--1083;&--1100; &--1076;&--1080;&--1089;&--1090;&--1080;&--1083;&--1083;&--1080;&--1088;&--1091;&--1084;, &--1086;&--1089;&--1090;&--1072;&--1074;&--1083;&--1103;&--1103; &--1078;&--1077;&--1083;&--1090;&--1086;&--1077; &--1084;&--1072;&--1089;&--1083;&--1086;, &--1082;&--1086;&--1090;&--1086;&--1088;&--1072;&--1103; &--1080;&--1084;&--1077;&--1077;&--1090; &--1087;&--1088;&--1080;&--1103;&--1090;&--1085;&--1099;&--1081; &--1079;&--1072;&--1087;&--1072;&--1093;. &--1045;&--1075;&--1086; &--1076;&--1086;&--1073;&--1072;&--1074;&--1083;&--1103;&--1077;&--1084; &--1082; 500 mls 10% &--1088;&--1072;&--1089;&--1090;&--1074;&--1086;&--1088;&--1072; NaOH (50/50 H20 EtOH) &--1080; &--1087;&--1086;&--1084;&--1077;&--1096;&--1080;&--1074;&--1072;&--1077;&--1084; &--1074; &--1090;&--1077;&--1095;&--1077;&--1085;&--1080;&--1077; 1-2 &--1095;&--1072;&--1089;&--1086;&--1074;, &--1080;&--1079;&--1074;&--1083;&--1077;&--1082;&--1072;&--1077;&--1084; &--1089; &--1090;&--1086;&--1083;&--1091;&--1086;&--1083;&--1086;&--1084; &--1080;&--1083;&--1080; &--1076;&--1080;&--1093;&--1083;&--1086;&--1088;&--1084;&--1077;&--1090;&--1072;&--1085;&--1086;&--1084; &--1080; &--1076;&--1080;&--1089;&--1090;&--1080;&--1083;&--1083;&--1080;&--1088;&--1091;&--1077;&--1084; &--1089;&--1086;&--1073;&--1080;&--1088;&--1072;&--1103; &--1092;&--1088;&--1072;&--1082;&--1094;&--1080;&--1102; &--1084;&--1077;&--1078;&--1076;&--1091; 210-220C, &--1089;&--1086;&--1073;&--1088;&--1072;&--1085;&--1086;&--1077; &--1060;&--1077;&--1085;&--1080;&--1083; 2 &--1055;&--1088;&--1086;&--1087;&--1072;&--1085;&--1086;&--1085; (&--1054;&--1082;&--1086;&--1083;&--1086; 35 gms).
In the Organic Reactions review of the Baeyer-Villiger there is a reference to the oxidation of alpha Methyl Cinnamaldehyde using H2O2 catalysed by a nitrobenzene selenic acid or something like that to give the same enol ester as above but in 90% yield.
(&--1090;&--1072;&--1084; &--1074;&--1086;&--1086;&--1073;&--1097;&--1077; &--1076;&--1086;&--1089;&--1090;&--1072;&--1090;&--1086;&--1095;&--1085;&--1086; &--1083;&--1102;&--1073;&--1086;&--1087;&--1099;&--1090;&--1085;&--1099;&--1081; &--1090;&--1086;&--1087;&--1080;&--1082;)
RCHO (R = Me, Et, Pr, Me2CH, MeOC6H4, PhCH:CH, Ph) - &--1082;&--1072;&--1082;&--1080;&--1077; &--1101;&--1090;&--1086; &--1088;&--1077;&--1072;&--1075;&--1077;&--1085;&--1090;&--1099;, &--1087;&--1086;&--1084;&--1086;&--1075;&--1080;&--1090;&--1077; &--1087;&--1086;&--1085;&--1103;&--1090;&--1100;

This a russion translation of what Bio and 2dogs were up to.

Below is a similar synthesis, but a slightly different route.

Experimental
The details of preparation of the dl-â-phenylisopropylamine and its 4-methoxy derivative differ only in the aldehyde used and the intermediate and final products isolated.

Condensation of Aldehyde and Nitroethane
0.2 Mole of aldehyde, 0.2 mole of nitroethane and 0.02 mole of n-amylamine were mixed and set aside at room temperature in the dark. After a day water began to separate from the mixture; after several days the mixture became quite solid. After two weeks, the mixture was dissolved to a homogeneous solution by warming with 50 ml of ethanol and then on cooling a fine crystal product was obtained. From benzaldehyde, 0.15 mole of phenylnitropropylene melting at 65-66°C was obtained. The melting point of this compound has been reported as 64°C2. From anisaldehyde, 0.15 mole of 4-methoxyphenylnitropropylene melting at 43-44°C was obtained. The melting point of this compound has been reported as 48°C3.

Reduction of Phenylnitropropylenes
0.1 Mole of phenylnitropropylene dissolved in a catholyte of 100 ml of ethanol, 50 ml of acetic acid and 50 ml of 12 N sulfuric acid was placed above a 40 cm2 mercury cathode in a porous cell surrounded by a 3 N sulfuric acid anolyte with a water-cooled lead anode. Four amperes was passed for twenty hours and the temperature in the catholyte was kept between 30-40°C.

The resultant catholyte was partially evaporated, then made strongly alkaline and the separated basic layer taken up with benzene. The desired amine was then extracted from the benzene by just neutralizing with dilute hydrochloric acid and separating the aqueous layer. This was then evaporated and the product crystallized. From phenylnitropropylene, 0.02 mole of dl-â-phenylisopropylamine hydrochloride melting at 144-145°C was obtained. The melting point of this compound has been reported as 145-147°C4. From 4-methoxy-phenylnitropropylene, 0.02 mole of dl-â-4-methoxyphenylisopropylamine hydrochloride melting at 205-209°C was obtained. The melting point of this compound has bees reported as 210°C2.

References
Piness, Miller and Alles, J. Am. Med. Assn. 94, 790 (1930)
Mannich and Jacobsohn, Ber. 43, 189 (1910)
Knoevenagel and Walther, Ber. 37, 4502 (1904)
Hey, J. Chem. Soc. 18 (1930)

Also here is a link for the basic schematics of the aldol

http://www.miracosta.edu/home/dlr/211exp5.htm

IndoleAmine · Dreamreader Deluxe

I (and surely many others) would appreciate it if you would complete what you announced. 8)

But its an acid-catalysed aldol condensation (usually they are done with NaOH, not acid), and the perborate/peracetic oxidation of the resulting unsaturated ketone intermediate is called Baeyer-Villiger-oxidation.

I_A (awaiting your next posts on the topic Wink

)

fan of zwitterion · Thu Feb 10, 2005 9:47 am

I think these are great reference experiments, I get permission, and have them uploaded the Watcher link Depository,

I just got a pm for the admin, and all the old hive files are starting to be indexed, Yippe

zitt

bio · Working Bee

Experimenters report in, you know who you are.

There is a pretty good thread on Wet Dreams with some valuable info on this reaction that some of you may already know about. I was thinking maybe the new stuff could be pasted here in this thread (possibly edited). I would do it if the moderator has no objections although it could be a little rough as notepad is my only forte in word processing, LOL.

...........I vaguely remember Bio saying that is also could be achieved with Acetone and benzene, respectfully .................

I am not sure what was meant by this statement but it could be a little misleading to some.

Phenylacetone from benzene and acetone can only be done one way as far as I know, the free radical reaction between the two utilizing Mn3OAc. Problem with this reaction is really not the yield so much but the dilution. I found regeneration of the Mn2 back to Mn3 works best electroliticly insitu using waaay less in the soup (about 20:1). Still have a bucket of perborate to use up so will be a while before doing more experimentation on this.

I read in the general forum something about an anonymous testing organization. What a great idea! My testing org. (sic) fell apart when the Hive dissolved.

The other two ways, if you count Halo derivatives, would be the Freidel/Crafts with haloacetone or the enol reaction with halobenzene.

Oh btw fan of zwitterion; did a google search a few weeks ago on Baeyer/Villiger and what do I stumble on but an article in Russian with the twodogs procedure transliterated from the Hive. Must be yours, good going.

Guest · Tue Feb 15, 2005 1:41 pm

We would love that excerpt, from wet dreams,
Copy and paste away,\

syn

IndoleAmine · Dreamreader Deluxe

The original thread from the Hive:

Subject: Benzaldehyde + MEK acid catalyzed aldol

Posted by: bio (Stranger)
Posted on: 08-03-03 07:28
Post No: 451381

I am prepared to do the subject reaction with Bayer Villager oxidation to P2P.
Where I am now I have no access to a library only the internet for references.
Does anyone have anymore details on this procedure? I feel the sketchy details
in Post 245942 (twodogs: "New method for P2P", Novel Discourse) are fraught
with pitfalls and I sure don't want to waste my analytical grade $80 a liter
PhCHO. Also I have been searching the internet for other catalysts other than
Hydrogen Chloride which would be suitable for this type reaction to no avail.
Any references or pointers would be highly appreciated. The Organic Reactions
volumes referenced don't seem to be available on-line and the Patents
referenced aren't very helpful. Anyway I will try it on a small scale soon and
will let you all know how it turns out.

Subject: Benzaldehyde + MEK
Posted by: twodogs (Newbee)
Posted on: 08-03-03 22:49
Post No: 451488

Sketchy details?? Jesus Christ ...how much detail do you want? If you follow
the procedure exactly as I have mentioned you will get a result.

Subject: Benzaldehyde + MEK
Posted by: bio (Stranger)
Posted on: 08-05-03 03:07
Post No: 451702

OK, Two Dogs thanks for the encouragment. Perhaps sketchy was a poor choice of
words. So I assume you have had success with this reaction. It does seem
fairly simple to do. Apparently a little H2O is not detrimental to the
condensation product yield as they performed it in an open beaker at freezing
temperature. This puzzled me somewhat as water is eliminated and usually I
used a Dean Stark tube or at least a drying tube in a sealed system for
similar PhCHO condensations. Also I wonder if the relatively low yields are
partly due to doing atmospheric distillation. At those high temps it seems a
lot of decomposition could occur. I will try a test batch tomorrow and see if
it will crystallize after removing the excess MEK. If you have done this
reaction could you share some more thoughts? I want to scale it up and think
the oxidation step could get by with way less MeCOOH.

Rated as: good read
Subject: Benzaldehyde + MEK acid catalyzed aldol
Posted by: twodogs (Newbee)
Posted on: 08-05-03 04:19
Post No: 451718

Bio...yes I have had sucess with this reaction but I felt that 35% was too low
for me. The aldol condensation part is very easy and as I mentioned can be
done with refluxing conc. HCl or with H2SO4 but you get the best result with
dry HCl. With the oxidation part, I would use peracetic acid or performic acid
if I were you as the perborate makes for a messy workup. If you use less
Acetic with the perborate you will end up with such a solid mass that you
won't be able to stir it. I don't do this shit any more but have a look at
this site from time to time but I know two another ways to the ketone from the
unsaturated ketone that is formed from the aldol condensation. The unsaturated
ketone can be oxidised with NaOCl to give the alpha- methyl cinnamic acid.
This can be decarboxylated to give phenyl propene that can be worked up with
performic etc or the methyl cinnamic can be oxidised with oxone and the
resulting epoxy acid decarboxylated to give the ketone. I was looking at these
reactions when I figured out that the Baeyer-villager worked as well and that
seemed easier. It is a pity you don't have a library handy as I think that the
Baeyer-Villager would work much better with a catalyst.

Subject: peracetic oxidation
Posted by: viki (Stranger)
Posted on: 08-05-03 05:49
Post No: 451737

question for two dogs.what strength peracetic would you recommend for the
oxidation?would 30-35 %work? viki

Subject: Benzaldehyde + MEK acid catalyzed aldol

Posted by: twodogs (Newbee)
Posted on: 08-05-03 06:17
Post No: 451739

Viki,yes that would work. Have a look at all the patents under Baeyer-Villager
and you will see all the different oxidisers used. Boesken used peracetic.

Subject: Benzaldehyde + MEK acid catalyzed aldol

Posted by: bio (Stranger)
Posted on: 08-06-03 05:32
Post No: 451987

Yea, twodogs the peracetic makes sense. I bought some 30% H2O2 intending to
try it or even regenerate the Na Perborate. Can the peracetic or performic be
made insitu? and would the same molar ratios be used. Also I have the
perborate tetrahydrate a monohydrate is also available, the 4 hydrate which is
NaBO3.H2O2.3H20 is ca. 10% O2. What is the actual mole ratio needed of O2 for
the Baeyer Villiger?

Again thanks for your assistance as the library here is in the wrong language
and only goes to the 10th grade (sic).

Subject: Baeyer-Villager
Posted by: twodogs (Newbee)
Posted on: 08-06-03 07:11
Post No: 452010

Bio
I am sorry but this was a while ago and I don't have any notes. I would have
thought that you would need at least 50% H2O2 to make a strong enough
peracetic. Performic pretty much has to be made on the spot as it deteriorates
quite quickly. Peracetic needs a catalyst like H2SO4 to form and that may need
to be neutralised before use. I had alot of difficulty in figuring out the
percentage of peracetic formed by combining H2O2 and acetic acid. A lot of
posts on the topic here at the Hive I think are wrong in that they assume too
high a percentage of peracetic in the final product. It is one of those
reactions where 1+1 doesn't equal 2. I couldn't buy peracetic and this is the
main reason why I went with the perborate as the quantities needed are easier
to work out. Have a look at US Patent 4988825 where I got the idea of using
perborate.

Rated as: good read
Subject: Peracid concentrations
Posted by: Rhodium (Chief Bee)
Posted on: 08-06-03 11:16
Post No: 452068

See J. Am. Chem. Soc. 907 (1946) (https://www.rhodium.ws/pdf/peracid.pdf)

Subject: Peracid concentrations

Posted by: twodogs (Newbee)
Posted on: 08-06-03 11:39
Post No: 452069

Thanks Rhodium. That is what I had read.. if you use 90% H2O2 with acetic acid
you can get the high concentrations of peracetic but 30% H2O2 only gives about
8%. I don't believe that you can buy 90% H2O2 any more. 35% peracetic seems to
be the reaction grade.

Subject: Peracid concentrations

Posted by: bio (Stranger)
Posted on: 08-07-03 06:33
Post No: 452240

OK, twodogs and Rhodium, thanks for the references. Doing my research now. By
the way Rhodium can P2P be distilled at atmospheric without decomposition (or
only minimal)? I always used about 10 torr and it stayed water white for days.

Subject: P2P distillation
Posted by: Rhodium (Chief Bee)
Posted on: 08-07-03 08:21
Post No: 452251

Yes, P2P can be distilled without vacuum, but you might get 10% better yield
by using vacuum. 10 mmHg is excellent in this case.

Subject: Benzaldehyde + MEK acid catalyzed aldol

Posted by: bio (Stranger)
Posted on: 08-09-03 06:16
Post No: 452559

Hi twodogs and Rhodium. The condensation went quite smoothly I added about
half the HCL gas before the color change started and it was just as you said
the next morning. I will try to crystallize my little test batch tonight
without distilling. Did you ever have any luck with this? When I crystallized
phenyl nitropropene w/o distillation it worked but only by seeding with a
grain or two of fine sand and this without removing the solvent or chilling. I
presume not as you mention the freezer trip. Anyway I will try it as it would
save a lot of work especially when scaled to the proportions planned. PhCHO is
sold as bacteriacide around here so it's about as common as formaldehyde.

Subject: Benzaldehyde + MEK acid catalyzed aldol

Posted by: bio (Stranger)
Posted on: 08-09-03 22:57
Post No: 452657

OK, It crystallized after freezing with scratching and seeding. Now trying to
determine a suitable recrys solvent. Any ideas. Will try abs IPA and Hexane or
Benzene first.

Subject: Post 208702 Post 451381 I've seen MEK (methyl...

Posted by: Herr_Ovalmeister (Stranger)
Posted on: 08-15-03 02:28
Post No: 453611

Post 208702 (Antoncho: "The easiest synth of benzaldehyde from toluene",
Chemistry Discourse)

I've seen MEK (methyl ethyl ketone) sold at one hardware store OTC.

Subject: CeMolybdate
Posted by: bio (Stranger)
Posted on: 09-09-03 03:36
Post No: 457817

The CeMolybdate vapor phase method is INMHO the best. See my other posts.

Subject: tried this...
Posted by: chilly_willy (Hive Bee)
Posted on: 09-25-03 03:40
Post No: 460868

Someone I know tried this reaction a while back. Seemed too good to be true!
Was it? During the condensation he found it impossible to weigh the gassed
liquid to determine any amount of absorbed HCl. Digi(good one) weighed NO
appreciable weight change. <--missing something here??.. He just kept gassing
and gassing until everything got blood red brown. It was left
overnight..washed, extracted, and distilled...a yellow oil was left over that
still smelled like cherries. What the hell?? Instinct told him something
went wrong. Anyway..for shits and giggles he left everything in some ice..and
to his surprise the whole lot of yellow oil solidified the next day..still
smelled like cherries..but crystals..yea! The cherry-smelling sulfur crystals
were added to the perborate w/ gaa..and heating started...a little too fast.
Whoops..a little boil-over. Shit! vinegar smell all over..oh well..fan took
care of that. Heating was properly maintained..crap...the crystasls werent
dissoving. Kept heating. Left for a couple hours...seemed as though
perborate and cherry xtals didnt dissove at all. That cant be right since the
p2p comes from the cherry xtals...? Dumped the whole mess. What the hell
happened? Bio please post as to what happened during your oxidation step.
Ne1 else please enlighten as to what happened/went wrong....

-------------------------------------------------------------------------------
<========>

Subject: Or you could steam distill the p2p.

Posted by: placebo (arrogant bee of the day)
Posted on: 09-25-03 12:26
Post No: 460953

Or you could steam distill the p2p.

-------------------------------------------------------------------------------
I'm not fat, I'm just too short for my weight.
http://www.whatreallyhappened.com

Subject: sodium perborate tetrahydrate

Posted by: bio (Stranger)
Posted on: 10-08-03 04:54
Post No: 463310

two dogs.......Please could you clarify for me if the ca. 8% peracetic from
30% H2O2 will oxidize the ester we discussed, given the perborates ca. 10%
H2O2? I did get the unsat ketone to crys w/o distill.

Subject: it worked
Posted by: bio (Stranger)
Posted on: 10-21-03 07:08
Post No: 465882

just like you said twodogs, thankyou very much. Only thing is I got a slightly
better yield

Subject: gassing MEK
Posted by: viki (Stranger)
Posted on: 11-06-03 05:23
Post No: 469038

If one were scaling this reaction up would it work if one were to gas say 3
litres of MEK first a la Argox, then add the MEK to the benzaldehyde say at
a litre a time?Cheers Viki

Subject: gassing MEK
Posted by: bio (Newbee)
Posted on: 11-06-03 19:23
Post No: 469174

Seems like it should work but I don't see the point here(storage maybe?) The
gassing took me over 3 hours for a 360g MePhBuO in a 2 liter RB using an ice
salt bath to keep the temp about 5 deg +/-. Then it would probably heat up
again when you add to the PhCHO. Maybe a colder bath would speed it up if it
wouldn't get too cold.

The left over MEK goes into the water wash. I was surprised to learn that MEK
holds 24% water.......... To recycle do you know if distilling this MEK/HCL
solution would damage the ketone?............. Or you could mix with the NaOH
wash to neutralize as some is in there too. I only use AR chems and hate
throwing it out but have been to busy to experiment with this idea. Also do a
1/2 vol sat salt wash to clear up the organic layer. This helps a lot.

Once you have some seeds the MePhBuO crystallizes nicely at room temp if
properly distilled. It's instantaneous.

Subject: The left over MEK goes into the water wash

Posted by: bio (Newbee)
Posted on: 11-08-03 03:07
Post No: 469564

Should have said a lot of it. You will get a small 74-84 deg fraction when
distilling the MePhBuO (196ml of 750ml) in the last run. It is full of HCl
even after washing with a 20% excess of lye.

Subject: baeyer-villiger catalyst

Posted by: chilly_willy (Hive Bee)
Posted on: 11-15-03 04:06
Post No: 470971

I just finished searching at the library for possible baeyer-villiger
catalysts and have come up with one that might seem promising. Ferric
chloride. Would using this alone with H2O2 stirring like mad do the job any
better? Yield-wise I mean. What about adding it in with the perborate in
twodogs original procedure. I am still tryiing to understand the dynamics of
the lewis-acid here so please correct me or point out why either suggestion
will or wont work. Thx...

-------------------------------------------------------------------------------
<========>

Subject: I haven't memorized the entire literature

Posted by: Rhodium (Chief Bee)
Posted on: 11-15-03 04:59
Post No: 470981

Post the procedures/references you have found, so that we have something to
work with. It is a little hard to give critique on something we haven't
read...

Subject: baeyer-villiger catalysts

Posted by: bio (Newbee)
Posted on: 11-15-03 05:25
Post No: 470993

Would using this alone with H2O2 stirring like mad do the job any better?

The oxidation is done by the per acid; acetic in this case.

What about adding it in with the perborate in twodogs original procedure.

This sounds feasible, would probably want the anhydrous ferric chloride as
water is a product of the condensation. What molar proportions were used in
the examples you found? I would think very little as FeCl3 is a good Friedel
Crafts reactant, not quite as strong as Aluminum chloride which might also
work.

Subject: Perborate oxidations of ketones

Posted by: bio (Newbee)
Posted on: 11-17-03 23:55
Post No: 471446

SPC/SPB Post 446838 (GC_MS: "SPC/SPB", Novel Discourse) ............Read this
Chilly Willy and if you or anyone else has acess to

Tetrahedron 1987,43,1753-1758

It is from the above article and is on room temp perborate oxidation of
ketones to ketones in acetic acid at room temperature in good to excellent
yields.

I'm still searching for a an oxidation catalyst to try and have seen MnSO4 a
couple times in .01-.1 molar ratio but it's not clear if this won't also
oxidise the ketone itself.

Rated as: excellent
Subject: Benzaldehyde + MEK acid catalyzed aldol
Posted by: bio (Newbee)
Posted on: 11-24-03 23:24
Post No: 472943

I don't have a lot of time to spend on this so if anyone sees any obvious boo
boos please let me know. Just trying to repay my debt to the Hive. And clear
my bad karma, how the hell did that happen?

Results of latest twodogs reaction.

1) Methyl Phenyl Butanone (MePhBuO)...... 400g PhCHO and 600g MEK (both RA
grade) were mixed in a 2L flask placed in an ice salt bath and cooled to -5
degrees. 80 grams of DRY HCL gas was passed over about 3 hours keeping the
temp below 5-7 degrees. Stirring with the thermometer. (This is about a 1 to
2.2 mole ratio as given by twodogs. Rhodium has posted an apparent improvement
of yield to 94% with 1 to 1 mole which has not been tried yet.) A saturated
solution is what is strived for here. Previous results indicated about 85% of
the calculated HCl was absorbed. An additional 15% was partly added to
compensate and the solution was saturated before it was all added. Flask
stoppered and left in bath to warm up overnight ca. 10 hours. The Vogel
method of dripping 37% HCl into 98% H2SO4 was used with a H2SO4 dryer. Trap
also used but not needed this time. Vogel says 31-33g HCl per 100ml.

2) The resulting deep reddish brown reaction mix was washed with an equal
volume of water separated then washed with a 20% excess of 10% NaOH separated
then washed with 1/2 volume of brine separated and filtered to give 845ml Ph
7-8 solution. This was distilled at atmospheric collecting most of the first
fraction 74-84 degrees PH1 and the second fraction at aspirator pressure most
was collected 119-140 degrees. MePhBuO clear yellow fruity smelling oil 506.7
gram includes the forerun and after run. This was allowed to cool to ambient,
then seeded causing immediate crystalization. Let set up in frig with stirring
for a couple hours. Filter on buchner wash with 95% EtOH dried for 430 grams
total very clean and dry light yellow (almost white) pleasant smelling
crystals. These initially set up as long transparent light yellow needles.
Happy now as had expected only 360 grams. Even returned to the vac dessicator
to insure they were dry. Recrys of a little test resulted in very little
improvement. This stuff is easy to crys in a relatively pure form. No GC/MS
sorry.

3) Baeyer-Villiger Oxidation....... To a 6 liter FB flask on the mag stirrer
hotplate in a water bath was added 2.3L Glacial Acetic Acid (RA) 615g
NaPerborate 4H2O and 430g MePhBuO with stirring. This starts endothermic and
mag stirring is inadequate until heat is added and the stuff dissolves. Added
the crystals over ca. 1/2 hour while heating to about 45 deg. After the
induction period added ice and or heating periodically to keep the solution
temp 55-65 deg. Can get into this more later if anyone actually is ready to
do it. Stir vigorously keeping the temp as above for 6 hours. If it gets
hotter as long as controllable it's OK. Be very carefull here I already had a
near runaway........ Proceed slowly and carefully........ Cool to ambient then
either dilute with water or recover the NaBO2 and acid first. Now extract with
toluene or DCM. I used DCM this time and wish I didn't. Anyway extracted with
1.2L DCM washed with water and brine then removed solvent to leave the enol
ester.

4) Hydrolysis and P2P...... enol ester added to 2.25L 10% NaOH in 50/50 w/w
EtOH/H2O and stirred 2 hours. Extracted with DCM 300/200/200ml (again wish I
had used PhMe) washed with water and brine removed solvent and collected 162g
P2P at aspirator pressure (almost all between 119-140 deg). OVER

Subject: collected 162g P2P
Posted by: bio (Newbee)
Posted on: 11-25-03 01:02
Post No: 472961

correction......collected 169.5g...... did not drain completely...takes time
you know

Subject: Benzaldehyde + MEK acid catalyzed aldol

Posted by: twodogs (Newbee)
Posted on: 11-25-03 11:20
Post No: 473050

Nicely done Bio. One thing that should be mentioned is that in the
condensation step, over gassing leads to some sort of
polymerisation...evidently. There is a paper mentioning this somewhere. This
is why I stated the weight of dry HCl in my original post of the set of
reactions instead of just saying gas the shit out of it.

Subject: polymerization
Posted by: bio (Newbee)
Posted on: 11-25-03 19:36
Post No: 473129

Well there is certainly a lot of the tarry polymer created using the 1 to ca.2
mole ratio. Perhaps going slower this time and watching temp more carefully
and not taking out of the ice right away helped the yield. Also there could be
a clue hidden in the reference to the gassing procedure (not given) which is
the key to the 94% yield with only a trace of tar. The statement regarding
saturation was gleaned from the JACS 65,1824(1943) article Rhodium posted. I
did notice that following your weights of HCL that saturation (or somewhere
close) was reached very near the end. What was not stated in the synthesis
part was the procedure or temp used when HCL gasing. There is a footnote to
this article saying they followed this procedure.,,,,,,,,,,,(5) Muller and
Harries, Ber., 36, 9BG (1902).,,,,,,,,,,,,if anyone could find this it would
be very helpfull.

Surely somebee has access to Ber. (berliner I think) and could dig it up to
assist.

Rated as: good read
Subject: Making this reaction more OTC . . .
Posted by: psychokitty («»)
Posted on: 10-11-04 08:41
Post No: 535306

I think the value of the following patent speaks for itself. If it's already
been posted before, please accept my apologies in advance. I tried to use
TFSE.

( 1 of 1 )
United States Patent 4,673,766
Buck , et al. June 16, 1987
Method of producing benzaldehyde

Abstract

A method is disclosed for producing benzaldehyde by fractionally steam
distilling benzaldehyde from cinnamaldehyde in the presence of hydroxide
catalyst and at a pH on the order of about 11 to about 13. Conversions of
cinnamaldehyde to benzaldehyde can be achieved on the order of about 75% or
more.
Inventors: Buck; Keith T. (Cincinnati, OH); Boeing; Anthony J. (Cincinnati,
OH); Dolfini; Joseph E. (Cincinnati, OH)
Assignee: Mallinckrodt, Inc. (St. Louis, MO)
Appl. No.: 856595
Filed: April 25, 1986

Current U.S. Class: 568/433; 568/458
Intern'l Class: C07C 045/51
Field of Search: 568/433,458
References Cited [Referenced By]

Other References

Guthrie et al., Can. Jour. Chem., vol. 62 (1984), 1441-1445.

Primary Examiner: Helfin; Bernard
Attorney, Agent or Firm: Wood, Herron &Evans
Claims

What is claimed is:

1. A method of making benzaldehyde com- prising

dispersing cinnamaldehyde in water,

converting the cinnamaldehyde to benzaldehyde under the action of heat in the
presence of a catalytic amount of hydroxide ion and at a pH of about 11 to
about 13,

fractionally steam distilling benzaldehyde and acetaldehyde from the
cinnamaldehyde, and

recovering benzaldehyde from the distillate.

2. The method of claim 1 which is conducted at a pH in the range of about 12
to about 12.5.

3. The method of claim 1 wherein the benzaldehyde distillate resulting from
the steam distillation is fractionally distilled for separation of the
benzaldehyde in substantially pure form.

4. The method of claim 1 wherein the acetaldehyde is vaporized during the
course of the conversion while the benzaldehyde is condensed.

5. The method of claim 1 conducted in the presence of an anionic surfactant.

6. The method of claim 1 conducted under shearing agitation to facilitate the
dispersion of the cinnamaldehyde in the water.

7. A method of making benzaldehyde com- prising

dispersing cinnamaldehyde in water in the presence of an anionic surfactant,

agitating the dispersion under the action of heat in the presence of a
catalytic amount of hydroxide ion and at a pH of about 12 to about 12.5 for
the conversion of cinnamaldehyde to benzaldehyde,

fractionally steam distilling benzaldehyde and acetaldehyde from the
cinnamaldehyde in a still having a pot temperature of about 105.degree. C. and
a column temperature of about 99.degree. C., and

fractionally distilling the benzaldehyde from the distillate for the
separation of substantially pure benzaldehyde to obtain a yield of at least
about 75% based upon the cinnamaldehyde.

8. The method of claim 7 wherein cassia oil is employed as a natural source
for the cinnamaldehyde employed in the conversion.
Description

BACKGROUND OF THE INVENTION

The retroaldol reaction of cinnamaldehyde is well known. In this reaction,
cinnamaldehyde is converted to benzaldehyde and acetaldehyde with various
potential side reactions. Recently, for example, an investigation of the
kinetics of the retroaldol reaction of cinnamaldehyde has been reported by J.
Peter Guthrie, et al, Can. J. Chem., Vol. 62, pp. 1441-1445 (1984). While the
conversion of the cinnamaldehyde to benzaldehyde has been long known and well
studied, it has not been heretofore known to produce benzaldehyde from
cinnamaldehyde in substantial yields and favorable reaction conditions for
production of such yields have not been reported.

SUMMARY OF THE INVENTION

This invention is directed to a method of making benzaldehyde by conversion of
cinnamaldehyde in the presence of water with surprisingly high yields
heretofore unachieved. The invention involves the dispersion of cinnamaldehyde
in water and, in the presence of an effective catalytic amount of hydroxide
ion, fractionally steam distilling benzaldehyde from the cinnamaldehyde. The
reaction is conducted at a pH on the order of about 11 to about 13 and,
unexpectedly, within this pH range it has been discovered that a substantial
conversion of cinnamaldehyde to benzaldehyde can be achieved on the order of
about 75% or more. It has also been found that the conversion may be achieved
at such a high pH without adverse side reactions.

In a preferred mode of conducting the method, the cinnamaldehyde is dispersed
in the water in the presence of shearing agitation and a surfactant. In
another aspect of this invention, it is preferred to employ an anionic
surfactant such as sodium lauryl sulfate. Preferably, the hydroxide ion is
furnished by means of sodium hydroxide which also achieves the pH in the range
of about 11 to about 13. It has critically been determined that the fractional
steam distillation of benzaldehyde from the cinnamaldehyde must be conducted
at a pH within the range of about 11 to about 13, preferably about 12 to about
12.5. Below and above this pH range, very poor conversions are obtained of 50%
or far less and competing reactions interfere with the production of
benzaldehyde. Outside of this critical pH range, side reactions,
polymerization and other adverse reactions prohibit any significant yield of
benzaldehyde. Yet, within the pH range of about 11 to about 13, especially
about 12 to about 12.5, significant yields on the order of 75% or greater are
achieved and benzaldehyde is recoverable in substantially pure form free of
side reaction products. These results are considered to be unexpected
especially at the high pHs of the reaction where it may have been expected
that side reactions would have significantly lessened or prevented the yield
for the desired product.

During the course of the fractional steam distillation of benzaldehyde from
the cinnamaldehyde, acetaldehyde is also vaporized and removed. The removal of
acetaldehyde thus prevents the forward polymerization reaction which otherwise
competes in the presence of the catalyst. The benzaldehyde which has been
steam distilled is then subsequently fractionally distilled for separation of
the benzaldehyde from other components in the distillate such as minor amounts
of acetaldehyde, terpenes and orthomethoxybenzaldehyde. It has also been found
that a natural source for the cinnamaldehyde such as cassia oil may be
employed containing a substantial amount of the natural cinnamaldehyde. Thus,
a natural product such as cassia oil may be employed in the fractional steam
distillation method of this invention and still the significant yields on the
order of about 75% or more are achieved.

DETAILED DESCRIPTION

The following detailed operating example illustrates the practice of the
invention in its most preferred form, thereby enabling a person of ordinary
skill in the art to practice the invention. The principles of this invention,
its operating parameters and other obvious modifications thereof will be
understood in view of the following detailed procedure.

OPERATING EXAMPLE

A solution was made up from 38.6 lbs. sodium hydroxide, 4 lbs. sodium lauryl
sulfate and 10 liters antifoam agent in 760 gallons of water. The solution was
stirred until a homogeneous solution was obtained. Then, 1320 lbs. of cassia
oil were placed in a 1150 gallon still. The oil contained approximately 72% by
weight of cinnamaldehyde. The still had a pot volume of about 1150 gallons
onto which was mounted a 4 foot fractionating column containing 1".times.1"
ceramic tubes and a water cooled condenser was thereafter connected in series
for condensing the benzaldehyde-water azeotrope.

The above prepared sodium hydroxide solution was then added to the cassia oil
and introduced into the pot of the still. The pot was equipped with a stirrer.
Using pressurized steam and vigorous stirring, the pot was heated to reflux
with a pot temperature of 105.degree. C. Reflux was established with a column
head temperature of about 99.degree. C. Once reflux was established, it was
continued for about 1 hour. During the course of the conversion of the
cinnamaldehyde in the cassia oil to benzaldehyde, pH was monitored and was
maintained at about 12 to about 12.5. In the event the pH fell below about 12,
sodium hydroxide was added to bring the pH back up to the range of about
12-12.5. After refluxing for about 1 hour, take-off of the water-benzaldehyde
azeotrope was initiated. The water cooled condenser was operated at
100.degree. F. thereby enabling the water-benzaldehyde azeotrope to be
condensed and collected in a chilled receiver. The acetaldehyde by-product was
principally vaporized at the temperature of the condenser and was taken off as
vapor. The distillate principally containing benzaldehyde in an amount of
about 75% or more with minor amounts of cinnamaldehyde, terpenes,
orthomethoxybenzaldehyde and acetaldehyde was obtained. The crude benzaldehyde
was thus collected in a chilled receiver and, in a continuous feed operation
the condensed water was continuously fed back to the still to replace what had
been taken off and the distillation of the azeotrope continued. The fractional
steam distillation of the crude benzaldehyde continued until about 670 lbs. of
crude benzaldehyde were obtained. The crude distillate containing benzaldehyde
was then dried under vacuum and fractionally distilled under vacuum of about
29" thereby providing a boiling point for the benzaldehyde at about 70.degree.
C. in order to obtain a substantially pure benzaldehyde free from residual
terpenes and other impurities.

Thus, by means of practicing the above process, the objectives of this
invention are achieved in that cinnamaldehyde is converted into benzaldehyde
in substantially pure form even from the natural source of cassia oil.
Surprisingly, it has been found that substantial yields in excess of 75% or
more of substantially pure benzaldehyde are achieved by this method. Moreover,
it has been found that there is a surprising window of high pH at which the
conversion may take place in a fractional steam distillation column in order
to separate the benzaldehyde and acetaldehyde from the reaction mixture and
still avoid the adverse side reactions from occurring.

Having described this invention and its operating parameters, variations may
be achieved without departing from the spirit and scope hereof.

Rated as: good read
Subject: The surprises never end, do they? . . .
Posted by: psychokitty («»)
Posted on: 10-11-04 08:45
Post No: 535307

And here's yet another good and useful patent:

( 1 of 1 )
United States Patent 4,766,249
Buck , et al. * August 23, 1988
Method of catalytically hydrolyzing alpha, beta-unsaturated carbonyl compounds

Abstract

Alpha, beta-unsaturated carbonyl compounds are hydrolyzed under alkaline
conditions in the presence of water to produce additional carbonyl-containing
compounds. High yields are obtained when the alkaline catalyst contains
hydroxide ion and the pH is maintained in the range of about 11 to about 13.
Inventors: Buck; Keith T. (Cincinnati, OH); Boeing; Anthony J. (Cincinnati,
OH); Dolfini; Joseph E. (Cincinnati, OH); Glinka; Jerome (Cincinnati, OH)
Assignee: Mallinckrodt, Inc. (St. Louis, MO)
+ Notice: The portion of the term of this patent subsequent to June 16,
2004 has been disclaimed.Appl. No.: 942491
Filed: December 24, 1986

Current U.S. Class: 568/433; 568/458
Intern'l Class: C07C 045/42
Field of Search: 568/426,433,435,437,440,458
References Cited [Referenced By]

Other References

Guthrie et al., "Can. J. Chem.", vol. 62, pp. 1441-1445, (1984).

Primary Examiner: Lone; Werren B.
Attorney, Agent or Firm: Wood, Herron &Evans
Parent Case Text

RELATED APPLICATION

This is a continuation-in-part of application Ser. No. 856,595, filed Apr. 25,
1986, invented by Keith T. Buck, Anthony J. Boeing and Joseph E. Dolfini, and
assigned to the assignee of this application, now U.S. Pat. No. 4,673,766.
Claims

What is claimed is:

1. A method of producing a carbonyl-containing compound which comprises

hydrolyzing by dispersing in water an alpha, beta-unsaturated carbonyl
compound of the formula ----STR3---- to produce a carbonyl-containing compound and
by-product according to the following formulas ----STR4---- wherein R' and R" are
hydrogen, aliphatic or aromatic hydrocarbon groups or substituted derivatives
thereof, and R"' is an aliphatic or aromatic aldehyde- or ketone-containing
group having the carbon to oxygen double bond of said aldehyde or ketone
conjugated with the alpha, beta double bond between C and R"' of alpha,
beta-unsaturated alpha,beta-unsaturated carbonyl compound, and

conducting said hydrolysis of the alpha, beta-unsaturated carbonyl compound
under the action of heat in the presence of a catalytic amount of hydroxide
ion and at a pH of about 11 to about 13.

2. The method of claim 1 which is conducted at a pH in the range of about 12
to about 12.5.

3. The method of claim 1 wherein the individual carbonyl-containing compounds
obtained from said hydrolysis reaction are fractionally distilled for
separation in substantially pure form.

4. The method of claim 1 conducted in the presence of an anionic or non-ionic
surfactant.

5. The method of claim 1 conducted under shearing agitation to facilitate the
dispersion of the alpha, beta-unsaturated carbonyl compound in the water.

6. The method of claim 1 wherein said alpha, beta-unsaturated carbonyl
compound is citral and the carbonyl-containing compounds produced are
6-methyl-5-hepten-2-one and acetaldehyde.

7. The method of claim 1 wherein said alpha, beta-unsaturated carbonyl
compound is pulegone and the carbonyl-containing compounds produced are
acetone and 3-methylcyclohexanone.

8. A method of producing a carbonyl-containing compound which comprises

hydrolyzing by dispersing in water under shearing agitation in the presence of
an anionic surfactant an alpha, beta-unsaturated carbonyl compound of the
formula ----STR5---- to produce a carbonyl-containing compound and by-product
according to the following formulas ----STR6---- wherein R' and R" are hydrogen,
aliphatic or aromatic hydrocarbon groups or substituted derivatives thereof,
and R"' is an aliphatic or aromatic aldehyde- or ketone-containing group
having the carbon to oxygen double bond of said aldehyde or ketone conjugated
with the alpha, beta double bond between C and R"' of said alpha,
beta-unsaturated carbonyl compound, and

conducting said hydrolysis of the alpha, beta-unsaturated carbonyl compound
under the action of heat in the presence of a catalytic amount of hydroxide
ion and at a pH of about 12 to about 12.5.
Description

BACKGROUND OF THE INVENTION

The retroaldol reaction of cinnamaldehyde is well known. In this reaction,
cinnamaldehyde is converted to benzaldehyde and acetaldehyde with various
potential side reactions. Recently, for example, an investigation of the
kinetics of the retroaldol reaction of cinnamaldehyde has been reported by J.
Peter Guthrie, et al, Can. J. Chem., Vol. 62, pp. 1441-1445 (1984). The
conversion of the cinnamaldehyde to benzaldehyde has been long known and well
studied. However, it has not been heretofore known to produce benzaldehyde
from cinnamaldehyde in substantial yields, and favorable reaction conditions
for production of such yields have not been reported. Similarly, citral has
been hydrolyzed via the retroaldol reaction to produce 6-methyl-5-hepten-2-one
and acetaldehyde. Again, however, product yield is low. Up to now, it has not
been known how to obtain carbonyl-containing reaction products in substantial
yields through the retroaldol hydrolysis of any of the alpha,beta-unsaturated
carbonyl compounds, of which cinnamaldehyde and citral are examples.

SUMMARY OF THE INVENTION

The invention disclosed in the above application Ser. No. 856,595 is directed
to a method of making benzaldehyde by conversion of cinnamaldehyde in the
presence of water with surprisingly high yields heretofore unachieved. The
invention involved the dispersion of cinnamaldehyde in water and, in the
presence of an effective catalytic amount of hydroxide ion, fractionally steam
distilling benzaldehyde from the cinnamaldehyde. The reaction was conducted at
a pH on the order of about 11 to about B 13 and, unexpectedly, within this pH
range it has been discovered that a substantial conversion of cinnamaldehyde
to benzaldehyde could be achieved on the order of about 75% or more. It has
also been found that the conversion may be achieved at such a high pH without
adverse side reaction.

It has also been found that members of the class of compounds known as
alpha,beta-unsaturated carbonyl compounds, of which cinnamaldehyde is an
example, can be hydrolyzed via the retroaldol reaction to produce
carbonyl-containing compounds in substantial yields.

In a preferred mode of conducting the method, the alpha,beta-unsaturated
carbonyl compound is dispersed in water in the presence of shearing agitation.
It will be understood that other water soluble or dispersible cosolvents such
as alcohols, ethers or the like may be used in the aqueous reaction medium. An
anionic surfactant such as sodium lauryl sulfate or a non-ionic surfactant
such as polyethylene glycol having a molecular weight in the range of 400 to
600 may be used. Preferably, the hydroxide ion is furnished by means of sodium
hydroxide which also achieves a pH in the range of about 11 to about 13. After
the starting materials have been charged to the flask, reaction is initiated
with the addition of heat. Once reaction has begun, separation of the products
is achieved through the production of water-product azeotropes which are
isolated by fractional distillation. It has been critically determined that
the fractional distillation must be conducted at a pH within the range of
about 11 to about 13, preferably about 12 to about 12.5. Reactions conducted
outside this pH range exhibit very poor conversion to desired product because
side reactions, polymerization and other adverse reactions occur.

Reactions conducted within the pH range of about 11 to about 13, and
especially between about 12 and about 12.5, produce significant yields on the
order of 75% or greater and are substantially free of side reaction products.
These results are considered to be unexpected especially at the high pH levels
of the reaction where it may have been expected that side reactions would have
significantly lessened or prevented the yield for the desired product.

The reaction products isolated by fractional distillation may be further
purified by means of additional separation techniques. The separation
technique employed may vary with the degree of purity sought. Pure
alpha,beta-unsaturated carbonyl compounds may be used as starting materials
for the reaction. However, product yield percentage is not adversely affected
when natural products containing the desired starting materials are used in
the reaction. Thus, a natural product such as cassia oil containing
substantial amounts of cinnamaldehyde may be used successfully in this
invention. Similarly, lemon grass oil containing citral may be used
successfully. Also, pennyroyal oil may be utilized under the teachings of this
invention as a source of pulegone, an alpha,beta-unsaturated carbonyl compound.

DETAILED DESCRIPTION

The method in its broader aspects is practiced by hydrolyzing after dispersing
in water an alpha,beta-unsaturated carbonyl compound having the formula
----STR1---- to produce a carbonyl-containing compound and a by-product having the
general formulas ----STR2---- The substituents R' and R" are hydrogen, aliphatic
or aromatic hydrocarbon groups or substituted derivatives thereof, and R"' is
an aliphatic or aromatic aldehyde- or ketone-containing group having the
carbon to oxygen double bond of the aldehyde or ketone conjugated with the
alpha,beta double bond between C and R"' of the alpha,beta-unsaturated
carbonyl compound. The hydrolysis reaction proceeds under the action of heat
and is catalyzed by hydroxide ion having a concentration level sufficient to
maintain the solution pH between about 11 and about 13.

A large number of alpha,beta-unsaturated carbonyl compounds may be hydrolyzed
according to the teachings of this invention. The compounds in the following
non-comprehensive list are included under the description of hydrolyzable
alpha,beta-unsaturated carbonyl compounds: cinnamaldehyde to produce
benzaldehyde and acetaldehyde; citral to produce 6-methyl-5-hepten-2-one and
acetaldehyde; pulegone to produce 3-methylcyclohexanone and acetone;
3-decen-2-one to produce heptanal and acetone; 2-dodecenal to produce decanal
and acetaldehyde; 2-heptenal to produce pentanal and acetaldehyde; 2-hexenal
to produce butanal and acetaldehyde; ionone to produce cyclocitral and
acetone; irone to produce 2,5,6,6-tetramethyl-cyclohex-1-ene-1-carboxaldehyde
and acetone; 1-(4-methoxyphenyl)-1-penten-3-one to produce
paramethoxybenzaldehyde and methyl ethyl ketone; 5-methyl-3-hexen-2-one to
produce isobutyraldehyde and acetone; alpha-methyl-iso-ionone to produce
citral and methyl ethyl ketone; 5-methyl-2-phenyl-2-hexenal to produce phenyl
acetaldehyde and 3-methylbutanal; 4-phenyl-3-buten-2-one to produce
benzaldehyde and acetone; and ortho-methoxy cinnamaldehyde to produce
ortho-methoxy benzaldehyde and acetaldehyde.

(to be continued . . .)

Subject: Continued from above . . .

Posted by: psychokitty («»)
Posted on: 10-11-04 08:47
Post No: 535308

OPERATING EXAMPLE I

A solution was made up from 38.6 lbs. sodium hydroxide, 4 lbs. sodium lauryl
sulfate and 10 liters antifoam agent in 760 gallons of water. The solution was
stirred until a homogeneous solution was obtained. Then, 1320 lbs. of cassia
oil were placed in a 1150 gallon still. The oil contained approximately 72% by
weight of cinnamaldehyde. The still had a pot volume of about 1150 gallons
onto which was mounted a 4 foot fractionating column containing 1".times.1"
ceramic tubes and a water-cooled condenser was thereafter connected in series
for condensing the benzaldehyde-water azeotrope.

The above prepared sodium hydroxide solution was then added to the cassia oil
and introduced into the pot of the still. The pot was equipped with a stirrer.
Using pressurized steam and vigorous stirring, the pot was heated to reflux
with a pot temperature of 105.degree. C. Reflux was established with a column
head temperature of about 99.degree. C. Once reflux was established, it was
continued for about 1 hour. During the course of the conversion of the
cinnamaldehyde in the cassia oil to benzaldehyde, pH was monitored and was
maintained at about 12 to about 12.5. In the event the pH fell below about 12,
sodium hydroxide was added to bring the pH back up to the range of about
12-12.5. After refluxing for about 1 hour, take-off of the water-benzaldehyde
azeotrope was initiated. The water-cooled condenser was operated at
100.degree. F. thereby enabling the water-benzaldehyde azeotrope to be
condensed and collected in a chilled receiver. The acetaldehyde by-product was
principally vaporized at the temperature of the condenser and was taken off as
vapor. The distillate consisted principally of benzaldehyde in an amount of
about 75% or more with minor amounts of cinnamaldehyde, terpenes,
orthomethoxybenzaldehyde and acetaldehyde. The crude benzaldehyde was thus
collected in a chilled receiver and, in a continuous feed operation the
condensed water was continuously fed back to the still to replace what had
been taken off and the distillation of the azeotrope continued. The fractional
steam distillation of the crude benzaldehyde continued until about 670 lbs. of
crude benzaldehyde was obtained. The crude distillate containing benzaldehyde
was then dried under vacuum and fractionally distilled under vacuum of about
29" thereby providing a boiling point for the benzaldehyde at about 70.degree.
C. in order to obtain a substantially pure benzaldehyde free from residual
terpenes and other impurities.

OPERATING EXAMPLE II

Into a 5-liter, 3-neck flask was charged 1012.5 g of pennyroyal oil,
containing a substantial portion of pulegone, 3.5 liters water and 30 g sodium
hydroxide having a minimum 90% purity. The initial charge of hydroxide
produced a pH of about 12. The pH was monitored during the subsequent
reaction, and additional sodium hydroxide was added as needed to maintain a pH
of about 12. The flask was equipped with a mechanical stirrer/drive motor
apparatus and a fractionating column. After agitation was initiated, heat was
applied to the mixture in the flask by means of a heating mantle.

As the agitated mixture of pennyroyal oil, sodium hydroxide and water was
heated, the pressure in the flask was maintained at atmospheric by permitting
the fractionating column to remain uncapped. At a pot temperature of
approximately 100.degree. C. and a head temperature of approximately
56.degree. C., distillation occurs and an azeotropic mixture of 96% acetone
and 4% water is collected off the top of the fractionating column. The
azeotrope was collected by means of the fractionating column.

The co-distillation of acetone occurred over a period of about six days.
Agitation and heating were discontinued when no additional distillate was
generated. The oil layer remaining in the flask was separated from the sodium
hydroxide solution and then water-washed to remove traces of sodium hydroxide.

The washed oil contained the hydrolysis product 3-methylcyclohexanone (b.p.
168.degree.-9.degree. C.), minor amounts of unhydrolyzed pulegone (b.p.
224.degree. C.), and other trace components attributable to the starting
pennyroyal oil. The acetone was subsequently assayed for purity, including a
determination of water content. The yield of acetone was approximately 73%.

OPERATING EXAMPLE III

Approximately 500 ml water, 5 g (90% active) sodium hydroxide, and 88 g
terpeneless lemon grass oil containing approximately 95% citral were charged
into a one-liter round bottom flask. The round bottom flask was equipped
additionally with a trap having means of permitting removal of the lower
density liquid while recirculating the higher density liquid, a fractionating
column, and a means for stirring.

The stirred contents of the flask were heated to reflux by means of a heating
mantle. The pH of the contents was set at 12 and maintained at that level
during the remainder of the run by addition of sodium hydroxide when
necessary. The contents were refluxed for one hour, after which time the steam
distillate was slowly collected. The distillate take-off was regulated so that
little or no citral distilled over. The distillation was continued until no
additional oil was collected.

The oil phase distillate was separated from the steam condensate. The
separated oil was then short-path vacuum distilled. The main cut yielded 72 g
of the citral hydrolysis product, 6-methyl-5-hepten-2-one. The other reaction
product, acetaldehyde, was vented from the flask through the fractionating
column during the reaction. The yield of 6-methyl-5-hepten-2-one was
approximately 90% under the above conditions.

Thus, by means of practicing the preferred processes listed above, the
objectives of this invention are achieved in that desirable products can be
obtained in good yield from alpha,beta-unsaturated carbonyl compounds. Pure
starting materials may be used, but good results are obtainable even from
natural sources of the alpha,beta-unsaturated carbonyl compounds. It is
critical to the teachings of this invention that reaction take place in an
alkaline hydroxide environment wherein the pH is maintained within a window of
about 11 to about 13. Unexpectedly, not only are products obtained in yields
exceeding 70 to 75%, but the reaction proceeds with a low level of competitive
side reactions, polymerization or other adverse reactions.

Having described this invention and its operating parameters, variations may
be achieved without departing from the spirit and scope hereof.

Rated as: good read
Subject: Another retroaldol cleavage of cinnamaldehyde?
Posted by: psychokitty («»)
Posted on: 10-12-04 01:05
Post No: 535419

Here's another way to get benzaldehyde using a variation of the retroaldol
reaction. 4-Phenyl-3-buten-2-one is oxidized to the epoxide via basic H2O2
and then cleaved by the NaOH to benzaldehyde and acetone. The yields are
supposedly higher that the then-utilized base-catalyzed "retrograde aldol
reaction" (retroaldol reaction) and the products of the reaction appear to be
cleaner. All in all, the method seems pretty simple and just as OTC as the
aforementioned retroaldol reaction using cinnamaldehyde as a precursor to
benzaldehyde.

The Epoxidation and Cleavage of a,B-Unsaturated Ketones with Alkaline Hydrogen
Peroxide
ROBERT D. TEMPLE
The Journal of Organic Chemistry Vol. 35, No. 6, May 1970

Abstract:

The kinetics of the reaction between 4-phenyl-3-buten-2-one and aqueous
alkaline hydrogen peroxide were studied. Four reactions occur in this system :
epoxidation by hydroperoxide ion to form 4-phenyl-3,4-epoxy-2-butanone,
oxidative cleavage of the epoxide by hydroperoxide to give benzaldehyde,
retrograde aldol reaction,and cleavage of the epoxide by hydroxide. The rates
of these reactions in water at 25 are 0.22,0.05,0.00016,and 0.0032 1. mol-
sec-l, respectively. The influence of substituents in the phenyl ring on
reaction rates and the relative reactivities of hydroperoxide and hydroxide
ions are discussed in terms of the reaction mechanisms. The oxidative cleavage
of a,p-epoxy ketones is mechanistically similar to several recently reported
fragmentation reactions. The cleavage reaction was shown to have general
synthetic utility in preparing diacids, keto acids, and ketones from
+-unsaturated ketones, alp-unsaturated aldehydes, and p diketones.

Preparative Oxidation Procedure:

To a solution of 0.01 mol of the a,B-unsaturated carbonyl compound in 50 ml of
methanol,12 ml of 30% aqueous hydrogen peroxide and then 30 ml of 1 N aqueous
sodium hydroxide solution were added with cooling. The mixture was then
stirred overnight at 40-50" (1 hr at 40" for the reaction with citral). The
resulting solution was evaporated to about half the original volume on a
rotary evaporator and then washed with ether. The aqueous solution was made
acidic with sulfuric acid, saturated with sodium sulfate, and extracted
thoroughly with ether. The extract was treated with FeSO4 or Na2SO3 to destroy
peroxides, dried (MgSO4), and evaporated. The residue, which was essentially
pure product, was recrystallized, distilled, or converted into a suitable
derivative as outlined below.

Note: 4-Phenyl-3-buten-2-one is not listed in the experimetal section of the
article.

Rated as: excellent
Subject: Baeyer-Villiger reaction using Oxone as oxidant
Posted by: psychokitty («»)
Posted on: 10-12-04 02:11
Post No: 535428

Maybe this might work to effect a more OTC Baeyer-Villiger transformation.

Facile Oxidation of Aldehydes to Acids and Esters with Oxone
Benjamin R. Travis, Meenakshi Sivakumar, G. Olatunji Hollist, and Babak Borhan*
ORGANIC LETTERS 2003 Vol. 5, No. 7 1031-1034

Abstract:

A highly efficient, mild, and simple protocol is presented for the oxidation
of aldehydes to carboxylic acids utilizing Oxone as the sole oxidant. Direct
conversion of aldehydes in alcoholic solvents to their corresponding ester
products is also reported. These reactions may prove to be valuable
alternatives to traditional metal-mediated oxidations.

Description of the art:

As a fortuitous extension of the solvent study, the oxidation of aldehydes
with Oxone in alcoholic solvents cleanly provided high conversion to esters.
Thus, the oxidation of benzaldehyde in methanol did not yield the expected
carboxylic acid, but instead the methyl ester was obtained. The present
strategy complements other known methods that directly convert aldehydes to
esters such as oxidation in the presence of alcohol with Br2 or I2, NBS/AIBN,
PDC, HCN/MnO2, or performed electrochemically.21-25 Additionally, we found
that other alcohols such as ethanol, n-propanol, and 2-propanol also provide
their corresponding esters in excellent yields, although oxidation in
tert-butyl alcohol furnished the carboxylic acid as the sole product (Table 3,
entries 1-9). It is important to note that the esters are not obtained as the
result of the oxidation of aldehydes to carboxylic acids followed by
Fischer-type esterification of the acids in alcoholic solvents. Incubation of
benzoic acid in methanol with Oxone for a prolonged period did not result in
the isolation of methyl benzoate, but in fact the starting acid was
re-isolated quantitatively.

The direct oxidation of a variety of aryl and alkyl aldehydes to their
corresponding methyl esters is also illustrated in Table 3 (entries 10-19).
Oxidation of aryl aldehydes with electron-withdrawing substituents showed slow
conversion to the esters (Table 3, entries 10 and 11) initially providing
dimethyl acetals in addition to the ester products. This was overcome by
heating the reactions to reflux overnight, which provided clean conversion to
the desired methyl esters 1b and 2b. Oxidation of 6 and 9 (electroneutral
aromatics aldehydes) and 19-23 (aliphatic aldehydes) proceeded smoothly at rt
to furnish the desired methyl esters in excellent yields. In the case of
electronrich aromatic substrates, as with the oxidations to carboxylic acids
in DMF, the Dakin products were observed. thus, 4-hydroxybenzaldehyde, 12, and
p-anisaldehyde, 13, provided primarily phenols 16 and 17 in 77% yield for both
(Scheme 3), along with small amounts of the corresponding sters (Table 3,
entries 14 and 15). Additionally, oxidation of 27 provided 75% yield of the
ç-ketomethyl ester product 30 (methyl ester of 29).

Noteworthy, is the fact that isopropyl esters are made with ease in high
yields. However, as mentioned above, tert-butyl esters cannot be accessed,
most probably due to the sterics of the bulky alcohol. Although at this time
conversion of aldehydes to esters proceed best if the reaction is performed
in the alcoholic solvent (in order to circumvent the formation of carboxylic
acids), studies are underway with mixed solvents and show promising
indications that the oxidation to carboxylic acids could be retarded in favor
of esterification. Thus, it could be possible to lessen the amounts of
alcohol used in the oxidation.

Although any mechanistic discussion is speculative at this point, we believe
that the oxidation proceeds via a Baeyer-Villiger process. As depicted in
Scheme 4, the proposed intermediates in the oxidation of aldehydes to
carboxylic acids and esters are mixed peroxyacetals A and B. Rearrangement of
intermediates A and B would yield the products by expelling bisulfate.
Corroboration for the proposed mechanism is based on the well-understood
oxidation of aldehydes to carboxylic acids with peroxyacids.26 Also, recently
it has been demonstrated that acetals are oxidized to their corresponding
esters with Oxone,10 and thus, intermediate B could be derived from either the
hemiacetal or acetal (Scheme 4). It should be pointed out that Oxone is
slightly acidic and, therefore, could catalyze the formation of the presumed
peroxyacetals. Presently, mechanistic studies including use of 18O-labeled
aldehydes and NMR experiments to observe transient intermediates are underway.

In conclusion, we have demonstrated a simple and effective one-pot protocol to
oxidize aldehydes directly to acids or esters. These reactions are facile,
high-yielding, and easy to work up (most do not require chromatography) and
should provide a mild oxidative alternative for organic chemists. The
mechanism of these transformations is being investigated and will be reported
in due course.

Experimental:

(A bit too simple.)

Aldehyde (1 equiv), Oxone (1 equiv), ROH (0.2 M), 18 h, rt.

Subject: Baeyer-Villiger reaction recycling

Posted by: bio (Hive Bee)
Posted on: 10-12-04 08:37
Post No: 535485

Some nice articles you found psychokitty.

Assuming you have a basic understanding of the procedure of this thread
(Rhodium posted some dwgs somewhere) I wanted to ask you if you have any input
on the following:

In the patent twodogs cited where he got the idea of using perborate it states
......(paraphrased)near quantitative yields of the B/V product can be achieved
in the oxidation by appropriate recycling..........

That's it no experimental, examples, discussion, nothing.
Will be making a few more runs with the MePhBuO soon and will try some
recycling ideas at small test scale. Ah.... so many reactions so little time...

Now I suppose that the simplest and easiest way to do this would be to simply
filter, add more perborate and run it again. Maybe removing some water
(dessicant) would be helpful. Hopefully the selectivity is such that the
ketone enol ester would not be damaged. Another place would be after the
isolation before the hydrolysis or even after the hydrolysis itself.

Any thoughts on this?????? I have various improvements on the overall
procedure but nobody seems to be interested enough in this method (except one
bee I know of) to
actually do it. So I don't waste my time but I do thank you and the Hive for
all the great stuff, especially Rhodium for finding several of the key
references for this and similar reactions.

-------------------------------------------------------------------------------

IndoleAmine · Dreamreader Deluxe

and the second part...

Subject: United States Patent 4,988,825

Posted by: psychokitty («»)
Posted on: 10-13-04 07:28
Post No: 535611

-------------------------------------------------------------------------------

In the patent twodogs cited where he got the idea of using perborate it states
......(paraphrased)near quantitative yields of the B/V product can be achieved
in the oxidation by appropriate recycling..........

That's it no experimental, examples, discussion, nothing.
Will be making a few more runs with the MePhBuO soon and will try some
recycling ideas at small test scale. Ah.... so many reactions so little time...

-------------------------------------------------------------------------------

Actually, the segment in the patent to which you refer goes like this:

-------------------------------------------------------------------------------

The present invention provides a safe and economical process for oxidizing
aldehydes and ketones using an alkali metal perborate, such as sodium
perborate, as the oxidant. Alkali metal perborates are safe and economical to
use, and the sodium borate by-product thus formed is safely handled and is a
valuable product that can be sold in its own right. In addition, the oxidation
is carried out under easily maintained reaction conditions and provides
selectivities approaching 100% so that all of the starting aldehydes or
ketones can be converted to final product by appropriate recycling. It can be
seen that the use of the alkali metal perborate provides a substantial advance
in the oxidation of aldehydes and ketones.

-------------------------------------------------------------------------------

All the authors are trying to say is that because the use of sodium perborate
is so exceptionally selective, there won't be any byproducts to the reaction,
and whatever starting materials are left over--in this case, the intermediate
aldol condensation product of benzaldhyde and MEK--can be reused in another
sodium perborate Baeyer-Villiger reaction.

Anyway, that's my interpretation. I could be wrong.

Here's the a text copy of the patent in question, for all those who would like
to read it:

( 1 of 1 )
United States Patent 4,988,825
Bove January 29, 1991
Oxidation of aldehydes and ketones using alkali metal perborates

Abstract

Aldehydes and ketones, other than acetone, are oxidized with an alkali metal
perborate in the presence of an acid.
Inventors: Bove; John L. (Ridgewood, NJ)
Assignee: Cooper Union Research Foundation, Inc. (New York, NY)
Appl. No.: 910615
Filed: September 23, 1986

Current U.S. Class: 549/272; 549/273; 549/295; 560/231; 562/528
Intern'l Class: C07D 313/18; C07D 313/04
Field of Search: 549/272,273,295 562/528 560/231
References Cited [Referenced By]
U.S. Patent Documents
3122586 Feb., 1964 Berndt et al.
3154586 Oct., 1964 Bander et al.
3483222 Dec., 1969 Sennewald et al.
3716563 Feb., 1973 Brunie et al. 549/524.
3833613 Sep., 1974 Field 549/272.
4160769 Jul., 1979 Higley.
4213906 Jul., 1980 Mares et al. 549/272.
4286068 Aug., 1981 Mares et al. 549/272.
4338260 Jul., 1982 Schirmann 260/502.
Foreign Patent Documents
1096967 Dec., 1967 GB 549/272.

Other References

Y. Ogata et al., Bulletin of the Chemical Society of Japan, vol. 52(2),
(1979), pp. 635-636.
A. Baeyer et al., Ber., 1899, 32, 3625-3633.
A. Baeyer et al., Ber., 1900, 33, 858-864.
Ogata et al., Chem. Abst. 90:167685, (1979).
McKillop et al., Tetrahedron Letters, 24, No. 14, (1983), 1505-1508.
McKillop et al., Tetrahedron, 43, pp. 1753-1758 (1987).
A. Rashid et al., J. Chem. Soc. (C) (1967), pp. 1323-1325.

Description

The present invention is directed to the oxidation of aldehydes and ketones to
the corresponding acids and esters, respectively using an alkali metal
perborate as the oxidant.

The oxidation of ketones, including cyclic ketones, to esters through the use
of peracids is known as the Baeyer-Villager Reaction (A. Von Baeyer and V.
Villager, Ber., 1899, 32, 3265; 1900, 33, 858) While widely applied,
particularly for the oxidation of cyclohexanone to epsilon-caprolactone,
nevertheless the use of a peracid presents problems of safety and disposal
and/or recycling of organic compounds.

The present invention provides a safe and economical process for oxidizing
aldehydes and ketones using an alkali metal perborate, such as sodium
perborate, as the oxidant. Alkali metal perborates are safe and economical to
use, and the sodium borate by-product thus formed is safely handled and is a
valuable product that can be sold in its own right. In addition, the oxidation
is carried out under easily maintained reaction conditions and provides
selectivities approaching 100% so that all of the starting aldehydes or
ketones can be converted to final product by appropriate recycling. It can be
seen that the use of the alkali metal perborate provides a substantial advance
in the oxidation of aldehydes and ketones.

In particular, the present invention provides a method of preparing acids or
esters, which comprises oxidizing an aldehyde (other than acetone) or a ketone
with an alkali metal perborate in the presence of an acid.

With the exception of acetone, the present invention is applicable to the
oxidation of aldehydes and ketones to form the corresponding esters and/or
acids. Aromatic and aliphatic aldehydes and ketones may be used, such as
benzaldehyde and methylethyl ketone and the like, as well as cyclic ketones,
such as cyclohexanone and the like. Aliphatic and cycloaliphatic aldehydes and
ketones containing olefinic unsaturation may likewise be employed to form the
corresponding unsaturated ester and/or acid. When ketones are oxidized
according to the present invention, the product obtained will be the
corresponding ester, but in some cases a mixture of the ester and acid will be
produced.

In a preferred embodiment, the present invention may be used for the
preparation of esters and/or acids of the formula (I) ----STR1---- which comprises
reacting an aldehyde or ketone of the formula (II) ----STR2---- wherein R.sup.1 is
alkyl or aryl, R.sup.2 is hydrogen, alkyl or aryl, or R.sup.1 and R.sup.2 are
both hydrogen, or R.sup.1 and R.sup.2 together represent alkylene, provided
that R.sup.1 and R.sup.2 may not both be methyl. When R.sup.1 and R.sup.2 is
alkyl, R.sup.1 and R.sup.2 may be straight or branched chain alkyl, suitably
straight or branched chain alkyl of from 1 to about 15 carbon atoms, such as
from 1 to about 10 carbon atoms. When R.sup.1 or R.sup.2 is aryl, R.sup.1 and
R.sup.2 may be aryl of from 1 to about 4 rings, including fused rings, and may
suitably contain from about 6 to about 30 carbon atoms. Suitably, R.sup.1 or
R.sup.2 maybe phenyl, naphthyl, biphenyl and the like. When R.sup.1 and
R.sup.2 together represent alkylene, the alkylene may suitably be straight or
branched chain alkylene of from about 1 to about 15 carbon atoms in the
carbon-to-carbon chain, such as from 1 to about 10 carbon atoms in the
carbon-to-carbon chain. Usually when R.sup.1 and R.sup.2 together represent
alkylene, there will be from about 1 to about 30 carbon atoms in total,
preferably from about 3 to about 15 carbon atoms in total.

In the above formulas (I) and (II), alkyl and alkylene may be unsubstituted or
substituted by aryl, halogen, nitro or the like, while the aryl may be
substituted by alkyl, preferably lower alkyl, i.e. from about 1 to about 6
carbon atoms, halogen, nitro or the like.

Preferably, R.sup.1 may represent alkyl of from about 1 to about 10 carbon
atoms, phenyl, or alkylene of from about 3 to about 15 carbon atoms with from
about 3 to about 9 carbon atoms in the carbon-to-carbon chain, said alkyl,
phenyl or alkylene being unsubstituted or substituted by halogen, cyano or
nitro or, in the case of phenyl, lower alkyl. Further, R.sup.2, or both
R.sup.1 and R.sup.2 may represent hydrogen.

While sodium perborate tetrahydrate will normally be used, both in terms of
economy and convenience, other alkali metal perborates may be employed of the
formula (III)

MBO.sub.3.nH.sub.2 O (III)

wherein M is an alkali metal, preferably sodium or potassium, and n is 1 to 4,
usually 4. Suitably, the oxidation is carried out with the perborate (III) in
the presence of an acid that hydrolyzes in water to form hydronium ions, such
as mineral acids, sulfonic acids, organic acids, and the like, but a
Lowry-Bronsted acid or Lewis acid may also be used, such as BF.sub.3. Glacial
acetic acid is safe and economical and hence is presently preferred. Other
useful organic acids include trifluoroacetic acid and formic acid.

When an organic acid is employed, it may also serve as a solvent. If a solvent
or co-solvent is required, any suitable inert solvent may be employed, such as
acetone, halogenated hydrocarbons, such as methylene chloride, chloroform and
the like, aliphatic and aromatic esters, benzene and the like. It is noted
that acetone, while a ketone, is nevertheless not oxidized by the perborate
(III) and hence may be used as a solvent, if desired.

Usually, the oxidation will be initiated at a temperature of from about
30.degree. to about 70.degree. C., usually from about 40 to about 60.degree.
C. While lower temperatures can be used, reaction rates will necessarily be
slower. Temperatures higher than about 70.degree. C. may be used, if required
or desired, depending upon the desired reaction rate. However, the reaction is
exothermic and hence external cooling may be needed to control the reaction
temperature, even at the lower temperatures employed.

The present invention is illustrated in terms of its preferred embodiments in
the following Examples. In this specification and the appended claims, all
parts and percentages are by weight, unless otherwise stated.

EXAMPLE 1

Preparation Of Epsilon-Caprolactone

To a 200 ml roundbottom flask was added 4.9 grams (0.05 mole) of
cyclohexanone, 50ml of glacial acetic acid, and 11.4 grams (0.075 mole) of
sodium perborate tetrahydrate. The mixture was heated to 50.degree. C. using a
water bath. The reaction temperature was maintained in the range of
50-55.degree. C., while stirring the mixture with a magnetic stirrer for four
hours, after which the reaction mixture was cooled to room temperature, and
the solid sodium borate was separated from the mixture using section
filtration. The acetic acid was stripped from the remaining liquid residue
using a rotary evaporator, and the remaining epsilon-caprolactone was purified
by vacuum distillation. Yield: 91% theoretical.

EXAMPLE 2

Preparation of Benzoic Acid

The procedure of Example 1 was followed using 5.3 grams (0.05 mole) of
benzaldehyde as the starting material. Crude benzoic acid formed was purified
by recrystallization. Yield: about 50% theoretical.

EXAMPLES 3-6

Following the procedure of Example 1, the ketones set forth below were
oxidized with sodium perborate at a temperature of about 55.degree. C. to
provide the esters and acid set forth in Table 1 below.

TABLE 1
______________________________________
Example
Starting Material
End Product Yield
______________________________________
----STR3----
----STR4---- 75%
4
----STR5----
----STR6---- 74%
5
----STR7----
----STR8---- 68%
6
----STR9----
----STR10---- 24%
HOOC(CH.sub.2).sub.5COOH
38%
The most current patent detailing this reaction process, which has links to
the relevant patent history of the prior art, is as follows:

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2t2=HITOFF=1=/netahtml/searc
h-bool.html=2=G=50&co1=AND&d=ptxt1=%27sodium+perborate%27=Baeyer-Villiger=%22so
dium+perborate%22+AND+Baeyer-Villiger=%22sodium+perborate%22+AND+Baeyer-Villige
r

Rated as: good read
Subject: Methyl-(a-alkyl-)-styryl ketones
Posted by: psychokitty («»)
Posted on: 10-13-04 09:35
Post No: 535629

Information in this post relevant to this thread taken from the PDF documents
found in Post 531053 (psychokitty: "Propenylbenzenes anyone?", Chemistry
Discourse):

SOME ALPHA-ALKYLCINNAMIC ACIDS AND THEIR DERIVATIVES
BY MARSTON TAYLOR BOGERT AND DAVID DAVIDSON
J.A.C.S. v. 54 pp.334-338 (1939)

The phenomenal success of a-amylcinnamic aldehyde and other a-alkylcinnamic
aldehydes as perfume bases, led us to prepare several of the corresponding
methyl ketones (methyl- (a-alkyl-)-styryl ketones) (111). These were
synthesized by condensing benzaldehyde with alkyl acetones (11) by means of
hydrogen chloride. . . .

. . . Ethyl, n-propyl, n-butyl and n-amyl derivatives are reported in this
paper. The attempt to prepare the isopropyl derivatives by starting with
isopropyl acetone, (CH3)2CHCH2COCH3, gave an anomalous result, since it was
not found possible to prepare a solid oxime from the supposed methyl
(a-isopropyl-)-styryl ketone, nor to oxidize it to a-isopropylcinnamic acid. .
. .

Experimental:

One-half mole of benzaldehyde was mixed with one mole of the alkyl acetone and
one-fourth mole of hydrogen chloride gas passed into the cooled mixture. The
mixture, which soon became red, was then shaken for sixteen to twenty hours.
At the end of this time the water formed in the reaction had separated as
aqueous hydrochloric acid and was removed. Without further treatment, the oil
was distilled under diminished pressure (about 20 mm.). Somewhat more than
half of the alkyl acetone was recovered and a small residue, probably
consisting of dibenzal-alkyl acetone (styryl-( a-alkyl-)- styryl ketone),
remained in the flask. The principal fraction, consisting of crude methyl
(a-alkyl-)-styryl ketone, was obtained in a yield of about 90% based on the
alkyl acetone consumed, or about 75% based on the benzaldehyde employed. The
crude alkyl acetone fraction was treated with one-half mole of benzaldehyde
and sufficient alkyl acetone to replace that consumed in the first reaction.
Hydrogen chloride was then added and the reaction carried out as before. The
process was repeated three times but could probably be carried on
indefinitely. By using two moles of alkyl acetone to one of benzaldehyde and
reworking the recovered alkyl acetone in this way, the amount of dibenzal
derivative formed was greatly reduced, with consequent improvement in the
yield of the desired product. The crude methyl (a-alkyl-)-styryl ketone may be
used directly for the preparation of the a-alkylcinnamic acids. To purify it,
the crude product was washed with saturated sodium bisulfite, followed by
water and then treated with alcoholic potassium hydroxide, thrown into water,
acidified with acetic acid, extracted with benzene, dried over sodium sulfate
and distilled. A middle fraction was taken for analysis. The methyl
(a-alkyl-)-styryl ketones are liquids having a greenish-yellow tinge, with a
floral odor which resembles, but is much weaker than, that of the
a-alkylcinnamic aldehydes.

Physiologically Active Phenethylamines. I. Hydroxy- and
Methoxy-alpha-methyl-beta-Phenethylamines (beta-Phenylisopropylamines)
E. H. WOODRUFF AND THEODORE W. CONGER
J.A.C.S. Feb 1938 v. 60 pp. 465-467

. . . An excellent preparation for a-alkylcinnamic acids is that recently
carried out by Bogert and Davidson" who oxidized with hypohalite methyl
(a-alkyl styryl) ketones prepared by condensing benzaldehyde with a methyl
alkyl ketone in the presence of dry hydrogen chloride gas. With modification
this was found to give excellent yields of the methoxy-a-methylcinnamic acids
The other steps in the synthesis follow essentially experimental procedures
already appearing in the literature. . . .

. . . When condensing the methoxy aldehydes with methyl ethyl ketone it was
necessary to cool the aldehyde-ketone mixture in an ice salt bath during the
addition of the hydrogen chloride gas and to allow the reaction to proceed in
an electric refrigerator at 0-5 °C or in the freezing chamber at -10 to -5 °C
for twenty-four to forty-eight hours, instead of at room temperature. It was
found further that a practical grade of methyl ethyl ketone could be used. In
this case instead of recovering the unused ketone the reaction mixture was
taken up in ether, neutralized with solid sodium carbonate and washed
thoroughly with water before drying with anhydrous magnesium sulfate and
distilling.

These changes were found to be of particular value in the case of the
m-methoxy compound.

Rated as: excellent
Subject: Two great articles
Posted by: psychokitty («»)
Posted on: 10-13-04 10:55
Post No: 535634

100 Years of Baeyer-Villiger Oxidations
Michael Renz, Bernard Meunier
European Journal of Organic Chemistry Volume 1999, Issue 4 , Pages 737 - 750

Abstract:

In the present review, we report the discovery of the formation of esters and
lactones by oxidation of ketones with a peroxide derivative, namely the
Baeyer-Villiger reaction. This reaction was first reported by Adolf von Baeyer
and Victor Villiger a century ago in 1899, just one year after the oxidant
they used (KHSO5) has been described. Furthermore, Baeyer and Villiger
established the composition of this new inorganic peroxide and showed that its
instability was the reason of a controversy between several European chemists
between 1878 and 1893. For the first 50 years the mechanism of the
Baeyer-Villiger reaction was a matter of debate. A side product,
1,2,4,5-tetraoxocyclohexane, was ruled out as an intermediate in the ester
formation by Dilthey. Criegee postulated a nucleophilic attack of the oxidant
on the carbonyl group. This mechanism was confirmed by von E. Doering by a
labeling experiment with [18O]benzophenone. The rearrangement step occurs with
retention of the stereochemistry at the migrating center. The competitive
migration and the rate-determining step are also discussed in this review.

Chemistry: How green was my ester
GIORGIO STRUKUL
Nature 412, 388 - 389 (26 July 2001); DOI:doi:10.1038/35086670

Introduction:

Hydrogen peroxide is an ideal oxidant. It cannot yet be used widely, because
viable catalysts aren't available for many industrially important processes.
But there are encouraging indications of progress.

Chemistry has turned green. The increased awareness of environmental problems
has generated an overly simplistic division, however, especially in the media,
between bad chemistry which first pollutes and then (sometimes) cleans up
and good, green chemistry. Chemists themselves are partly responsible for
setting up this misleading contrast. But they are nonetheless among the
leaders in trying to find less wasteful or damaging ways to handle the
planets resources.

Subject: B/V recycling
Posted by: bio (Hive Bee)
Posted on: 10-14-04 06:05
Post No: 535753

Another good batch of reading material you found, psychokitty.

I have been intending to try the "distill direct" method for the MePhBuO,
after mechanical HCl removal, from the article you posted. Also extracting
with PhMe or Hexane from the start helps minimize emulsions and the washings
go fast. But why even wash if it's not needed.

I've gone straight to the oxidation w/o crystallizing (fractionate only) but
yields suffered somewhat. You can crystallize w/o distilling with good results
but it is much easier and faster to just distill it. Also it does help to
keep the condensation mixture cold to avoid tar formation and process it right
away if it sets solid faster than usual. Had one batch setup in 6 hours (11
hours from gassing).

Regarding your statement...............

All the authors are trying to say is that because the use of sodium perborate
is so exceptionally selective, there won't be any byproducts to the reaction,
and whatever starting materials are left over--in this case, the intermediate
aldol condensation product of benzaldhyde and MEK--can be reused in another
sodium perborate Baeyer-Villiger reaction................

Yes, this is also my understanding. My request for suggestions was
>>>>>WHERE>>>>>> do you think would be the best place in the procedure? The
unreacted unsaturated ketone could be isolated before the hydrolysis step in
pure form by fractionating, but perhaps this would not be necessary. The ester
made it through once (the oxidation) why not just run it again. Water removal
might be the sticking point here though.

Ever wonder why they call them LABORatories? I think you know what I mean. Not
enough hours in the day, without the technicians and assistants, to do it
all.

Subject: how about replacing the perborate with percarbonat

Posted by: Mendeleev (Stranger)
Posted on: 10-27-04 05:05
Post No: 538031

Sodium percarbonate has been known to form peracids as well: Post 415088
(GC_MS: "The synthesis of peracids", Chemistry Discourse)

However there are few details in this post. Could you use percarbonate
instead of the perborate? Not that obtaining sodium perborate is difficult,
it's just that sodium percarbonate happens to be OTC and obscenely cheap.

-------------------------------------------------------------------------------
Trogdor was a man. A dragon man. Or maybe just a dragon...

Subject: Na Percarbonate
Posted by: bio (Hive Bee)
Posted on: 10-27-04 10:30
Post No: 538078

The percarbonate should also work but I would suggest perhaps keeping the
active O2 content equal or better than the perbotate and any hydrated or
insipient water to a minimum.

The reaction conditions are somewhat different though. See the
Percarbonate/Perborate review article on Rhodiums site. It offers many
references and insights, one of which is that the perborate tetrahydrate is
just as effective as the monohydrate, which is unexpected, and suggests a
reaction mechanism which is only postulated.

The percarbonate I saw in the store was only 10% and would surely be a real
pain in the ass to separate from all the other crap. Most dry bleaches have
one or the other. Never checked but the straight stuff may be available at
industrial cleaning suppliers. I just can't see spending days to separate a
little from soap powder etc. that is so cheap and easily available as
perborate although the percarbonate is cheaper.

If, for whatever reason, you must make or extract the stuff OTC I would
suggest just getting borax and H2O2 as being much easier and the product would
be clean and fresh. Sounds like a soap commercial, lol.

Subject: The temperature of the reaction may be the problem

Posted by: psychokitty («»)
Posted on: 10-28-04 05:12
Post No: 538243

If the temperature of the perborate reaction--forming, as I understand it,
peracetic acid in situ--is above 30°C, that may in fact be the problem with
the low 35% yields as the peracetic acid oxidation of 2-acetyl-propenylbenzene
is recommended to take place well below that temperature.

For example:

https://www.rhodium.ws/chemistry/dillapiole.analogs.html

This compound was quantitatively methylated to 9 in preparation for the
Baeyer-Villiger and subsequent hydrolysis of the formate ester to form 10. The
conversion of 9 to 10 was carried out using 1 equiv. of MCPBA in CHCl3 at 0°C
for 18 h and afforded the formyl intermediate in 71% isolated yield,
saponification of which gave 10. Under these conditions competition by the
alkene moiety for the peracid to give an epoxide was minor; at room
temperature the rates of desired Baeyer-Villiger and the epoxidation were
quite comparable. Finally, methylation of 10 with CH3I-K2CO3 in acetone
afforded pure dillapiol.

For the buffered peracetic acid reaction as per Chromic's instruction, see all
the relevant posts in the following thread: Post 250788 (Chromic: "Peracetic
in DCM - dreams of success", Methods Discourse)

For an example of the diluted buffered peracetic acid Baeyer-Villiger
oxidation of a,B-unsaturated ketones, see the following thread (EDIT; SORRY
MOO!): Post 504867 (moo: "Baeyer-Villiger on unsaturated ketones", Novel
Discourse)

Can anybee speak french? I wonder what the exact details are to the 1936
french article listed in Post 487934 (Rhodium: "Peracid oxidation of
unsaturated ketones", Novel Discourse)

Also, using aqueous HCl might be a better way to carry out the hydrolysis of
the phenylacetone enol acetate as use of aqueous NaOH may be contributing to
the polymerization of the final product.

For more details about NaOH polymerization, see Post 336996 (Rhodium:
"Base-catalyzed polymerization of P2P", Chemistry Discourse); for an example
of HCl hydrolysis, see Post 476334 (Chromic: "HCl is so good it's GOLDEN!",
Chemistry Discourse).

It would appear that the advantages to the peracid oxidation of alkenes to
epoxides or diols is comparable to the peracid oxidation of a,B-unsaturated
ketones to enol esters.

I'll bee back soon with more information.

Subject: Posted already. Post 504867

Posted by: moo (Hive Addict)
Posted on: 10-28-04 18:36
Post No: 538339

Posted already, also see Rhodium's on the subject. Post 504867 (moo:
"Baeyer-Villiger on unsaturated ketones", Novel Discourse)

-------------------------------------------------------------------------------
fear fear hate hate

Subject: Oxidation time and temperature

Posted by: bio (Hive Bee)
Posted on: 10-29-04 13:59
Post No: 538513

You may have hit on the key here, psychokitty!

Reviewing the Boeseken relative article (Rec Trav Chim 55,786-790, 1936) on
page 788 where the oxidation of interest experimental is described I can make
out 35 degrees and terminee (terminate?) 24 hours. I would paste it up but
can't do it from that PDF. It also appears they did hydrolyse with HCl at 80
deg.

If somebee could please do a quicky translation of a couple paragraphs on Page
788. It is under the heading "Oxydation de la cetone II" see Post 487934
(Rhodium: "Peracid oxidation of unsaturated ketones", Novel Discourse)

Somebee I know is running a few more batches and wants to try it and I'm sure
he would report back the findings to me.

The part on the HCl hydrolysis is on the first page and mentions the time,
temp but no strength for a similar compound.

Anyway keep them cards and letters coming psychokitty

Rated as: excellent
Subject: A better way with MEK
Posted by: bio (Hive Bee)
Posted on: 11-02-04 06:21
Post No: 539173

Here I go again ing to my own post. CW you are going to love this, 80% of
the work is now eliminated in the MePhBuO prep.

The method below with slight modifications was tried at 1M test scale with
great results. 77% molar yield or 124.4g from 106g PhCHO.

The HCl was passed slowly keeping the temp < minus 5 deg (all absorbed)and
stirred for 16 hours at ice bath temp. Immediate when stopped stirring into
sep funnel. This shit loves to form emulsions with the oily phase trapping
below the water in gobs when washing. After 3 hours no water separated (not
surprised) so just proceded anyway.

Now let me ask anyone who actually might be paying attention. How is this
possible???.........."The mixture...shaken for sixteen to twenty hours. At the
end of this time the water formed in the reaction had separated as aqueous
hydrochloric acid and was removed." I guess I don't know how to shake. What
probably really happened was 2 days later the water separated, from my
experience.

The one to one method was not what it was cracked up to be. Sat too long and
way more tar and labor to separate the crap.

from JACS 54, 336
.....................One-half mole of benzaldehyde was mixed with one
mole of the alkyl acetone and one-fourth mole of hydrogen chloride gas passed
into the cooled mixture. The mixture, which soon became red, was then shaken
for sixteen to twenty hours. At the end of this time the water formed in the
reaction had separated as aqueous hydrochloric acid and was removed. Without
further treatment, the oil was distilled under diminished pressure (about 20
mm.). Somewhat more than half of the alkyl acetone was recovered and a small
residue, probably consisting of dibenzal-alkyl acetone (styryl-(
a-alkyl-)-styryl ketone), remained in the flask. The principal fraction,
consisting of crude methyl (a-alkyl-)-styryl ketone, was obtained in a yield
of about 90% based on the alkyl acetone consumed, or about 75% based on the
benzaldehyde employed. The crude alkyl acetone fraction was treated with
one-half mole of benzaldehyde and sufficient alkyl acetone to replace that
consumed in the first reaction. Hydrogen chloride was then added and the
reaction carried out as before. The process was repeated three times but could
probably be carried on indefinitely. By using two moles of alkyl acetone to
one of benzaldehyde and reworking the recovered alkyl acetone in this way, the
amount of dibenzal derivative formed was greatly reduced, with consequent
improvement in the yield of the desired product. from JACS 54,
336...................

Anyway back to the grind.

Subject: Calling all Peracid Guru's

Posted by: bio (Hive Bee)
Posted on: 11-02-04 08:36
Post No: 539184

Chromics method for 15% peracetic from ca.35% H2O2 is about to be tried.

Now Bio had an idea that if he used the perborate 4hydrate (same moles
peroxide) instead of the Hydrogen Peroxide, which is mostly water, he should
end up with an almost equal peracetic concentration with wayyyy less water,
which if I understand correctly is detrimental to peracid oxidations.

The perborate doesn't like to dissolve too well in the GAA so a lot must be
used (10:1 ratio per the Perborate/Percarbonate review article. The little
Oxygen bubbles just seem to bubble right on out. So.......what if the room
temp moderated mixture was sealed and allowed to develop a few atmospheres of
pressure? Thoughts anyone?

Bio loves his new low pressure bomb, it makes things so easy and he gets more
too!

Sulfuric Acid catalyzed Peracetic acid with NaPerborate
1:10M SPB:GAA @ 40deg (20deg??)
Required for 100g,624mm MePhBuO per twodogs procedure!

1)500-625ml Glacial acetic acid ........ ca 10M
CH3COOH 60.05 g/m x 10 = 600.5g x .995 = 597.5g/1.05d = 569ml

2)143g 929mm Na Perborate ............ca 1M 34.0g/m H2O2
NaBO2.H2O2.3H2O = 153.8 g/m

3)AcOH 597.5g + H2O2 34g/m = 631.5 x .01 = (6.31g x .9 Cool

/1.84d = 3.36ml H2SO4

Rhodium if you get a chance, please look this over. Will try it insitu the
normal way and also premade peracetic (modified Chromic method as above)It is
supposed to be sulfuric acid 1% weight of total contents that you referenced
for me.(JACS,907,1946, Greenspan F.P.)

Also the unreacted MePhBuO will be fractionated prior to the hydrolysis (HCl
instead NaOH) although the concentration and time is still not clear per your
excerpt from the 1936 Boeseken article. .........Phenylacetone by
Bayer-Villiger Oxidation of 2-acetyl-1-phenylprop-1-ene
Boeeseken &Jacobs
Recl. Trav. Chim. Pays-Bas 55, 786 (1936)

Peracetic acid treatment of 2-acetyl-propenylbenzene
(3-methyl-4-phenyl-but-3-en-2-one) below 30°C resulted in the formation of
phenylacetone enol acetate (2-acetoxy-1-phenylprop-1-ene), mp 131°C and bp
103°C/3mmHg. Heating the crude reaction mixture with aqueous HCl at 80°C gave
phenylacetone.

Subject: heres my results
Posted by: abacus (Hive Bee)
Posted on: 11-06-04 09:18
Post No: 540001

Bio,

Swim has been carrying out a few experiments of his own and seeing how you are
still interested in this procedure, like me, i may as well share some results.

360g distilled benzaldehyde was mixed with 260g MEK in a 1L FBF and stirred in
an ice bath (around equimolar amounts).

HCL gas was slowly added over two hours so that the weight of benzaldehyde/MEK
mix increased by 75g.

The flask was stoppered, removed from the ice bath and the blood reddish
solution was then allowed to sit for 2-3 days at room temperature.

The HCL was then removed by dissolving the resulting methyl phenyl butanone in
DCM and washing with NaOH solutions, brine, then clean water.

The DCM was removed by distillation, residual water stripped off under vacuum,
and then MPB vacuum distilled to give 360g.

btw, no tar or polymerisation was ever observed.

Not too bad.

Baeyer Villager oxidation using sodium perborate then proved quite successful
with similar results to your posts.

Steam distillation was employed to seperate the resulting P2P.

The down side is the use of large amounts of GAA, so experiments involving
recycling the GAA and unreacted MPB are currently on the drawing board.

Subject: ?
Posted by: indole_amine (Hive Bee)
Posted on: 11-07-04 16:14
Post No: 540201

What was the final yield of purified propanone with the described procedure?

indole_amine

Hope this helps. Wink

I_A

Astrum · Sat Feb 19, 2005 2:05 am

SWIM tried this reaction recently. After distilling the final product (fraction 210-220C, no suitable vacuum was present at the time) SWIM got a brownish liquid that smells like P2P, obviously has roughly the same BP. The yield was high though, expected ~28g and got 38.2g. SWIM must have made an error somewhere and will be doing it a second time, we'll see how that turns out.

IndoleAmine · Dreamreader Deluxe

astrum: you should redistill under vacuum and see if you get cleaner product? Most likely your ketone is contaminated and therefore the "high yield"...

Does anyone know about using standard peracetic acid (Chromic method, 35% H2O2, GAA & H2SO4, let stand for 12-16h) for this "Baeyer/Villiger"-oxidation of an unsaturated ketone?

In other words, is the perborate essential or can standard peracids be used; and if this is the case: are additional solvents needed (like DCM or acetone), or does the methylphenylbutenone dissolve equally bad in aequous performic solutions, with or without solvent?

I_A

bio · Working Bee

Net's been giving me a fit so might be a day or two before I post the edited WD stuff.

...............Does anyone know about using standard peracetic acid (Chromic method, 35% H2O2, GAA & H2SO4, let stand for 12-16h) for this "Baeyer/Villiger"-oxidation of an unsaturated ketone?............................

This is on the experiment list also the buffered version sans the carbonate. I believe chromics procedure calls for standing the mix 3-5 days. If you look at the previous posts on perborate w/ 1% H2SO4 you will see the max peracid concentration is in only 2-3 hours versus something like 80 hours w/ aqueous H2O2. I did use the 1% SA last run but can't tell how much of the yield increase was from this as also the reaction at RT was done simultaneously for the first time. Boeseken used 20% peracetic so it obviously will work although no yield is given in the original article or any other one that I can find.

I'll get around to it sooner or later but it sure would help if the experiments were split up. Where is CW and A when I need them. My sense is that the perborate MAY actually give better yield as there is only water of hydration present
4H2O versus using 35% H2O2. Haven't done the calcs but is probably equal to around 80% hydrogen peroxide water equivalent. How about run the calcs Indole, also for the monohydrate.
Look in the JACS article in the posts mentioned above. The peracetic concentration versus time matches the 80 or 90% fairly close.

...........In other words, is the perborate essential or can standard peracids be used; and if this is the case: are additional solvents needed (like DCM or acetone), or does the methylphenylbutenone dissolve equally bad in aequous performic solutions, with or without solvent?..........................

The MPB dissolves just fine in acetic acid and no solvent should be needed. More acid could be used I suppose but the MPB melts so low that it doesn't really matter although a healthy excess of acid should of course be used. One bee actually dripped in the liquid MPB with good results. Have never tried this as I have my own pet theories about why portionwise SPB is better. Maybe somebee could prove me wrong. That would be nice. Chromic used DCM, I think, just to try and achieve a more homogeneous solution.

Astrum, IA is correct. You are weighing contamination although 46g is my best yield (per 100g) so far of clear product collected over 6 deg at 6mm. If you expect a pure product it must be slowly fractionated correctly. Aspirator vac is OK even 50mm works fine as long as it's steady. Take fractions over about 20-40 degrees to get it all if your vac is unstable. Make sure to cut the fractions say 10 deg above and below.

Anyway back to work, this place looks like a disaster zone, reduced iron and rusty electrodes everywhere. That red shit is a bitch to get off the
labware.

IndoleAmine · Dreamreader Deluxe

Rust everywhere? Hmm - did you maybe use a bit much HCl gas lately? Laughing

As I understand the peracid formation, the acid catalyst is for dehydration purposes, and more than 1% H2SO4 can be used if the peracid is either vac distilled or buffered. In both cases, the sulfuric is removed; and in case of using a buffer, salts are formed which bind even more water in their crystal structure/when dissolving, so the peracid should form even more readily once any buffer is added (see patent US2802025 for details).

Thinking this, SWIA takes 800ml GAA, adds 190ml H2O2 30% and 10ml H2SO4 97% and lets it stand overnight (16h). The next day, he adds some 10ml more H2SO4 (temperature rise of +1°C noted Very Happy

) and lets it stand another 10 hours (24 hours total). He places the supposed-to-be peracetic in a 2000ml RBF and starts stirring, while slowly adding 25g NaHCO3 to mostly neutralize the sulfuric (CO2 evolution). He thinks "well some sodium acetate and/or sulfate should've formed now; they can form hydrates - good thing, less water available in there", and adds 85g MePhBuO dissolved in 75ml CHCl3...
...and then starts to wonder if sodium tetraborate (borax) would help in any way, since it normally is present when using perborate.

So, he adds some few grams of borax to the reaction - somewhat seems to get it going, temp. rise to 24°C. Maybe just neutralization heat. Placed in 10°C water bath. Maybe more salts were formed, accelerating peracid formation, SWIA thinks - and is remembered that not all peracid is formed already and some still will be made during rxn. As he wants to recycle his GAA, he doesn't want any residual peracid during distillation. So what to do? Peracid formation will still take some hours, it was not really old peracid...

So SWIA adds some more 75g PhBuO dry and in portions, to make sure all peracid becomes consumed in the oxidation of the PhBuO. Temperature is still 24°C; ca. 1,5h have elapsed. The mePhBuO dissolution is endothermic, so the temp. can be somewhat kept down adding it in portions.

"Since one can recycle the unreacted a,b-unsaturated ketone prior to ester hydrolysis, not much is lost here - I can as well add a healthy excess of it", SWIA thinks. And then he realizes that this excess may in fact even drive the reaction forward, similar to using excess GAA for peracid formation.

After 3 hours, the temp. had dropped to 21°C (=ambient) again - before, it had climbed to 24°C, even with external cooling. The thermometer has a fruity smell (somewhat similar to P2P) when dipped into the rxn (and afterwards being rinsed with a little H2O to remove the peracid), SWIA thinks this may well be the desired ester. Its not MPB, for sure...

He told me he was planning to let it stir for 18h total, and that he would report back as soon as he would get to know anything about the outcome.

UPDATE: after 5 hours reaction time, 10ml H2O2 30% were added, followed by 5ml H2SO4 97% dropwise. The sulfuric caused a reddish coloration with every drop, wchich quickly disappeared on stirring. Slight exothermic reaction, caused temp rise to 24°C.
After 7 hours, 4.5g anhydrous Na2CO3 were added to mostly neutralize the additional H2SO4, resulting in much CO2 evolution. Reaction cleared up from milky-white to clean again within 5 minutes. Again rise in temp. from 21°C to 24°C. After 9 hours, the whole thing had heated up to 31°C and had to be placed back into the cooling water bath.
This is were SWIA left it. He almost can smell the ketone already, now definately (a few drops of the rxn mixture dripped into 20ml of pH 8 water gave an oily film smelling very familiar, and absolutely not like the starting material. Good old nose chromatography... Laughing

)

EDIT 2: after almost 17h reaction time, the rxn had warmed up to 27°C again. still something going on there. Replaced the cooling bath with a fresh one, and will let stir until no exotherm rxn can be seen anymore (and five more hours from that point on).

Any comments?

i_a

bio · Working Bee

Well, you've certainly added enough variables to the equation. I hope you get a 90% yield, then I will follow it verbatim, lol.

Good going. More later, there are some good ideas in your post.

Maybe you could take part of the ester and run an acid hydrolysis. Boeseken used HCl ( I suggest large excess 15%) only aqueous given in article. 80deg for 8hours in MeOH is all I can make out from the french. Dammit why won't somebody translate this fxxxx article from 1936? I' ve asked for over a year and the words have so many meanings I finally gave up trying from a dictionary going word by word for hours.

If it's possible to post an image I would paste the hydrolysis paragraph here. but you probably have the articles. Rhodium found them and put them up on the Hive.

IndoleAmine · Dreamreader Deluxe

Yeah maybe Indole tweaking too much again here, probably... Laughing

(the whole shebang is still brawling along with a slight exotherm at 24°C, this after 33h rxn time: maybe the additional peroxide/sufuric wasn't that good either. We'll see...)

About the articles: I don't have them, sadly. (Java hope you read this) Crying or Very sad

Give me the article in question (and the others too please), and I will translate it as good as possible (although mon francais est pas si bon peut-être anymore, by now... Wink

), you could send them to my hushmail account if the size is <2MB...

About acid hydrolysis: I am familiar with a procedure calling for 10% HCl and EtOAc at 80°C for 5 hours, but I prefer the basic one - it makes for a simpler workup, since no traces of acid have to be removed after distillation when NaOH is used. What about NaOH/H2O with some additional EtOAC (which of course would immediately become hydrolyzed to EtOH and GAA anyway, giving some sodium acetate, buffering the harsh lye conditions and maybe reducing polymerization of product)?
(SWIA is planning to maybe steam distill directly after hydrolysis, he hates aspirator noise)

About diagrams: I found this one in a patent yesterday - looks like some original hand drawing from Boeseken himself... Laughing

http://www.shroogle.org/synthetika/files/mephbuo_oxidation_989.gif

Greets

i_a

Astrum · Tue Feb 22, 2005 10:04 am

Well SWIM redistilled it under vacuum and got a light yellow liquid, 17.7g. That was from 75g of MePhBuO. SWIM still has another 75g of MePhBuO so SWIM will try it out again.

bio · Working Bee

That's about 70% of the minimum you should have gotten and would be due to decomposition during the atmospheric distillation (see any smoke in the flask) and excessive manipulation; everything else being perfect. Holdup can also be a problem with small amounts if you don't have the mini setup.

Light yellow is OK and should be good to gogo if the product was collected under say 15deg or so