Author Topic: Dehalogenation of cinnamyl alcohol (Read 388 times)

zgoat65 · « **on:** March 05, 2012, 03:17:38 AM »

A friend wants to halogenate cinnamyl alcohol (ref attached). He has heard that the HBr method works and will give 3-(bromopropenyl)benzene. My question is, has anyone tried (with success) the method using HCl that is mentioned in the attached document? It seems like an easier route than messing with Hbr, but will it make dehalogenation to propenylbenzene tougher?

no1uno · « **Reply #1 on:** March 05, 2012, 03:58:06 AM »

No but I'd be very interested to see a report from your friend on the procedure, it seems too good to be true

jon · « **Reply #2 on:** March 05, 2012, 04:12:20 AM »

no way that would work either PBr3 or SOCl2 or POCl3

java · « **Reply #3 on:** March 05, 2012, 11:55:05 AM »

.....then you would have to deal with removal of the primary halide......tell me how...java

zgoat65 · « **Reply #4 on:** March 05, 2012, 02:46:35 PM »

My friend says Zn/AA, or Zn/Cu couple to dehalogenate to propenylbenzene . Fe seems like it can be used too.

Ref
http://www.sciencedirect.com/science/article/pii/030438949400117Y

java · « **Reply #5 on:** March 05, 2012, 03:22:33 PM »

Reference information

Zinc Copper Couple..,

http://chemistry.tutorvista.com/organic-chemistry/reactions-of-amines-substitution-and-elimination-of-amines.html

Synthesis of Zinc Copper Couple......,

"Synthesis Zinc-copper couple has been prepared by numerous methods, which vary mainly with respect to the source of copper, but also by the ratio of copper to zinc, the physical state of the zinc (e.g. powder or granules), the use of protic acids and other additives, and temperature of the preparation. Most often the couple is generated and isolated prior to use, but routes have been described to storable forms of the alloy. Most methods involve reduction of an oxidized copper species with zinc, which is used in excess.

An early method for the synthesis of zinc-copper couple entailed treatment of a mixture of zinc dust and copper(II) oxide with hydrogen gas at 500 °C.[1] A more convenient and cheaper method proceeds by treatment of zinc powder with hydrochloric acid and copper(II) sulfate.[3] Treatment of zinc powder with copper(II) acetate monohydrate in hot acetic acid is reportedly highly reproducible.[4] The couple may also be generated in situ by reaction of one equivalent of zinc dust with one equivalent of copper(I) chloride (or copper powder) in refluxing ether.[5]

The choice of method is dictated primarily by the application. The development of newer methods was motivated by the need for zinc-copper couple with reproducible behavior."

......source,

http://en.wikipedia.org/wiki/Zinc-copper_couple

zgoat65 · « **Reply #6 on:** March 05, 2012, 03:31:13 PM »

Thanks java. I was looking for the ref in my pc. I need to organize better.

sooooo.......whatcha think ? Btw, I added a ref to my previous post. Seems to be feasible on paper don't it?

jon · « **Reply #7 on:** March 05, 2012, 10:22:31 PM »

you entitled your thread halogenation not dehalogenation.
somewhat misleading.

Polonium · « **Reply #8 on:** March 05, 2012, 10:53:39 PM »

Jon, he is trying to halogenate the alcohol before dehalogenating/eliminating the halide.

There is a reference to the bromination of cinnamyl alcohol in Organic Synthesis (http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv5p0249).

The authors cite a 1918 German paper where it is claimed that cinnamyl bromide can been prepared from cinnamyl alcohol by the action of hydrogen bromide in cold acetic acid. I'm don't know why these conditions wouldn't also brominate the alkene double bond. I don't have access to the paper so I'm afraid I can't help more. You might be able to brominate the alcohol and the halide in one step. If you could selectively dehalogenate the primary, you should be able to from the 2-Bromo-1-phenylpropane. You can then convert the halide to the iodide with the Finkelstein reaction in acetone. (http://en.wikipedia.org/wiki/Finkelstein_reaction). Finally you should be able to aminate the iodide with methylamine in dry IPA as Jon has shown with iodosafrole.

Also zgoat65, attached is the reference you mentioned.

zgoat65 · « **Reply #9 on:** March 06, 2012, 12:01:50 AM »

Thanks, Polonium, thatd is exactly what I was aiming at.

Polonium · « **Reply #10 on:** March 06, 2012, 01:02:44 AM »

I have attached a diagram of the reactions. I'm pretty confident about everything except the third step. I'm really not sure if there is a selective way of eliminating a primary iodide and not effecting the secondary halide, at least not with accessible reagents.

The phenyl-2-iodopropane can be aminated directly to either methamphetamine or amphetamine by SN1 reaction with methylamine or ammonia respectively. The reaction must be carried out in anhydrous IPA otherwise the elimination reaction will be favored to form allylbenzene or its isomer.

None of this has been tried by me on this particular substrate, just to clarify I am only theorizing, more than likely incorrectly at that!

In step 3 you have bromines in your schematic and yet call it 1,2-diiodo-3-phenylpropane...correct it...java

zgoat65 · « **Reply #11 on:** March 06, 2012, 01:12:44 AM »

Awesome. Even if incorrect...........good foods for further thought.

no1uno · « **Reply #12 on:** March 06, 2012, 09:13:38 AM »

Quote from: zgoat65 on March 05, 2012, 02:46:35 PM

My friend says Zn/AA, or Zn/Cu couple to dehalogenate to propenylbenzene . Fe seems like it can be used too.

Ref
http://www.sciencedirect.com/science/article/pii/030438949400117Y

That paper doesn't really support what you are after, while it does support the partial-dehalogenation of carbon tetrachloride to chloroform where the tet is in ppm levels, you are dealing with a much longer chain - requiring total dehalogenation in way better than ppm ratios (while dehalogenation to B-methylstyrene suggests there is real potential for polymer formation - not such an issue with either chloroform/carbon tetrachloride).

Anyone got a reference for dehalogenation of cinnamyl chloride, I've found some extra references on the preparation via HCl (although they all seem to suggest the cinnamyl chloride is too impure for their use - eg. Grignard formation) and would be seriously interested.

The HCl route to cinnamyl chloride 'seems' to be one that could be easily modified for use with extemporised equipment, but getting the Cl off the end of the chain might be more than trivial (I'd hope not).

Here is one paper I've found, in which the C-Cl bond is cleaved by Cr(II) (formed by reacting CrCl3 with LiAlH4 - OTC as all fuck):

Omoto, et al, "Revisit to the reduction of allylic chlorides to less substituted olefins by a low-valent chromium species in the presence of a proton source" (2001) Vol.42 pp.939-941 (link)

In what are described as quantitative yields, with almost total conversion to the Allylbenzene (but at what cost in sourcing reagents & solvents ffs). Presumably CrCl3 would be reduced to Cr(II) in Li/NH3 but this would still mean avoiding the Birch-Benkeser reduction of the benzene ring - so it would have to be formed first, the Li all reacted then added to the Cinnamyl Chloride.

Goldmember · « **Reply #13 on:** March 07, 2012, 07:27:30 AM »

This seems like a preferable route to the alcohol from raw essential oil. The MPV reduction works o.k, but has its sticking points especially when attempted on unrefined oil. Yields are comparable, if not better considering work-up etc.
This is the only place Iron fits into the equation. WizardX has also posted something similar pertaining to Crotyl alcohol in another thread.

Excuse for the cut and paste but I dont have the whole article saved.
Citation comming from A.C.S website

From the ref:

THE UTILIZATION OF CASSIA OIL FOR THE SYNTHESIS OF CINNAMYL ALCOHOL
BY ARTHUR J . HILL AND EDITH. NASON

By the Action of Iron and Acetic Acid on Pure Cinnamic Aldehyde.-

Thirty-nine g. of pure cinnamic aldehyde was heated on a steam-bath for twelve hours with 600 cc. of50% acetic acid and 160 g. of iron filings; 30 g. of an aldehyde-free distillate was obtained; b. p., 135150' (18 mm.). The yield of the cinnamyl acetate thus obtained was 5770 of that calculated, a result practically as good as that obtained by the reduction of cinnamyl diacetate.

By the Action of Iron and Acetic Acid,on Cassia Oil.-

Twenty-scven g. of cassia oil, containing 19.5 g. of cinnamic aldehyde, was treated with 85 g. of iron filings and 300 cc.
of 50% acetic acid under thc usual conditions. The product of the reaction boling at 327-143' (11 mm.) was aldehyde-free, and represented a 77% yield of crude cinnamyl acetate. Although aldehyde-free, the ester was contaminated with some of the impurities of the cassia oil. The purity of the cinnamyl alcohol obtained by the hydrolysis of this material will be discussed later.

Cinnamyl Alcohol

The Hydrolysis of Cinnamyl Acetate.

-A few preliminary experiments with several hydrolytic agents, such as hydrochloric acid, sulfuric acid, barium hydroxide, potassium
carbonate and sodium hydroxide, demonstrated the unfeasibility of all but sodium hydroxide in an alcoholic medium. A more detailed investigation of the latter was then made, and the most favorable conditions resulting from this have been incorporated in the following description. A mixture of 67 g. of cinnarmyl acetate and one molecular proportion of a 570 alcoholic solution of sodium hydroxide was digested on the steambath for 45 minutes. The solution was then diluted with 3 volumes of water, and the cinnamyl alcohol extracted with ether, dried over anhydrous sodium sulfate, and distilled.
The boiling point of the purest product, thus obtained, was 148-153" at 20 mm.;
yield, 49 g., or 96%.

A new method of purification is described below.

When smaller quantites of the acetate are used, the time of hydrolysis may be shortened to 30 minutes. Extension of time beyond 45 minutes, as well as the use of larger amounts of alkali, occasions some polymerization and consequent loss of the alcohol. This point is being further investigated.

CINNAMYL ALCOHOL FROM CASSIA OIL 2245

Purification.-The purification by fractional distillation of the cinnamyl alcohol resulting from the hydrolysis described above was found to be somewhat unsatisfactory.
The crude product boiled within 15' (20 mm.), 83% distilling within 5". The larger fraction (b. p., 147-153"; 20 mm.) solidified in ice and remained solid up to 30" (the melting point of the pure alcohol is 33"). The smaller fraction solidified when cooled in ice water, thus showing the presence of a relatively large amount of the alcohol, but the melting point of this fraction was about 20". Attempts to better the alcohol content of this fraction by distillation were unsuccessful.
Purification by alternate freezing and pressure filtration was found to entail large mechanical losses.
It is wcll known that calcium chloride forms addition compounds with certain alcohols. An application of this principle to the purification of cinnamyl alcohol was
successful, after preliminary tests had shown that purc cinnamyl alcohol could be quantitatively recovered by this procedure.

Five parts by weight of cinnamyl alcohol were treated with 35 parts of anhydrous ether and 10 parts of powdered anhydrous calcium chloride.
The addition product which was completely formed after twelve hours was filtered off, washed thoroughly with dry ether and decomposed by treatment with cold water. The cinnamyl alcohol was then extracted with ether, dried and weighed.
Since phenylpropyl alcohol was the probable impurity in the crude cinnamyl alcohol, the same process was repeated with this compound. No addition occurred.
Flirthermore, when a known mixture of cinnamyl and phenylpropyl alcohols was similarly treated, the cinnamyl alcohol was obtained from the filtered and washed calcium chloride addition product in 90% yield, and the phenylpropyl alcohol was recovered on evaporation of the ether washings.
This method was applied to the alcohol obtained by the hydrolysis of the cinnamyl acetate from the three sources, namely cinnamyl diacetate, cinnamic aldehyde and cassia oil. When cinnamyl diacetate and cinnamic aldehyde were the sources of the acetate, the products of the hydrolysis contained 90% of cinnamyl alcohol, while that obtained from the reduction of cassia oil contained but 80%. This lower percentage in the latter case was due to impurities contained in the original cassia oil.

Zinc,Cr aside, Something different, Carbon,white oil and Rust.

Reductive dehalogenation of organic halogen compounds

US4943671
US6649044
US4824956

Ill dig up some Zinc refs I have sometime soonish.

Tsathoggua · « **Reply #14 on:** March 08, 2012, 11:21:16 AM »

Toady just figured, whilst he is not a stimulant fan by any means, he would throw a bone for the eager hymenopterans of the tweaker persuasion.

He has noted, in his typical autie detail-probing manner, systematically going around a hardware store and examining each and every potential source of chemicals of any kind, that there exist, at least in britain at least one brand of an aerosol product marketed as a graffiti remover, that contains cinnamaldehyde and some polymer goop. He has not attempted its purification, but he surmised at the time that there may be some potential precursor value via its dilution.

Hopefully rendering the polymer shite more amenable to either distillation or formation of the bisulfite adduct and hence rextylization.

The amphibian God himself will be too busy with his converting a room into lab space and consequentially being in general a busy bee with A-clearing up the SHITtip the pigs left the place as and B-installation of the lab facilities. And setting up a pretty nice microscopy station.

So attempting to obtain cinnamaldehyde from this source is for those more dedicated. The Toad Lord does envision that perhaps similar techniques, or rather, the principles involved in the separation of MeNO2, although he himself doesn't need to synth the lower nitroalkanes, plenty of people do via dilution of the oil and distillation under reduced pressure to recover the nitromethane. And likewise, dilution followed by distillation, and in the case of cinnamaldehyde from this/these graffiti removers purification of the cinnamaldehyde fraction of the distillate via its bisulfite adduct.

Toady is unsure of the cinnamaldehyde content of the graff remover but suspects it may be a signo

Borohydride or LAH would do the job of reducing the aldehyde too the alcohol, as would diborane..not sure if diborane will leave the double bond intact. if 'ol' toady remembers right, certain lanthanide halides are very versatile reducing agents when it comes to carbonyl compounds, both aldehydes and ketones being reduced to alcohols and also effective at reducing nitro groups also being effective for the removal of aliphatic halides and dehalogenation of aromatic rings.
.
Seems that by 'tuning' the (co)solvent(s) used in a given rxn, and the kinetics, samarium(II) iodide can be used to reduce various functional groups, and effect the aforementioned dehalogenation reactions (Hmmm....jon....maybe SmI2 might be the reagent to pull that loperamide dehalogenation if done right, if you are still working on/interested in that, although thats not a thread I've followed much, just a thought)

Preparation of samarium di-iodide appears quite practically doable. Simple reflux of elemental samarium in a THF solution of diiodomethane or 1,2-diiodoethane apparently gives pretty much max theoretical yields, and the resultant solution can be used as is, or in admixture with various cosolvent systems, the wiki for samarium (II) diiodide, and there is a pronounced effect on both functional group preference. The more polar the solvent/s the more efficient reductant.

This one seems to have a fetish for HMPA. Which is nasty stuff.

java · « **Reply #15 on:** March 09, 2012, 04:34:16 AM »

Preparation of Alkynes by Dehydrohalogenation

The last reaction shown above suggests that alkynes might be prepared from alkenes by a two stage procedure, consisting first of chlorine or bromine addition to the double bond, and secondly a base induced double dehydrohalogenation. For example, reaction of 1-butene with bromine would give 1,2-dibromobutane, and on treatment with base this vicinal dibromide would be expected to yield 1-bromo-1-butene followed by a second elimination to 1-butyne.

CH3CH2CH=CH2 + Br2 ——> CH3CH2CHBr–CH2Br + base ——> CH3CH2CH=CHBr + base ——> CH3CH2C?CH

.....it seems selective dehalogenation doesn't occur as one wishes.....java

source,

http://el-fellah.com/alkyl_halides.htm

no1uno · « **Reply #16 on:** March 09, 2012, 05:18:14 PM »

Goldmember,

I'll throw up the article, there is also another article on dehydrating hydrocinnamyl acetate directly to allybenzene & B-methylstyrene but the sticking point is the hydrogenation of cinnamyl acetate to hydrocinnamyl acetate in the middle.

Anyone got any other reduction ideas? Seems the acetate hydrocinnamyl acetate is the way to go, the trouble is getting there - ideas wanted:P

java · « **Reply #17 on:** March 09, 2012, 05:35:15 PM »

There are some interesting tips in this thread......,

....as per Nicodem at SM,

Quote:
1. - Cinnamaldehyde + HCl--> 3-Phenyl-2-chloropropanal. But may it self-condenser?

Of course you can't do a Michael addition on such an aldehyde due to reasons already stated. But in case aldehyde polymerisation would not be a problem one would get the 1,4-addition product, hence 3-chloro-3-phenylpropanal.
Quote:
Now you could electrophilic add HI, HBr or maybe HCl to the double bond, yielding Phenyl-2-halopropan (Ph-CH2-CH(X)-CH3) by the majority (makovnikow).

According to those rules (the nucleophile adds on the position where the most stable carbocation can form) you would obviously get 1-halo-1-phenylpropane by hydrohalogenating 1-phenylpropene.

I would say the reduction to cynamyl alcohol (or its aquisition given that it's pretty cheap), substitution with conc. HCl to yield cynamyl chloride, reduction with Zn/AcOH to yield 1-phenylpropene from which the route proceeds by well known reactions. "

https://www.sciencemadness.org/whisper/viewthread.php?tid=6380

zgoat65 · « **Reply #18 on:** March 09, 2012, 06:10:38 PM »

If Nicodem says it works, I believe it. problem is, he gave no refs. in tne long winded ref I gave at the top of this thread, about 3/4 of the way down (in the experimental section ) it tells of hcl substitution . Would this not work? It seems too easy.

Wizard X · « **Reply #19 on:** March 09, 2012, 10:40:26 PM »

DEHYDROHALOGENATION http://orgsyn.org/orgsyn/orgsyn/prepContent.asp?rxntypeid=106&prep=CV2P0017

HOCH2CH2CH2Cl + KOH => CH2=CHCH2OH + NaCl

Ref: http://127.0.0.1/talk/index.php/topic,313.msg17441.html#msg17441

Author Topic: Dehalogenation of cinnamyl alcohol (Read 388 times)

zgoat65

Dehalogenation of cinnamyl alcohol

no1uno

Re: Halogenation of cinnamyl alcohol

jon

Re: Halogenation of cinnamyl alcohol

java

Re: Halogenation of cinnamyl alcohol

zgoat65

Re: Halogenation of cinnamyl alcohol

java

Re: Halogenation of cinnamyl alcohol

zgoat65

Re: Halogenation of cinnamyl alcohol

jon

Re: Halogenation of cinnamyl alcohol

Polonium

Re: Halogenation of cinnamyl alcohol

zgoat65

Re: Halogenation of cinnamyl alcohol

Polonium

Re: Halogenation of cinnamyl alcohol

zgoat65

Re: Halogenation of cinnamyl alcohol

no1uno

Re: Halogenation of cinnamyl alcohol

Goldmember

Re: Halogenation of cinnamyl alcohol

Tsathoggua

Re: Halogenation of cinnamyl alcohol

java

Re: Halogenation of cinnamyl alcohol

no1uno

Re: Halogenation of cinnamyl alcohol

java

Re: Halogenation of cinnamyl alcohol

zgoat65

Re: Halogenation of cinnamyl alcohol

Wizard X

Re: Halogenation of cinnamyl alcohol