Author Topic: AlCl3 and Md compounds  (Read 6152 times)

0 Members and 1 Guest are viewing this topic.

Vibrating_Lights

  • Guest
AlCl3 and Md compounds
« on: August 17, 2002, 04:56:00 AM »
I believe it has been said before that AlCl3 could not be used in conjunction with any of the MDx synths.  Is this because of the vulnerability of the Md Bridge.  Is it safe to employ AlCl3 into other ring substitution patterns.  Does it negativly affect Methoxy(2,5 dimethoxy) patterns.

Also Could a 4-clorination be done with NaCl And oxone or HCL and oxone in (Aq)enviroment or would it be better to do a biphasic with DCm or something.  DCM would also keep the rxn at a workable temp to reduce side rxns. When emploeying the Oxone halogenation would it be best to run the rxn with freebase added to a preprepared solution or with the hcl salt in conjuncton with HCL/Oxone adding the oxone as it is needed.
Vl_

So much game I could sell a hooker some pussy
Vl_

Vibrating_Lights

  • Guest
bump
« Reply #1 on: August 28, 2002, 01:43:00 AM »
::)

So much game I could sell a hooker some pussy
Vl_

Chromic

  • Guest
Freebase or salt, doesn't matter.
« Reply #2 on: August 28, 2002, 04:21:00 AM »
Freebase or salt, doesn't matter. I'd follow some literature references if I were you.

carboxyl

  • Guest
Yes, it is beecause of the MD bridge.
« Reply #3 on: August 28, 2002, 05:08:00 AM »
Yes, it is beecause of the MD bridge.

Anydrous AlCl3 is a relatively strong Lewis acid. It bonds with the lone pairs of electrons on the oxygens in the ethers. When this complex is hydrolyzed, the ether is cleaved. When you do this to safrole, you can definately expect a mess, since the methylenedioxy ring gets cleaved, and things can get even more out of hand from there.

https://www.thevespiary.org/rhodium/Rhodium/chemistry/safrole.eugenol.txt



The above post is purely fictional. Any resemblance to "real-life" is purely coincidental.

Osmium

  • Guest
Methoxies will be affected by AlX3 too.
« Reply #4 on: August 28, 2002, 11:05:00 AM »
Methoxies will be affected by AlX3 too.

I'm not fat just horizontally disproportionate.

Kinetic

  • Guest
Hydroxies
« Reply #5 on: September 10, 2002, 10:50:00 PM »
I have been thinking along the same lines, as I'm currently doing a little light reading on substituted cathinone analogues. Since propionyl chloride/AlCl3 + 1,3-benzodioxole will not work, I was wondering whether whether propionyl chloride/AlCl3 will affect hydroxies, such as from catechol, which can then have the methylenedioxy bridge added as the next step.

Rhodium

  • Guest
If you choose a milder lewis acid, such as TiCl4 ...
« Reply #6 on: September 11, 2002, 12:46:00 AM »
If you choose a milder lewis acid, such as TiCl4 instead of AlCl3, you will experience a lot less ether breakage problems.

The problem isn't just the MD-bridge may be torn off, it most certainly won't be torn off cleanly either in a friedel-crafts alkylation, so instead of just collecting the debris after the reaction and reattach any MD bridge, you will have all sorts of breakdown products (a.k.a. tar), which cannot be fixed. Better never break it in the first place.

Kinetic

  • Guest
So,
« Reply #7 on: September 11, 2002, 09:02:00 PM »
Is TiCl4 a strong enough Lewis base to remove the chloride from an acid chloride, without greatly affecting yields? Being a weaker base, yields may be affected. Does anyone have a reference to compare Friedal-Crafts acylations with AlCl3 to those with TiCl4?

Rhodium

  • Guest
Here is an example with TiCl 4 , the yields are ...
« Reply #8 on: September 12, 2002, 12:44:00 AM »
Here is an example with TiCl4, the yields are only moderate, mostly because friedel-crafts alkylations with nitroalkenes is not optimal - it is fantastic that the reaction worked that good at all!

https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdp2p.nitroalkylation.html


Nemo_Tenetur

  • Guest
TiCl4 + 1,3-benzodioxole = boilover
« Reply #9 on: September 12, 2002, 12:45:00 PM »
Since AlCl3 and 1,3-benzodioxole doesn't work I've tried TiCl4 and 1,3-benzodioxole in DCM with EtCOCl (external water/ice cooling). After several seconds a violent boilover produced so much gaseous CH2Cl2 that my dropping funnel (with pressure equalization !) was blown away. It seems that the "milder" lewis acid TiCl4 isn't the right choice for acylations of 1,3-benzodioxole.

Kinetic

  • Guest
Vibrating_Lights, what are you trying to do with ...
« Reply #10 on: September 12, 2002, 04:47:00 PM »
Vibrating_Lights, what are you trying to do with AlCl3 and the methylenedioxy bridge? Are you trying to acylate 1,3-benzodioxole? It seems from this thread that this will definitely not work with AlCl3, and not with TiCl4 in DCM either. However, if AlCl3 doesn't affect hydroxies, you could acylate catechol. I assume it doesn't because in the link I give below there is a demethylation using AlI3 in which the hydroxy stays intact. My question is:

Could you use a method of forming the methylenedioxy bridge (such as those in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.html#DCM

) without affecting the ketone of the molecule? This would give the interesting (for me) 3,4-(Methylenedioxy)propiophenone.

PrimoPyro

  • Guest
Catechol Acylation
« Reply #11 on: September 13, 2002, 04:36:00 AM »
Will have a very low yield if any at all. The phenolic protons will interfere, and also both of those hydroxy groups are electron withdrawing groups, and will inhibit Friedel-Crafts reactions by diminishing the attraction of the electrophile toward the ring.

PrimoPyro

Will perform sexual favors for females in exchange for 1,2-dimethylaziridine. PM for details.

Vibrating_Lights

  • Guest
rearrange epoxides
« Reply #12 on: September 13, 2002, 05:39:00 AM »
I found a ref that would Preform a pinicol rearrangement on aromatic epoxides.  I'll FInd it and post the link.  IN the procedure ANhydrous AlCl3 was added to epoxide without solvent. I was thinking that one could mix the epoxide with NaHCO2 to neutralize the hcl as it is formed when the Hcl is produced.  I think the probvlem with the AlCl3 is the Hcl correct.  It would eat the bridge???
VL_

So much game I could sell a hooker some pussy
Vl_

Osmium

  • Guest
Huh? > I think the probvlem with the AlCl3 is ...
« Reply #13 on: September 17, 2002, 03:23:00 PM »
Huh?

> I think the probvlem with the AlCl3 is the Hcl correct.
>  It would eat the bridge???

No. The AlX3 will eat the bridge, not the HCl produced during workup.



I'm not fat just horizontally disproportionate.

Antoncho

  • Guest
A better way of Friedel-Craftsing.
« Reply #14 on: January 20, 2003, 08:17:00 AM »
Here's some useful info from the russian article Rhodium sent me yesterday. It talks about acylating various substrates, methylendioxybenzene among them.

The other ones are :

Here's the typical synthetic proc (all the same for each one, the only difference being the catalyst and the temperature.

To a mixtr of 25mls unhydrous CH2Cl2, 37mmoles of the acylated comp'd, 37mmoles acyl chloride kept at specified temperature, there's added over the course of 0,5hrs 40mmoles anhydrous Friedel-Crafts catalyst. The rxn is further stirred 1h at 20 C, poured onto ice, acidified w/HCl , xtracted w/DCM, pooled xtracts washed w/water, dried and the solvt removed.

1,3-benzodioxole: catalyst - SnCl4, temp = 0 C
all the others: catalyst - AlCl3, temp = -10 C

Yield for methylenedioxypropiophenone - 58% (almost the worst of them all, generally the yields are 60-70%)



A great article, shall i say!


Antoncho

Kinetic

  • Guest
Beautiful!
« Reply #15 on: January 20, 2003, 06:50:00 PM »
Antoncho, you don't know how much this means to me. Thankyou so much! Your translation is infinitely better than the '??!.????!.' Babelfish churned out :P . Thanks also to lugh for finding the original article for me (recently requested in Wanted References). This will be tested out for benzodioxole/propionyl chloride within a few weeks, hopefully giving a decent yield of 3,4-methylenedioxypropiophenone :) .

Antoncho

  • Guest
A _possibly_ ABSOLUTELY BEST way of F-C'ing
« Reply #16 on: January 21, 2003, 08:59:00 AM »
Hey, bees, look what i found, mapping the faraway honeyfields of Uspatland :)  :)  :)

Looks like all we need to make aceto- and propiophenones from all sorts of stuff is:

a) Tosic acid (make some yourself from toluene and H2SO4)

b) Dean-Stark trap





Patent US5041616



"I have discovered that aryl ketones may be obtained by heating a carboxylic acid with certain aromatic compounds in the presence of (1) a volatile, organic compound which forms an azeotrope, i.e., a constant boiling mixture, with water and (2) a catalytic amount of an organic sulfonic acid, whereby the water of reaction is removed as an azeotrope from the reaction mixture. "

"The carboxylic acid employed is not critical and may be selected from a wide variety of unsubstituted and substituted, aliphatic, cycloaliphatic and aromatic carboxylic acids containing from 2 to 20 carbon atoms."

"...Phenols and benzenediols, as well as ethers and esters thereof, may be acylated using methanesulfonic and toluenesulfonic acids. In the case of less reactive aromatic compounds such as alkylaromatic compounds, e.g., toluene and xylene, a more acidic sulfonic acid such as a perhaloalkylsulfonic acid, e.g., trifluoromethanesulfonic acid normally is required to achieve satisfactory reaction rates."


EXAMPLE 3

Hydroquinone (11.0 g, 0.1 mole), octanoic acid (30.2 g, 0.21 mole), heptane (110 mL), and methanesulfonic acid (10 mL, 0.14 mole) were heated at reflux (98.degree. C.) for 5 hours in a 300 mL flask equipped with a Dean-Stark trap. During this time, 3 mL of water was collected. The sulfonic acid layer was separated, and the heptane layer was washed once with 50 mL of water and twice with 50 mL portions of saturated, aqueous sodium bicarbonate solution. The mixture was filtered to remove 5 g of product, octanoylhydroquinone octanoate ester, while evaporation of the organic layer gave 17.3 g. The total yield of octanoylhydroquinone was 22.3 g, 94% of theory.





Now, don't you think that 'CiHKAL' is a nice name for a book? ;)  ;)  ;)



Antoncho

P.S. BTW, this rxn is also great since it allows one to watch its progress by measuring the amt of water - something of great importance when adjusting conditions to different substrates and reagents.

Aurelius

  • Guest
US Patent 5041616 (all examples)
« Reply #17 on: January 21, 2003, 09:49:00 PM »
US Patent 5041616

Preparation of Aryl Ketones


Example 1:

A mixture of p-toluic acid (22.2g, 0.163mol), p-xylene (100ml), and trifluromethanesulfonic acid (5ml, 0.056mol) was heated at reflux for 21 hours in a 300ml flask equipped with a Dean-Stark trap, after which time 3ml of water had been collected in the trap.  The progress was measured with GC as well as by the amount of water collected.  After 6 hours, 22% of the starting material had been converted to 2,5,4’-trimethylbenzophenone.  The mixture was extracted with water, with 5% sodium hydroxide and again with water.  Evaporation of the organic layer gave 24g (0.11mol) of 2,5,4’-trimethylbenzophenone, 66% of theory.

Example1; modified:

The procedure in Example 1 was repeated without a Dean-Stark trap.  After 4 hours of reflux, only about 6% of the starting material had been converted to product.  The amount of product was not increased significantly after refluxing an additional 6 hours.

Example 2:

Benzoic acid (20g, 0.16mol), p-xylene (100ml), and trifluoromethanesulfonic acid (5ml) were heated at reflux in a 300ml flask equipped with a Dean-Stark trap.  After 16 hours, the mixture was extracted with 100ml of 6% sodium hydroxide, washed with 100ml of water, dried over Mg sulfate and evaporated to give 15.4g (0.073mol) of 2,5-dimethylbenzophenone.  The aqueous sodium hydroxide extract was acidified to give 8.1g (0.066mol) of unreacted benzoic acid.

Example 3:

Hydroquinone (11.0 g, 0.1 mole), octanoic acid (30.2 g, 0.21 mole), heptane (110 mL), and methanesulfonic acid (10 mL, 0.14 mole) were heated at reflux (98.degree. C.) for 5 hours in a 300 mL flask equipped with a Dean-Stark trap. During this time, 3 mL of water was collected. The sulfonic acid layer was separated, and the heptane layer was washed once with 50 mL of water and twice with 50 mL portions of saturated, aqueous sodium bicarbonate solution. The mixture was filtered to remove 5 g of product, octanoylhydroquinone octanoate ester, while evaporation of the organic layer gave 17.3 g. The total yield of octanoylhydroquinone was 22.3 g, 94% of theory.


Kinetic

  • Guest
Stability of SnCl4?
« Reply #18 on: January 27, 2003, 08:39:00 PM »
Does anyone have experience working with SnCl4? The procedure above doesn't mention any special precautions need to be taken, and I was wondering how stable it is to hydrolysis, compared to, say, AlCl3 or SiCl4. Is a syringe necessary, as in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/iap.html

?:

10g (84.6 mmol) of indane was dissolved in 100ml dichloromethane and cooled to 0°C on an ice bath. With vigorous stirring, 15ml (127 mmol) SnCl4 was added all at once via syringe, folllowed by the dropwise addition of 9.72g (7.65ml, 84.6 mmol) dichloromethyl methyl ether over a 10-minute period.


Or will it happily sit in a dry dropping funnel exposed to the atmosphere for 30 minutes while it's added to the reaction mixture? I really hope it isn't as hard to work with as SiCl4 would be in a clandestine setting!


Rhodium

  • Guest
SnCl4 will smoke heavily in air, forming ...
« Reply #19 on: January 27, 2003, 09:05:00 PM »
SnCl4 will smoke heavily in air, forming SnO2/HCl. It is similar to TiCl4 in that respect.

Kinetic

  • Guest
Oh...
« Reply #20 on: January 27, 2003, 10:35:00 PM »
Thanks for the quick reply Rhodium, even though it wasn't what I wanted to hear! I had a feeling that would be the case, knowing the delights of letting a syringe block up with SiO2 within seconds of letting similar (to SnCl4) SiCl4 come in contact with air, and having heard that SnCl4 is packaged under argon...

I think a slight change of plan would be a good idea, which may not be too bad seeing as the article translated by Antoncho above adds the reagents in quite an odd order anyway. If someone who isn't me was to modify Kinetic's proven:

Preparation of butyrophenone

To 133.3g (1 mole) anhydrous aluminium chloride in 350ml anhydrous dichloromethane was added 106.6mL (1.02 moles, 108.7g) butyryl chloride. The mixture was stirred until all AlCl3 has been dissolved. With external ice-bath cooling, 89.8mL (1 mole, 78.1g) of benzene was added over an hour. Stirring was continued for an additional hour.
The yellow-orange reaction mixture was slowly added to 600mL stirred water/ice mixture; the pale lower layer was collected, and all volatiles were removed under vacuum.
The ketone was vacuum distilled, to give 1-phenyl-butan-1-one as a colourless oil.
Yield: 132.1g (89%)


by replacing AlCl3 with SnCl4 (obviously changing the other reagents too), would the solvation of SnCl4 by DCM slow the hydrolysis enough to allow the acylation to proceed? The first step in Rhodium's Indanylamphetamine synthesis has an excellent yield without any protective atmosphere :) .

BTW, that synthesis is from a two-step 1-phenyl-2-methylaminobutane synthesis which I'll post if anyone's interested. The second step only has a 40% yield, but it's very easy. Maybe other bees could have a play around with it; there's no doubt it would give methcathinone if propionyl chloride was used instead of butyryl chloride.


Rhodium

  • Guest
Yup, here is a reference for that rxn
« Reply #21 on: January 27, 2003, 11:06:00 PM »
Reactant: benzo[1,3]dioxole, propionyl chloride
Product: 1-benzo[1,3]dioxol-5-yl-propan-1-one
Yield:   58 percent
Reagent: SnCl4
Solvent: CH2Cl2
Time: 1 hour
Temperature: 20°C
Ref: Journal; Daukshas, V. K.; Gaidyalis, P. G.; Pyatrauskas, O. Yu.; Udrenaite, E. B.; Gasperavichene, G. A.; Raguotene, N. V.;  Pharm.Chem.J.(Engl.Transl.); EN; 21; 5; 1987; 341-345; KHFZAN; Khim.Farm.Zh.; RU; 21; 5; 1987; 569-573.

Offline Whenimgone

  • Subordinate Wasp
  • ***
  • Posts: 175
Re: A better way of Friedel-Craftsing.
« Reply #22 on: September 18, 2015, 04:26:19 PM »
Here's some useful info from the russian article Rhodium sent me yesterday. It talks about acylating various substrates, methylendioxybenzene among them.

The other ones are : <a href="https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000346121-file_fmw6.gif" title="View this image">[/url]

Here's the typical synthetic proc (all the same for each one, the only difference being the catalyst and the temperature.

<font color="blue">To a mixtr of 25mls unhydrous CH2Cl2, 37mmoles of the acylated comp'd, 37mmoles acyl chloride kept at specified temperature, there's added over the course of 0,5hrs 40mmoles anhydrous Friedel-Crafts catalyst. The rxn is further stirred 1h at 20 C, poured onto ice, acidified w/HCl , xtracted w/DCM, pooled xtracts washed w/water, dried and the solvt removed.

1,3-benzodioxole: catalyst - SnCl<sub>4</sub>, temp = 0 C
all the others: catalyst - AlCl<sub>3</sub>, temp = -10 C

Yield for methylenedioxypropiophenone - 58% (almost the worst of them all, generally the yields are 60-70%)
</font>


A great article, shall i say!


Antoncho

Any chance you could send me the link to this article?
Knowledge is free