Author Topic: First published direct reduction of COOH to CH3  (Read 2092 times)

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Rhodium

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First published direct reduction of COOH to CH3
« on: May 17, 2001, 05:47:00 AM »
I can think of the use of this in the reduction of phenylalanine to amphetamine, and reduction of tryptophan to AMT.

A Direct Reduction of Aliphatic Aldehyde, Acyl Chloride, Ester, and Carboxylic Functions into a Methyl Group
Gevorgyan, V.; Rubin, M.; Liu, J.-X.; Yamamoto, Y.

Journal of Organic Chemistry 66, 1672-1675 (2001)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/carboxylic2methyl.pdf)
DOI:

10.1021/jo001258a



Abstract
Aliphatic carboxyl groups was efficiently reduced to the methyl group by triethylsilane in the presence of a catalytic amount (5 mol%) of the non-traditional lewis acid B(C6F5)3. To the best of our knowledge, this is the first example of exhaustive reduction of an aliphatic carboxyl function to a methyl group. Aliphatic aldehydes, acid chlorides and acid anhydrides also underwent complete reduction under similar reaction conditions.

All yields from all the published substrates range between 91 and 99%.

Experimental conditions:

Triethylsilane (30 mmol) was added under an argon atmosphere to a mixture of the carboxylic acid (5 mmol) and B(C6F5)3 (0.25 mmol) in 5 ml DCM. The mixture was stirred at RT for 20h, the reaction quenched (Et3N, 0.25 ml), filtered through Celite and concentrated. The residue was mixed with 40% HF (5-7 ml) in ethanol (30 ml) and refluxed for 7h. Water (60 ml) was added, the product extracted with 3x30ml pentane, The extracts washed with water, dried over MgSO4 and the solvent and Et3SiH was removed under vacuum. The residue was purified by flash column chromatography on silica gel to afford the products in 91-99% yield.

halfapint

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Re: First published direct reduction of COOH to CH3
« Reply #1 on: May 17, 2001, 08:58:00 AM »
Would that Lewis acid bee pronounced tri-perfluorophenyl borane? Don't have any on me right now. (Wouldn't ever care to get any on me, come to that...) Non-traditional, well I can believe that.

Chemistry is a science in which the "impossible" is continually happening. As long as it is thermodynamically allowed, somebody is always going to find a new way to produce some reaction, which had previously been ruled out. These new developments, I'm sure, are always surprising to those well versed in the field. Keep on finding 'em, Rhodium.


Turning science fact into <<science fiction>>

foxy2

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Re: First published direct reduction of COOH to CH3
« Reply #2 on: May 17, 2001, 12:44:00 PM »
That triethyl silane could be some useful shit.
Time to pick up a few kilos before its watched

Post 191102 (missing)

(Twist: "Re: Pulling Caffine", Stimulants)




Do Your Part To Win The War

Rhodium

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Re: First published direct reduction of COOH to CH3
« Reply #3 on: May 17, 2001, 01:34:00 PM »
Too bad 100g of the stuff costs $150 (Aldrich).


http://rhodium.lycaeum.org


Osmium

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Re: First published direct reduction of COOH to CH3
« Reply #4 on: May 17, 2001, 03:36:00 PM »
Meaning the actual value is more like 7.50-15$/100g  ;)

I better not ask how much the perfluorotriphenylborane costs...

b159510

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Re: First published direct reduction of COOH to CH3
« Reply #5 on: May 17, 2001, 05:07:00 PM »
Would that Lewis acid bee pronounced tri-perfluorophenyl borane?...tris(pentafluorophenyl)borane

Phosphole

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Re: First published direct reduction of COOH to CH3
« Reply #6 on: May 18, 2001, 09:00:00 AM »
Os, since you really wanted to know: :o


SS-DD: Same Shit - Different Day

akata

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Re: First published direct reduction of COOH to CH3
« Reply #7 on: July 23, 2001, 04:41:00 PM »
triethylsilane:

It seems to be quite a handy thing see;

Post 183270 (missing)

(The_Animal: "Triethylsilane", Stimulants)

superhybrid

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Re: First published direct reduction of COOH to CH3
« Reply #8 on: July 24, 2001, 06:18:00 AM »
If this was indeed economically feesible one could react l-dopa with 2 molar equivilents NaH and then react with dichloromethane to produce the methylenedioxy derivative. I am not sure though of what the concsequence would be to the methylene dioxy group after the tranformation of the carboxylic group to a alpha methyl constituent by the above said methods.

foxy2

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Re: First published direct reduction of COOH to CH3
« Reply #9 on: July 25, 2001, 05:23:00 PM »
Sphybrid
What is the purpose of the Sodium Hydride?
Did you mean NaOH?

Do Your Part To Win The War

Rhodium

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Re: First published direct reduction of COOH to CH3
« Reply #10 on: July 25, 2001, 05:35:00 PM »
The purpose of the sodium hydride (NaH) is the same as for NaOH, to deprotonate the OH groups on the aromatic ring. NaH does this more effectively and irreversibly than NaOH, as the reaction with sodium hydride goes PhOH + NaH => H2 + PhONa, while with hydroxide water is formed, and the reaction is reversible.

https://www.rhodium.ws


superhybrid

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Re: First published direct reduction of COOH to CH3
« Reply #11 on: July 26, 2001, 02:27:00 AM »
I guess one other problem would be the DCM connecting with the amine group. What would happen if one would say acetylate the amine as a protecting group. This would possibly disallow cojugation with the amine from the mono chloro intermediate.

Dope_Amine

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Re: First published direct reduction of COOH to CH3
« Reply #12 on: July 26, 2001, 10:55:00 PM »
I hope anybody thinking of trying this reaction realizes just how dangerous HF is!

something for your mind.......

Alphabeta121

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Re: First published direct reduction of COOH to CH3
« Reply #13 on: July 26, 2001, 11:06:00 PM »
if you reacted 1 equiv. of DCM with the deprotonated dopamine, my assumption would be that it would methylenedioxy-ate before it alkylated the amine.
but you know what happens when one assumes...
alphabet

obituary

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Re: First published direct reduction of COOH to CH3
« Reply #14 on: July 26, 2001, 11:44:00 PM »
as the alkylation is potentially reversible, you're probably right, once that ring is formed, it's not coming back undone- the ionic salt formed is going to stay that way


Rhodium

  • Guest
Preparation of triethylsilane
« Reply #15 on: August 28, 2001, 10:40:00 PM »
Preparation of triethylsilane

Journal of the American Society, v69, page 2108 (1947)
Whitmore,Pietrusza, and Sommer.

"Triethylsilane-Preparation of this compound in 56.5% yield by the simulataneous addition of equivalent amounts of trichlorosilane and ethyl magnesium bromide has been reported. The following procedure is more convenient and give yields of 70-78%.

Ethylmagnesium bromide, 12.6 moles, was prepared in a 5-litre, three-necked flast, fitted with an efficient stirrer, dropping funnel and large bulb condenser, each connected to a trap, cooled in Dry Ice and acetone. A cold solution of trichlorosilane, 406.5 g., 3.0 moles, in 1200 cc. of anhydrous ethyl ether was added in six hours with cooling and vigorous stirring. The mixture was stirred for eight hours at room temperature and  then heated to reflux for five hours. Ether was removed from the reaction mixture through a 20-plate column and the residue was heated on the steam-bath for ten hours. With cooling, the solid residue was hydrolyzed with 180 cc. of water, followed by 372cc of contrated hydrochloric acid. The aqueous layer was sepearated and extracted twice with 500cc. portions of ether. The ether extracts and product were comobined, washeed with water, and then dried over 150g. of anhydrous potasssium carbonate for two hours.  Fractional distillation through the 20-plate column gave 270.3 g. of thriethylsilane, bp 107 at 733mm., ----- 77.5% yield"


ibid.
Kraus and Nelson

"Trichlorosilance. - edited

Preparations were made in a horizontal, electricallly heated, Pyrex tube, 3cm. in diamter and 45cm. in lenght, with its entrance connected to a uslric acid drying tower and calibrated flow meter. The exis was attached to a water- cooled condenser, which led to a flask cooled in salt-ice. As a precation against moisure and loss of material the flask connected to a trap immerser in Dry Ice and aceton, which led tta a sulfutic acid drying tower. The tube was chearged with 375g. granyular ferrosilicon, and the system was dried by passing nitrogen through it for twenty-four hours at a furnace temperature of 300 c. Dry hydrogen chloride was then passed in at 350 c until liquid condensed in the receiver. The temperature was then lowered and kept at 290-310 c, while maintaining the flow at 0.6-0.8 mole per hour. Nitrogen was passed through for ten minutes at approximately ten-hour intervals. In sixty hours, this 1370m of liquid product.______________  Fractionation of the liquid product through a column of about 15 theoritical plates gave 1045g. of trichlorosilance, bp 31.5-32 c at 729mm., 77%  of the crude liquid, the remainder being mainly silicon tetrachloride. ___"

Journal of the American Chemical Society, v.56, page 196 (1934)

"Triethylsilance.- ____ was first prepared by Ladenburg (Ann.164,300(1872)) by teating silicon tetraethyl ester with sodium and diethylzinc. Paper (Ann.222,354(1883)) prepared tripropylsilance by treating silicochloroform with dipropyulzinc.  Kahler (unpublished) has shown that triethylsilance may be prepared conveniently by the interaction of the ethyl Grignand reagent with silicochloroform. Sin the the is very connient and we ahve had occasion to lemploy it in preparing quatities of triethylsilance, it will be described briefly.

After adding the two reagents, the mixture is allowed to stand for fifteen hours and is then boiled with reflux condenser for twenty hours. Acidulated water was is added to deocompose the excess ehtymagnesium bromide, the ether layer is seperated, dried over calcium chlordie and the solvent diwstilled.

In our preparation the residue was fractionated through a long Eastman column and the product coming over from 100-125 c was refractionated, the fraction coming over at 107-110 c being retained. The average yield was 56.5%."

abc123

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Re: First published direct reduction of COOH to CH3
« Reply #16 on: September 14, 2001, 05:59:00 AM »
As luck would have it I've been able to procure some of the funky fluoro compound.... However triethylsilane isn't available directly as of yet. I was wondering if it would be possiable to subsitute trimethylsilane in it's place in an equimolar amount. TMS is abundant as we use it for the NMR... Also TMS is more affordable and less suspicious than it's ethyl analog. I'm going to review your quoted reference and see what it has to say for myself, and see if I can gain any addtional insight. Perhaps there is a way to get around this existing  reagent problem. Let me know what you bees think and I'll keep you posted!

Yours in thought

Calamus

Rhodium

  • Guest
Re: First published direct reduction of COOH to CH3
« Reply #17 on: September 14, 2001, 07:16:00 AM »
What is usually used in NMR is tetramethylsilane (TMS), which is unreactive, and won't work in this reaction. Triethylsilane is Et3SiH.

abc123

  • Guest
Re: First published direct reduction of COOH to CH3
« Reply #18 on: September 15, 2001, 01:43:00 AM »
Rhodium,
Thanks for pointing out what I should have known.If TMS really was an acronym for trimethylsilane it couldn't be used in NMR because the protons on the molcule wouldn't be identical. I haven't had a chance to grab the article yet, but I'm guessing that the hydrogen attached to the silicone atom is essencial in the mechanism of this reduction. I better just read what I need to and quit talking before I put another foot in my mouth. Thanks for the info.

Calamus :-[

abc123

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Re: First published direct reduction of COOH to CH3
« Reply #19 on: September 15, 2001, 05:45:00 AM »
I Think that perhaps if you reduced dopa first to an amphetamine via the subject method, and then reacted the amine with acetic anhydride as a protecting group, you could then perform your addtion of DCM to make a methelenedioxy structure. You could then remove the acetyl amide protecting group as you see fit to yeild the product of your choice.

armageddon

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DOPA to 3,4-methylenedioxy..
« Reply #20 on: September 04, 2004, 04:50:00 AM »
I don't know if it has been posted before, but if someone wants, I can upload an article which is about getting 3,4-dihydroxy-phenylacetone from methyl-DOPA ("degradation of alpha-methyl-3,4-dihydroxyphenylalanine"; H.L. Slates, D. Taub, C.H. Kuo, N.L. Wendler, dunno the paper)..

Greetz A


java

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Reduction of COOH to CH3 milder acid changes....
« Reply #21 on: September 05, 2004, 02:42:00 PM »
I think I should have posted this study here, to keep the thread alive and keeping the theme going with new developments.....and so here it is,

Post 529479

(java: "Reduction of Carbonyl Function to a Methyl Group", Chemistry Discourse)