Author Topic: Condensation of BnCN + EtO = ?  (Read 178 times)

no1uno

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Condensation of BnCN + EtO = ?
« on: February 13, 2012, 07:39:26 PM »
Most have read about (at least) the Benzoin condensation - where two moles of BnO are with one another to form Benzoin using a catalyst (Vitamin B1/Cyanide for example).

There are also literature examples on crossed condensations of this type...

BnCN is fairly easily made (apparently), as is acetaldehyde and a condensation of the two would presumably give the same product as noted in orgsyn for the acylation of BnCN, which is then transformed to P2P.

Just seems to me that such a condensation would avoid having to fuck around with strong bases, etc.

Any ideas?
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fishinabottle

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Re: Condensation of BnCN + EtO = ?
« Reply #1 on: February 13, 2012, 10:09:22 PM »
Was this not acetylacetone what goes to P2P by condensation with BzCN and follwing hydrolysis?
But IIRC alcoholates are needed for a base.

Which are easier made the acetaldehyde for there was a method for making them (methyl/ethyl) with only NaOH and a simple so tricky setup with a heated tube where the hydroxide sucks the formed water out at the bottom whilst the alcoholate is removed from the top. 
Now tell me your easy methods of making BzCN and acetaldehyde, as for the second I had been searching damned long with no avail (just to find in the end out that it as not acetaldehyde but pyruvate I really needed   :-\ ).

There are many ways to skin a cat but these days not many have the drive to do and to talk about it as it seems (understandable when one takes into account how many favorable routes have become much harder just because the names of compounds and their sources were splattered over a dozen boards - usually by ppl who NEVER had the true intention, not to talk of the whiff and balls, to pull the synth off).

So many routes nevertheless if one dares to venture through thousands of posts on dozen of boards and top this by a heap of articles barely more reliable.

/ORG




Sedit

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Re: Condensation of BnCN + EtO = ?
« Reply #2 on: February 14, 2012, 04:29:45 AM »
Oxidation of EtOH using Dilute HNO3 produces a clear and strong scent of Acetaldahyde yet concentrated Nitric goes all the way to Acetic acid in relatively good yields. It would do the community well if this synthesis was stream lined and workup better understood.
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Goldmember

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Re: Condensation of BnCN + EtO = ?
« Reply #3 on: February 14, 2012, 06:46:27 AM »
Has nobody tried Strecker degradation of Alanine with bleach? Fits in well if you are planning on making BnCN from Phe/TCCA.

Passing a current through a carbon bed anode/EtOH with a touch of H3PO4 produces an instant and very strong whiff of Acetaldehyde, moreso than any copper pipe experiments Ive done.

no1uno

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Re: Condensation of BnCN + EtO = ?
« Reply #4 on: February 14, 2012, 02:03:19 PM »
I've done the Strecker degradation of Phenylalanine with bleach, worked it out in fact (from the vague reports available online all I got was red tar - great yields but), >2 equivalents of OCl are required in order to make the gem-dichloramine which is the intermediate in the synthesis (I'm still unsure why Strecker gets the kudos, Langheldt was the original worker/publisher on the route).

That said, there are easier methods to acetaldehyde (ethanol and a heated tube) and the Strecker degradation on Phenylalanine gives the nitrile. TCCA + phenylalanine is reported to give the BnCN in good yields though.

There are also reports in the literature of such reactions being run with Phenylacetonitrile + aromatic/aliphatic aldehydes, at RT (or in a MW), sans solvent, with solid KOH as the base to give excellent yields. I'm going to try and get at the relevant papers, it could be a fucking useful short-route to medium size reactions if it worked.
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..."

fishinabottle

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Re: Condensation of BnCN + EtO = ?
« Reply #5 on: February 14, 2012, 11:46:40 PM »
Virtually all attempts on pro producing acetaldehyde gave an optimistic typical smell. And that was about everything. This compares well to "yields by GC" versus "isolated yields" in the now standard mmol literature.
Why oh why are these two numbers least 15% apart, well running up to 90% vs. nada in realworld. Usually achieved with solvent ratios which when scaled up to useful levels make one wanna cry.

Ok, there are exceptions, I am exaggerating. But just a little bit.

/ORG

Balkan Bonehead

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Re: Condensation of BnCN + EtO = ?
« Reply #6 on: February 15, 2012, 07:25:26 PM »
Easier just to hydrolyze the benzyl cyanide and proceed by more tried and true ways.

zgoat65

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Re: Condensation of BnCN + EtO = ?
« Reply #7 on: June 01, 2012, 12:18:51 AM »
I have been reading a lot about this particular route, and I mean a lot considering a few 27 page threads on other forums about phenylalanine.  This is one of the old methods :

"An insight of the reaction of amines with trichloroisocyanuric acid"
De Luca & Giacomelli
Synlett 2004, No. 12, pp 2180


R-CH(COOH)NH2 ------> R-C#N (TCCA/H2O/NaOH/5 C)

Amino acid Nitrile time(h) Yield(%)
----------------------------------------------------------------
Ph-CH2-CH(COOH)NH2 Ph-CH2-C#N 0.4 98
HOOC-CH2-CH(COOH)NH2 HOOC-CH2-C#N 1.0 99
HOOC-CH2-CH2-CH(COOH)NH2 HOOC-CH2-CH2-C#N 0.5 90
BnOPh-CH2-CH(COOH)NH2 BnOPh-CH2-C#N 1.0 93
CH3-CH2-CH(CH3)-CH(COOH)NH2 CH3-CH2-CH(CH3)-C#N 0.5 98


The reaction can be preformed with 2/3 equivalents of TCCA directly on an aqueous solution of the alpha-aminoacid under basic conditions: after 30 minutes to 1 hour, the nitriles can be recovered quantitatively without any trace of byproducts.
It is worth mentioning to note that in the case of amino acids having multiple chiral centers such as isoleucine the reaction occurs without any racemization of the adjacent chiral center.

[...]

General One-Pot Procedure.

The reported procedure is representative: L-Phenylalanine (1.2 g, 7.6 mmol) was dissolved in an aq solution of 2 N NaOH (3.8 mL) and treated with TCCA (1.17 g, 5.1 mmol) at 25 C. After 10 min, when TLC analysis showed the complete absence of the L-phenylalanine, the reaction mixture was treated with HCl (15 mL), followed by an aq solution of 3 N HCl (2.5 mL). After 10 min the mixture was extracted twice with Et2O (15 mL). The organic layers were washed with H2O (10 mL), dried on Na2SO4, filtered and concentrated in vacuo to yield phenylacetonitrile (0.87 g, 98%)
(exerpt from the Hive)

I know that there have been quite a few advances made to this route.  The thread that this came from was a bit open ended.  Noone actually claimed success with this method.  Lots of runaway rxns tho.  That problem was actually solved.  Slow addition and an ice bath.  Anyone actually tried this method?  If not, then someone is about to......as soon as his Kg of phenylalanine arrives. 
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atara

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Re: Condensation of BnCN + EtO = ?
« Reply #8 on: June 09, 2012, 05:48:49 PM »
Easier just to hydrolyze the benzyl cyanide and proceed by more tried and true ways.
I feel like this is right. Nitriles aren't strong electrophiles nor are they good enough electron withdrawing groups to create a very labile carbanion (pKa = 21.9 is quite high for BnCN).

One wacky idea would be to try a 1,3-dipolar cycloaddition of the nitrile oxide with trichloroethylene and see if you couldn't basify the product to a sort of P2P-oxime...

The rearrangement would proceed like this: alkyl nitrile oxide + trichloroethylene --> 3-alkyl-4,5,5-trichloroisoxazolidine -- (KOH) --> 3-alkyl-(2H)-isoxazolin(5)one --(KOH)--> 3-alkyl-(4H)-isoxazolin(5)-one --> alkyl chloromethylcarboxylic acid oxime --> alkyl chloromethyl oxime
« Last Edit: June 09, 2012, 06:13:54 PM by atara »