Alanine, Strecker synthesis

There are several laboratory-size methods for synthesizing amino acids, but few of these have been scaled up for industrial production. Glycine and m.-alanine are made by the Stnecker synthesis, commencing with formaldehyde and acetaldehyde, respectively. In tile Strecker synthesis, aldehydes react with hydrogen cyanide and excess ammonia to give amino niiriles which, in turn, are converted into a -amino adds upon hydrolysis. 

Isoleucine has a sec-butyl group for its side chain. Remember that CH3 — CHO undergoes Strecker synthesis to give alanine, with CH3 as the side chain. Therefore, sec-butyl—CHO should give isoleucine. 

It is possible to make amino acids quite straightforwardly in the lab. The scheme below shows a synthesis of alanine, for example. It is a version of the Strecker synthesis you met in Chapter 12. 

Strecker 7 first synthesized alanine by the action of hydrocyanic add on aldehyde ammonia. The present procedure is based on Zelinsky s modification of the Strecker synthesis.8... 

Similar to the cyanohydrin synthesis for hydroxy acids is the Strecker synthesis of amino acids. Aldehydes and ketones are converted to a-amino cyanides by ammonia and hydrogen cyanide or by aqueous ammonium chloride and sodium cyanide solutions. Amino cyanides may also be obtained by the action of gaseous ammonia on cyanohydrins (cf. method 391). The preparation of DL-alanine (60%) is typical. "... 

An amino nitrile may be formed instead of a cyanohydrin if the carbonyl compound is treated with aqueous ammonium chloride and sodium cyanide. Hydrolysis of the amino nitrile gives an a-amino acid as in the Strecker synthesis of r>L-alanine (Scheme 3.46). 

Problem 36.11 Acetaldehyde reacts with a mixture of KCN and NH4CI (Strecker synthesis) to give a product, C3H6N2 (What is its structure ), which upon hydrolysis yields alanine. Show bow the Strecker synthesis can be applied to the synthesis of glycine, leucine, isoleuctne, valine, and serine (start with C2H5OCH2CH2OH). Make all required carbonyl compounds from readily available materials. 

Kitayama, T., Watanabe, T., Takahashi, O., Morihashi, K., Kikuchi, O. Parity-violating energy forthe chirality-producing step in Strecker synthesis of L-alanine. THEOCHEM 2002, 584, 89-94. 

As an example, consider the synthesis of alanine via the Strecker synthesis ... 

The synthesis of alanine was described by Adolf Strecker of the University of Wurzburg (Germany) in a paper published in 1850... 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

The first known synthesis of an amino acid occurred in 1850 in the laboratory of Adolph Strecker in Tubingen, Germany. Strecker added acetaldehyde to an aqueous solution of ammonia and HCN. The product was a-amino propionitrile, which Strecker hydrolyzed to racemic alanine. 

Huguenot, F. and Brigaud, T. (2006) Concise synthesis of enantiopure a-trifluoromethyl alanines, diamines, and amino alcohols via the Strecker-type reaction.. /. Org. Chem., 71, 7075-7078. 

---