Alanine Strecker

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. 

In some cases, Bucherer s process is employed also, but strict control of reaction conditions is needed because the reactivity of formaldehyde is different from other aldehydes. DL-Alanine (212) is produced by either Strecker s or Bucherer s process from acetaldehyde. 

Of the naturally occurring amino acids alanine only was prepared synthetically many years before it was discovered as a constituent of the protein molecule. Its name was given to it by its discoverer, Strecker, who prepared it in 1850 from aldehyde ammonia, which, when treated with hydrogen cyanide gives the aminocyanohydrin, and this by hydrolysis is then converted into the amino acid —... 

The occurrence of alanine in proteins was first shown by Schutzen-berger, who did not actually identify his product with the synthetical one Weyl in l88i obtained it as a decomposition product of silk and showed that his preparation was similar in properties to Strecker s synthetical alanine. He thus established it as a constituent of a protein molecule. The researches of Emil P ischer have shown that alanine is a constant constituent of all proteins. It is worthy of note that of the eighteen definitely determined units of a protein molecule, six of them, namely, isoleucine, phenylalanine, tyrosine, serine, histidine and tryptophane, are derivatives of a-aminopropionic acid. 

Harada 106) gelang der Aufbau von L-Alanin aus Acetaldehyd, (5)-a-Phenylathylamin und HCN in einer as5anmetrisch gelenkten Strecker-Synthese mit p = 90 %. 

Both the ninhydrin reaction and pyridoxal phosphate-catalyzed decarboxylation of amino acids (Chapter 14) are examples of the Strecker degradation. Strecker reported in 1862 that alloxan causes the decarboxylation of alanine to acetaldehyde, C02, and ammonia.c... 

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. 

This important flavor compound was identified in the head-space volatiles of beef broth by Brinkman, et al. (43) and although it has the odor of fresh onions, it is believed to contribute to the flavor of meat. This compound can be formed quite easily from Strecker degradation products. Schutte and Koenders (49) concluded that the most probable precursors for its formation were etha-nal, methanethiol and hydrogen sulfide. As shown in Figure 5, these immediate precursors are generated from alanine, methionine and cysteine in the presence of a Strecker degradation dicarbonyl compound such as pyruvaldehyde. These same precursors could also interact under similar conditions to give dimethyl disulfide and 3,5-dimethyl-l,2,4-trithiolane previously discussed. 

Rohan had suggested that the operative reaction in the development of chocolate aroma might be a Strecker degradation of the amino acid fraction. Bailey et al. (8) demonstrated quantitatively that three aldehydes, which could be related to leucine, valine, and alanine, were prominent in the volatiles from a typical sample of roasted, ground cacao beans. 

Thus, IQ may arise from creatinine, 2-methylpyridine and formaldehyde or a related Schiff base, formed from glycine through Strecker degradation. The initial step may be a Mannich reaction or an aldol condensation. By analogy MelQ may arise from creatinine, alanine and 2-methylpyridine, and MelQx from creatinine, glycine and 2,5-dimethylpyrazine according to the scheme in Figure 1. 

Strecker Aldehyde Formation. Formaldehyde, acetaldehyde and iso-butyraldehyde were formed by Strecker degradation of glycine, alanine and valine, respectively. Relative concentrations of aldehydes produced by microwave and conventional heating to comparable temperature is shown in Table I. Significantly higher concentrations were observed for microwave heated samples. 

Table 3.5 Arrhenius rates used to fit the experimental concentrations of pyrroles, furans, Strecker aldehydes, and pyrazines from a glucose-alanine system as a function of time and temperature130...

More than 300 compounds had been identified in cocoa volatiles, 10% of which were carbonyl compounds (59,60). Acetaldehyde, 2-methylpropanal, 3-methylbutanal, 2-methylbutanal, phenylacetaldhyde and propanal were products of Strecker degradation of alanine, valine, leucine, isoleucine, phenyl-acetaldehyde, and a-aminobutyric acid, respectively. Eckey (61) reported that raw cocoa beans contain about 50-55% fats, which consisted of palmitic (26.2%), stearic (34.4%), oleic (37.3%), and linoleic (2.1%) acids. During roasting cocoa beans these acids were oxidized and the following carbonyl compounds might be produced - oleic 2-propenal, butanal, valeraldehyde, hexanal, heptanal, octanal, nonanal, decanal, and 2-alkenals of Cg to C-q. Linoleic ethanal, propanal, pentanal, hexanal, 2-alkenals of to C q, 2,4-alkadienals of Cg to C-q, methyl ethyl ketone and hexen-1,6-dial. Carbonyl compounds play a major role in the formation of cocoa flavor components. 

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. 

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. 

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. 

Strecker [34] discovered that the reaction between amino acids (glycine, alanine, leucine) and the tricarbonyl compound alloxan yields CO2 and aldehydes. The Strecker degradation of amino acids occurs also with dicarbonyl compounds [35] including those that are formed in the course of the Maillard reaction, in particular deoxyglycosones and some of the smaller sugar fragments like 7 and diacetyl. Fig. 3.22 shows the reaction pathway that involves the formation of an imine 8, followed by decarboxylation and liberation of the resulting aminoketo compound and the Strecker aldehyde from the intermediate 10. Odour-active Strecker aldehydes which... 

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