Amino acids reaction with, phosgene

Wilchek, M., Ariely, S., and Patchornik, A., The reaction of asparagine, glutamine, and derivatives with phosgene, J. Org. Chem. 33, 1258-1259, 1968 Hamilton, R.D. and Lyman, D.J., Preparation of A-carboxy-a-amino acid anhydrides by the reaction of copper(II)-amino acid complexes with phosgene, J. Org. Chem. 34, 243-244,1969 Pohl, L.R., Bhooshan, B.,... 

Fig. 44. The modified metering flask of a piogram-controlled peptide synthesizer for the direct preparation of N-protected amino acid anhydrides with phosgene. (A) Solutions of N-protected amino acid salts in dichloromethane or tetrahydrofurane (B) Solution of phosgene in tetrahydrofurane (C) Dry air inlet for stirring (D) Vacuum jacket (E) Drain valve (V) Vent line. Photo sensor levels to meter (2) The solution of N-protected amino add salts (1) The addition of the phosgene solution (3) The draining of the reaction flask...

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

In an attempt to form orally active penicillins unrelated to ampicillin, use was made of the fact that certain spiro a-aminoacids, such as 9, are well absorbed orally and transported like normal amino acids. Reaction of cyclohexanone with ammonium carbonate and KCN under the conditions of the Bucherer-Bergs reaction led to hydantoin 10. On acid hydrolysis, a-amino acid 11 resulted. Treatment with phosgene... 

The y-amino-p-hydroxy acid derived oxazolidinones 55 are prepared from the corresponding N-unprotected y-amino-p-hydroxy ester derivatives by reaction with phosgene,1119,391 carbonyl diimidazole,[41] or benzyl chloroformate.[86] Alternatively, cyclization is obtained from the N-carbamate protected derivatives, i.e. from the TV-isopropenyloxycarbonyl derivatives under heating,[381 or from the TV-Boc or N-Z derivatives under basic conditions. [68 81 87] By analogy, the p,y-diamino acid analogue is converted into the imidazolidinone 57 by treatment of the unprotected compound with phosgene.[83 88]... 

SYNTHESIS Similar to the s)mthesis of poly(7-benzyl-L-glulamate) (see the entry on Poly( y-benzyl-i-glutamate) in this handbook) involves the conversion of the amino acid to the N-carboxyanhydride (NCA) monomer by reaction with phosgene gas followed by polymerization of the NCA with an appropriate initiator (e.g., n-butyl amine). Typical comonomers include other amino acid NCAs. 

N-carboxy anhydrides of amino acids (326), obtained fromN-benzyloxy-amino acids as crystalline derivatives by reaction with phosgene. Acylation of glycine methyl ester by (326) gave the corresponding peptides... 

The preparation of 4-(3-pyridylmethyl)oxazolidine-2,5-dione 1194, the NCA of j8-pyridylalanine, is made difficult by the presence of a pyridyl group in the amino acid. The pyridyl group complicated attempts to phosgenate the amino acid, since hydrogen chloride generated in the phosgenation reaction formed insoluble salts with the amino acid and with any anhydride that may have formed [877]. 

Formation of N-Carboxy-(X-Amino AeidAnhydride (NCA) (85), NCAs are important as starting materials for amino acid polymers. They are prepared by the reaction of amino acids with phosgene in an aptotic solvent. 

FIGURE 7.18 Preparation of Fmoc-amino-acid chlorides by reaction (A) of thionyl chloride,47 phosgene from triphosgene,54 l-chloro-2,A7,A7-trimethyl-l-propene- 1-amine, [Schmidt et al., 1988] or oxalyl chloride, [Rodriguez, 1997] with the parent acid and (B) of hydrogen chloride with the mixed anhydride.51... 

The traditional use of phosgene in Scheme 4 can be avoided by substituting it with the less toxic triphosgene, which gives comparable yields of the M-car-boxyanhydrides. Diphosgene may also be used to form the NCA, but the reaction requires the use of charcoal and is not as reliable. Free amino acids have also been converted to their corresponding NCAs by the use of benzyl chloroforma-te with thionyl chloride. 

In this method, an ale soln of benzene-sulfonic acid(previously standardized with phosgene by weighing the pptd diphenyl-carbamide) is added from a burette to a sample of aniline(or its nitrated compd not jiighvr thsji tctrsnitro-) until the 3ppcufuptcc of a dirty-bluish coloration, when a drop of the reaction mist is placed on a filter paper previously impregnated with amino-/3-naphthol indicator(spot test). This method is not applicable for analysis of penta-nitroani ine(Ref 15)... 

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