Amino acids and esters

Phosgene reacts with 2-amino acids (usually suspended in an ether solvent) to give oxazolidine-2,5-diones (A/-carboxy anhydrides) [562,626,702,957,1064,2003]  

The iV-substituted carbamoyl chloride is considered to be the intermediate of this reaction [626]. W-methyl-2-amino acids [1152] and N-benzyloxy-2-amino acids [22] react simiiarly to give the corresponding oxazolidine-2,5-diones. Phosgene has been used as a reagent for the enantiomeric resolution of iV-methyl-2-amino acids by gas chromatography [1152], 

The dehydration of asparagine, glutamine, and derivatives, with phosgene results in the formation of nitriles [2187]  

Amino acids containing a hydroxyl group can give the corresponding chloroformate derivative as a co-product hence, serine reacts with COCij according to [1029]  

Reaction of the potassium salt of 3-aminobenzo[h]thiophene-2-carboxylic acid with phosgene gave the corresponding anhydride [412]  

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Some workers avoid delay. Pai)adium-on-carbon was used effectively for the reductive amination of ethyl 2-oxo-4-phenyl butanoate with L-alanyl-L-proline in a synthesis of the antihyperlensive, enalapril maleate. SchifTs base formation and reduction were carried out in a single step as Schiff bases of a-amino acids and esters are known to be susceptible to racemization. To a solution of 4,54 g ethyl 2-oxO 4-phenylbutanoate and 1.86 g L-alanyl-L-proline was added 16 g 4A molecular sieve and 1.0 g 10% Pd-on-C The mixture was hydrogenated for 15 hr at room temperature and 40 psig H2. Excess a-keto ester was required as reduction to the a-hydroxy ester was a serious side reaction. The yield was 77% with a diastereomeric ratio of 62 38 (SSS RSS)((55). 

A. F. Abdel-Magid, J. H. Cohen, C. A. Maryanoff, Chemical Process Synthesis of /3-Amino Acids and Esters , Curr. Med. Chem. 1999, 6, 955-970. 

Dioxanes (337) are also conveniently obtained by acid-catalyzed condensation of oxiranes with glycols, while use of ethanolamine gives morpholine (338). Base-catalyzed reaction of oxiranes with a-amino acids and esters gives tetrahydro-l,4-oxazin-2-ones, e.g. propene oxide + RNHCH2C02H — (339). 1,4-Dithianes have been prepared by the dimerization of thiiranes either in the vapor phase or in the presence of acid catalysts. 

Scheme 16 Synthesis of Mono-iV-alkyl Amino Acids and Esters by Temporary Protection with Dpm 119 ...

The amine function of a-amino acids and esters reacts with nitrous acid in a manner similar to that described for primary amines (Section 23-10A). The diazonium ion intermediate loses molecular nitrogen in the case of the acid, but the diazonium ester loses a proton and forms a relatively stable diazo compound known as ethyl diazoethanoate ... 

In addition to the mobile phase composition, the effect of other parameters such as temperature, flow rate, pH, and structure of the analytes were also studied, but only a few reports were available in the literature. In 1995, Lin and Maddox [66] studied the effect of temperature on the chiral resolution of amino acids and esters. The temperature was varied from 5°C to 25°C and it was reported that the resolution improved at low temperature. Hyun et al. [48-50,67] carried out the effect of temperature on the chiral resolution of amino alcohols, amines, fluoroquinolones, and other drugs. Again, lowering of temperature resulted in better resolution. The effect of temperature on the chiral resolution of phenylalanine, phenylglycine, and 2-hydroxy-2-(4-hydroxy-phenyl)-ethyl amine is shown in Table 5 [50], which indicates an increase in retention factors at lower temperature, but the best separation occurred at 20°C. These experiments indicated the exothermic nature of chiral resolution on CCE-based CSPs. Lin and Maddox [66] also studied the effect of flow rate on the chiral resolution of... 

Dotsevi, G, Sogah, Y., Cram, D. J. (1976) Total Chromatographic Optical Resolutions of Amino Acid and Ester Salts Through Chiral Recognition by a Host Covalently Bound to Polystyrene Resin, J. Am. 

Ligand Variations in the Rh-Catalyzed Hydrogenation of Dehydro-Amino Acids and Esters... 

First study of co-polymerisation by Wagner-Jauregg Early theories of rubber-elasticity (Mark, Meyer, Guth, Kuhn and others) Carothers famous work proves by means of organic synthesis that polymers are giant, stable molecules. He first proves it by the discovery of neoprene (polychloro-butadiene), then by the condensation polymerisation of amino acids and esters. As a consequence the first fully synthetic textile fibre, nylon, is developed. In Carothers group Flory elucidates the mechanisms of radical and condensation polymerisation... 

G. Dotsevi, Y. Sogah, and D. J. Cram, Host-guest complexation. 14. Host covalently bound to polystyrene resin for chromatographic resolution of enantiomers of amino acid and ester salts, / Am. Chem. Soc. 101 (1979), 3035. 

The Ullmann biaryl amine condensation was used in the synthesis of SB-214857, a GPIIb/llla receptor antagonist. D. Ma and co-workers coupled aryl halides with 3-amino acids and esters under relatively mild conditions using Cul as a true catalyst. 

N-ProtecHon of amino acids. The reagent reacts readily with amino acids and esters (aqueous dioxane, MgO) to give f-butyloxycarbonylamino acids, which are not otherwise available, since /-butyl chloroformate, (CHslsCOCOCl, is too un-... 

Akabori amino acid reactions. (1) Formation of aldehydes by oxidative decomposition of a-amino acids when heated with sugars. (2) Reduction of a-amino acids and esters by sodium amalgam and ethanolic hydrochloric acid to the corresponding a-amino aldehydes. (3) Formation of alkamines by... 

Scheme 1. Protonation of amino acids and ester derivatives...

Due to the relative ease of synthesis of the phosphoramidites, it is simple to introduce variations within the ligand, especially the substitution on the nitrogen atom. In turn, this allows for rapid screening of ligands to hnd the best one for a specific substrate. The screen can be used to not only increase enantioselectivities but also to turn over numbers and frequencies. In a number of cases, the piperidine analogue (20b) has been found to be superior for a-amino acid and ester production over MonoPhos The best ligands in terms of enantioselectivity are 19c ... 

The chiral recognition ability of 4.2 was examined by two-phase liquid-liquid extraction experiments of racemic mixtures of amino acids and ester guests. Cram and coworkers developed an enantiomer-resolving machine based on such chiral corand receptors and found that the /f,/f-host was selectively able to extract the D-enantiomer of amino acids. 

The CD spectra of aliphatic N-(3-methyl-2-quinoxaloyl)-L-a-amino acid and ester 1,4-dioxides are similar to those of aromatic L-a-amino acid and ester derivatives a weak negative band at 370 nm, a weak positive one at 325 nm, and strong positive bands at about 268 and 230 nm (in acetonitrile). A number of these compounds also have a weak positive Cotton effect in their CD spectrum at about 395 nm. On the other hand, the CD spectra of the quinoxaline derivatives of aliphatic-L-a-amino acids and esters are... 

The CD spectra of JV-salicylidene derivatives of a-amino acids and esters formed in situ in methanol show Cotton effects at about 315 nm (band I), 253 nm (band II), and 230 nm (band III). In most cases, Cotton effects are also observed at about 400 nm (usually weaker than band I) and about 275 nm (intensity comparable with band II). These were first attributed to the quinoid tautomer (Smith et al, 1977), but in a more recent publication (Smith et al, 1979, and references therein) the 275-nm band is assigned to the n-7T transition of the azomethine group, strongly coupled to the electrically allowed n-n transitions of the carboxylate group below 200 nm. 

The conditions of the Robinson-Schopf condensation allow for a wide breadth of nucleophilic amines. In addition to alkyl amines, hydroxyalkyl, benzylic, aromatic, heterocyclic amines, as well as a-amino acids and esters are sufficiently reactive to participate in this reaction. ... 

Reduction of a-amino acids and esters by sodium amalgam and ethanolic hydrogen chloride to the corresponding a-amino aldehydes ... 

Chiral crown ethers derived from binaphthol, pentahelicene, bi-phenanthrol, and other natural precursors have been prepared in recent years. Their chiral recognition in complexation equilibria towards various primary alkylammonium and amino acids and ester salts as well as the structural requirements of this phenomenon have been investigated. The crown ethers based on 18-crown-6 structure are known to form most... 

Lingenfelter, D. S., Helgeson, R. C., and Cram, D. J., Host-guest complexation. 23. High chiral recognition of amino acid and ester guests by hosts containing one chiral element, J. Org. Chem., 46, 393 (1981). 

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