Glycine derivatives amides

Heteroaromatic esters such as 493 and amides are produced by the carbo-nylation of heterocyclic bromides[347,348]. Even dichloropyrazine (494) and chloropyridine are carbonylated under somewhat severe conditions (120 C, 40 atm)[349]. The carbonylation of trifluoroacetimidoyl iodide (495) proceeds under mild conditions, and can be used for the synthesis of the trifluoromethyl-glycine derivatives 496 and 497(350]. 

Benzoic acid in the free state, or in the form of simple derivatives such as salts, esters, and amides, is widely distributed in nature. Gum benzoin (from styrax ben in) may contain as much as 20% benzoic acid in the free state or in combinations easily broken up by heating. Acaroid resin (from anthorrhoca haslilis) contains from 4.5 to 7%. Smaller amounts of the free acid are found in natural products including the scent glands of the beaver, the bark of the black cherry tree, cranberries, pmnes, ripe cloves, and oil of anise seed. Pern and Tolu balsams contain benzyl benzoate the latter contains free benzoic acid as well. The urine of herbivorous animals contains a small proportion of the glycine derivative of benzoic acid, hippuric acid [495-69-2] (CgH CONHCH2COOH). So-called natural benzoic acid is not known to be available as an item of commerce. 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Conden-... 

Ethonam (99), an imidazole derivative with a very different substitution pattern, is also reported to possess antifungal activity. To prepare it, alkylation of aminotetralin 94 with methylchloro-acetate gives the glycine derivative 95. Heating with formic acid then affords the amide 96 this compound is then reacted with ethyl formate to yield hydroxymethylene ester 97. Reaction with isothio-cyanic acid gives the imidazole-2-thiol 98. (The... 

If quinoline derivatives are expected to be synthesized by this procedure, the starting cycloalkene should contain a cyclobutene ring. When cyclobutene derivative 65c is reacted with Ig under ethylene gas, isoquinoline derivative 66c is obtained in 60% yield. Furthermore, cyclic amino acid ester 66d is obtained from glycine derivative 65d in 75% yield by a one-step reaction. Various isoquinolone derivatives 66e-66i are also synthesized from cyclobutenyl amides... 

As a prochiral glycine-derived SchifFbase, not only esters but also amides can be used as suitable substrates for asymmetric alkylation under phase-transfer conditions. 

Amide 202 is a key intermediate for the synthesis of various antifungal compounds (TAK-456 and TAK-457). Amide 202 is prepared via the coupling reaction of substituted triazole amine 200 and glycine derivative of tetrazole 201 using DEPC.76... 

Similar results have been obtained for the formation of 1-amidoalkyl radicals starting from A -ort/fo-halobenzyl amides. For instance, the synthesis of y-lactam from glycine derivatives was reported (Scheme 34, Eq. 34.1) [126]. A new route to spirooxindole based on 1,5-hydrogen transfer followed by cyclization onto an activated indole was recently published (Eq. 34.2) [127]. 

In 1957, Schlogl reported the synthesis and characterization of several ferrocene amino acids, including ferrocenylala-nine (Fer, 14 Scheme 18). Other organometallic amino acids include alanine, phenylalanine (Phe), glycine derivatives, as well as further ferrocene-based amino acids, which are discussed below. The Schlogl paper also describes the reaction of ferrocene carboxylic acid and ferrocene carbaldehyde with amino acids. The chemistry was later picked up in numerous publications, and ferrocene carboxylic acid amides or ferrocene imines with basically all amino acids and many dipeptides were reported. Such conju tes may serve as ligands for other transition metal ions. " Kraatz has prepared ferrocene carboxylic acid conju tes with short peptides that serve as enzyme inhibitors. ... 

Initial attempts using vigorous stirring of glycine derivatives and allyl iodide in aqueous lithium hydroxide-TBAB in dichloromethane required one to two days to reach completion and suffered from competitive hydrolysis of the amide bond. Sonication dramatically increased the alkylation rate, and a 79% yield of piirified product was obtained after only 5 min sonication at -10°C. The a-alkylated amino acid is liberated by a classical treatment by aqueous hydrogen chloride. 

The first amino acid and dipeptide ferrocenoyl derivatives of this kind, Fc-CO-Aaa-OEt (Fc = (C5H5)FeC5H4, Aaa = Gly, Leu, Phe, Met), Fc-CO-Gly-OH and Fc-CO-Gly-Leu-OEt, were reported by Schlogl as early as 1957 [1], Since then, well over two dozen similar ferrocenoyl amides have been prepared from ferrocene carboxylic acid 3 and amino acids, di-, tri- and tetrapeptides. These compoimds, as exemplified for the glycine derivative Fc-GO-Gly-OH (4, Scheme 5.1), have been studied extensively with respect to their electrochemical properties and their structure in the solid state as well as in solution. A comprehensive discussion is foimd in a recent review from my group [9]. Kraatz has also recently summarized his work in the field [10],... 

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