Reaction with /9-bromopropionic acid

Enholm [12] has also prepared an enantiomerically pure soluble polymer support 82 by couphng xylose-derived chiral auxiliary 81 with 77 (Scheme 18). The chiral support was then treated with bromopropionic acid 83 to give substrate 84. Eree radical allyl transfer from allyltributyltin imder thermal conditions provided 85 in 93% yield, and basic cleavage from the resin gave (R)-(-)-2-methylpent-4-enoic acid 86 in 80% yield and 97% ee, with a 92% yield of recovered 82. Previous studies of the same process in solution had found the addition of Lewis acids to be crucial for high selectivities to be obtained. Interestingly, the addition of Lewis acids to the reaction on polymer support led to cleavage of the carbohydrate from the polymer backbone. En-... 

Shortly after the product launch, the original process was modified (Scheme 2). Zinc chloride was removed from the coupling reaction, and ethyl bromopropionate was replaced with bromopropionic acid magnesium chloride salt. Most importantly, the resolution agent cinchonidine was replaced with A -alkylglucam-ine, which can be readily obtained from the reductive amination of o-glucose. 

Kojic acid was brominated at position 6 with bromine water4 the 2-(chloromethyl) derivative of kojic acid was brominated with N-bromo-succinimide,87 and chlorinated with sulfuryl chloride and aluminum chloride,88 in both cases probably at C6. The C-benzoylation89 and C-acetylation90 of kojic acid, likewise at C6, was accomplished by Woods using a modification of the Friedel-Crafts reaction. The 2-carboxyethyl side chain was introduced at C6 in a reaction with 2-bromopropionic acid.91... 

Fentiazac (134) is a member of the biarylacetic acid class of nonsteroidal antiinflammatory agents. Its. synthe.sis also involves the Htintzsch reaction, niiobcnzamide (133) is reacted with 3-(4-chIorobenzoyI)-3-bromopropionic acid (132) to give feiitiazoc (134) 46. ... 

Carboxy-2-pyridylthio)propionic acids, prepared by the reaction of 2-mercatopyridin-3-carboxylic acid with 3-bromopropionic acid in aqueous KOH, undergo cyclization upon treatment with anhydrous sodium acetate and acetic anhydride to afford 2,3-dihydrothiopyrano[2,3-3]pyridin-4(4//)-ones. These products undergo further reaction with phenylhydrazine to give the phenylhydrazone (isolated) and then Fischer indole cyclization to give novel 5/7,1177-pyrido[2, 3 2,3]thiopyrano[4,3-3]indoles <2000JHC379>. 

Reaction of l-mercapto-4-cyano-5,6,7,8-tetrahydroisoquinolin-3(2//)-one with 3-bromopropionic acid in boiling ethanol in the presence of sodium acetate gave octahydro[l,3]thiazino[2,3-a]isoquinoline-4,6-dione (216) (89PS203). 

Reaction of 2-amino-4-pyrimidinone (229) with an excess of acrylonitrile gives the intermediate (230). This intermediate can be cyclized to the product (231) in excellent yield by heating in glacial acetic acid (6UOC1891). Similarly, 3,4-dihydro-6,8-dimethyl-pyrimido[ 1,2-a ]pyrimidin-2-one hydrobromide (233) is prepared by the reaction of 2-amino-4,6-dimethylpyrimidine (232) with 3-bromopropionic acid. This reaction also proceeds via a pyrimidinylpropionic acid intermediate (61JOC1891). 

The benzylbromomalonic acid containing water is now heated in an oil bath to 125°—130°, and the fused mass evolves carbon dioxide and a certain amount of hydrobromic acid. The reaction is complete in the course of 30—45 minutes. The residue is a yellow oil, which even at a low temperature does not crystallise, and which in the main consists of phenyl-a-bromopropionic acid. For the purpose of purification it is washed with water, taken up in ether, and dried with anhydrous sodium sulphate the ether is then distilled off. The mobile, almost colourless oil remaining is dissolved in 5 times its volume (excess) of 25% aqueous ammonia, and either heated for 3 hours to 100° in a sealed tube or allowed to stand for 3 to 4 days at ordinary temperature. On evaporation of the ammo-niacal solution an almost colourless residue is left, and this chiefly consists of ammonium bromide and phenylalanine. On boiling with absolute alcohol the amino-acid is left undissolved and is recrystallised from hot water. 

Racemic mixtures of carboxylic adds can be resolved by esterification using lipases in organic media. Figure 21 illustrates such a process when racemic a-bromopropionic acid is stereoselectively esterified with n-buta-nol using a lipase from the yeast Candida a/lindraceae (68). This reaction was carried out in virtually anhydrous hexane. 

Bradbury and Smyth (1973) advocate the use of 3-bromopropionic acid in the place of iodoacetic acid, or its amide, in the alkylation reaction. S-carboxyethylcysteine was found to be completely stable at acid pH, and could be readily quantitated by amino acid analysis ( 2.5.3). The half-life of the reaction of the SH-group of cysteine (2 jumoles/ml) with 3-bromopropionate (200 pmoles/ml) at pH 8 and 30°C was approximately 10 min. Under the same conditions, the reaction of cysteine and iodoacetate was found to be virtually instantaneous (Bradbury and Smyth 1973). 

A number of syntheses of (V-hydroxy-a-amino acids and derivatives thereof have been reported. a-Bromocarboxylic acids or their r-butyl esters can be treated with hydroxylamine or 0-alkylated hydroxylamines to give the corresponding hydroxylamine derivatives. yV-Benzyloxy-t-alanine has been obtained by reaction of (/ )-a-bromopropionic acid with O-benzylhydroxylamine. But due to bromide exchange the optical yield was low. Anchimeric assistance of a suitable attached thio group can bring... 

Thiazolo[2,3-h]quinazolines [C S-C JV2-CeJ. The cycloaddition reaction of alkah-metal salts of 2-mercapto-4(3/f)-quinazolinones with 3-benzoyl-3-bromopropionic acids and esters gives acids (250) and lactones (251). ... 

Dibasic acids in which the carboxyl groups are linked to different carbon atoms behave on decomposition by heat as succinic acid does, that is, they lose water and anhydrides are formed. Isosuccinic acid is prepared from a-bromopropionic acid by the reactions with which the student is familiar. The acid forms crystals, which melt at about 130°. 

The temperature at which the reaction is carried out, and the proportion of bromine used, determine the number of bromine atoms introduced. Thus, propionic acid when treated at 100° with phosphorus and bromine gives a-bromopropionic acid, CHsCHBr.COOH and at 220° with an excess of bromine, a, o-dibromopropionic acid, CH3CBr2.COOH. 

Lithium 3-lithiopropionate, LiCHaCHaCOOLi (1). Mol. wt. 85.94. This carbanion can be prepared by reaction of -bromopropiooic acid with 1 equiv. of -butyl-lithium in THF followed by reaction in the same solvent with lithium naphthale-nide (2, 288-289 3, 208 4, 348-349 5, 468 6, 415), The reagent is formed only in low yield by reaction of j3-bromopropionic acid with 2.2 equiv. of n-butyl-lithium. 

For larger scale synthesis of this new and because of its vanadium selectivity extremely interesting sequestering agent the reaction of 2-bromopropionic acid has been chosen. L-HIDP can be obtained stereoselectively by condensation of hydroxyl-amine with D-bromopropionic acid (Fig. 4). The enantiomeric purity and comparison of educts and products again can be checked by chromatography on Chirasil-Val. L-HIDP from amavadin is identical in all properties with the synthesized L-HIDP. 

Thiapyrylium-fused Systems.—Thieno[6]thiapyrylium salts (646) and (647) have been prepared by the reaction of thiophen-2- and -3-thiol with acetyl-acetone. The benzo[6]thiophen analogues were prepared similarly. The parent compounds (648) and (649) were prepared from the benzo[6]thio-phenthiols with j8-bromopropionic acid followed by cyclization of the acid chlorides to (650) and (651). Reduction with sodium borohydride to the... 

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