Halo acids conversion

Ring contractions of pyran derivatives are occasionally valuable. The contraction of 3-halo-2-pyrones to 2-furoic acids under the influence of alkali has been studied and the conditions defined.58112113 The method is adaptable to the preparation of 3-furoic acid via furan-2,4-dicarboxylic acid58 and of 3,4,5-triphenylfuran-2-carboxylic acid.113 Another ring contraction involving halides is the conversion of 4-chloromethylpyrylium salts into furylmethyl ketones as indicated in Scheme 21.114 Pyridine oxides may be transformed with unexpected ease into furans through treatment with a thiol (Scheme 22).115... 

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

The acid chlorides have served as useful synthetic intermediates leading to ketones via the malonic acid synthesis and Friedel rafts reaction, thiadiazole acetic acid derivatives, and halo ketones via the Arndt Eistert synthesis and carbinols by hydride reduction <68AHC(9)107>. The dialkylcadmium conversion of acid chlorides into ketones fails in the 1,2,5-thiadiazole series. The major product is either a tertiary carbinol or the corresponding dehydration product, by virtue of the high reactivity of the intermediate ketone. 

In order to improve this reaction, a proper understanding of all parameters affecting product yield is desired. Clearly, the high enzyme consumption is a major obstacle for an efficient and economically feasible process. A likely cause of the inefficient use of DERA in this conversion is enzyme deactivation resulting from a reaction of the substrates and (by-) products with the enzyme. In general, aldehydes and (z-halo carbonyls tend to denature enzymes because of irreversible reactions with amino acid residues, especially lysine residues. From the three-dimensional structure it is known that DERA contains several solvent-accessible lysine residues [25]. Moreover, the complicated reaction profile as shown in Scheme 6.5 indicates the potential pitfalls of this reaction. 

The cyclizations of halo acetals, introduced by Stork66 and Ueno,67 are among the most popular of all radical methods because the precursors are easy to prepare, the cyclizations are very rapid, and the products can be converted to a variety of different heterocycles. The conversion of (26) to (28 Scheme 17) illustrates the basic procedure.68 Standard bromoacetalization of an alcohol provides the precursor (27). After tin hydride cyclization and acidic oxidation, lactone (28) is formed in excellent yield with 97%... 

The conversion of p,y- or y,<5-unsaturated acids into iodolactones (Halo-... 

An enzymatic process has been developed for the preparation of 4-halo-3-hydroxybutyric acid derivatives by ketoreductase-catalyzed conversion of 4-... 

COOH — —CHO. This conversion can be effected in one flask by treatment of the carboxylic acid with N,N dimethylchloromethyleniminium chloride (prepared from DMF and oxalyl chloride) and pyridine to form a betaine, which is then reduced to the aldehyde by the hydride in the presence of a catalytic amount of Cul at — 78° The reaction is applicable to aliphatic and aromatic acids, and can tolerate halo, cyano, ester, and even carbonyl groups. Yields are usually —65-80%. 

Olefins, addition—Continued of diazoacetic ester, 498 of halo ethers, 232 of halogen, 106 of hydrogen cyanide, 603 of hydrogen halide, 105 of hypohalous acid, 109 of polyhalides, 107 to cyanides, 571 allylic bromination, 36, 104 condensation, with halides, 108 with phenols, 179 conversion to amides (Wi 11 gerodt),... 

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