Halo acids, reduction

The biochemical reduction of a, -unsaturated -haloaliphatic acids by means of Clostridium kluyveri yielded halogen-free satmated acids. The same products were obtained from saturated -halo acids. However, the same microorganism converted ix, -unsaturated a-halo acids to saturated a-halo acids with R configuration. Yields of reduction of a-fluoro-, a-chloro- and a-bromocrotonic acid ranged from 30% to 100% [330]. 

Halo-carboxylic acids, reduction by trivalent uranium, 34 80... 

Preparation. The general preparation of u-hydroxy acids is by the hydrolysis of an a-halo acid or by Ihe acid hydrolysis of the cyanohydrins of an aldehyde or a ketone. 0-Hydroxy acids may be made by catalytic reduction of 0-keut esters followed by hydrolysis. 0-Hydroxy acids can also he prepared by ihe ReformaCsky reaction y-Hydroxy acids are seldom obtained in the free slate because of ihe case wilh which they form... 

Alcohols containing heterocyclic nuclei, halo, and alkoxyl groups as well as double bonds may be prepared. Without doubt, this is the best general procedure for the formation of the primary alcohol grouping from compounds at the oxidation level of a carboxylic acid. Reductions by this reagent were reviewed in 1951. °°... 

A possibly special stereochemical situation is presented by a-halocarbonyl compounds in the cyclopropane series. Electrochemical reduction of the a-halo acid (14) proceeds predominantly with stereochemical inversion, whereas reduction of the corresponding carboxylate proceeds predominantly with retention of configuration. 

The limitations of this approach can be seen in the reaction of a saturated solution of ammonia in 90% ethanol with ethyl bromide in a 16 1 molar ratio, under which conditions the yield of primary amine was 34.2% (at a 1 1 ratio the yield was 11.3%). Alkyl amines can be one type of substrate that does give reasonable yields of primary amine (provided a large excess of NH3 is used) are a-halo acids, which are converted to amino acids. A-Chloromethyl lactams also react with amines to give good yields to the A-aminomethyl lactam. Primary amines can be prepared from alkyl halides by 10-43, followed by reduction of the azide (19-32), or by the Gabriel synthesis (10-41). 

Electrocatalytic reductive coupling of aryl chlorides to afford biphenyls can be accomplished with dichloro(l,2-bis(di-propylphosphino)benzene)nickel(II) in yields as high as 96% with 2 mol % of the catalyst in polar, coordinating solvents (55). Similar couplings can also be achieved with nickel-2,2 -bipyridyl and Pd(PPh3)2Cl2 as catalysts (56, 57). Indirect electrochemical reduction of vicinal dibromides to alkenes occurs efficiently with iron and cobalt porphyrins as mediators (58). Vitamin B12 is a mediator for the indirect electrochemical reduction of a-halo acids (59). 

Already in the last century Hantzsch (155) observed that reaction of a-halo acids (127) with excess hydroxylamine leads to oximes of a-keto acids (31) as the result of an oxidation-reduction process (Scheme 28). This process, as a method of synthesis of (31), was later thoroughly studied by Barry and Hartung (156). The oxidation-reduction reaction is responsible for the fact that later attempts to obtain the title compounds (1) from (127) by this route were never efficient (81,100) although sometimes they were patented (157). 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

Pyridazine N-ethoxycarbonylimide photolysis, 3, 13 Pyridazine, 4-gJycosyloxy-rearrangement, 3, 15 Pyridazine, halo-applications, 3, 56 Pyridazine, hexahydro-, 3, 40 photoelectron spectra, 2, 20-21 Pyridazine, hydrazino-reductive cleavage, 3, 34 synthesis, 3, 35 Pyridazine, hydroxy-acidity, 3, 4 Pyridazine, 3-hydroxyl-oxide... 

Formation of oxiranes on the sterically more hindered side of the steroid ring system is usually carried out via /raw -halohydrins which afford oxiranes on treatment with base (c -Halohydrins yield ketones on exposure to base). Two general methods are available for the synthesis of tm s-halohydrins (1) the reduction of a-halo ketones and (2) the addition of a hypohalous acid to unsaturated steroids. 

Although 3y5-hydroxy-A -l9-aldehydes can be obtained from the corresponding oxime by acid treatment, the most efficient method for the production of A -19-aldehydes is nitrosation of the oximes followed by zinc reduction of the 5a-halo hemiacetal. ... 

Unsaturated 19-norsteroids are also obtained by thermal decarboxylation of A -19-acids (obtained by zinc reduction of the 5a-halo-6/3,19-lactones). 

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