Ring-contracted acid

Wiberg and Koch 167) also disagreed with Littler s results, and found that the major product (75%) obtained on treatment of cyclohexanone with aqueous thallium(III) perchlorate was cyclopentanecarboxylic acid (XL). 2-Hydroxycyclohexanone was isolated in only 3 % yield unchanged starting material accounted for the remainder of the product. Wiberg and Koch were unable to detect any cyclohexane-1,2-dione in the product mixture, but did prove that 2-hydroxycyclohexanone did not function as the precursor to the ring-contracted acid. From the results obtained from a study of the oxidation of 2,2,6,6-[Pg.196]

The stereoselective total synthesis of tt)-campherenone was accomplished by T. Uyehara and co-workers based on a photochemical Wolff rearrangement. The bicyclic ketone was treated with 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) under homogeneous basic conditions and the a-diazo ketone was obtained in excellent yield. The photochemical rearrangement of the diazo ketone was conducted in a THF-water mixture using a high-pressure 100 W mercury lamp. The ring-contracted acid was isolated as a 4 1 mixture of endo and exo products. 

CycloaUcanecarboxylic acids. On treatment with TTN in dichloromethane cyclic ketones undergo ring contraction to give ring-contracted acids (6 examples, 36-98%). 

The oxidation of steroid ketones by H202-Se02 has been investigated by Caspi. Oxidation of cholestane-3-one gives a mixture of ring-contracted acids and a... 

Irradiation of paracyclophane diazo ketone 98 affords the ring contraction acid 221 in 25% yield.35 Photolysis of the a-diazobenzocycloheptanone (68) in methanol effected the Wolff rearrangement to give the tetralin ester (222).25 Irradiation of 2-diazoindan-1 -one in THF/H2O produces benzcyclobutane carboxylic acid (223).39... 

In these constrained molecules, the Favorskii rearrangement leads essentially to the ring-contracted acid or ester in good yields. However, the formation of ring-opened products has been reported when polyhalogenated strained ketones react according to the quasi-Favorskii mechanism. Results using this type of substrate are reported in Table 8. 

Another useful route to cyciopentanes is the ring contraction of 2-bromo-cydohexanones by a Favorskii rearrangement to give csrdopcntanecarboxylic acids. If a 0 dibromoketones are used, ring opening of the intermediate cydopropanone leads selectively to, y-unsaturated carboxylic acids (S.A, Achmad, 1963, 1965 J. Wolinsky, 1965). 

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

The base-promoted ring contraction of 3-bromo-2-pyrones to 2-furoic acids cf. Scheme llOd) is a well exemplified reaction 01CB1992,69JCS(C)1950,73JCS(P1)1130> which has also been applied to the obtention of benzofuran-2-carboxylic acids frorn 3-bromocoumarins 08CB830,70KGS(S2)166), Similar base treatment of 3-amino-2-pyrones provides pyrrole-2-carboxylic acids (Scheme IlOe) 75JHC129). 

A third approach to 3-amino-/3-lactams is by Curtius rearrangement of the corresponding acyl azides. These are readily prepared from r-butyl carbazides, available via photochemical ring contraction of 3-diazopyrrolidine-2,4-diones in the presence of f-butyl carbazate (c/. Section 5.09.3.3.2). Thus treatment of (201) with trifluoroacetic acid followed by diazotiz-ation gives the acyl azide (202) which, in thermolysis in benzene and subsequent interception of the resulting isocyanate with r-butanol, yields the protected 3-amino-/3-lactam (203) (73JCS(P1)2907). 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

The benzilic acid rearrangement of steroid a-diketones is often the preferred method for ring contraction. Yields are generally excellent, and in several instances the reaction has been shown to be stereospecific. Preparation of the starting a-diketones is discussed below and illustrated with several excellent experimental procedures. 

Kubota and co-workers describe a novel oxidative rearrangement of the diosphenol (58) of 17iS-hydroxyandrost-4-ene-2,3-dione to the A-nor-A -1,2-diketone (59) in 33 % yield by the action of specially prep d manganese dioxide in boiling acetone. The rate of ring contraction is very sensitive to the source of the oxidant, and a trace of dilute sulfuric acid in the reaction mixture causes oxidative fission of ring A. 

Ring contraction by Baeyer-Villiger oxidation of 5-hydroxy-6-keto steroids—cyclization of keto acids 3/S-acetoxy-B-norandrost-5-en-17-one from 3/3-acetoxyandrost-5-en-17-one, 434... 

Ring contraction by benzilic acid rearrangement of a-diketones... 

Benzidine rearrangement of fluonnated hydrazobenzenes proceeds with a high yield in the presence of a strong acid [57] (equation 12) Ring contraction occurs when 2-bromoheptafluoronaphthalene is treated with antimony pentafluoride [52] (equation 13)... 

The application of this addition to aminomethylene ketones provides a convenient synthesis of monoamides of pimelic acid (508). It should be noted that the corresponding oxidation of hydroxy methylene cyclohexanone leads to ring contraction and formation of cyclopentanoic acid. 

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