Indazoles acids, 4,5,6,7-tetrahydro

N-Amination of indazole affords a mixture of 60% (271) and 40% (272), which compares with the 55 45 ratio obtained in methylation (Section 4.04.2.1.3(viii)). A camphopyrazole derivative (a mixture of tautomers 275 and 276) when treated with hydroxylamine O-sulfonic acid yields exclusively the (4S,7i )-4,7-methano-2-amino-7,8,8-trimethyl-4,5,6,7-tetrahydro-2H-indazole (277) (79YZ699). 

Support for this suggestion comes from many quarters. Reduction of the jS-carboline anhydro-bases with sodium and alcohol or with tin and hydrochloric acid gives the 1,2,3,4-tetrahydro derivatives, as does catalytic reduction over platinum oxide in an alkaline medium. On the other hand, catalytic reduction with platinum oxide in acetic acid results in the formation of the 5,6,7,8-tetrahydro-j3-carbolinium derivatives (see Section III,A,2,a). It should be noted, however, that reduction of pyrido[l,2-6]indazole, in which the dipolar structure 211 is the main contributor to the resonance hybrid, could not be effected with hydrogen in the presence of Adams catalyst. 

As reported by Steel et al. three structural isomers of bis(camphor-pyrazol-l-yl)methane (21a, 21b and 21c) are formed by coupling of camphorpyrazole 10 [i.e., (4S,7i )-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-l(2)H-indazole] with CH2CI2 (121). Isomer 21c can be separated from the other two structural isomers by crystallization or column chomatography. Deprotonation at the bridging carbon atom, subsequent reaction with carbon dioxide and acidic workup yields the enantiopure bis(camphorpyrazol-l-yl)acetic acid Hbpa (8) (Scheme 17, Fig. 19) (116). Due to missing substituents at the p5rrazolyl carbon C5 and a hence likely ortho metallation, isomers 21a and 21b are not suited for his reaction (72). 

With respect to time and cost, this method is superior to the five-step synthesis from anthranilic acid. Older literature sources have been cited in an earlier volume of Organic Syntheses. Indazole has also been prepared recently by the reaction of 2-hy-droxymethylenecydohexanone with hydrazine and dehydrogenation of the 5,6,7,8-tetrahydro derivative. ... 

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