2- Hydroxy-5-methyl-3-nitrobenzaldehyde

The first lithiopyrazine derivative was prepared by Hirschberg et al. (1015) from 3-iodo-2,5-dimethylpyrazine and butyllithium in ether subsequent reaction with (a) carbon dioxide gave 3-carboxy-2,5-dimethylpyrazine, and (b) several aromatic aldehydes gave the carbinols (62, R = H, p-methoxy, m-nitro) (1015). Similar reactions were observed when 2-formylpyridine and 2-acetylpyridine (1016) were used as the carbonyl compounds, but with acetaldehyde attempted reactions were unsuccessful (1015). A patent also describes the preparation of many carbinols from 2,5-disubstituted 3-iodopyrazines (164). The lithio reagent derived from 3-iodo-2,5-dimethylpyrazine (with butyllithium in hexane) with 2-nitrobenzaldehyde gave 2,5-dimethyl-3[ 1 -hydroxy-1 (2"-nitrophenyl)methyl] pyrazine (1017). 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

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