Acid bromides metal hydrides

Preparation of the aldehyde required for the synthesis of cyclothiazide (182) starts by carbonation of the Grignard reagent obtained from the Diels-Alder adduct (186) from allyl bromide and cyclopentadiene.The resulting acid (187) is then converted to the aldehyde (189) by reduction of the corresponding diethyl amide (188) with a metal hydride. 

The keto ether (187) on treatment with diethyl carbonate in presence of sodium hydride in 1,2-dimethoxyethane afforded the keto ether (188), which was made to react with methyl-lithium in ether, to obtain the tertiary alcohol (189). This on being refluxed with methanolic hydrochloric acid yielded the phenol (190). It was methylated to yield(191) and heated with zinc, zinc iodide and acetic acid to produce pisiferol (192). Its methyl derivative (193) on oxidation with Jones reagent at room temperature, followed by esterification, furnished the keto ester (194). Reduction of (194) with metal hydride produced an alcohol whose tosyl derivative on heating with sodium iodide and zinc dust furnished the ester (195). Its identity was confirmed by comparing its spectral data and melting point with an authentic specimen [77]. The transformation of the ester (195) to pisiferic acid (196) was achieved by treatment with aluminium bromide and ethanethiol. The identity of the resulting pisiferic acid (196) was confirmed by comparison of its spectroscopic properties (IR and NMR) with an authentic specimen [77]. 

An alternative route was also developed for the synthesis of ( )-pisiferic acid (196) as described in "Fig (17)". The starting material for the present synthesis was the already described alcohol (15), which on tetrahydropyranylation yielded the derivative (197). Metal hydride reduction of (197) afforded a mixture of alcohols whose tosyl derivative on heating with lithium bromide and lithium carbonate in dimethylformamide afforded the oily olefin (198). These conditions not only provoked the dehydrosulphonation but also the hydrolysis of the tetrahydropyranyl group, thus shortening the reaction sequence by one step. The oily olefin (198) on oxidation yielded the ketone (199), which was formylated, and subjected to Robinson annelation with methyl vinyl ketone prepared in situ following the procedure of Howell and Taylor [74]. The resulting adduct without purification was heated by boiling with sodium methoxide in methanol to obtain the tricyclic ketone (200). It was treated with... 

The molecules of the types and of their derivatives were complete units, and the arrangement constituted a syst me unitaire . The sulphides, tellurides, oxides, acids, bases, salts, alcohols, ethers, etc., belong to the water type chlorides, bromides, iodides, fluorides and cyanides to the hydrochloric acid type nitrides, phosphides, arsenides, etc., to the ammonia type metallic hydrides and metals to the hydrogen type. More complicated compounds are formed by substitution of radicals for hydrogen in the types. Unknown compounds could be predicted in large numbers by this scheme of classification. 

Hydrogen chloride gas, like the bromide and iodide, has a curious power of forming solid compounds of definite composition with certain anhydrous salts of oxy-acids, especially the sulphates, phosphates, and phosphites of di- and trivalent (mainly transitional and B) metals.443 Many of these are formed at the ordinary temperature, and do not decompose below 200°, where the HCl compounds lose their HCl, but those ofHBr and HI usually have the anion of the oxy-acid reduced, with liberation of the halogen. These compounds have as many molecules of halogens hydride to one metal atom as the latter has valencies thus salts M" P04 have three molecules, but M SO4, M HP04, and M (HP02)2 only two molecules of the halide to 1 M. 

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