By Grignard syntheses

Hydroxypyrroles. Pyrroles with nitrogen-substituted side chains containing hydroxyl groups are best prepared by the Paal-Knorr cyclization. Pyrroles with hydroxyl groups on carbon side chains can be made by reduction of the appropriate carbonyl compound with hydrides, by Grignard synthesis, or by iasertion of ethylene oxide or formaldehyde. For example, pyrrole plus formaldehyde gives 2-hydroxymethylpyrrole [27472-36-2] (24). The hydroxymethylpyrroles do not act as normal primary alcohols because of resonance stabilization of carbonium ions formed by loss of water. 

At low temp., ketones are obtained in excellent yield by Grignard synthesis with anhydrides.—E n-Butyl-MgBr added slowly with rapid stirring at ca. —70° to acetic anhydride over a period of 2 hrs. -> 2-hexanone. Y ca. 80%. Adding the anhydride to the Grignard reagent causes a large drop in yield. (F. e. and details on the reaction s. M. S. Newman and A. S. Smith, J. Org. Ohem. 13, 592 (1948).) s. a. 2, 734... 

Hydrocarbons may be prepared by Grignard synthesis (cf. pages 762 et seq.) according to the general scheme ... 

Carboxylic acid amides by Grignard synthesis with addition of 1 C-atom from halides... 

Tertiary alcohols can be prepared by a variation of the Grignard synthesis that uses esters as the source of the carbonyl group Methyl and ethyl esters are readily available and are the types most often used Two moles of a Grignard reagent are required per mole of ester the first mole reacts with the ester converting it to a ketone... 

Thiophenethiols are prepared by reduction of the sulfonyl chlorides or, more conveniently, by the reaction of Grignard rea-gents or thienyllithium compounds with sulfur. They have also been obtained by cleavage or thienyl alkyl sulfides with sodium in liquid ammonia. 3-Thiophenethiol is a by-product in the commercial thiophene synthesis. Thiophenethiols have recently also been prepared by a synthesis involving Friedel-Crafts reaction of 2,4-dinitrobenzenesulfenyl chloride with thiophenes, followed by basic cleavage of the resulting sulfide. ... 

Halo-l-benzothiepins 4 can be synthesized by the treatment of 7a-halobenzo[fe]cyclopropa-[e]thiopyran-7-ols 2 with hydrogen bromide and subsequent hydrogen bromide elimination from the 2,4-dihalo-2,3-dihydro-l-benzothiepins 3 by l,5-diazabicyclo[4.3.0]non-5-ene (DBN).9 The alcohols 2 are prepared by Grignard reaction of the corresponding 7a-halobenzo[ft]cyclopropa[c]thiopyran-7-ones l18 and are used for the synthesis without purification. The intermediate dihalodihydro-l-benzothiepins 3 are not isolated due to their thermal lability related and more stable compounds are described in Section 2.1.2.1. 

Of greater potential practical significance, however, are the note193 and full papers194,195 in which Fabre, Julia and Verpeaux describe a new stereoselective synthesis of trisubstituted alkenes in which vinyl sulphones are attacked by Grignard reagents in the presence of iron or nickel catalysts (equations 82-84). 

Problems of acyl anion equivalents met above in the synthesis of similar TMs disappear if (25) is made from the alkene (26), A Wittig is the obvious method to make (26) and reaction between (27) and PhgCO will probably give (26), An alternative is the dehydration of (28), made by Grignard addition to ester (20), Osmium tetroxide was used for the hydroxylation. 

Acetylenic precursors employed in the syntheses of sugars may be divided into three groups (a) aldehydes (usually in the form of acetals), (b) alkyl alkynyl ethers, and (c) alkynols or alkynediols. Some of them are commercially available (for example, 2-butyne-l,4-diol), and others are prepared by Grignard-type reactions between 1-alkynylmag-nesium halides or lithium alkynes and suitable aldehydes, ketones, or epoxides. In this way, the synthesis of substrates having the desired number of carbon atoms, as well as the necessary functional groups, can be achieved. The next step consists in partial saturation of the triple bond to afford the desired cis- or trans-alkene. ct.s-Alkene systems... 

Precursor y-halogeno alcohols are frequently prepared by the classic sequence of addition of hydrogen halide to a,/3-unsaturated aldehydes, ketones, acids or esters, followed by Grignard reaction or hydride reduction. Recently a novel and general synthesis of 3-methoxyoxetanes from 3-phenylseleno-2-propenal was reported. This method comprises a sequence of Grignard addition to the aldehyde function, treatment with two equivalents of MCPBA, and then reaction with methanolic sodium hydroxide (equation 78) (80JOC4063). 

For a review of the synthetic applications of metallation by Grignard reagents at positions other than at triple bonds, sec Blagocv Ivanov Synthesis 1970, 615-628,... 

M. Malanga and O. Vogl, Head-to-head polymers. XXIV. Synthesis of head-to-head polyisobutylene by grignard coupling reaction, ]. Polym. Sci., Part A Polym. Chem., 21(9) 2629-2648,1983. 

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