Diazomethane reaction with aldehydes

Homologation of aldehydes. Reaction with diazomethane gives epoxides. It should be noted that MeAl(OAr>2 promotes formation of ketones. 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Although aldehydes and ketones can also be converted to epoxides by reaction with diazomethane (CH2N2), it is not uncommon to find that methylene insertion occurs at the same time (often preferentially) as shown in Scheme 9.59. 

CHEC-II(1996) <1996CHEC-II(8)345> covered a range of reactions of substituents, including hydrolyses of esters to carboxylic acids and geminal dihalides to aldehydes, reduction of aldehydes and halogens directly attached to the ring, O-methylation with diazomethane, and reduction of nitroso compounds. A selection of reactions which have... 

Arndt, F. Eistert, B. Ber. Dtsch. Chem. Ges. 1935, 68, 200. Fritz Arndt (1885—1969) was bom in Hamburg, Germany. He discovered the Arndt—Eistert homologation at the University of Breslau where he extensively investigated the synthesis of diazomethane and its reactions with aldehydes, ketones, and acid chlorides. Fritz Arndt s chain-smoking of cigars ensured that his presence in the laboratories was always well advertised. Bernd Eistert (1902-1978), bom in Ohlau, Silesia, was Arndt s Ph.D. student. Eistert later joined I. G. Earbenindustrie, which became BASE after the Allies broke the conglomerate up after WWII. 

An alternative method for dialkyl peroxide synthesis is the nucleophilic addition of an alkyl hydroperoxide to an alkene under acid catalysis reported by Davies and coworkers (Scheme 31, path B) ". A similar reaction is the nucleophilic addition of alkylhy-droperoxides to vinyl ethers under acid catalysis, producing perketals. Perketals can be deprotected under mild conditions (THF/water/acetic acid) and this hydroperoxide protection-deprotection sequence has been used by Dussault and Porter as a means for the resolution of racemic hydroperoxides (see also Section II.A.2) . In this respect more detailed studies were carried out with the perketals 75, which were prepared via reaction of alkyl hydroperoxides with vinyl ethers (Scheme 33). Weissermel and Lederer reported that in the presence of teri-butyl hypochlorite, a-chlorodialkyl peroxides can be formed in yields between 12% and 45% (Scheme 31, path C)". a-Alkoxydialkyl peroxides and diperoxyacetals were prepared by Rieche and coworkers via acid catalyzed reaction of one or two equivalents of alkyl hydroperoxides with acetals, ketals or aldehydes (Scheme 31, path D)" or by methylation of the corresponding a-alkoxy hydroperoxides with diazomethane (yields 11%, 27%)" . The diperoxyacetals 76 were isolated in yields ranging from 39 to 77%. 

Aldehydes and ketones176 can be converted to their homologs177 with diazomethane.178 Formation of the epoxide (6-61) is a side reaction. Although this reaction appears super-... 

C. D. Gutsche, The Reaction of Diazomethane and Its Derivatives with Aldehydes and Ketones, Org. React. 1954, 8, 364M29. 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

Fragmentation Products. All ozonides except for the tetrasubstituted ones are cleaved quantitatively by many solvents. While symmetrically disubstituted ozonides give one mole of acid and one mole of aldehyde as products, and trisubstituted ozonides yield one mole acid and one mole of a ketone, in the case of monosubstituted or unsymmetrically 3,5-disubstituted trioxolanes, two kinds of acids and two kinds of aldehydes are possible. The fragmentation products in these cases were treated with diazomethane, and the mixture of the methyl esters was analyzed by gas chromatography. The results are shown in Table VI. In all of these examples, the reactions go predominantly in one direction. When R and R are more similar, however, both kinds of reaction products would be expected in more nearly equal amounts. 

Vinylselenophene was obtained from selenophene-2-aldehyde in three ways decarboxylation of /3-(selenien-2-yl)acrylic acid,111 the Wittig reaction,112 and dehydration of l-(selenien-2-yl)ethanol.ni The most convenient method is the last, conducted in the vapor phase. 2-Vinylselenophene is brominated112 and formylated in the side chain,111 and it reacts with diazomethane and p-nitrophenyl-diazonium chloride.112 2-Cyclopropylselenophene (12, R = H) was... 

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