Diazomethane groups

The nitro group increases the acidity of the hydrogen born by the exocyclic nitrogen, and alkylation of 2-nitraminothiazole with diazomethane is possible (87), The formed 2-(A"-methylnitramino)-thiazole also may be obtained from the reaction of 2-nitraminothiazole with dimethylsulfate in basic medium (194). 

Oxo substituents are, in a few cases, methylated with diazomethane to give methoxy derivatives in addition to the major iV-methylation, and oxo groups in the 3-deazaflavins have been acylated. 

A versatile oxirane synthesis via (64) is the sulfur ylide approach (B-75MI50504, cf. 76TL457), which in effect inserts a CR2 group into a carbonyl group (Scheme 71). Older, less generally useful versions of this insertion utilize diazomethane or dibromomethane-butyllithium. 

Galipoline, C19H19O3N. A process for the extraction and separation of the angostura bark alkaloids was described by Spath and Eberstaller,i and from the phenolic bases obtained Spath and Papaioanou isolated this alkaloid. It crystallises from water, has m.p. 193°, contains two methoxyl groups, and on methylation by diazomethane yields galipine. 

In general, reaction of diazomethane with a, -unsaturated carbonyl compounds affords pyrazolines in which the nucleophilic methylene group is attached to the carbon atom of the carbonyl compound. According to Huisgen, the reactions belong to the general class of 1,3-dipolar cycloadditions. 

The presence of a 21-acetoxy group is also compatible with good yields during diazomethane addition. ... 

The addition of diazomethane to 17j -hydroxy-5a-androst-l-en-3-one (7) gives the A -pyrazoline (8) in which the C=N bond is conjugated with the 3-keto group. °°... 

In the 6-chloro-A " series diazomethane addition and pyrazoline cleavage require more strenuous conditions. " An unexpected result is observed with the 4-chloro-A system (15) which adds two equivalents of diazomethane to give the 4-chloro-la,2a 6, 7 -dimethylene compound (16) in 16% yield after cleavage of the labile crude bispyrazoline with a catalytic amount of perchloric acid. The assignment of the -configuration to the 6,7-methylene group is based on the shift of the 19-H NMR resonance to higher field. 

A valuable extension of the diazomethane reaction for the preparation of A-homosteroids was discovered by Johnson, Neeman and Birkeland " who found that a,j5-unsaturated ketones are homologated by reaction with diazomethane in the presence of either fluoroboric acid or boron trifluoride. The main product is formed by the insertion of a methylene group between the carbonyl group and the unsaturated a-carbon to give a / ,y-unsaturated ketone. 

B-Homosteroids have also been prepared by acid-catalyzed reaction of diazomethane with a,/5-unsaturated ketones. 3/ -Hydroxycholest-5-en-7-one acetate (57) reacts with diazomethane in the presence of concentrated fluoroboric acid, boron trifluoride etherate or aluminum chloride to give 3yS-hydroxy-B-homo-cholest-5-en-7a-one acetate (67). The 7a-keto group is reported to be chemically less reactive than an 11-keto group. 

Reactions of fluorinated dipolarophiles. Electron-deficient unsaturated species generally make better dipolarophiles, therefore, fluonnated alkenes become better dipolarophiles when vinylic fluonnes are replaced by perfluoroalkyl groups For example, perfluoro-2-butene is unreactive with diazomethane, but more highly substituted perfluoroalkenes, such as perfluoro-2-methyl-2-pentene, undergo cycloadditions in high yields [5] (equation 2) Note the regiospecificity that IS observed in this reaction... 

Reactions offluorinated dipoles. In recent years, much effort has been devoted to the preparation of tnfluoromethyl-substituted 1,3-dipoles with the goal of using them to introduce trifluoromethyl groups into five-membered nng heterocycles Fluorinated diazoalkanes were the first such 1,3-dipoles to be prepared and used in synthesis A number of reports of cycloadditions of mono- and bis(tnfluo-romethyl)diazomethane appeared prior to 1972 [9] Other types of fluonne-substi-tuted 1,3-dipoles were virtually unknown until only recently However, largely because of the efforts of Tanaka s group, a broad knowledge of the chemistry of tnfluoromethyl-substituted nitrile oxides, nitnle imines, nitnle ylides, and nitrones has been accumulated recently... 

The addition of diazo compounds generally leads to three membered tings, although in special cases, linear adducts with an intact diazo group [110] or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and aziridines [112,113,114] Aziridines are obtained exclusively on reaction of certain polyfluorinated acyl imines with diazomethane [115]... 

The hydroxythiophenes which exist predominantly as the thiolen-2-ones also show reactions characteristic of the enol form. They can be methylated at the oxygen with dimethyl sulfate of diazomethane and they can also be acylated. - - They also react as thio-lene-2-ones showing a reactive methylene group which can be condensed with benzaldehyde. The danger of using chemical reactivity data for drawing conclusion as to the physical state of these tautomerizable systems has been pointed out. ... 

The pyrimidine compounds are known to undergo a rearrangement of the 0-alkyl derivatives to the iV-alkyl ones. The methoxy derivatives of 1,3,5-triazine display a similar behavior. On applying methyl iodide to 2,4-dimethoxy-l,3,5-triazine one of the methyl groups is shifted giving rise to l-methyl-4-methoxy-derivative (22). This compound was also obtained by methylation of 4-methoxy-2-oxo-1,2-dihydro-1,3,5-triazine (18) with diazomethane. At higher temperature (100°C) in presence of methyl iodide a shift of both methyl groups takes place and methiodide is formed simultaneously (23). Similarly,... 

The hexahydro derivatives are weakly basic substances, some of them forming hydrochlorides. Dioxohexahydrotriazine yields a 1,5-diacetyl derivative (35), in which the positions of the acetyl groups were determined by acetylation of the A-alkyl derivatives and methylation with diazomethane according to Scheme 4. ... 

---