Diazomethane, reaction with dimethyl ether

Diazomethane, reaction with 2,4,6-tri-nitrobenzenesulfonic acid and dimethyl ether, 46,122 Diazonium xanthates, detonation of, 47, 107... 

The reaction of ( + )-bulbocapnine methyl ether (42) with excess boron trichloride in methylene chloride containing 0.3% ethanol produces the catechol (43) together with the monophenol (44). However, with boron tribromide, it is the diphenol (45) which is produced. Both compounds (44) and (45) can be O-methylated with diazomethane to the dimethyl ether (46), and hydrolysis of (46) with dilute hydrochloric acid leads to (+)-corytuberine (47).43 Alternatively, methylation of (43), using diazomethane, affords (+)-corydine methyl ether (48). 

Methylation of 2-amino-3-hydroxypyrazine (62) with methyl iodide and sodium methoxide afforded 3-amino-l-methyl-2-oxo-1,2-dihydropyrazine (63), and when an excess of methyl iodide was used, a mixture of compound (63) and its methio-dide (64) was isolated. Reaction with dimethyl sulfate and alkaU gave compound (63) and l,4-dimethyl-2,3-dioxo-l,2,3,4-tetrahydropyrazine (66) the latter was presumed to be formed by hydrolysis of an intermediate quaternary salt since it was also obtained by treatment of the methiodide (64) with aqueous sodium hydroxide. Reaction of 2-amino-3-hydroxypyrazine with ethereal diazomethane produced a mixture of N- and 0-methyl derivatives, (63) and 2-amino-3-methoxy-pyrazine (65). With methyl toluene-p-sulfonate the quaternary salt 2-amino-3-hydroxy-1-methylpyrazinium toluenesulfonate (67) was obtained on alkaline hydrolysis it gave 3-hydroxy-l-methyl-2-oxo-l,2-dihydropyrazine (68) (832). Pulcherriminic acid with diazomethane gave a dimethyl derivative (99). 

Diazomethane reacts with 2,4,6-trinitrobenzenesulfonic acid with ring opening similar to that observed with 1,3,5-trinitrobenzene.6 Hence an excess of the reagent is to be avoided. The yellow color is not due to the presence of diazomethane itself. The reaction time is highly sensitive to the temperature of the xylene solution and to the flow rate of gaseous dimethyl ether. The reaction time is usually 20-40 minutes. 

Phenolic methyl ethers were usually prepared by treatment of the alkaloid with dimethyl sulfate and sodium hydroxide or with diazomethane 17). In the first case a side reaction was N-methylation or even cleavage of the lactone (3). In decodine (6) the C-17 OH group was methylated on treatment with ethereal diazomethane. The hindered C-21 OH group was alkylated with methanolic CH2N2 (77). 

Dimethyl ether, methylation by diazomethane and 2,4,6-trinitroben-zenesulfonic acid to form tri-methyloxonium 2,4,6-trinitroben-zenesulfonate, 46,123 reaction with triethyloxonium fluo-borate, 46,120... 

Khydroxypyrazine (which was converted into its jV -dimethyl derivative by treatment with dimethyl sulfate and alkali) gave, on reaction with an excess of ethereal diazomethane a mixture of its N,N-, 0,N-, and 0,0-dimethyl derivatives (58-60) (832). 2-Hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenylpyrazine with ethereal diazomethane gave predominantly 2,5-dimethoxy-3,6-diphenyl-pyrazine and only minor amounts of A -methylated products (832). Methylation of 2-hydroxy-6-methoxypyrazine with ethereal diazomethane produced a mixture of 0- and A -methyl derivatives in which the 0-methyl derivative predominated but the corresponding reaction of 2-benzyloxy-6-hydroxypyrazine gave almost exclusively the 0-methyl derivative (832) [the results of these methylations were correlated with the carbonyl stretching frequency (1103) in the parent lactam (832)]. 

Further general route to 2-alkyl-2-butenolactones via the retro Diels-Alder reaction was developed. Fig, 5, [23]. Hydrolysis of a known lactone (15), subsequent esterification with diazomethane, and treatment with dihydropyran afforded a stereoisomeric mixture of pyranyl ether. Alkylation of the pyranyl ether with various alkyl halide yielded alkylated products (16). The retro Diels-Alder reaction of 16 was performed by heating at 200-280 C in a sealed tube to give 2-alkyl-2-butenolactones (17). The utility of the butenolactones was demonstrated by the synthesis of hinokinin (18) and dehydrolappaol A dimethyl ether (19). Similarly rather mild, simple synthesis of a-methylene-y-alkylbutyrolactones was deviced using dimethylfulvene as a protective group for the double bond, Fig. 6. [24], The... 

Miscellaneous Reactions. Diazomethane has been shown to react with vinylsilanes derived from a. -unsaturated esters to provide the corresponding allylsilane by insertion of CH2 into the C-Si bond (eq 49). The reaction has been shown to be stereospecific, with c/s-vinylsilane providing cts-allylsilanes however, the mechanism of the reaction has not been defined. Diazomethane has also been used in the preparation of trimethyloxoirium salts. Treatment of a solution of dimethyl ether and trinitrobenzenesul-fonic acid with diazomethane provides trimethyloxonium trini-trobenzenesulfonate, which is more stable than the fluoroborate salt. ... 

The value of methylation studies in structural determination of carbohydrates is well known. Methylation of sucrose has generally been achieved by the use of dimethyl sulfate-sodium hydroxide,34,35 methyl iodide-silver oxide-acetone,20 sodium hydride-methyl io-dide-N,N-dimethylformamide,35 or diazomethane-boron trifluoride etherate.36,37 The last method (already applied to monosaccharides38,39) has been found particularly useful for sucrose, because it proceeds without concomitant migration of acyl groups. The reaction of 2,3,6,T,3, 4, 6 -hepta-0-acetylsucrose (21) and 2,3,4,6,1, 3, 4 -hepta-O-acetylsucrose (22) with diazomethane in dichloromethane in the presence of a catalytic proportion of boron trifluoride etherate for 0.5 h at —5° gave the corresponding 4-methyl (23) and 6 -methyl (24)... 

The reaction of the O-tosyloxime of dimethyl mesoxalate with diazomethane at 0 to — 5°C in methylene chloride-ether for 1 hr gives a quantitative yield of the triazoline361 however, at 20°C the triazoline cannot... 

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