Dimethoxy dimethyl methoxide

A simple two-step synthesis of the a-pyrone ring system209 has been applied to the synthesis of bufadienolides.210 Reaction of the known a/3-unsaturated aldehyde (416) with the dimethyl acetal of chloroketen [ClCH=C(OMe)2] gave a 57% yield of the intermediate 2,2-dimethoxy-3 -chloro-3,4-dihydropyran (417) which on reaction with sodium methoxide in DMSO afforded the a-pyrone (418) directly in 64% yield. 

Trichloropyridazine is converted, upon dimethylation, into a 6-chloro-3,4-dimethoxy derivative, a molecular complex of the latter compound, and 3-chloro-4,6-dimethoxypyridazine in a ratio of 1 1. The complex had been described previously as pure 3-chloro-4,6-dimeth-oxypyridazine (68MI5) and could not be separated into components (87(3PB350). On the other hand, methoxylation of 3,4,5-trichloropyrida-zine with an equivalent amount of sodium methoxide afforded three mono-methoxy derivatives, i.e., 3-, 4-, and 5-methoxy-dichloropyridazines in the ratio of 1 3 6(87CPB421). 

The following alkoxypyrazines have been prepared from the corresponding dichloropyrazines and alkoxide ions 2,3-dimethoxy-5,6-dimethyl(and diphenyl) (797) 2,3-dibenzyloxy (sodium benzyl oxide in benzyl alcohol at reflux for 24 hours (883)] [but 23-dichloropyrazine with sodium hydride and benzyl alcohol in xylene gave l,4-dibenzyl-2,3-dioxo-l,2,3,4-tetrahydropyrazine)(988)] 2-chloro-5-methoxy (838) 2,5-diethoxy-3,6-dimethyl (872) 2methanolic sodium methoxide refluxed for 2 h) 2,5-dimethoxy-3-phenyl (817) 2-chloro-5-methoxy(and ethoxy)-3,6-diphenyl (817) 2,5-dimethoxy-3,6-dimethyl (and diisopropyl) (844) 2,5-dimethoxy-3-isopropyl-6-methyl (methanolic potassium methoxide at reflux for 6 days) (844) 2(5)-s-butyl-3-chloro-6-ethoxy-5(2)-isobutyl (93) 2-chloro-6-methoxy (838, 883) 2,6-dimethoxy (reflux for 8h) (832) 2,6-diethoxy (reflux for 14 h) (883) 2-benzyloxy-6-chloro (1 equiv. of sodium hydride and benzyl alcohol in benzene at reflux) (832) 2,6-dibenzyloxy (5 equiv. of sodium benzyloxide in benzene at reflux gave 70%) (832) and 3,5-dimethoxy-2-methyl (535). 

The reaction between dimethyl 2-bromo-l-phenylpropylidenemalonate and sodium methoxide in methanol affords a complex reaction mixture consisting of dimethyl 2-methyl-3-phenyl-2-cyclopropene-l,l-dicarboxylate (303,19%), dimethyl (2,2-dimethoxy-l-methyl-2-phenylethyl)malonate (304, 4%), dimethyl 2-methoxy-l-phenylpropyl-idenemalonate (305, 11%), dimethyl 2-bromo-l-phenyl-1-propenylmalonate (306 -isomer, 10% Z-isomer, 13%) and dimethyl (l,2-dimethoxy-l-phenylpropyl)malonate... 

When isomerization of the double bond of the intermediate cyclopropene into the exo methylene position is energetically unfavored, double elimination followed by double addition of base can occur. Thus, reaction of (cu/tra i )-l,l-dichloro-2-methyl-3-vinylcyclopropane (9) with potassium terf-butoxide plus methoxide in dimethyl sulfoxide gave a mixture of cis- and trans-, -dimethoxy-2-methyl-3-vinylcyclopropane (10). Both double bonds formed via elimination appear to be conjugated with the vinyl group and do not migrate to the exo position. The similar reaction of l,l-dichloro-2-[( )-propenyl]cyclopropane (11) gave a small amount of 1-/ert-butoxy-2-(prop-2-enylidene)cyclopropane (13) in addition to products of double addition. Without added methoxide, 13 was the only product isolated. ... 

The kinetics and equilibria of the reaction of 4,6-dinitrobenzofuroxan with water (forming 235),494 496and of the cyclization of 7-(hydroxyethoxy)-4-nitrobenzofuroxan with alkali, in water and in dimethyl sulfoxide (Eq. II)497 have received detailed study. Proton NMR spectroscopy has shown that methoxide ions add more quickly to the 5-position of 7-methoxy-4-nitrobenzofuroxan, but the thermodynamic product is the 7,7-dimethoxy adduct (237) (Eq. 12).498 Methoxide adducts are also formed with 4-nitro-benzofuroxan.499 The impetus for much of this work was provided by the suggestion that antitumor and antileukemic properties which have been observed in some benzofuroxans might be connected with their ability to form Meisenheimer complexes of the types illustrated in this section.300,416,500... 

The heterocyclic intermediates for bensulfuron methyl and chlorimuron methyl are prepared from 2-amino-4,6-dichloropyrimidine (XVII) (Equation 14). This intermediate was prepared by the reaction of dimethyl malonate and guani ne carbonate to yield 2-amino-4,6-dihydroxypyrimidine which is converted to the dichloro compound by phosporus oxychloride. Treatment of the dichloro intermediate with sodium methoxide and methanol gave the dimethoxy intermediate (XVin) for bensulfuron methyl, whereas with potassium carbonate and methanol the product is the 4-chloro-6-methoxy intermediate (XIX) for chlorimuron methyl. 

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