Methyl amide reagent

V-dimethylaminomethylene derivatives of primary amides Add 250 fjL 1 of Methyl-8 reagent to less than 1 mg of sample. Heat at 60° for 20-30 min. 

Addition of organolithium or organomagnesium reagents to N-methoxy- N-methyl amides gives a tetrahedral intermediate that is stabilized by chelation of the magnesium atom by the two oxygen atoms. This intermediate collapses, to give a ketone, only when acid is added at the end of the reaction. 

Pyrrolidines. The Grignard reagent 2, obtained from 3-bromopropylamine protected as the stabase adduct with 1, reacts with the N-methoxy-N-methyl amides 3 (11, 201-202) to form an intermediate ketone that cyclizes to an imine on liberation of the free primary amino group. Reduction of the imine results in a 2-substituted pyrrolidine (4). 

Methylation of amides- Diazomethane in the presence of silica gel forms methyldiazonium silicate, which can methylate amides. Thus this reagent converts caprolactam (1) into O-methylcaprolactim (2) in 957o yield in 15 minutes. 

The Wittig-Horner reaction of protected 3-formylindazoles with iV-(benzyloxycarbonyl)-a-phosphonoglycine trimethyl ester has been developed as a new practical synthesis of dehydro 2-azatryptophans and amino acid derivatives <2007TL2457>. Nucleophilic addition of Grignard or lithiated reagents of 3-A -methoxy-A -methyl-amides of indazole afforded a library of 3-keto and 3-formylindazoles <2007T419>. 

When the proportion of acetone is restricted, the main products are mono-O-isopropylidene-D-galactoses. Thus, the furanoid 5,6- and pyranoid 3,4- and 4,6-isopropylidene acetals were obtained in yields of 22, 15, and 13%, respectively. The absence of 1,2-acetals is significant, and is attributed to an effect of A/,/V-dimethylfonnamide.23-24 A similar, low activity of the anomeric hydroxyl group has been noted with the 2,2-dimethoxypropane-A/,A/-di methyl form amide reagent.25... 

An even more direct route would evolve from the connection of the two reagents shown below. Interestingly, the photochemically mediated reaction of a quinone with an imine has never been reported. If we can identify suitable reaction conditions for this transformation, we will have secured an exceptionally direct route to the benzodiazepine ring system. The imine required for this reaction has been previously synthesized and can readily be generated in multigram quantities by the condensation of benzaldehyde with the N-methyl amide of glycine. Even though the... 

A -Methoxy-A -methyl-amide. Due to the chelation effect, nucleophilic addition of an organometallic reagent adds only once to give ketone, whereas normal amides would have led to double addition to afford tertiary alcohol. 

Place 10 ml. of pure benzaldehyde (Section IV,115) and 100 ml. of concentrated aininonia solution (sp. gr. 0-88) in a 250 ml. wide-mouthed reagent bottle. Cork the bottle securely, shake vigorously for 10 minutes and allow to stand with occasional shaking for 24 hours. By this time the benzaldehyde should be converted into a hard mass of hydrobenz-amide. Break up the solid mass with a spatula or a thick glass rod, filter with suction, wash with water, and drain thoroughly. RecrystalUse from absolute alcohol (or absolute methylated spirit). The yield of hydrobenzamide (colourless crystals), m.p. 101°, is 7 g. It is easily hydrolysed by cold dilute acids. 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

Me3SiBr, CH2CI2, 0°, 8-9 h, 80-97% yield.This reagent also cleaves the acetonide, THP, trityl, and r-BuMe2Si groups. Esters, methyl and benzyl ethers, r-butyldiphenylsilyl ethers, and amides are reported to be stable. 

The other three methods have not been studied extensively. The dimethyl-cadmium route has been used on a 17a-methyl-17 -carboxylic acid. ° The reaction of the acid amide with a Grignard reagent is described only in a Spanish patent,with a high yield claimed, and the methyllithium reaction has apparently been tried only on D-norsteroids. ... 

---