Methyl imino acetic acid

In the reaction of 5-phenyl-3-methyl-2-imino-l,3,4-oxadiazoline and EMME at 130°C for 30 min, N-( 1,3,4-oxadiazolin-2-ylidene)aminomethy-lenemalonate (66) was obtained in 34% yield (70AP501). The reaction of 5-amino-4-phenyl-1,2,3-triazole and EMME in the presence of acetic acid in boiling benzene for 30 hr, or in boiling toluene for 3 hr, gave (1,2,3-triazol-5-ylamino)methylenemalonate (67) in 64-89% yields [71JCS (02156]. 

When 4-imino-9-methyl-4//-pyrido[l, 2-a]pyrimidine-3-nitrile reacted with sodium azide in a solvent at 60-70°C for 3-6 hours, ring-opened 3 - [(3 - methyl-2- py ridy l)amino]-2- (1 -H- tetrazol-5- yl)-2- propenenitrile was obtained, but the bicyclic 4-imino-9-methyl-3-(l//-tetrazol-5-yl)-4//-pyrido[l,2-a]pyrimidine could be isolated when the reaction was carried out in acetic acid at 115°C (90EUP385634). The latter product was also obtained from the ring-opened product by heating in IN hydrochloric acid at 100°C for 1 hour, or in IN potassium hydroxide at 100°C for 3.5 hours. Reaction in acetic acid was also extended to 9-phenoxymethyl, 9-(4-acetyl-... 

To a stirred mixture of the above amine hydrochloride (55.0 g, 0.22 mole) and [[(2,4-dioxo-l-imidazolidinyl)imino]methyl]formyl chloride (42.0 g, 0.22 mole) was added a solution of 440 ml of dimethylformamide and 44 ml of pyridine. The mixture was stirred for 20 h and poured into 2 L of water. The solid was collected by filtration and washed with ethanol and ether to give 36.0 g (28%) of N-[2-(4-bromophenyl)-2-oxoethyl]-[[(2,4-dioxo-l-imidazolidinyl)-imino]methyl]formamide, melting point 267°-269°C (recrystallization from 2200 ml acetic acid). 

Unlike their benzenoid counterparts, halogen substituents at C-2 and C-4 are sensitive to nucleophilic displacement by an addition-elimination mechanism. There is a parallel to the reaction of imino halides and acyl halides (see Scheme 4.27a). There are a number of other parallels to carbonyl chemistry. Thus a methyl group at C-2 or C-4 undergoes condensation reactions (Scheme 4.27b) and an acetic acid residue at C-2 undergoes decarboxylation (Scheme 4.27c). 

An jV-benzyl group, inserted for protection, has usually been removed by stirring in liquid ammonia while sodium chips were added until a blue color persisted. Thus 9-benzyl-l,6-dihydro-6-imino-l-methyl-8-azapurine furnished l,6-dihydro-6-imino-l-methyl-8-azapurine, and 9-benzyl-6-butylamino-8-azapurine gave 6-butylamino-8-azapurine in 75% yield. Hydrogenation over palladium was used to debenzylate 9-benzyl-7-methyl-2,6-dioxo-8-azapurinium betaine (similar to 18) at 45 C. 9-Benzyl-l-methyl-8-azapurin-6-one resisted all of these conditions, but hydrogenation over palladium in butanol-acetic acid at 117°C provided a 72% yield of 1 -methyl-8-azapurin-6-one. ... 

The 3-imino group of 4-cyano-2-ethyl-3-imino-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione was acylated with phenyl isocyanate (78MI1). The imino group of l-imino-4-cyano-3-methylthio-l//-pyrido[l,2-cjpyrimidine was alkylated and acylated with methyl iodide and acetic anhydride (75YZ13). Reaction of 3-amino-4-phenyl-4-[2-(A, N-di-n-pro-pylamino)ethyl-4,4 a,5,6,7,8-hexahydro-l //-pyrido[l, 2-c ]pyri midin-l-one with acetic anhydride in pyridine and with sodium nitrite in aqueous acetic acid afforded 3-acetamido and perhydro-l,3-dioxo derivatives, respectively (87USP4680295). 

The above structure for the colorless desoxyvomicine fails to offer a satisfactory explanation for the formation of a methiodide by this base, while vomicine fails to react with methyl iodide under similar conditions. Reduction of an acetic acid solution of desoxyvomicine methiodide by sodium amalgam yields the base C23H30O3N2 with two imino-methyl groups (29) (desoxydihydrovomicine and methane result from a similar reduction of desoxydihydrovomicine methiodide (32)). Base C2JH30O3N2 reacts smoothly with methyl iodide, while thermolysis of the derived metho-hydroxide yields trimethylamine. It would seem difficult to find an adequate explanation for the formation of trimethylamine on the present formula for desoxyvomicine. 

The desulfuration of 6-unsubstituted-3-methyl-2,3-dihydro-677-l,3,4-thiadiazines 61 (R = Me, Pr ) in boiling glacial acetic acid affords pyrazoles 62 <2003SL2392>. In contrast to the rapid sulfur extrusion of 6-phenyl- or 6-ethoxycarbonyl-6/7-l,3,4-thiadiazines 59 (R = Ph, C02Et) to pyrazoles, a much longer reaction time (40h) was required to achieve a complete desulfuration of 61 (Equation 5). The treatment of 4/7-1,3,4-thiadiazine 63 with concentrated hydrochloric acid or hydrobromic acid (48%) afforded the 5-imino-l,2-dimethylpyrazoles 64 in 40% and 30% yield, respectively (Equation 6). The yield was increased to 53% by the use of glacial acetic acid. The sulfur extrusion proceeded very rapidly and precipitation of considerable amounts of sulfur was observed even after stirring for only 5 min. 

C9H1sBrN203, 1-Methyl-3-imino-4-a-hydroxyethylidenecyclopent-1-ene-2-carbonamide hydrobromide monohydrate, 27, 945 C9H15NO6, trans-1-Amino-l,3-dicarboxycyclopentane (acetic acid solvate), 41B, 163... 

For example, treatment of imino chloride 144 derived from 7p-(2-phenyl-2-bromo) acetamido-3-methyl 3-cephem benzhydryl ester (143) and phosphorus pentachloride, with an excess of methanolic lithium methoxide in THF at -78°C for 20 min, followed by quenching with acetic acid, afforded 7 -phenylketenimino-7a-methoxy- -lactam (146) in 60% yield. This material was reasonably stable to silica gel chromatography and, when treated with trifluoroacetic acid followed by aqueous quenching, quantitatively afforded 7p-phenylacetamido-7a-methoxy-3-methyl-3-cephem-4-carboxylic acid. Similar treatment of imino chlorides (144) or ketenimines (146) with lithium methoxide at -20 C provided iminoethers (147) in good yield. In the case of the imino chloride formed from 7p-dichloroacetamido-7-deacetoxycephalosporanic acid methyl ester, the corresponding iminoether (147) was obtained in 80% yield with lithium methoxide, even at — 78°C. The same imino chloride reacted... 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

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