Ammonia methyl derivatives

The analogous 6-methyl derivative (126) was prepared by the same authors from 6-methyl-3,6-dithioxo derivative (123) as the corresponding monothioxo derivative is not easily available. Even here the substitution with ammonia took place selectively in position 4 (124) and the remaining sulfur atom was replaced with oxygen by oxidation with alkaline potassium permanganate (125). A similar procedure is protected by a patent. ... 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

Certain oxopyrimidines react almost as readily as non-oxygenated compounds. Thus, 6-chloro-l,3-dimethylpyrimidine-2,4-dione and its 5-methyl derivative react with ammonia and primary or secondary amines at 20° or on very brief warming. 

Dichloro-l,3,5-triazanaphthalene and its 6-methyl derivative react at the 4-position (70-90% yields) with ammonia in dioxane (20°, 15 min) or in water (95°, 1.5 hr) and with diethylamine in dioxane (20°, 15 min). The dichloroazine yields the 4-(A-ethyl-anilino)-2-chloro derivative under acidic conditions. Amination of the 2,4-dithioxo derivative with concentrated ammonia (95°,... 

Chloro-7-(2-fluorophenyl)-5/f-dibenz[c,e]azepine (54) has been prepared in a similar manner from 2-[2-(bromomethyl)phenyl)-5-chloro-2 -fluorodiphenyl ketone (53, X = Br),93 but can be obtained in a superior yield (85%) as the methanesulfonate salt by cleavage of the [(dimethylamino)methyl] derivative 53 (X = NMe2) with cyanogen bromide followed by treatment with ethanolic ammonia.94... 

Methylation of the 6,7-dimethyl derivative of 133 with methyl iodide in sodium hydroxide or sodium ethoxide gave two S,N-dimethyl derivatives, whereas in sodamide or ammonia, only the 5-methyl derivative was obtained. Methylation with diazomethane gave four methyl derivatives and with methyl chloride two di-jV-methyl and one 5,/V-dimethy] derivative were obtained (80H1139). Methylation of 153, obtained from 152, gave 4-methyl-3-methylthio-triazinoindole 155, whose hydrolysis or oxidation gave 154 (76T1735). On the other hand, methylation of 156 gave methiodide... 

Exactly this problem was the subject of synthetic experiments carried out by J. Oro et al. (1984), which were intended to clarify the possible formation of these condensation agents. They used simple compounds, such as formaldehyde, acetaldehyde, glyoxal and ammonia as starting materials, and were able to synthesize imidazole as well as its 2- and 4-methyl derivatives. 

Tris(diphenylstibino)amine (Ph2Sb)3N is formed by ammonolysis of Ph2SbCl in liquid ammonia. The Sb3N core is almost planar.1 u In addition, crystals of the analogous methyl derivatives (Me2M)3N (M = As, Sb) contain molecules with planar M3N cores.181,182... 

Figure 6-17 Methyl derivatives of ammonia. Methylamine Dimethylamine...

Fischer and Bergmann 75 adapted the method of Hinsberg 76 for the N-methylation of benzenesulfonamides in the synthesis of Sar, 5-aminopentanoic acid, and racemic Orn. Two years later Fischer and Lipschitz 73 succeeded in the synthesis of optically active, N-methylated derivatives of Ala, Leu, Phe, and Tyr. TV-Tosyl amino acids were N-methylated with two equivalents of iodomethane at 65-68 °C in a sealed pressure tube. The tosyl group was then deprotected either with sodium in liquid ammonia or with hot hydrochloric acid, but partially racemic products were obtained that were purified by crystallization with optically active bases. 77 Cheung and Benoiton did not observe racemization during deprotection with sodium in liquid ammonia. 78 ... 

In 1958, Ikekawa10 synthesized 2,7-naphthyridine and various substituted derivatives. His approach involved the reaction of 4-methylnicotinic acid with formaldehyde to afford the lactone 99 (R = H). The reaction of 99 with ammonia in methanol yields the amide (100) which, on oxidation with chromium trioxide, afforded 2,7-naphthyridin-l-one (101). This substance was converted into 2,7-naphthyridine (102, R = H) by consecutive treatment with phosphorus oxychloride, hydrazine, and copper sulfate. The 3-methyl derivative was similarly prepared starting with acetaldehyde. 

Studies have been made of the covalent amination of 3-nitro-l,X-naph-thyridines (X = 5,6, and 8).27 35 In contrast to the parent systems and their halogen and methyl derivatives, 3-nitronaphthyridines undergo covalent amination with weak nucleophilic liquid ammonia at — 45 C. The electrophilic character of the naphthyridine system is enhanced by the presence of the nitro group. 3-Nitro-l,8-naphthyridine (41a) undergoes addition at... 

Meszaros, Hermecz et al. transformed the quaternary 6,7.8,9-tetrahydro-pyrido[1.2-u]pyrimidinium salts (204) with acid to the carboxylic acids (205 R1 = H)257 and with sodium hydrogen carbonate solution to the l,6,7,8-tetrahydropyrido[l,2- ]pyrimidines (205 R = alkyl).7x2 8 From the alkaline hydrolysis reaction mixture, compounds 206 and 207 were also isolated.133 The quaternary salt (204 R = Me) was transformed with hydrazine hydrate to 6-methylpiperidone and with ammonia to 6-methyl-4-oxo-6.7,8,9-tetrahydro-4//-pyrido[1.2- ]pyrimidine-3-carboxamide and its A-methyl derivative.133... 

The Strecker reactant, i.e., the a-dicarbonyl, picks up ammonia during the Strecker reaction and can then form heterocyclic volatiles, particularly pyrazines. The most powerful odorants among these are the 2-ethyl-3,5-dimethyl- (0.04) and the 2,3-diethyl-5-methyl-derivatives (0.09). It is worth noting that most other alkylpyrazines have much higher thresholds and thus make relatively little contribution to the aroma of heated foods. 

The stability of 3,5-diphenyl-l,2,4-oxadiazole (Section 4.21.5.4.2) contrasts with that of the 3-methyl derivative (113) which hydrolyzes in acid to acetamidoxime. In basic solution, acetonitrile and ammonia are formed. The ring is stable to mild reducing agents (Section 4.21.6.6). 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

---