Methyl methylamines

Ethyl 1 -substituted 7-hydroxy-5-oxo-1,2,3,5-tetrahydropyrido[ 1,2,3-<7e] quinoxaline-6-carboxylates were reacted with A- [3,5-bis(trifluoromethyl)-phenyl]methyl methylamine to yield carboxamides (01MIP12). 

The first synthesis of a 3//-3-benzazepine, e.g. 65 (R1 = R2 = Me), was achieved by the condensation of phthalaldehyde with a bis[(alkoxycarbonyl)methyl]methylamine.24"25 With sodium methoxide as the base, A%V-bis[(methoxycarbonyl)methyl]pheiiylaniine condenses with the dialdehyde in a similar manner to give dimethyl 3-phenyl-3//-3-benzazepine-2,4-dicar-boxy late (65, Rl — Ph R2 — Me).99 However, replacement of methoxide by potassium tert-butoxide results in formation of 3-phenyl-3//-3-benzazepine-2,4-dicarboxylic acid (65, R1 = Ph R2 = H).25... 

Di (methyInitraminomethyl)-methylnitramino-methyl)-methylamine 2 B149—B150... 

Sample preparation 2 mL Plasma -I- 100 jiL 1 i,g/mL dicyclomine in water -I- 1 mL MeCN, vortex, allow to stand for 10 min, add 200 xL 1 M pH 9.4 trisQiydrojgr-methyl)methylamine (TRIS), add 5 mL hexane, shake horizontally for 10 min, centrifuge at 2000 g for 5 min. Remove the aqueous layer emd add it to 3 mL hexane, shake horizontally for 10 min, centrifuge at 2000 g for 5 min. Combine the hexane layers and add them to 1 mL 100 mM HCl, shake for 10 min, centrifuge. Remove the aqueous layer and evaporate it to dryness under vacuum, reconstitute in 250 pL mobile phase, inject a 100 (jlL aliquot. 

The solutions of all the methylamines in water are alkaline, but the alkalinity decreases with the number of methyl groups. 

Determine the methylamine content of the commercial solution by titration with standard acid using methyl orange as indicator. Adjust the quantity of methyl-amine solution in accordance with the methylamine content for some commercial samples, the figure may be 33-40 per cent. 

For example, the action of a-thiocyanatoacetone on ammonia in ether solution gives 4-methyl-2-aminothiazole but in very low yield (137). Methylamine in ether at 0°C gives in a first step S-acetonyl N-methylisothiourea (196) in 80% yield (Scheme 102) (137). The cycliza-tion of this intermediate occurs either after a prolonged rest at room temperature, either by fusion or by heating with dilute hydrochloric acid to afford the 4-methyl-2-methylaminothiazole (197). 

Methamphetannne is a notorious street drug One synthesis involves reductive amination of benzyl methyl ketone with methylamine What is the structure of methamphetamine ... 

A convenient method for the synthesis of these low boiling materials consists of the reaction of /V,/V-dimethy1iirea [96-31-1] with toluene diisocyanate to yield an aUphatic—aromatic urea (84). Alternatively, an appropriate aUphatic—aromatic urea can be prepared by the reaction of diphenylcarbamoyl chloride [83-01-2] with methylamine. Thermolysis of either of the mixed ureas produces methyl isocyanate ia high yield (3,85). 

Isoprene [78-79-5] (2-methyl-1,3-butadiene) is a colorless, volatile Hquid that is soluble in most hydrocarbons but is practically insoluble in water. Isoprene forms binary azeotropes with water, methanol, methylamine, acetonitrile, methyl formate, bromoethane, ethyl alcohol, methyl sulfide, acetone, propylene oxide, ethyl formate, isopropyl nitrate, methyla1 (dimethoxymethane), ethyl ether, and / -pentane. Ternary azeotropes form with water—acetone, water—acetonitrile, and methyl formate—ethyl bromide (8). Typical properties of isoprene are Hsted in Table 1. 

Methylamines are produced from the vapor reaction of methanol with ammonia over a siUca—alumiaa catalyst. Methyl esters result from the reaction of methanol with the corresponding organic or inorganic acid as shown, eg, for methyl methacrylate. 

Naphthol is mainly used in the manufacture of the insecticide carbaryl (59), l-naphthyl A/-methyicarbamate/ iJ-2j5 - (Sevin) (22), which is produced by the reaction of 1-naphthol with methyl isocyanate. Methyl isocyanate is usually prepared by treating methylamine with phosgene. Methyl isocyanate is a very toxic Hquid, boiling at 38°C, and should not be stored for long periods of time (Bhopal accident, India). India has developed a process for the preparation of aryl esters of A/-alkyl carbamic acids. Thus l-naphthyl methylcarbamate is prepared by refluxing 1-naphthol with ethyl methylcarbamate and POCl in toluene (60). In 1992, carbaryl production totaled > 11.4 x 10 t(35). Rhc ne-Poulenc, at its Institute, W. Va., facihty is the only carbaryl producer in United States. 

Fig. 3. Synthesis of fluoxetine (31). 3-ChIoro-I-phenyl-I-propanol reacts with sodium iodide to afford the corresponding iodo derivative, followed by reaction with methylamine, to form 3-(methyl amin o)-1-phenyl-1-propan 0I. To the alkoxide of this product, generated using sodium hydride, 4-fluorobenzotrifluoride is added to yield after work-up the free base of the racemic fluoxetine (31), thence transformed to the hydrochloride (51)...

Methyl-2-Pyrrolidinone. N-Meth5l-2-pyrrohdinone [872-50-4] (44) (NMP or methyl-2-pyrrohdone, M-Pyrol) was fkst reported in 1907 as prepared by alkylation of 2-pyrrohdinone with methyl iodide (81). The present commercial route, ie, condensation of butyrolactone with methylamine, was first described in 1936 (50). 

Methyl chloride reacts with ammonia alcohoHc solution or ia the vapor phase by the Hofmann reaction to form a mixture of the hydrochlorides of methylamine, dimethylamine, trimethyl amine, and tetramethyl ammonium chloride. With tertiary amines, methyl chloride forms quaternary derivatives. 

Methylene chloride is easily reduced to methyl chloride and methane by alkaU metal ammonium compounds in Hquid ammonia. When the vapor is contacted with reduced nickel at 200°C in the presence of excess hydrogen, hydrogen chloride and elementary carbon are produced. Heating with alcohoHc ammonia at 100—125°C results in hexamethylenetetramine, (CH2) N4, a heterocycHc compound with aqueous ammonia at 200°C, hydrogen chloride, formic acid, and methylamine are produced. 

Other Polyimides. In 1979, Rohm Haas introduced Kamax resin, which was thought to be an /V-methylamine imidization product of poly(methyl methacrylate) (118). The product was then withdrawn, but was reintroduced in the late 1980s. The partly imidized resins are similar to poly(methyl methacrylate) but have a higher glass-transition temperature. 

The alkylthio group is replaceable by nucleophiles. The positions 7 and 4 react under mild conditions in that order the 2-alkylthio functions require more drastic treatment. Conversion of l-methyl-4-methylthiopteridin-2-one (157) into the 4-methylamino derivative (158) can be achieved by stirring with methylamine at room temperature (equation 48). The reactivity of an alkylthio group can often be further enhanced by oxidation to the corresponding sulfoxide and sulfone. Thus, reaction of l,3-dimethyl-7-methylthiolumazine (160) with m-chloroperbenzoic acid yields 7-methylsulfinyl- (161) and 7-methylsulfonyl-l,3-dimethyllumazine (162 equation 49) (82UP21601). 4-Amino-2-methylthio-7-... 

Migration to the developing electron sextet at nitrogen is not restricted to hydrogen. In (79) there is methyl migration with formation of methylamine and acetone in the acid-catalyzed decomposition of (80), phenyl migration leads to aniline and acetaldehyde. 

Acid hydrolysis of (161) yields acetone and methylamine by N—N cleavage and methyl migration. 

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