Methyl amine reactions

The Leuckart reaction uses formic acid as reducing agent. Reductive alkylation using formaldehyde, hydrogen, and catalyst, usually nickel, is used commercially to prepare methylated amines. These tertiary amines are used to prepare quaternary ammonium salts. 

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)...

Fractionally distd under vacuum, then fractionally crystd twice from its melt. Impurities include acetic acid, methyl amine and H2O. For detailed purification procedure, see Knecht and Kolthoff, Inorg Chem 1 195 1962. Although /9-methylacetamide is commercially available it is often extensively contaminated with acetic acid, methylamine, water and an unidentified impurity. The recommended procedure is to synthesise it in the laboratory by direct reaction. The gaseous amine is passed into hot glacial acetic acid, to give a partially aq soln of methylammonium acetate which is heated to ca 130° to expel water. Chemical methods of purificatn such as extractn by pet ether, treatment with H2SO4, K2CO3 or CaO can be used but are more laborious. 

In addition to the Ross-Schiessler process, utilising p-CH20 and AN, the synthesis of RDX/ HMX mixts has also been reported starting with other smail molecules (Ref 7), namely, methyl-amine nitrate methylene diamine dinitrate and nitramine (NH2N02) in combination with CH20. In these reactions, the intermediate formation of Hexamine or a cyclic analog, is not necessarily established... 

One should also note the hydrolysis of Rh(PPh3)2(CNCR3)Cl, which gives Rh(PPhj)2(CO)Cl (11). This reaction is suggested to occur by addition of RjO to the coordinated isocyanide followed by elimination of methyl-amine [Eq. (24)]. 

Evidently this is a hydrogenation and the source of the hydrogen is benzylamine as indicated by the production of benzaldehyde and ammonia in equivalent amounts presumably the benzylamine is dehydrogenated to the imine C,HjCH =NH, which is then hydrolysed. In the absence of hexamine, the maximum yield of benzaldehyde is 50 per cent. When hexamine is added to the reaction mixture, the yield of aldehyde is increased and that of methylbenzylamine is decreased, and methyl-amine is present at the end of the reaction. Hexamine reacts as the methylene derivative of ammonia, CH2=NH, which is hydrogenated to methylamine. The fundamental stage of the Sommelet reaction may be written as ... 

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

A liquid-phase double-replacement reaction between bromine cyanide (A) and methyl-amine takes place in a PFR at 10°C and 101 kPa. The reaction is first-order with respect to each reactant, with kA = 2.22 L mol 1 s 1. If the residence or space time is 4 s, and the inlet concentration of each reactant is 0.10 mol L-1, determine the concentration of bromine cyanide at the outlet of the reactor. 

The amination of styrene, however, led to two products (1-phenyl-1-ethylamine and 2-phenyl-l-ethylamine) in a 1 3 ratio [113], indicating that the hydrozirconation was not completely regioselective [114,115]. Since it is well known that hydrozirconation of trisubsti-tuted alkenes places zirconium at the least hindered carbon of the chain by a process involving zirconium migration, this class of alkenes was not investigated [5,116], On the other hand, hydrozirconation/amination of 3-methyl-l,2-butadiene gave an allylic amine. Reaction of the latter could either occur at the terminal carbon or proceed with... 

Initial theoretical studies focused on steps (1) and (2). Several model systems were examined with ab initio calculations.1191 For the reaction of methyl amine with methyl acetate, it was shown that the addition/elimi-nation (through a neutral tetrahedral intermediate) and the direct displacement (through a transition state similar to that shown in Figure 5a) mechanisms for aminolysis had comparable activation barriers. However, in the case of methyl amine addition to phenyl acetate, it was shown that the direct displacement pathway is favored by approximately 5 kcal/mol.1201 Noncovalent stabilization of the direct displacement transition state was therefore the focus of the subsequent catalyst design process. 

Under the same conditions (batch or GL-PTC) discussed for CHg-acidic compounds, primary aromatic amines also react with DMC. In this case, although the reaction yields selectively the mono-A-methylated amines with no dimethylated by-products, sizable amounts of methyl carbamates (ArNHCOgMe) are formed. ° Much better results can be gathered in the presence of zeolites, particularly alkali metal exchanged Y and X faujasites. These aluminosilicates posses pseudospheri-cal cavities (supercavities) of 11-8 A in diameter, which can be accessed through channels whose size is 7.4 kP ... 

Then, contrary to our previous hypothesis, the reaction proceeds via a Bai2 displacement of aniline on DMC. The product, mono-A -methyl aniline (PhNHMe), plausibly adsorbs into the zeohte in a different way with respect to anihne, because different H-bonds (N H — O-zeolite) take place with the solid. As recently reported by Su et al., A-methyl amines also may interact with NaY by H-bonding between the protons of the methyl group and the oxygen atoms of the zeolite this probably forces the molecule a bit far from the catalytic surface in a fashion less apt to meet DMC and react with it. This behavior can account for the mono-A-methyl selectivity observed, which is specific to the use of DMC in the presence of alkali metal exchanged faujasites in fact, the bis-A-methylation of primary aromatic amines occurs easily with conventional methylating agents (i.e., dimethyl sulfate). ... 

Photoinduced electron transfer promoted cyclization reactions of a-silyl-methyl amines have been described by two groups. The group of Pandey cyclized amines of type 135 obtaining pyrrolidines and piperidines 139 in high yields [148]. The cyclization of the a-silylated amine 140 leads to a 1 1 mixture of the isomers 141 and 142 [149]. The absence of diastereoselectivity in comparison to analogous 3-substituted-5-hexenyl radical carbocyclization stereochemistry [9] supports the notion that a reaction pathway via a free radical is unlikely in this photocyclization. The proposed mechanism involves delocalized a-silylmethyl amine radical cations as reactive intermediates. For stereochemical purposes, Pandey has investigated the cyclization reaction of 143, yielding... 

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

The reaction of methyl-amine with propanal to form an... 

Synthesizing amines with nucleophilic substitution reactions is normally an Sp 2 process. This means that methyl amines react more readily than primary cimines, and secondary and tertiary amines show very little reactivity. 

A series of solid-state reactions has been explored by Kaupp et al., in which gaseous amines were reacted with aldehydes to give imines. Analogous reactions with solid anhydrides, imides, lactones or carbonates, and isothiocyanates were used to give, respectively, diamides or amidic carboxylic salts or imides, diamides, carbamic acids, and thioureas [24]. In general the yields were found to be quantitative. Ammonia and other gaseous amines, in particular methyl-amine, have also been shown to aminolyse thermoplastic polycarbonates [25]. 

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