Methylamine salt formation

Iminium ions bearing an electron-withdrawing group bonded to the sp carbon of the iminium function are very reactive dienophiles. Thus, iminium ions 26 generated from phenylglyoxal (Scheme 6.15, R = Ph) or pyruvic aldehyde (R = Me) with methylamine hydrochloride, react with cyclopenta-diene in water at room temperature with good diastereoselectivity [25] (Scheme 6.15). If glyoxylic acid is used, the formation of iminium salt requires the free amine rather than the amine hydrochloride. 

Marchand and co-workers reported a synthetic route to TNAZ (18) involving a novel electrophilic addition of NO+ NO2 across the highly strained C(3)-N bond of 3-(bromomethyl)-l-azabicyclo[1.1.0]butane (21), the latter prepared as a nonisolatable intermediate from the reaction of the bromide salt of tris(bromomethyl)methylamine (20) with aqueous sodium hydroxide under reduced pressure. The product of this reaction, A-nitroso-3-bromomethyl-3-nitroazetidine (22), is formed in 10% yield but is also accompanied by A-nitroso-3-bromomethyl-3-hydroxyazetidine as a by-product. Isolation of (22) from this mixture, followed by treatment with a solution of nitric acid in trifluoroacetic anhydride, leads to nitrolysis of the ferf-butyl group and yields (23). Treatment of (23) with sodium bicarbonate and sodium iodide in DMSO leads to hydrolysis of the bromomethyl group and the formation of (24). The synthesis of TNAZ (18) is completed by deformylation of (24), followed by oxidative nitration, both processes achieved in one pot with an alkaline solution of sodium nitrite, potassium ferricyanide and sodium persulfate. This route to TNAZ gives a low overall yield and is not suitable for large scale manufacture. 

Iron(ii) complexes of ethylenedithiodiacetic acid, diethylenetrithioacetic acid, and ethylenetetrathiotetra-acetic acid have all been reported. " " Isonitrile and other complexes. Refluxing [Fe(CNMe) ](HSOj2 "hh excess methylamine for 12 h in methanol gives the cation [Fe(CNMe)gNH2Me] which can be precipitated as its PF salt. " The structure of this cation has been determined by X-ray methods and is shown in (52). The location of the protons was confirmed by n.m.r. and the suggested mechanism of formation is as shown. 

According to the first scheme, demethylation takes place by the reaction of amitriptyline (7.1.4) with methyliodide, which leads to the formation of a quaternary ammonium salt (7.1.16), the reaction of which with methylamine at a relatively high temperature gives the desired nortriptyline (7.1.17) [25]. 

The analysis of polymeric and gaseous products of the reaction of PMMA and di-methylamine at low dimethylamine levels shows that there was a clean reaction that produced 1 eq of anhydride (NOT Amide) per 1 eq of dimethylamine and per 1 eq of MMA. Note that this is in most close agreement with pathway 2a- 3a (Figure 2) in which most of the MMA carbonyls have been converted to COOH or alkylammonium COO salts followed by closure to anhydride. This shows that direct acyl addition (2c— 3c) to form amide, or reaction of carboxylate with adjacent ester (2b- 3b) to form anhydride (which liberates MeOH after proton transfer, and requires only 0.5 eq. dimethylamine per MMA group) are not the predominant pathways under these conditions. The Flory limit effect is consistent with random initial MAA formation, which after cyclization to anhydride (Figure 2) eventually leads to some groups trapped between rings which remain in the uncyclized acid form. 

The position of the equilibrium between imine and carbonyl may be perturbed by interaction with a metal ion. We saw in Chapter 2 how back-donation of electrons from suitable orbitals of a metal ion may stabilise an imine by occupancy of the jc level. It is possible to form very simple imines which cannot usually be obtained as the free ligands by conducting the condensation of amine and carbonyl compounds in the presence of a metal ion. Reactions which result in the formation of imines are considered in this chapter even in cases where there is no evidence for prior co-ordination of the amine nucleophile to a metal centre. Although low yields of the free ligand may be obtained from the metal-free reaction, the ease of isolation of the metal complex, combined with the higher yields, make the metal-directed procedure the method of choice in many cases. An example is presented in Fig. 5-47. In the absence of a metal ion, only low yields of the diimine are obtained from the reaction of diacetyl with methylamine. When the reaction is conducted in the presence of iron(n) salts, the iron(n) complex of the diimine (5.23) is obtained in good yield. 

This reaction allows the preparation of tertiary methylamines from secondary amines via treatment with formaldehyde in the presence of formic acid. The formate anion acts as hydride donor to reduce the imine or iminium salt, so that the overall process is a reductive amination. The formation of quaternary amines is not possible. 

In a later development by Bedenbaugh et methylamine was used as solvent and lithium as electron donor. No proton donor was required, suggesting that the lithium salt (28) of hemiaminal (27) is stable under the reaction conditions (both aldehydes and aldimines are reduced by the reagent cf. the analogous reduction of carboxylic acids, Section 1.12.2 and Scheme 2). Yields of aldehydes produced by this method are shown in Table 8. It is notable that only tertiary amides are reduced satisfactorily. A major limitation of the reaction is the substantial formation of side products resulting from transamid-ation by the methylamine solvent (/. e. RCONHMe from RCONR 2). 

The Birch and Benkeser reactions of some unsaturated organic compounds [318 and references therein], which consist of a reduction by sodium or lithium in amines, can be mimicked electrochemically in the presence of an alkali salt electrolyte. The cathodic reaction is not the deposition of alkali metal on the solid electrode but the formation of solvated electrons. Most of the reactions described were performed in ethylenediamine [319] or methylamine [308,320]. A feature of these studies is variety introduced by the use of a divided or undivided cell. In a divided cell, the product distribution appears to be the same as that in the classic reduction by metal under similar conditions. In contrast, in an undivided cell the corresponding ammonium salt is formed at the anode it plays the role of an in situ generated proton donor. Under such conditions, the proton concentration... 

While it is cooling down, the underground chemist gets ready for the next step in the process. He is going to recover the unused methylamine for use in the next batch. This cuts his consumption of methylamine to about half of what it would be without this technique. What he is going to do is react the unused N-methylformamide with a strong solution of sodium hydroxide. The N-methylformamide is hydrolyzed to form methylamine gas and the sodium salt of formic acid (sodium formate). In chemical writing, this reaction is as follows ... 

Benzopyrylium Salts. - Dichloromethoxybutane has been used in the cycliz-ation of the benzyl phenyl ketone (134) to give (after addition of perchloric acid) the pyrylium salt (135). The latter reacted normally with methylamine to form the isoquinolinium salt (136). A complex series of transformations has been suggested to account for the formation of the pyrylium salt (138) by the reaction of the chromone (137) with malononitrile-acetic anhydride. ... 

The tertiary nature of the nitrogen in this strong base is demonstrated by its quantitative reaction with one mole of alkyl halide (methyl iodide (21), ethyl iodide (14) ) with the formation of quaternary salts. Secondly, the isolation of methylamine as one of the products of fusion of tropine with alkali (sodium hydroxide (22), barium hydroxide (14) ) suggests the... 

The reactions of methylamine confirm in a striking manner the structure which has been assigned to it. It resembles ammonia markedly in chemical properties. The gas fumes when brought into contact with hydrochloric acid as the result of the formation of a salt—methylammonium chloride —... 

When methyl iodide and ammonia are heated together, the reaction does not stop with the formation of the salt of the secondary amine. The amine is liberated, and by the addition of another molecule of the iodide is converted into the salt of tri-methylamine, (CH3)3NHI. Still another step in the reaction takes place. The tertiary amine is set free and a quarternary ammonium salt is formed as the result of the addition of methyl iodide —... 

---