Methylation amine primary

These compounds are exactly analogous to mono-methyl amine, primary di-methyl amine, secondary, and tri-methyl amine, tertiary and the reactions distinguishing the three groups of aromatic compounds are analogous to those given for the aliphatic amines (p. 59). The resulting products, however, are in some cases distinctly different, showing a difference between the paraffin and benzene compounds. 

Methylation of Primary and Secondary Fatty Amines. This is done by the Leuckait reaction (1,30) or reductive methylation (1,29,31,32). 

Alkyl dimethyl and dialkylmethyl tertiary amines are commercially available. These amines are prepared by reductive methylation of primary and secondary amines using formaldehyde and nickel catalysts (1,3,47,48). The asymmetrical tertiary amines are used as reactive intermediates for preparing many commercial products. 

The liquid anion exchangers at present available are based largely on primary, secondary and tertiary aliphatic amines, e.g. the exchangers Amberlite LA.l [A/-dodecenyl(trialkylmethyl)amine] and Amberlite LA.2 [A/-lauryl(trialkyl-methyl)amine], both secondary amines. These anion exchange liquids are best employed as solutions (ca 2.5 to 12.5% v/v) in an inert organic solvent such as benzene, toluene, kerosene, petroleum ether, cyclohexane, octane, etc. 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

Organic derivatives of ammonia are called amines. Because nitrogen is trivalent, amines can be primary (attached to one carbon), secondary (attached to two carbons), or tertiary. All amines are basic, and their strength as bases increases with the number of alkyl groups attached to the nitrogen that is, methyl amine is a stronger base than ammonia and trimethylamine is stronger than dimethylamine. Amines can be prepared from ammonia and an alkyl halide ... 

Neural cells convert tyrosine to epinephrine and norepinephrine (Figure 31—5). While dopa is also an intermediate in the formation of melanin, different enzymes hydroxylate tyrosine in melanocytes. Dopa decarboxylase, a pyridoxai phosphate-dependent enzyme, forms dopamine. Subsequent hydroxylation by dopamine P-oxidase then forms norepinephrine. In the adrenal medulla, phenylethanolamine-A -methyltransferase uti-hzes S-adenosyhnethionine to methylate the primary amine of norepinephrine, forming epinephrine (Figure 31-5). Tyrosine is also a precursor of triiodothyronine and thyroxine (Chapter 42). 

The Af-methylation of primary aromatic amines by means of 1 -(hydroxymethyl)- 1H-indazole has been described (equation 46)135. 

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). ... 

More recendy, the use of MEC was also reported by us in the methylation of primary aromatic amines (P-XC6H4NH2, X = H, Cl, NO2) and of ambident anilines such as those listed in Scheme In the presence of a NaY faujasite... 

Reductive methylation of primary or secondary amines using formaldehyde and formic acid. Cf. Leuckart-Wallach reaction. 

Reductive methylation is achieved by the reaction of formaldehyde with ammonium chloride. It is carried out by heating the components at 100-120° and gives mono-, di- and trimethylamine in high yields (Eschweiler reaction) [312, 962]. No catalyst is needed part of the formaldehyde provides the necessary hydrogen while the other part is oxidized to formic acid. The same reaction can be applied to methylation of primary and secondary amines [962]. Reductive alkylation can also be accomplished by reducing mixtures of amines with acids which are first reduced to aldehydes (p. 171). 

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. 

As it may be a useful comparison, it is asked what is the enthalpy change for the formal, simple insertion of an oxygen atom in the NH bond of an amine (W-hydroxylation) For ammonia, the change to hydroxylamine is only +4 kJ moH . The exothermicity of the comparable change for the primary methyl amine is —27.2 kJmoH (g) and for the secondary diethyl amine it is —49.3 kJmoH . 

The formation of anionic -adducts resulting from the primary attachment of neutral nucleophiles followed by proton elimination has been described only occasionally. A definite example is the reaction of methyl-amine with 2-nitrophenazine 10-oxide in DMF, leading to adduct 118.161 This structure is well supported by spectral evidence. It is characterized by two... 

Table 1 shows that methyl dodecanoate is easily converted into amine in the presence of CuCr deposited on alumina or on titania. Nevertheless one can observe that the methylation reaction is rather difficult and favoured by alumina. Moreover, a significant increase of N-dimethyl dodecylamine is obtained when the reaction is carried out with a large excess of hydrogen. Due to the mechanism of the reaction this is unexpected indeed it is generally considered that the methylation of primary amine with methanol requires i) the dehydrogenation of alcohol into a carbonyl compound and ii) a further reaction of this compound with primary amine or secondary amine via imine or enamine intermediates. 

Instead of alkyl halides other electrophiles, such as imines or iminium ions, are also used for the nucleophilic attack of enolates. Primary amines react with aldehydes and ketones to produce imines °. For example, the reaction of acetophenone with methyl amine gives... 

The method is employed extensively for the methylation of primary and secondary to the corresponding tertiary amines by the action of formaldehyde and formic acid. 

Methylation of amines. The classical method for methylation of primary or secondary amines is the Eschweiler -Clarke reaction. The reaction involves treatment of an amine with formaldehyde and formic acid ... 

Introduction, Amines are organic derivatives of ammonia, with one, two, or three hydrogen atoms replaced by an organic radical. The three types of amines, primary (RNHj), secondary (RjNH), and tertiary (R3N), may be prepared by the reaction of mono-halides with ammonia. In the case of reactive halides, like methyl iodide, the reaction proceeds to the formation of the quaternary salt— tetramethylammonium iodide ... 

The reaction of benzothiazolium iodide (105) with 2 mol of a primary alii tic amine or 1 mol each of an aromatic amine and triethylamine gave benzothiazolimine (106). Methylation of (106) and subsequent treatment of the resulting amidinium salts (107) with butylamine afforded the corresponding fV-methyl-amine (Scheme 47). ... 

The most extensively studied primary amine by far is methyl-amine (47,224-230), and only little information is available on other primary amines ethylamlne (230), n-butylamlne (224) and n-amylamine (224). Products and their quantum yields from methylamlne as reported by Michael and Noyes (226) are given in Table 20. 

The mechanism of all of the above mentioned reactions is essentially the same. However, some steps in the mechanism are still not fully understood. The following steps are believed to be involved in the Eschweiler-Clarke methylation 1) formation of a Schiff-base (imine) from the starting primary or secondary amine and formaldehyde via an aminoalcohol (aminal) intermediate 2) hydride transfer from the reducing agent (e.g., formic acid, cyanoborohydride, etc.) to the imine to get the corresponding A/-methylated amine along with the loss of CO2 and 3) if the starting amine was primary, then steps 1 and 2 are repeated. 

Eschweiler-Clarke methylation One-pot reductive methylation of primary and secondary amines to the corresponding tertiary amines using formaldehyde and a reducing agent. 160... 

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