Amines aromatic, alkylation

All lation of Aromatic Amines and Pyridines. Commercially important aromatic amines are aniline [62-53-3] toluidine [26915-12-8], phenylenediamines [25265-76-3], and toluenediamines [25376-45-8] (see Amines, aromatic). The ortho alkylation of these aromatic amines with olefins, alcohols, and dienes to produce more valuable derivatives can be achieved with soHd acid catalysts. For instance, 5-/ f2 butyl-2,4-toluenediamine (C H gN2), which is used for performance polymer appHcations, is produced at 85% selectivity and 84% 2,4-toluenediamine [95-80-7] (2,4-4L)A)... 

The nitrogen of aHphatic and aromatic amines is alkylated rapidly by alkyl sulfates yielding the usual mixtures. Most tertiary amines and nitrogen heterocycles are converted to quaternary ammonium salts, unless the nitrogen is of very low basicity, eg, ia tn phenylamine. The position of dimethyl sulfate-produced methylation of several heterocycles with more than one heteroatom has been examined (22). Acyl cyanamides can be methylated (23). Metal cyanates are converted to methyl isocyanate or ethyl isocyanate ia high yields by heating the mixtures (24,25). 

Low concentiations of alkylated paiaphenylenediamines such as -di-ti t-butyl-j )-phenylenediamine [69796 7-OJ are added to gasoline to inhibit oxidation (see Amines, AROMATic-PHENYLENEDiAMiNEs). 

The N,]S -dialkyl-/)-PDAs are manufactured by reductively alkylating -PDA with ketones. Alternatively, these compounds can be prepared from the ketone and -lutroaruline with catalytic hydrogenation. The /V-alkyl-/V-aryl- -PDAs are made by reductively alkylating -nitro-, -nitroso-, or /)-aminodipheny1 amine with ketones. The AijAT-dialkyl- PDAs are made by condensing various anilines with hydroquinone in the presence of an acid catalyst (see Amines-aromatic,phenylenediamines). 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

Aromatic rings containing more than one hetero atom also yield active antihistamines. Alkylation of 2-aminopyrimidine (6S) with p-methoxybenzyl chloride gives the corresponding secondary amine (66). Alkylation with the usual chloroamine affords thonzylamine (67), Application of the same sequence to 2-aminothiazole (68) affords zolamine (70). ... 

Amoxicillin 6-[D-)-a-Amino-p- hydroxyphenylacetamido] penicillanic acidc Aromatic alkylation, amination, imine formation, amidation (sidechain), fermentation, and deamidation (penicillin nucleus)... 

Aromatic amines - [ALKYLATION] (Vol 2) - [AMINES - AMINES, AROMATIC - ANILINE AND ITS DERIVATIVES] (Vol 2)... 

In contrast to aliphatic amines, aromatic amines hardly react with C02 [21a] because of their poorer basicity. However, in the presence of suitable auxiliary bases (B) (such as amidines or penta-alkylguanidine superbases), carbamate salts (BH)02CNRAr (R = H, alkyl) can be generated in solution, as supported by spectroscopic and reactivity data [29]. It has been shown that even tributylamine may be effective if a suitable alkali metal salt is also present in solution in the latter case, the N-arylcarbamate has been isolated as an alkali salt (Equation 6.3)... 

Amines can be prepared by SN2 alkylation of ammonia or 1° and 2° amines. Aromatic amines are made by reduction of the corresponding nitro compounds. Amides, nitriles, and imines can also be reduced to amines. 

Tertiary amines can serve as amine substrates for the boron-Mannich reaction, providing aromatic alkylation products of N,N-dialkyl-3-alkoxyanilines (Equation (125))573 and 1,3,5-alkoxy- or hydroxybenzenes (Equation (126)).574 The use of chiral diol esters of ( )-2-phenylethenylboronic acid for enantioselective alkylation resulted in 6-15% ee.575... 

We are going to do a little more than simply give the reactions that eventually made up the synthesis of dofetilide. We are going to put ourselves in the place of the chemists who invented the synthesis and try to see what led them to the reactions they chose. First, we should inspect the structure of the molecule. There are two sulfonamides, one at each end. We have seen how to make sulfonamides earlier in this chapter when saccharin was being discussed. The usual way is to react the amine with a sulfonyl chloride. In this case we shall need to react methane sulfonyl chloride (MeS02Cl or MsCl) with the aromatic amines. This is a well-known reaction and should work well here. The other functional groups—tertiary amine and alkyl aryl ether—should not interfere so no protection is needed. 

Uses. Tetramethylene sulfone has high solvent power for aromatics and has been used extensively by Olah and co-workers for Friedel-Crafts type nitrations and for studies of the mechanism of nitronium tetrafluoroborate nitration of alkyl-benzenes and halobenzenes in homogeneous solution. It is a superior solvent for quaternization of tertiary amines with alkyl halides, since it has a high dielectric constant and does not enter into side reactions observed with nitrobenzene and dimethylformamide. For example in the synthesis of the acridizinium salt (3), Bradsher and Parham effected quaternization of (1) with benzyl bromide in tetramethylene sulfone at room temperature in excellent yield. Several other salts analagous to (2) were obtained in good yield and in crystalline form with use of tetramethylene sulfone, whereas with other solvents the products were colored... 

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