Tertiary anilines

The Bischler-Mohlau indole synthesis was applied in the synthesis of fluvastatin sodium (Lescol) to assemble its indole core. As shown below, reaction of a-chloroketone with iV-/-Pr-aniline at elevated temperature generated a tertiary amine. The resulting A-/-Pr-aniline tertiary amine... 

Phosphorus trichloride reacts readily with three equivalents of an alcohol e.g, ethanol, in the presence of a tertiary amine such as pyridine, dimethyl-aniline, or diethylaniline, to form triethyl phosphite and hydrogen chloride, the latter being immediately neutralised by the tertiary amine. 

Secondary and tertiary amines are not generally prepared in the laboratory. On the technical scale methylaniline is prepared by heating a mixture of aniline hydrochloride (55 parts) and methyl alcohol (16 parts) at 120° in an autoclave. For dimethylaniline, aniline and methyl alcohol are mixed in the proportion of 80 78, 8 parts of concentrated sulphuric acid are added and the mixture heated in an autoclave at 230-235° and a pressure of 25-30 atmospheres. Ethyl- and diethyl-anihne are prepared similarly. One method of isolating pure methyl- or ethyl-aniline from the commercial product consists in converting it into the Y-nitroso derivative with nitrous acid, followed by reduction of the nitroso compound with tin and hydrochloric acid ... 

The quinaldine is separated from any unreacted aniline and from the alkyl-anilines by treatment with acetic anhydride, basified with sodium carbonate and steam distilled. Only the primary and secondary amines are acetylated the acetylated amines are now much less volatile so that separation from the steam-volatile quinaldine (a tertiary amine) is facile. 

Fluoroaromatics are produced on an industrial scale by diazotization of substituted anilines with sodium nitrite or other nitrosating agents in anhydrous hydrogen fluoride, followed by in situ decomposition (fluorodediazoniation) of the aryldiazonium fluoride (21). The decomposition temperature depends on the stabiHty of the diazonium fluoride (22,23). A significant development was the addition of pyridine (24), tertiary amines (25), and ammonium fluoride (or bifluoride) (26,27) to permit higher decomposition temperatures (>50° C) under atmospheric pressure with minimum hydrogen fluoride loss. 

The benzylation of a wide variety of aHphatic, aromatic, and heterocycHc amines has been reported. Benzyl chloride is converted into mono-, di-, and tribenzyl amines by reaction with ammonia. Benzylaniline [103-32-2] results from the reaction of benzyl chloride with aniline. Reaction with tertiary amines yields quaternary ammonium salts with trialkylpbospbines, quaternary phosphonium salts and with sulfides, sulfonium salts are formed. 

This compound is also described as diethanol-p-toluidine in the older literature. Anilines bearing hydroxyl groups are preferred because they are less volatile than anilines without polar substituents. Tertiary aromatic amines with para-halogen substitution have also been reported for use in adhesives [42]. 

Possible impurities of the tertiary amine include primary and secondary amines. The presence of aniline slows the reaction, while the presence of A-methylaniline actually accelerates the polymerization [51]. As the secondary amine may be formed during polymerization (especially in the presence of water) reaction kinetics may be complicated. 

C-alkylation of secondary and tertiary aromatic amines by hexafluoroacetone or methyl trifluoropyruvate is performed under mild conditions [172] (equation 147) The reaction of phenylhydrazme with hexafluoroacetone leads selectively to the product of the C-hydroxyalkylation at the ortho position of the aromatic ring The change from the para orientation characteristic for anilines is apparently a consequence of a cyclic transition state arising from the initial N hydroxy alky lation at the primary amino group [173] (equation 148)... 

HOBt, aniline, DMF. These conditions give the amine as the HOBt salt, which may be acylated without the addition of a tertiary amine. 

Nearly every substitution of the aromatic ring has been tolerated for the cyclization step using thermal conditions, while acid-promoted conditions limited the functionality utilized. Substituents included halogens, esters, nitriles, nitro, thio-ethers, tertiary amines, alkyl, ethers, acetates, ketals, and amides. Primary and secondary amines are not well tolerated and poor yield resulted in the cyclization containing a free phenol. The Gould-Jacobs reaction has been applied to heterocycles attached and fused to the aniline. 

The well-known photopolymerization of acrylic monomers usually involves a charge transfer system with carbonyl compound as an acceptor and aliphatic tertiary amine, triethylamine (TEA), as a donor. Instead of tertiary amine such as TEA or DMT, Li et al. [89] investigated the photopolymerization of AN in the presence of benzophenone (BP) and aniline (A) or N-methylaniline (NMA) and found that the BP-A or BP-NMA system will give a higher rate of polymerization than that of the well-known system BP-TEA. Still, we know that secondary aromatic amine would be deprotonated of the H-atom mostly on the N-atom so we proposed the mechanism as follows ... 

The end group of the polymers, photoinitiated with aromatic amine with or without the presence of carbonyl compound BP, has been detected with absorption spectrophotometry and fluororescence spectrophotometry [90]. The spectra showed the presence of tertiary amino end group in the polymers initiated with secondary amine such as NMA and the presence of secondary amino end group in the polymers initiated with primary amine such as aniline. These results show that the amino radicals, formed through the deprotonation of the aminium radical in the active state of the exciplex from the primary or secondary aromatic amine molecule, are responsible for the initiation of the polymerization. 

Photolysis of aryl azides in amine solution, with a tertiary amine as cosolvent to promote stabilization of the singlet nitrene, has met with some success. For example, the yield of 2-piperidino-3 W-azepme. obtained by the photolysis of phenyl azide in piperidine, is increased from 35 to 58% in the presence of A A /V. /V -tetramethylethylenediamine (TMLDA).180 Also, an improved yield (36 to 60 %) of A,(V-diethyl-3W-azepin-2-amine (38, R = Et) can be obtained by irradiating phenyl azide in triethylamine, rather than in dicthylaminc, solution.181 Photolysis (or thermolysis) of phenyl azide in TMEDA produces, in each case, 38 (R = Et) in 40% yield.181 In contrast, irradiation of phenyl azide in aniline with trimethylamine as cosolvent furnishes jV-phenyl-377-azepin-2-amine (32, R = Ph) in only low yield (2%).35... 

Notes on the preparation of secondary alkylarylamines. The preparation of -propyl-, ijopropyl- and -butyl-anilines can be conveniently carried out by heating the alkyl bromide with an excess (2-5-4mols) of aniline for 6-12 hours. The tendency for the alkyl halide to yield the corresponding tertiary amine is thus repressed and the product consists almost entirely of the secondary amine and the excess of primary amine combined with the hydrogen bromide liberated in the reaction. The separation of the primary and secondary amines is easily accomplished by the addition of an excess of per cent, zinc chloride solution aniline and its homologues form sparingly soluble additive compounds of the type B ZnCl whereas the alkylanilines do not react with sine chloride in the presence of water. The excess of primary amine can be readily recovered by decomposing the zincichloride with sodium hydroxide solution followed by steam distillation or solvent extraction. The yield of secondary amine is about 70 per cent, of the theoretical. 

Reaction of amines with butadiene has been studied (31). Both aromatic and aliphatic amines react with butadiene to give tertiary amines. The following order of the reactivity with butadiene was observed with aniline derivatives. 

Thoma A process for alkylating aniline with methanol or ethanol, to produce mixtures of mono- and di-alkylanilines. Operated in hot, concentrated phosphoric acid in a vertical tubular reactor. The proportions of secondary and tertiary amines can be partly controlled by controlling the ratios of the reactants the products are separated by fractional distillation. Invented in 1954 by M. Thoma in Germany. 

Julolidine (3) and benzoquinuclidine (4) can be considered as aniline derivatives with parallel and perpendicular electron lone-pairs, respectively. Relative to N,N-dimethylaniline (5), the simplest tertiary aromatic amine, the n orbital of julolidine is destabilized by 0.20 eV, while that of benzoquinuclidine is destabilized by 0.80 eV42. In the latter compound there is no n/jt conjugation while in the former it has a maximum value and, accordingly, the splitting of the first and the third IP is much smaller (0.70 eV) than in the former (2.55 eV) compound. 

The solution basicities in water at 25 °C of ortho-, meta- and para-substituted primary, secondary and tertiary anilines have been widely discussed by Smith1. Preliminary gas-phase data were reported by Bohme2. Subsequently, the gas-phase basicities (proton... 

Aniline may complex (as a proton donor) not only with tertiary amines (proton acceptors) such as 7V,7V-dimethylaniline, pyridine or A,A-diethylcyclohexylamine, but also with apparently neutral molecules such as CCI492, benzene93 or chloroform, which acts as proton donor toward amines94. 

The amino group (-NH2) is found in primary amines, which are organic bases that form stable salts with strong acids. They may be aliphatic, aromatic, or mixed. Depending on the nature of the functional groups, they are classified as (1) primary methylamine (primary aliphatic), aniline (primary aromatic), (2) secondary dimethylamine (secondary aliphatic), diphenylamine (secondary aromatic), and (3) tertiary trimethylamine (tertiary aliphatic), triphenylamine (tertiary aromatic). 

A different mode of reaction, however, is observed in photoreductions of nitroaromatics by aromatic tertiary amines. Irradiation of benzene solutions of N-methylated anilines and either m-chloronitrobenzene or 1-nitronaphthalene results in oxidative demethylation of the amines accompanied with reduction of the nitro compound to the corresponding arylamine 49). The authors suggest that hydrogen abstraction from the methyl group takes place as the primary chemical event. 

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