N-Alkyl aromatics

Fig. 4.57). In some cases, particularly N-alkyl aromatic cyclic amines, the carbinolamines that are formed are stable enough to be isolated. 

N-Ethyl-/>-chloroaniline has been prepared by alkylation of / -chloroaniline with ethyl bromide 4 5 and by reduction of aceto-/-chloroanilide with lithium aluminum hydride.6 The present procedure, which is based on the results of an investigation by Roberts and Vogt,3 is a convenient general method for preparation of pure N-alkyl aromatic amines. 

Burch, R. R., Manring, L. E. N-Alkylation and Hofmann elimination from thermal decomposition of R4N salts of aromatic polyamide polyanions synthesis and stereochemistry of N-alkylated aromatic polyamides. Macromolecules 99, 24, 1731-1735. 

The primary products of the telomerization reaction are n-alkyl aromatics. More than one product may be formed when two or more different types of hydrogen are available on the aromatic telogen for transmetalation. Thus the primary products from benzene in which all hydrogens are equivalent are exclusively the even-numbered homologous 1-phenyl-n-alkanes. With toluene, 90 mole % of the primary product stems from transfer to the benzylic carbon atom while the remainder results from nuclear attack. Thus 90% of the primary product consists of homologous odd-numbered 1-phenyl-n-alkanes and 10% of homologous even-numbered, methylphenyl-n-alkanes. Ethylbenzene is attacked... 

Mixtures of N-alkyl aromatic amines and N-alkyl-N-hy-droxyalkyl aromatic amines using the 1.5-/i first overtone of the NH stretching absorption and the first overtone of OH at 1.4 n. Beer s law was not followed for CCU solutions at 1.4 g due to H bonding through the OH group Mixtures of aniline and N-ethyl aniline (up to 99% of either) in CCU solution at 10 cm thickness, using 1.972 /i for aniline and 1.493 n for N-ethylaniline (aniline interference at the latter wavelength was considerable). Both followed Beer s... 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

A surpnsing feature of the reactions of hexafluoroacetone, trifluoropyruvates, and their acyl imines is the C-hydroxyalkylation or C-amidoalkylaOon of activated aromatic hydrocarbons or heterocycles even in the presence of unprotected ammo or hydroxyl functions directly attached to the aromatic core Normally, aromatic amines first react reversibly to give N-alkylated products that rearrange thermally to yield C-alkylated products. With aromatic heterocycles, the reaction usually takes place at the site of the maximum n electron density [55] (equaUon 5). 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

On the basis of this successful application of 23d, this catalyst was applied in a series of reactions (Scheme 6.22). For all eight reactions of nitrones 1 and alkenes 19 in which 23d was applied as the catalyst, diastereoselectivities >90% de were observed, and most remarkably >90% ee is obtained for all reactions involving a nitrone with an aromatic substituent whereas reactions with N-benzyl and N-alkyl nitrones led to lower enantioselectivities [65]. 

Many pharmacologically active compounds have been synthesized using 5-bromoisoquinoline or 5-bromo-8-nitroisoquinoline as building blocks.6 7 8 9 10 11 The haloaromatics participate in transition-metal couplings 81012 and Grignard reactions. The readily reduced nitro group of 5-bromo-8-nitroisoquinoline provides access to an aromatic amine, one of the most versatile functional groups. In addition to N-alkylation, TV-acylation and diazotiation, the amine may be utilized to direct electrophiles into the orthoposition. 

The lack of clear-cut hallucinogen-type activity for the 2-aminotetralins could be explained in several ways. The known deleterious effect of molecular bulk in the alpha-position would seem to direct attention to the steric effect of the reduced ring of the tetralins as detrimental to activity. In 18b, however, it has been noted (156) that the 5-methoxy group is forced out of plane by the adjacent 6-methyl and 4-methylene groups. The importance to activity of maintaining the methoxy groups coplanar with the aromatic ring has been emphasized earlier. Both substituent orientation and N-alkylation must also be important to activity, and it may not be realistic to make direct comparisons between the phenethyl-amines and the 2-aminotetralins. 

N-Alkylation of primary aromatic amines increases their nucleophilic character, making them couple much more readily, the introduction of the azo group occurring in the 4-position. Thus, in contrast to aniline, N-methylaniline couples readily and N,N-dimethyl-aniline very readily with simple diazonium salts. Diphenylamine also couples in the 4-position, but less readily than N-methylaniline. 

When N-alkyl-N-allenylaniline 311 was treated with magnesium monoperoxy-phthalate in aqueous MeOH, the corresponding N-oxides 312 were formed initially, which would then undergo sequential [2,3]- and [3,3]-sigmatropic rearrangement and aromatization to afford N-alkyl-2-ethenylindoles 316 [152],... 

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

Spurred by our desire to avoid use of expensive dipolau aprotic solvents in nucleophilic aromatic substitution reactions, we have developed two alternative phase transfer systems, which operate in non-polar solvents such as toluene, chlorobenzene, or dichlorobenzene. Poleu polymers such as PEG are Inexpensive and stable, albeit somewhat inefficient PTC agents for these reactions. N-Alkyl-N, N -Dialkylaminopyridinium salts have been identified as very efficient PTC agents, which are about 100 times more stable to nucleophiles than Bu NBr. The bis-pyridinium salts of this family of catalysts are extremely effective for phase transfer of dianions such as bis-phenolates. 

The reactivity of seven resin-bound thiophenol esters toward 3,4-dimethoxy-phenethylamine (42) was consistent with the trend seen in n-butylamine cleavage reactions i.e. benzimidazole > alkyl > aromatic. However, the rate constant for the same thiophenol esters with 3,4-dimefhoxyphenethylamine was decreased by two to three fold compared with that with n-butylamine. The rate constant of ben-... 

The reaction of substituted diazomethanes with ethyl Ai-nitrocarbamate, followed by hydrolysis of the ethyl N-alkyl-N-nitrocarbamate, has been used to prepare some primary arylnitramines where aromatic ring nitration is not required, and so limits the use of conventional N-nitrating agents.The method has not been fiilly investigated. 

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