Ortho-alkylation, aniline

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)... 

This procedure illustrates a general method for the ortho-alkylation of anilines.4 It can be uttttzcd ftJT both anilines and mono-A7-substitu ted... 

During the same year, both an acid-catalyzed [60] and a TiCl4-catalyzed [61] ortho-alkylation of anilines with styrene were published, but offering only a very low selectivity. The reaction of anisole and styrene catalyzed by Mo(CO)6 [62] afforded the corresponding branched diaryl product with a comparable yield and selectivity as shown by our protocol. Furthermore, Michelet and coworkers successfully employed substituted styrenes in a gold-catalyzed tandem Friedel-Crafts-type addition-carbocyclization reaction [63]. 

Ortho-Alkylation of aromatic amines. OassmanamlGnietzmacher have described a simple, high-yield procedure for specific orr/io-mcthylation of anilines. The aniline (1) is treated with 1 eq. of/-butyl hypochlorite (1,90 2,50 3, 38) or ofN-chlorosuceini-mide(l, 139 2,69- 70 3, 36,142) in methylene chloride at -65°. Then dimethyl sulfide (3 eq.) is added at the same temperature. After 40 min, sodium mcthoxide (1.2 eq.) in... 

Problem 4.16. Upon mixing an A-chloroaniline and an a-mercaptoester, a nucleophilic substitution occurs, followed by a [2,3] sigmatropic rearrangement. An ortho-alkylated aniline is ultimately obtained. Draw the mechanism for this reaction. 

Synthesis of ortho alkyl anilines (Rosini) by reductive C-alkylation of nitroarenes. Also synthesis of indoles (Bartoli) by reaction of 2-substituted nitroarenes with vinyl Grignard reagents. 

Indoxyls are normally prepared from anthraiiilic acids via alkylation with a haloacetic acid followed by a cyclising Perkin condensation. It is also possible to directly chloroacylate an aniline, ortho to the nitrogen. ... 

S. Shiobara, R. Kamiyama, S. Tajima, H. Shizuka, S. Tobita, Excited-state proton transfer to solvent of protonated aniline derivatives in aqueous solution a remarkable effect of ortho alkyl goup on the proton-dissociation rate, J. Photochem. Photobiol. A 154, 53-60 (2002)... 

This reaction has been used for the preparation of anilines with alkyl, vinyl, formyl, and benzyl groups at the ortho-position. 

In order to obtain a comparative picture of the relative effects of various substituents on the pIST value Wepster has used the same method as for the derivatives of aniline, but with an additional term to allow for the steric inhibition of resonance of the base. Thus he adds to the pKg value of dimethylaniline contributions of +0-4 units for each para or ortho alkyl group and 0-15 units for each meta alkyl group. The extra term is calculated from the extinction coefficient e of the... 

N- Arylimines of type (61) are produced by alkylation of the dilithium aldimine (60), a versatile intermediate capable of reaction with a variety of reagents. Since the hydrolysis of (61) yields the ortho-alkylated aniline (62), the overall reaction sequenceof Scheme 37 represents a procedure for the orr/io-alkylation of anilines. 

A procedure has now been published in Organic Syntheses for the ortho-alkylation of anilines by the Gassman method (ylide 2,3-sigmatropic rearrangement). The previous approach has been extended to polycyclic aromatic amines, modified, and applied to the orr/10-alkylation of anilides. ... 

Rearrangement of N-aryl dimethylsulphimides into o-methylthiomethyl-anilines in the presence of NEt, has been studied over a number of years, and recently developed into a specific ortho-alkylation procedure and into a versatile indole synthesis. ... 

V-Alkylaniline and /V,/V-di alkyl aniline hydrochlorides can be rearranged to C-alkyl anilines by heating the salts to 200—300°C. In this reaction, known as the Hofmann-Martius rearrangement, the alkyl group preferentially migrates to the para position. If this position is occupied, the ortho position is alkylated. 

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)... 

Polyfluorinated a-diketones react with 1,2-diainino compounds, such as ortlio-phenylenediamine, to give 2,3-substituted quinoxalmes [103] Furthermore, the carboxyl function of trifluoropyruvates offers an additional electrophilic center. Cyclic products are obtained with binucleophiles [13, 104] With aliphatic or aromatic 1,2-diamines, six-memhered heterocycles are formed Anilines and phenols undergo C-alkylation with trifluoropyruvates in the ortho position followed by ring closure to form y-lactams and y-lactones [11, 13, 52, 53, 54] (equation 23). 

Condensation of the triacid with aniline gave an imide 8 for which the barrier to rotation about the CaryrNimid<, bond indicated was about 13 kcal/mole9). However, ortho substituents stop this rotation and fix the conformation in such a way that the alkyl (or practically any other group) is directed away from the carboxyl function as in 9. The seemingly passive methyl groups of this structure thereby limit the internal rotations and enforce a fairly rigid structure. 

The X-substituted benzene (aniline, Figure 11.2) is activated toward electrophilic attack since the HOMO is raised significantly. The electrophile would be directed to the ortho, para, and ipso positions of the ring and to the X substituent itself. The ipso channel is usually nonproductive since the common heteroatom-based X substituents are not easily displaced as Lewis acids. Loss of substituent is frequently observed with tertiary alkyl-substituted benzenes. Attachment of the electrophile to the X substituent is most likely if... 

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