Other aniline derivatives

Acetanilide is obtained from aniline and acetic anhydride. It is mainly used in the production of sulfonamide chemotherapeutics those are obtained by the reaction of acetanilide with chlorosulfonic acid, followed by reaction with a primary amine and subsequent deacylation. 

In human medicine, sulfamethoxazole (in combination with trimethoprim) is commonly used as an important antimetabolite for the treatment of bacterial infections, while other sulfonamides are mainly restricted to veterinary medicine, because of possible side effects. 

Production of 4,4 -diaminobiphenyl (benzidine) and its derivatives is normally carried out by reduction of the corresponding nitrobenzenes with zinc powder in high-boiling solvents, such as o-dichlorobenzene, to yield the respective hydrazo-benzene, which is converted into the benzidine form in acid solution. Since benzidine is carcinogenic, special care should be taken in its production manufacture is banned in many countries, because of its toxicity. 

Benzidine derivatives, especially 3,3 -dichloro- and 3,3 -dimethylbenzidine, are important intermediates used in the production of azo dyes, o-nitrochlorobenzene and o-nitrotoluene being the respective starting materials for these two examples. 

Selective introduction of alkyl groups to the benzene nucleus of aniline, as, for example, in the production of 2,6-diethylaniline, is not economically viable by normal electrophilic substitution of aniline since the amino nitrogen is also attacked electrophilically.2,6-Diethylaniline is therefore produced with organome-tallic catalysts, such as diethylaluminum chloride. The reaction with ethylene under a pressure of 70 bar at a temperature of around 150 °C produces 2,6-diethyl-aniline in a yield of over 85%. 2,6-Diethylaniline is used mainly for the production of the herbicide alachlor, which is consumed in the USA in quantities of around 42,000 tpa the largest producer is Monsanto, 2,6-Diethylaniline is made to react with formaldehyde to yield 2,6-diethylmethyleneaniline, which is then converted into alachlor by treatment with chloroacetyl chloride and methanol. 

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Production figures for the aminophenols are scarce, the compounds usually being classified along with many other aniline derivatives (86). Most production of the technical grade materials (95% purity) occurs on-site as they are chiefly used as intermediate reactants in continuous chemical syntheses. World production of the fine chemicals (99% purity) is probably no more than a few hundred metric tons yearly, at prices of about 45 per kg in 1990. 

Addition of potassium iodide solution to diazotised 3-toluidine was accommpanied on 3 occasions by an eruption of the beaker contents. This was not observed with the 2- and 4-isomers or other aniline derivatives. 

Experimental studies of the reactivity of other aniline derivatives in substitution reactions are far more limited, de la Mare and Hassan (1958) and Bradfield and Jones (1928) examined the influence of acyl substituents on the amino function on the rate of halogenation at the para position. These interesting data are too limited to be useful for the evaluation of a linear free-energy relationship and are not included in Table 4. 

Copolymers from aniline and another monomer (e.g., o-phenylenediamine [253]) or even from aniline and two other aniline derivatives [307] have also been eleetrosyn-thesized and eharaeterized (see later). 

Some other phenol derivatives are somewhat local in appHcation. Eor example, aniline is produced from phenol at only two plants, one in Japan and one in the United States. Likewise, phenol is used in the production of nylon, via caprolactam (qv) or adipic acid (qv) by only one United States producer and one European producer. These markets, like the phenoHc resin and polycarbonate markets, are quite cycHcal. Thus, the entire phenol market tends to be cycHcal and closely tied to the housing and automotive markets. 

Other nucleophiles add to conjugated systems to give Michael-type products. Aniline derivatives add to conjugated aldehydes in the presence of a catalytic amount of DBU (p. 488). Amines add to conjugated esters in the presence of InCla, La(OTf)3, or YTb(OTf)3 at 3kbar, for example, to give P-amino esters. This reaction can be initiated photochemically. An intramolecular addition of an amine unit to a conjugated ketone in the presence of a palladium catalyst, or... 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis,Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition metals have also been used. Microwave irradiation has been used to facilitate this reaction. Aniline derivatives react with a-diazoketones, in the presence of a... 

If only N-substituted aniline derivatives are considered, the IP( 2) value is observed close to that of the parent compound and to vary in a rather narrow range (8.8-9.1 eV). On the other hand, for IPfe) (7.0-7.7 eV) and IP(rtN) (9.5-10.3 eV) larger deviations relative to unsubstituted aniline and greater variation with substitution are found. This can be explained by perturbations of the corresponding benzene MOs by the substituents which is minimal for H2, because it has no coefficients on C-l and N (Cs symmetry). In asymmetric aniline derivatives also JI2 is expected to interact to a substantial extent with n n-... 

A number of other amines containing electron-withdrawing groups undergo facile N-nitration (Table 5.1). The direct A-nitration of aniline derivatives is limited to amines of... 

Aniline is a simple aromatic compound composed of an amino group attached to a benzene ring. Other aromatic amines are aniline derivatives. Some examples of aromatic amines are shown in Figure 13-2. 

These addition reactions require formation of an imino-cyclohexadiene intermediate (Fig. 13.41). In cases where the ipso substituent is a proton, tautomeriza-tion to form the substituted aniline derivative is fast, and such intermediates have not been isolated. On the other hand, in situations where the nucleophile adds to a substituted ring position, the intermediate can undergo further secondary reactions. For example Novak et al. showed that the 4-biphenylylnitrenium ion reacts with water forming the imine cyclohexadiene intermediate 74, which in turn experiences an acid-catalyzed phenyl shift reaction to 76 via 75 (Fig. 13.42). 

Very interesting results were obtained from the reaction of magnesium alkylidene carbenoids with mefa-substituted arylamines (Table 8) . The reaction of magnesium alkylidene carbenoids 157 and 161 with three mefa-substituted anilines was carried out and the results are summarized in Table 8. The reaction of 157 with meta-anisidine gave two products 163 and 164 (in a 30 13 ratio) in 43% yield. The main product was found to have the alkenyl group at the more hindered position (163). As shown in the Table, all the other meto-substituted aniline derivatives also gave the more hindered alkenylated compounds as the main product in variable ratio. 

Preliminary results in the validation of a novel short term test. Mutat. Res., 46, 305-310 Watanabe, T., Ishihara, N. Ikeda, M. (1976) Toxicity of and biological monitoring for 1,3-diamino-2,4,6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene. Int Arch, occup. environ. Health, 37, 157-168 Yoshimi, N., Sugie, S., Iwata, H., Niwa, K., Mori, H., Hashida, C. Shimizu, H. (1988) The genotoxicity of a variety of aniline derivatives in a DNA repair test with primary cultured rat hepatocytes. Mutat. Res., 206, 183-191... 

Group IV substituents, especially the trimethylsilyl group, apparently enhance the electron affinity of aromatic systems. The effect is particularly noticeable in aniline derivatives. The strong electron-releasing effect of the amino group decreases the electron affinity of the aniline derivatives and hinders reduction to the radical anions. Nitroanilines may be reduced to radical anions (65). The only other aniline radical anions that have been reported bear silyl substituents either at nitrogen (62) or on the ring (83, 85, 86). 

The combination of the formation of palladium(II) complexes in the oxidative addition of unsaturated halides onto palladium(O), and the palladium(II) mediated ring closure of olefins allows for the elimination of the oxidant. The ring closure of the methallyl-aniline derivative shown in 3.67. in the presence of /J-bromostyrcnc and a catalytic amount of palladium led to the ring closed - coupled product.84 The ring closure might also be accompanied by other follow-up reactions. 2-Methallyl-anilines were converted for example to indolylacetic acid derivatives in the presence of carbon monoxide.85... 

Other donors very often used in combination with fullerenes comprise ferrocene, phthalocyanine, transition metal complexes, aniline derivatives, tetrathiafulvalene and oligoacenes, carotenoids, oligoarylene, and oligothiophene and many examples are collected in recent reviews and books dedicated to this subject.3a,7e 28... 

Portoghese and coworkers also considered other naltrindole derivatives substituted in position 6 or 7 with aryl, benzyl or aniline moieties to evaluate the effect of flexible aryl groups on selectivity, but obtained non-selective compounds only. This result demonstrates that the conformational flexibility of these aryl groups causes them to reside preferentially in regions of space that are not accepted by the 8 opioid receptor (Portoghese et al., 1994). A more rigid compound however, 7-benzylidene-naltrindole (BNTX) proved to be a potent and highly... 

Syntheses of category Ilac can properly be called the most important category of indole synthesis. Fundamentally, the reason for this is the use of aniline or its derivatives as starting materials. Besides the easy availability of many aniline derivatives, the aromatic starting material is monofunctional whereas many other annelation procedures require a specific ortho substitution pattern in the aromatic starting material. 

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