Aniline, basicity synthesis

The low structural specificity in the local anesthetic sell cs is perhaps best illustrated by phenacalne (91), a local an-I -.lhetic that lacks not only the traditional ester or amide func-I ion but the basic aliphatic nitrogen as well. First prepared at I lie turn of the century, a more recent synthesis starts by con-ili iusation of p-ethoxyaniline with ethyl orthoacetate to afford I he imino ether (90), Reaction of that intermediate with a sec-I liil mole of the aniline results in a net displacement of ethanol, iiobably by an addition-elimination scheme. There is thus ob-I.lined the amidine, 91, phenacalne. 

Our task was to develop a feasible synthesis for diamino resorcinol. From several possibilities [1-4] the resorcinol and anihne were chosen as starting materials. The diazotated aniline was coupled with resorcinol among basic conditions giving 4,6-bisphenylazo resorcinol. Hydrogenation of the latter resulted in diamino resorcinol and aniline, which could be recycled (scheme 14.2). This chemistry is well known [5-13] therefore, the research work focused on finding the optimal parameters and catalyst and finally on elaborating a process for scale-up. 

Sandmeyer s valuable isatin synthesis involves the removal of sulphur from diphenylthiourea (I) (p. 169) with basic lead carbonate. Hydrogen cyanide is combined with the reactive diphenylcarbodiimide (II) so obtained, and the nitrile (III) produced is converted by means of hydrogen sulphide into tbe thioamide (IV). Concentrated sulphuric acid brings about ring closure and the product is the a-anil of isatin (V). Then, by hydrolysis with dilute sulphuric acid, aniline is removed ... 

In the reaction with a less basic amine such as aniline, mixtures of naphthylamines 153 and isoquinolinium salts 152 were obtained (71KGS1437 88UP2). The alternative pathway of formation of naphthylamines 153 from isoquinolinium salts 152 by isomeric recyclization (81T3425) is completely excluded, since model experiments with isoquinolinium salts showed no reaction under the conditions of synthesis of naphthylamines 153. 

Osteryoung and coworkers have also investigated the use of chloroaluminate ionic liquids for the synthesis of polyaniline [62, 63]. Unlike pyrrole and thiophene, aniline was successfully polymerized in acidic, neutral and basic chloroaluminate melts, although the best results were obtained using the neutral composition. 

Cesium-exchanged zeolite X was used as a solid base catalyst in the Knoevenagel condensation of benzaldehyde or benzyl acetone with ethyl cyanoacetate [121]. The latter reaction is a key step in the synthesis of the fragrance molecule, citronitrile (see Fig. 2.37). However, reactivities were substantially lower than those observed with the more strongly basic hydrotalcite (see earlier). Similarly, Na-Y and Na-Beta catalyzed a variety of Michael additions [122] and K-Y and Cs-X were effective catalysts for the methylation of aniline and phenylaceto-nitrile with dimethyl carbonate or methanol, respectively (Fig. 2.37) [123]. These procedures constitute interesting green alternatives to classical alkylations using methyl halides or dimethyl sulfate in the presence of stoichiometric quantities of conventional bases such as caustic soda. 

What type of amine is C Do you expect it to be more or less basic than ammonia Than aniline What product do you expect from Hofmann elimination of C What significant absorptions might be seen in the IR spectrum of C What information can be obtained from the mass spectrum Plan a synthesis of D from benzene. 

Compounds which are vanishingly weakly basic in H20, such as nitro-anilines, nitro-aromatic or halo-nitro-aromatic compounds are protonated to a greater or less extent in superacids, allowing them to be used as indicators in Hammett Acidity Function measurements. Cl- which has essentially zero base strength in H20 is protonated by the superacids to HC1, which being monomolecular is expelled as a gas from the highly associated solvents. This provides a commonly-used important route to synthesis of anhydrous fluorides, fluorosulfates and triflates. 

The conversion of amines to amides is useful in the synthesis of substituted anilines. For example, aniline itself does not undergo Fiiedel-Crafts reactions (Section 18.1 OB). In.stead, its basic lone pair on N reacts with the Lewis acid (AICI3) to form a deactivated complex that does not undergo further reaction. 

An electrophilic cyclization of 7V-(2-alkynyl)anilines was developed that allow the synthesis of a variety of substituted quinolines 115. Illustrated in Scheme 32 the cyclization of the propargylic aniline 116 by ICl afforded 117, which then could be converted to 115 under basic conditions. 

Synthesis. Methods of synthesis have changed litde since the synthesis of Basic Red 2. One method starts with o-toluidine [95-53-4], C H9N, which is diazotized and coupled to form amino azotoluene [97-56-3], C14H15N3. Amino azotoluene is reduced to one mole each of o-toluidine and 2,5-diaminotoluene [95-70-5], C7H10N2. Condensation and oxidation with aniline [62-53-3], C HyN, gives the desired dye (13). 

Control of the pH is also of importance for the Mannich-based bispidine synthesis. Formation of an aldol product competes with the Mannich condensation in the basic pH region. It is for this reason that, in some cases, the reaction is sensitive to the order in which the reactants are added to the reaction mixture. It is possible to add the aldehyde and amine components one after another to a solution of the CH-acidic compound, but sometimes the aldol reaction can be disfavored by changing the order. This allows the imminium ion to be formed in advance. The precursors of 45 and 46 have been prepared by this method. In some cases, it has been useful to use a protonated amine component as the acetate salt (e.g., 49 or precursors for 44, 47, and 48), as the chloride salt (e.g., 11) or to carry out the reaction in acetic acid. Aromatic amines (e.g., aniline) give rise to para-substituted aromatic amines if the solution is not approximately neutral. In a very elegant procedure, a condensate of formaldehyde and aniline, which is the trimeric methyleneaniline, was prepared separately, and treated in the Mannich reaction with dimethyl acetonedicarboxylate and formaldehyde to yield the 3,7-diphenylbispidone... 

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