Aromatic amines, primary, selective

Nitroso compounds are formed selectively via the oxidation of a primary aromatic amine with Caro s acid [7722-86-3] (H2SO ) or Oxone (Du Pont trademark) monopersulfate compound (2KHSO KHSO K SO aniline black [13007-86-8] is obtained if the oxidation is carried out with salts of persulfiiric acid (31). Oxidation of aromatic amines to nitro compounds can be carried out with peroxytrifluoroacetic acid (32). Hydrogen peroxide with acetonitrile converts aniline in a methanol solution to azoxybenzene [495-48-7] (33), perborate in glacial acetic acid yields azobenzene [103-33-3] (34). 

A variation of this method led to the generation of bis-benzimidazoles [81, 82], The versatile immobilized ortho-phenylenediamine template was prepared as described above in several microwave-mediated steps. Additional N-acylation exclusively at the primary aromatic amine moiety was achieved utilizing the initially used 4-fluoro-3-nitrobenzoic acid at room temperature (Scheme 7.72). Various amines were used to introduce diversity through nucleophilic aromatic substitution. Cyclization to the polymer-bound benzimidazole was achieved by refluxing for several hours in a mixture of trifluoroacetic acid and chloroform. Individual steps at ambient temperature for selective reduction, cyclization with several aldehydes, and final detachment from the polymer support were necessary in order to obtain the desired bis-benzimidazoles. A set of 13 examples was prepared in high yields and good purities [81]. 

Under the same conditions (batch or GL-PTC) discussed for CHg-acidic compounds, primary aromatic amines also react with DMC. In this case, although the reaction yields selectively the mono-A-methylated amines with no dimethylated by-products, sizable amounts of methyl carbamates (ArNHCOgMe) are formed. ° Much better results can be gathered in the presence of zeolites, particularly alkali metal exchanged Y and X faujasites. These aluminosilicates posses pseudospheri-cal cavities (supercavities) of 11-8 A in diameter, which can be accessed through channels whose size is 7.4 kP ... 

In order to clarify the different behavior of anion 2 and 3 (Scheme 4.10) toward DMC, various anions with different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) were compared with regard to nucleophilic substitutions on DMC, using different reaction conditions. Results were in good agreement with the hard-soft acid-base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH2 acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first... 

Then, contrary to our previous hypothesis, the reaction proceeds via a Bai2 displacement of aniline on DMC. The product, mono-A -methyl aniline (PhNHMe), plausibly adsorbs into the zeohte in a different way with respect to anihne, because different H-bonds (N H — O-zeolite) take place with the solid. As recently reported by Su et al., A-methyl amines also may interact with NaY by H-bonding between the protons of the methyl group and the oxygen atoms of the zeolite this probably forces the molecule a bit far from the catalytic surface in a fashion less apt to meet DMC and react with it. This behavior can account for the mono-A-methyl selectivity observed, which is specific to the use of DMC in the presence of alkali metal exchanged faujasites in fact, the bis-A-methylation of primary aromatic amines occurs easily with conventional methylating agents (i.e., dimethyl sulfate). ... 

The efficient At-nitration of secondary amines has been achieved by transfer nitration with 4-chloro-5-methoxy-2-nitropyridazin-3-one, a reagent prepared from the nitration of the parent 4-chloro-5-methoxypyridazin-3-one with copper nitrate trihydrate in acetic anhydride. Reactions have been conducted in methylene chloride, ethyl acetate, acetonitrile and diethyl ether where yields of secondary nitramine are generally high. Homopiperazine is selectively nitrated to At-nitrohomopiperazine or At, At -dinitrohomopiperazine depending on the reaction stoichiometry. At-Nitration of primary amines or aromatic secondary amines is not achievable with this reagent. 

Because of their basicity (lower than that of aliphatic amines), aromatic primary amines can be selectively nitrosated179 in the presence of aliphatic amines at low pH. An example is provided by the deamination of 3 -amino-3 -deoxyadenosine, although the yield of the product isolated, 3 -amino-3 -deoxyinosine, was180 only about 4%. Some 50% of the starting material remained unchanged, and hydrolysis released adenine (30%). 

Secondary amines can be prepared from the primary amine and carbonyl compounds by way of the reduction of the derived Schiff bases, with or without the isolation of these intermediates. This procedure represents one aspect of the general method of reductive alkylation discussed in Section 5.16.3, p. 776. With aromatic primary amines and aromatic aldehydes the Schiff bases are usually readily isolable in the crystalline state and can then be subsequently subjected to a suitable reduction procedure, often by hydrogenation over a Raney nickel catalyst at moderate temperatures and pressures. A convenient procedure, which is illustrated in Expt 6.58, uses sodium borohydride in methanol, a reagent which owing to its selective reducing properties (Section 5.4.1, p. 519) does not affect other reducible functional groups (particularly the nitro group) which may be present in the Schiff base contrast the use of sodium borohydride in the presence of palladium-on-carbon, p. 894. 

Note Some of the foregoing acyloxypyrazines proved to be selective acylating agents for primary aromatic amines.1311... 

The heterobimetallic complexes [N(n-Bu)4] [Os(N)R2(/u.-0)2Cr02] catalyze the selective oxidation of alcohols with molecular oxygen. A mechanism in which alcohol coordinates to the osmium center and is oxidized by B-hydrogen elimination (see -Hydride Elimination) is consistent with the data. The hydroxide adduct of OSO4, [0s(0H)204], with ferric cyanide and other co-oxidants catalyzes the oxidative dehydrogenation of primary aromatic and aliphatic amines to nitriles, the oxidation of primary alcohols to carboxylic acids, and of secondary alcohols to ketones. Osmium derivatives such as OsCb catalyze the effective oxidation of saturated hydrocarbons in acetonitrile through a radical mechanism. ... 

Hydrogenation of aromatic nitriles over platinum or rhodium catalysts produced the secondary amines with good selectivity. With palladium the primary amine was the main product when octane or ethanol was used as the solvent, but in benzene, palladium gave the secondary amines. ... 

With a primary aromatic amine such as aniline and under the same conditions as with n-octylamine, conversion and seleetivity evolve similarly-from N-methylated aniline at low conversion to N,N-dimethylated aniline at high conversion [18]. Selectivity is, moreover, better because 90% iV-monomethylaniline is produced at 45 % conversion and 85 % dimethylated product at total conversion. By-products resulting from C-alkylation of the aromatic ring are also formed at high conversion (Table 2), although they never exceed 10%. 

By using dialkylthiophosphoryl chlorides in aqueous alkaline medium, a selective and sensitive method for the determination of aliphatic and aromatic amines by GC-FPD has been developed. In particular, secondary amines can be selectively converted into their A -diethylthiophosphoryl (DETP) derivatives with diethyl chlorothiophosphate (DECTP) after treatment with o-phthaldial-dehyde (OP A), because OP A reacts only with primary amino groups. On the other hand, secondary amines are detected irrespective of pretreatment, because they do not react with OPA (Eigure 11.7 and Eigure 11.8). 

The synthesis of primary amines in biphasic operation has been developed via selective reductive amination of aromatic and aliphatic carbonyl compounds using aqueous ammonia in the presence of water-soluble transition metal catalysts [17]. The use of [Rh(cod)Cl]2 with TPPTS as catalyst and ammonium acetate in water/ THF afforded benzylamine from benzaldehyde in 86% yield. This method is also feasible for the synthesis of aliphatic primary amines from aliphatic aldehydes in... 

Dimethylcarbonate (DMC) is an environmentally friendly substitute for dimethylsulfate (DMS) and methyl halides in methylation reactions. It is also a very selective reagent. The reactions of DMC with methylene-active compounds produce monomethylated derivatives with a selectivity not previously observed. The batchwise monomethylation of arylacetonitriles, arylacetoesters, aroxyacetonitriles, methyl aroxyacetates, ben larylsulfones and alkylarylsulfones with DMC achieve >99% selectivity at 180-220°C in the presence of K2CO3. Mono- -methylation of primary aromatic amines at 120-150 °C in the presence of Y- and X-type zeolites, achieved selectivities up to 97%. At high temperature (200°C) and in the presence of potassium carbonate as the catalyst, DMC splits benzylic and aliphatic ketones into two methyl esters in contrast, DMC converts ketone oximes bearing a methylene group to 3-methyl-4,5-disubstituted-4-oxazolin-2-ones. Dibenzylcarbonate... 

Selective Mono-N-Methylation of Primary Aromatic Amines... 

It also catalyses oxidation reactions with an oxidant, e.g. the methylene group in cyclopropylmethyl-compormds to a carbonyl group in the presence of metaperiodate pTasegawa et al. Chem Lett (Jpn) 1385 1985, Carlsen et al. J Org Chem 46 3936 1981, cf Review Gore Platinum Metals Rev 27 111 1983], It catalyses the synthesis of 2-ethyl-3-methylqirinohnes from primary aromatic amines and triallylamine [Cho et al. Tetrahedron Lett 40 1499 1999], and has been used for the selective hydrogenation of unsaturated aldehydes pujita et al. J Catal 255 95 2004]. 

Under the same conditions, DMC also reacts with primary aromatic amines and phenols to selectively give mono-N-methylated anilines and anisoles, respectively (17,18). 

Acetylation may occur with -NHg, -OH, and -SH groups. Acetylation of primary aromatic amines and sulfonamide nitrogens are the most important of these reactions in the inactivation of drugs. These reactions occur in most laboratory and domestic animals. The dog is unable to acetylate aromatic amines or hydrazines, probably due to a lack of selective acetylating enzymes. Deacetylation of the conjugate may occur in certain species, e.g. the chicken de-acetylates aromatic amines, and dogs deacetylate aliphatic amino acids. Acetylation reactions have also been reported to occur in amphibia, fish, and a few insect species [20]. 

Primary Amines.—The aromatic nitro-to-amine conversion has figured prominently in the current literature/ with the emphasis once again on selectivity. Thus, sodium borohydride-stannous chloride, lithium cobalt(i)... 

A new approach to the amination of organometallics offers several advantages. Azidomethyl phenyl sulphide (1), a synthon for NHa, reacts with organometallic reagents to give triazenes (2), which can be isolated or hydrolysed directly to the corresponding primary aromatic amines (Scheme 1). Steric factors are minimal and selectivity is consistent with the products of directed metallation. Efforts to extend this procedure to aliphatic and heteroaromatic systems have been unfruitful. 

Primary Amines.— The aromatic nitro-to-amine conversion has once again received considerable attention, " especially those reductions which offer selectivity. Thus, dodecacarbonyltri-iron on basic alumina, sodium sulphide in aqueous 1,4-dioxan, triethylammonium formate in the presence of T0% Pd-C, and hydrogenation over a platinum catalyst all effect the nitro-to-amine conversion in the presence of other functionality. Azides and hydrazines are also reduced to aromatic amines by molybdenum trichloride. ... 

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