Aromatic nitriles, synthesis

Cyano-de-diazoniations of the Sandmeyer type have been used for the synthesis of aromatic nitriles for many decades (example Clarke and Reed, 1964), as cyanide ions are comparable to bromide and iodide in many respects. A homolytic cyano-de-diazo-niation that does not use metal ions as reductant or ligand transfer reagent was described by Petrillo et al. (1987). They showed that substituted diazosulfides (XC6H4 — N2 — SC6H5), either isolated or generated in situ from arenediazonium tetrafluoroborates and sodium benzenethiolate, react with tetrabutylammonium cyanide in dimethylsulfoxide under photon stimulation, leading to nitriles (XC6H4CN). The method worked well with eleven benzenediazonium ions substituted in the 3- or 4-position, and was also used for the synthesis of phthalo-, isophthalo-, and tere-... 

Regarding the series of hetero aromatic pentacyclic compounds with three heteroatoms, an accelerated synthesis of 3,5-disubstituted 4-amino-1,2,4-triazoles 66 under microwave irradiation has been reported by thermic rearrangement of dihydro-1,2,4,5 tetrazine 65 (Scheme 22). This product was obtained by reaction of aromatic nitriles with hydrazine under microwave irradiation [53]. The main limitation of the method is that exclusively symmetrically 3,5-disubstituted (aromatic) triazoles can be obtained. 

A further demonstration of the efficacy of photolysis of ArTlXj compounds is the recently described synthesis of aromatic nitriles by photolysis of solutions of arylthallium ditrifluoroacetates in aqueous potassium cyanide... 

Arenes, on complexation with Cr, Fe, Mn, and so forth, acquire strongly electrophilic character such complexes in reactions with nucleophiles behave as electrophilic nitroarenes.71 Synthesis of aromatic nitriles via the temporary complexation of nitroarenes to the cationic cyclopentadienyliron moiety, cyanide addition, and oxidative demetalation with DDQ has been reported (Eq. 9.43).72... 

Type G syntheses are typified by the 1,3-dipolar cycloaddition reactions of nitrile sulfides with nitriles. Nitrile sulfides are reactive 1,3-dipoles and they are prepared as intermediates by the thermolysis of 5-substituted-l,3,4-oxathiazol-2-ones 102. The use of nitriles as dipolarophiles has resulted in a general method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 103 (Scheme 11). The thermolysis is performed at 190°C with an excess of the nitrile. The yields are moderate, but are satisfactory when aromatic nitrile sulfides interact with electrophilic nitriles. A common side reaction results from the decomposition of the nitrile sulfide to give a nitrile and sulfur. This nitrile then reacts with the nitrile sulfide to yield symmetrical 1,2,4-thiadiazoles <2004HOU277>. Excellent yields have been obtained when tosyl cyanide has been used as the acceptor molecule <1993JHC357>. 

A synthesis of novel spirodioxazole systems by the 1,3-dipolar cycloaddition reactions of 3,5-di-ferf-butyl-1,2-benzoquinone with aromatic nitrile oxides has been described (Scheme 1.31). Though yields are high (80%-100%), the regios-electivity is low, the regioisomer ratio 181 182 being dependent on the Ar nature (349). 

Scheme 11.40. Synthesis of 1-arylcyclo-propylamines from aromatic nitriles by reaction with diethylzinc in the presence of MeTi(0/Pr)3 and NaO/ Pr [138].

Aromatic nitrations, 17 160-161 by-products of, 17 161 kinetics of, 17 162 Aromatic nitriles, 17 243 Aromatic nucleophilic displacement, polyimide synthesis via, 20 273 Aromatic phosphines, 19 60, 62 Aromatic poly(monosulfide ketone)s, 23 709 Aromatic poly(monosulfide)s, 23 706 Aromatic polyamide copolymers, laboratory synthesis of, 19 720 Aromatic polyamide fibers, 24 614 Aromatic polyamides, 10 210-212 19 713-738. See also Aliphatic polyamides (PA)... 

Sandmeyer s synthesis of aromatic nitriles is far more elegant than the removal of water from the ammonium salts of carboxylic acids, which latter reaction is also applicable to benzene derivatives. In particular, the former synthesis permits of the preparation of carboxylic acids via the nitriles, and so provides a complete substitute for Kolbe s synthesis (alkyl halide and potassium cyanide), which is inapplicable to aromatic compounds. The simplest example is the conversion of aniline into benzoic add. The converse transformation is Hofmann s degradation (benzamide aniline, see p. 152). 

Reports on the synthesis of five-membered heterocycles by intramolecular nitrogen—nitrogen bond formation (N1—N5) came some years ago from our laboratory [79CC891 81 JCS(Pl) 1891 83JCS(P1)2273]. Thus, 4-alkyl(aryl)amino-l-azabutadienes 2, which are readily available in large scale from alkyl(aryl)imines 1 and aliphatic or aromatic nitriles (70S 142 ... 

Earlier work in this laboratory showed that chromium oxide supported on alumina is a good catalyst for the conversion of olefins (ref. 1) as well as paraffins (ref. 2) to nitriles with high selectivities, by reaction of NO with the hydrocarbons (nitroxidation). Recent work (ref. 3) reported preliminary results of the nitroxidation of paraxylene as an extension of the use of C Oj-Al Oj to the catalytic synthesis of aromatic nitriles. It should be mentioned that only few data are available in the literature related to the nitroxidation of aromatic hydrocarbons. Teichner et al (ref. 4 ) reported interesting results of selective synthesis of benzonitrile by nitroxidation of toluene on NiO-AlgO catalysts. Improvements of the catalytic activity and selectivity in this reaction were reached by use of C Og-Al. which also exhibits striking properties in the synthesis of paratolunitrile by contact of NO with paraxylene (ref. 3). 

A similar rapid microwave one-pot synthesis of substituted quinazolin-4-ones was also reported, which involved cyclocondensation af anthranilic acid, formic acid (or an orthoester) and an amine under solvent-free conditions (Scheme 3.37)61. A complimentary approach was adopted to synthesise 4-aminoquinazolines in very good yields, involving the reaction of aromatic nitrile compounds with 2-aminobenzonitrile in the presence of a catalytic amount ofbase (Scheme 3.38)62. The reactions were performed in a domestic microwave oven and required only a very short heating time. A microwave-assisted synthesis of a variety of new 3-substituted-2-alkyl-4-(3H)-quinazolinones using isatoic anhydride, 2-aminobenzimidazole and orthoesters has also been described (Scheme 3.38)63. 

Some of these procedures are exemplified in Expt 5.160. Dehydration of aldoximes proceeds under milder conditions, acetic anhydride being frequently used. The method is particularly applicable to the synthesis of aromatic nitriles (see Expt 6.170). 

The hydrolysis of nitriles under either acidic or basic conditions, which has already been discussed in Section 5.11.2, p. 671, for alkyl and aralkyl nitriles, is equally applicable to the synthesis of aromatic carboxylic acids (Expt 6.153). The aromatic nitriles are readily obtained by the Sandmeyer reaction (see Section 6.7.1, p. 923). 

Camuzat-Dedenis, B. Provot, O. Moskowitz, H. Mayrargue, J. Reaction of phosphonium ylides and aromatic nitriles under Lewis acid conditions and easy access to aryl-substituted a-methoxyacetophenones. Synthesis 1999, 1558-1560. 

Fig. 16.8. Rosenmund-von-Braun synthesis of aromatic nitriles taking the preparation of pora-acetylbenzonitrile as an example.

A one-pot synthesis of 3,5-disubstituted 7-hydroxy-3//-l,2,3-triazolo[4,5-d]pyrimidines (130) has been carried out by using benzyl azide, cyano-acetamide, ethyl or methyl esters of the appropriate carboxylic acid, and sodium ethoxide as catalyst. The reaction proceeds via a 5-amino-l-benzyltriazole-4-carboxamide intermediate (85JHC1607). 7-Amino-3H-l,2,3-triazolo[4,5-d]pyrimidines 133 (R2 = H) were prepared starting from benzyl azide, malononitrile, and an aliphatic or aromatic nitrile, or by reaction of 130 with phosphorus oxychloride followed by amination. Compound 132 was formed in most reactions from two molecules of the 5-amino-4-cyano-l-benzyltriazole intermediate by an intermolecular nucleophilic at-... 

The synthesis of the anti-inflammatory drug broperamole illustrates modification of a tetrazole using its anion. The tetrazole is again constructed from the nitrile—it s an aromatic nitrile with an electron-withdrawing substituent so this will be a good reaction. 

The cyclocondensation of enaminones with an aromatic nitrile was previously used for the synthesis of 9-aminoacridines52 analogous to Tacrine, which is a pharmaceutical agent against Alzheimer s disease (equation 34). Similarly acyclic enaminones serve as useful precursors for synthesis of the quinoline ring system as shown in equation 3553. 

Yildirim, S., Franco, T., Wohlgemuth, R., Kohler, H.P., Witholt, B. and Schmid, A. (2005) Recombinant chlorobenzene dioxygenase from Pseudomonas sp. P51 a biocatalyst for regioselective oxidation of aromatic nitriles. Advanced Synthesis Catalysis, 347,1060 1073. 

Scheme 20.1 Synthesis of aromatic nitriles by catalytic ammoxidation.

Besides selectivity to aromatic nitriles, the minimization of the direct ammonia oxidation to N2 side-reaction is a critical factor, because otherwise runaway conditions may be possible. There is always competition between NH3 oxidation and ammoxidation on the catalyst surface. Furthermore, contact between ammonia and the catalyst surface, particularly at high temperatures, causes a partial reduction of the oxide surface because of NH3 oxidation to N2. Therefore, control of the rate of unselective oxidation of ammonia to N2 is an important factor in determining the selectivity of the nitrile product, because this side reaction limits the availability of the surface ammonia species that are necessary for nitrile synthesis. 

Nitriles may be converted to their imino chloride salts by the action of dry hydrogen chloride in ether. These intermediates ate reduced by anhydrous stannous chloride to stannic aldimonium chlorides, which on hydrolysis yield aldehydes. Chloroform may be added to facilitate the solution of the nitrile. The quality of the stannous chloride catalyst is important the preparation of an active and dependable form has been described. The yields are usually high for many aromatic nitriles, as in the preparation of /3-naphthaldehyde (95%). The reaction has also been employed in the heterocyclic series, as in the synthesis of 4-methyl-thiazole-5-aldehyde (40%). The reduction of the cyano group in the... 

Aromatic nitriles are also prepared by heating amides with phosphorus pentoxide, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, and ammonium sulfamate. In addition, the action of a double salt of aluminum and sodium chlorides, NaCl- AlClj, gives excellent yields of nitriles from both aliphatic and aromatic amides. Heating an amide with phthalic anhydride causes dehydration. A novel synthesis consists in treating a mixture of an aromatic acid and p-toluene-sulfonamide with phosphorus pentachloride the yields of nitriles range from 63% to 79%. ... 

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