Alkylation aromatic nitrile

This method has the great advantage over method (A) in that it can be applied in particular to those aromatic nitriles in which the aryl group is readily sulphonated clearly, it can also be applied to nitriles in which the alkyl or aryl portion contains groups which are in any other way affected by concentrated sulphuric acid, or by concentrated aqueous alkalis. 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

An unusual solvent effect was observed in cycloadditions of aromatic nitrile N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60 40) the reaction rates were 14-fold greater than those in chloroform (148). The use of ion pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary bearing an ionic group and an associated counterion provides enhanced selectivity in the cycloaddition the intramolecular salt effect controls the orientation of the... 

Baker s yeast catalyzed the regioselective cycloaddition of stable aromatic nitrile oxides ArCNO [Ar = 2,6-C12C6H3, 2,4,6-Me3C6H2, 2,4,6-(MeO)3C6H2] to ethyl cinnamate, ethyl 3-(p-tolyl)acrylate, and tert-butyl cinnamates (218). Reactions of dichloro- and trimethoxybenzonitrile oxides with all three esters proceeded regio- and stereoselectively to form exclusively alkyl tran.v -3,5-diary 1 -... 

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). 

The addition of sodium azide to nitriles to give IH-tetrazoles is shown to proceed readily in water with zinc salts as catalysts. The scope of the reaction is quite broad a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. 

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 ... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

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. 

Reaction conditions which are particularly applicable to aromatic nitriles involve the use of an aqueous solution of sodium hydroxide containing hydrogen peroxide, but alkyl cyanides do not always give good results the method is illustrated by the preparation of toluamide (Expt 6.167). 

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). 

Aromatic ketones arylations, 10, 140 asymmetric hydrogenation, 10, 50 G—H bond alkylation, 10, 214 dialkylzinc additions, 9, 114-115 Aromatic ligands mercuration, 2, 430 in mercury 7t-complexes, 2, 449 /13-77-Aromatic nitriles, preparation, 6, 265 Aromatic nucleophilic substitution reactions, arene chromium tricarbonyls, 5, 234... 

Ainmoxidation, sometimes also termed oxidative ammonolysis, describes the process of catalytic oxidation of hydrocarbons (particularly alkenes, alkanes, alkyl-aromatics and alkyl-pyridines) to organic nitriles in the presence of ammonia, typically using mixed oxide catalysts ... 

For the chelation-assisted catalytic reaction, Jt-electrons in a nitrile group are able to function as a directing group. The ruthenium-catalyzed alkylation of aromatic nitriles with triethoxyvinylsilane takes place predominantly at the ortho position (Eq. 9.10) [24]. This regioselectivity indicates the possibility of Jt-coordination of the CN group to the ruthenium in the catalytic cycle. 

Bauld and coworkers, especially, developed the analogous Diels-Alder (4 + 2) cycloaddition reactions. These reactions are conveniently catalyzed by tris(4-bromophenyl)aminium hexachloroantimonate (78) or by photosensitization with aromatic nitriles. The radical cation-catalyzed Diels-Alder reaction is far faster than the uncatalyzed one, and leads to some selectivity for attack at the least substituted double bond for the monoene component (Scheme 18, 79 —> 80), but only modest endo selectivity (e- and x-80) [105]. Cross reactions with two dienes proved to be notably less sensitive to inhibition by steric hindrance of alkyl groups substituted on the double bonds than the uncatalyzed reactions, as cyclohexadiene adds detectably even to the trisubstituted double bond of 2-methylhexadiene (82), producing both 83 and 84. Dienes such as 85 react with donor-substituted olefins (86) to principally give the vinylcyclobutene products 87, but they may be thermally rearranged to the cyclohexene product 88 in good yield [105]. Schmittel and coworkers have studied the cation radical catalyzed Diels-Alder addition of both... 

Among the cycloaddition reactions which lead to imidazole products is the [3 + 2] cycloaddition of imines to 2-azaallenyl radical cations (derived from azirines by photolysis) which yields 1-substituted imidazoles <91AG(E)1336,93CB543). Similar addition of 2-azallyl anions (made by deprotonation of A-alkylated Schilf bases) to aromatic nitriles can give rise to either 3-imidazolines or imidazoles depending on the substitution pattern in the azaallyl species (229) <83CB492>. These reactions have been reviewed (Scheme 164) <90CHE1>. 

The base-catalysed intermolecular condensation of nitriles of the type RCH2CN is one of the oldest known methods for the preparation of -enaminonitriles, and in the case of simple self-condensation it leads to aliphatic analogues of the cyclic ji-ena.-minonitriles formed in the classical Thorpe-Ziegler cyclization. For example, the base-catalysed dimerization of acetonitrile with sodium gives 3-amino-crotononiirile Cross-condensation between acetonitrile and aromatic nitriles or higher aliphatic nitriles leads to substituted j8-enaminonitriles 156 (R = alkyl, aryl). 

It is known that nitrilium salts can be prepared by alkylation of nitriles , via the reaction of imidoyl chlorides with Lewis acids as well as by Beckmann rearrangement of oximes . The application of nitrilium salts in organic synthesis is summarized in a number of reviews " . In this connection it is appropriate to mention another three-component one-pot synthesis of 5,6-dihydro-4. -l,3-oxazines 40 based on the reaction of aldehydes with iV-tcr/-butylnitrilium salt 41 which, however, proceeds without the participation of Af-acyliminium ions . The reaction is carried out by mixing the aliphatic or aromatic aldehyde, tcrt-butyl chloride and Lewis acid (SbCljjSnC ) in benzonitrile solution (equations 16 and 17). 

Thermolysis70 of saccharin itself yields the benzoxazinone 49, which may be regarded as the dimer of the hypothetical imino ketene 50 produced by the elimination of sulfur dioxide from 41. Flash vacuum pyrolysis of 3-arylpseudosaccharins (46 R = Ar) affords reasonable yields of 2-arylbenzo-xazoles 3-alkyl compounds (46 R = alkyl) yield aromatic nitriles only.71... 

Polycyclic aromatic hydrocarbons Alkylated aromatic hydrocarbons Chlorinated aromatic compounds Chlorobenzenes Polychlorinated biphenyls Polychlorinated dibenzo[l,4]dioxins Chlorinated guaiacols and catechols Nitrogen-containing aromatic compounds Azaarenes and aromatic nitriles Oxygenated aromatic compounds 2,4-Dipentyl phenol Polycyclic quinones and ketones Aliphatic carboxylic acids Cs and C, dicarboxylic acids... 

Chloromethyl)aniline hydrochloride reacts at 160°C with the stannic chloride complex of acetonitrile to give 2-methyl-3,4-dihydroquinazoline (see 1). The nitrilium salt 78 is presumed to be the intermediate. Yields were excellent when other aliphatic and aromatic nitriles were used. JV-Methyl-2-(chloromethyl)aniline gave 2-alkyl- or 2-aryl- 1,4-dihydroquinazolines in excellent yields.74... 

Ammonia reacts catalytically with alkyl or alkanyl side chains on aromatic hydrocarbons to form aromatic nitriles, or with olefins, and to some extent alkanes, to form aliphatic nitriles. It also reacts catalytically with methane (natural gas) in the presence of a regulated amount of oxygen to form hydrogen cyanide. The following equations illustrate the reactions involved with substituted aromatic compounds ... 

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