Preparation of aromatic nitrile

Reactions that employ copper(I) salts as reagents for replacement of nitrogen m diazo mum salts are called Sandmeyer reactions The Sandmeyer reaction using copper(I) cyanide is a good method for the preparation of aromatic nitriles... 

The preparation of aromatic nitriles from diazo-compounds will be discussed later (p. 291). 

As usual in Sandmeyer reactions, the product, if volatile, is separated by distillation in steam if non-volatile, extraction or filtration is used. The manner in which the cuprous salt reacts is not exactly known it certainly unites at first with the diazonium compound to form a double salt (c/. Reaction CLXVI.). The method is widely applicable, and as the yields are usually good, it is a standard method for the preparation of aromatic nitriles. 

Reaction mann reactions (Figure 16.4-16.6). Regarding the preparation of aromatic nitriles, this reaction presents an alternative to the Sandmeyer reaction of aryl diazonium salts with CuCN (cf. Figure 5.53). 

A quite important process for the preparation of aromatic nitriles is certainly the substitution of diazo groups by a cyanide function (equation 18). Following this route, the nitro or a primary amino group is, in principle, replaced by a CN ligand. The most important procedures are summarized in review articles and in some shorter accounts. ... 

The preparation of aromatic nitriles by an 5rn1 process was described recently.Suitably substituted diazo sulfides, either isolated or only generated in situ, reacted with tetrabutylammonium cyanide under photon or electron stimulation (equation 21), leading to aryl cyanides with yields that are comparable with those of the Sandmeyer reaction. Bromo- and chloro-substituted aryl diazo sulfides afforded the corresponding dinitriles in high yields. 

This reaction has general application in the preparation of aromatic nitriles. 

The present synthetic sequence offers an alternative approach to the preparation of aromatic nitriles. The classic route to this class of compounds is to use the Sandmeyer reaction. The key steps in this latter pathway involve the diazotization of an aromatic amine followed by reaction of the diazonium salt, which is not isolated (it is explosive ), with CuCN to give the aromatic nitrile directly. Aromatic halides (Br or Cl) may also be prepared in this manner using the corresponding copper(l) halides, as shown here ... 

The Sequence E reactions illustrate the oxidation of a benzylic alcohol to its corresponding aldehyde and the subsequent two-step conversion of this aldehyde via an intermediate aldoxime to an aromatic nitrile. This synthetic route is an attractive alternative to the preparation of aromatic nitriles via the Sand-meyer reaction. 

Lai G, Bhamare NK, Anderson WK (2001) A one-pot method for the efficient preparation of aromatic nitriles from aldehydes using ammonia, magnesium sulfate, and manganese dioxide. Synlett 2 230-231... 

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 preparation of toluamide (Expt 6.167) illustrates a useful procedure for the conversion of aromatic nitriles into acid amides with the aid of alkaline hydrogen peroxides (see discussion, Section 5.12.4, p. 708). 

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

This method provides easy access to 4-alkylbenzoyl chlorides, which are useful intermediates in the preparation of diaryl esters that have mesomorphic properties.20 Benzoyl chlorides substituted in the 4-position also serve as starting materials for the preparation of aromatic aldehydes21 and nitriles,622 whereas the acids, derivable quantitatively from the acid chlorides, are good precursors via the Schmidt reaction to 4-substituted anilines.23... 

Two methods for the preparation of enamides from nitriles are generally used. Reaction of ethylmagnesium bromide with a variety of aromatic nitriles in refluxing ether and subsequent treatment of the suspension of the iminomagnesium bromide with acetyl or benzoyl chloride or with a variety of esters638-640 yielded the enamides in 25-60% yield (equation 44). 

Aromatic carboxylic acids can be prepared by oxidation of the corresponding benzyl alcohols and benzaldehydes. An aromatic methyl group is also sufficiently activated by the aromatic ring for it to be oxidized to the acid under vigorous conditions, such as heating with chromium(VI) oxide. Other conventional methods include the hydrolysis of aromatic nitriles and the carboxylation of aromatic Grignard reagents with carbon dioxide. 

Table 11 Yields of Aldehydes Prepared by the Stephen Reduction of Aromatic Nitriles ...

Addition of HaS to nitriles (73) represents an important method for the synthesis of primary thioamides (74 equation 33). The reaction is carried out under base or acid catalysis. The base-catalyzed process is particularly useful in the preparation of aromatic thioamides, i.e. for R = aryl, hetaryl in (73) triethylamine in molar proportion or pyridine, which at the same time also serves as solvent, are employed most commonly. The approach tolerates the presence of various other functionalities such as an amide, hydrazone, enamine, a-oxo, a-acetoxy ° or a-amino group. Moreover, the reaction has been applied to the synthesis of thioasparagine as such or incorporated into a dipeptide, as shown... 

In Older to avoid the handling of poisonous hydrogen selenide, two other useful syntheses have been devised. One method uses the reaction of aromatic nitriles with aluminum selenide in the presence of pyridine, triethylamine and water (Scheme 24), while the other is performed by the reaction of nitriles with selenium, carbon monoxide and water in the presence of triethylamine (Scheme 25). These methods are exceedingly convenient in terms of manipulation without the isolation of hydrogen selenide for the preparation of selenoamides. Using these methods, a variety of aromatic and heterocyclic selenoamides can be obtained from the corresponding nitriles in high yields. 

Prepared by the reaction of aluminum ethoxide with sodium hydride, it is a colorless, microcrystalline powder stable for several weeks in the absence of air and is used in ether or THF. A somewhat milder reducing agent than lithium aluminum hydride, it is recommended particularly for the reduction of aromatic nitriles to aldehydes C H,C N — C H.,CHO (95%). 

Another method for the preparation of 3-aryl-4//-l,2,4-oxadiazin-6(5.H )-oncs 4 is the reaction of aromatic nitrile oxides with ethyl esters of x-amino acids, which is thought to proceed via the esters of the A-(carboxymethyl)amide oximes discussed above. The nitrile oxides are generated from hydroxiinoyl chlorides7 and react in situ with the esters. If the esters are derived from optically active amino acids, optically active oxadiazinones are obtained.13... 

For the preparation of aromatic cyanides from aromatic halides Rosenmund and von Braun introduced copper cyanide in place of the alkali cyanide the halide is warmed with copper cyanide, if necessary with addition of a little pyridine, at 150-250°. The reaction can be accelerated by small amounts of a nitrile or of copper sulfate.444... 

Synthesis of 4(6)-amino-l,3,5-triazine-2-ones and 2-thiones starting from benzotriazole derivatives has been reported <01JOC6797>. The first template photochemical synthesis of a 1,3,5-triazine derivative as a receptor capable of differentiating between thymine and uracil has been described <01CC1446>. A new solid phase synthesis of trisubslituted 6-amino(substituted)-2,4-dioxo-3,4-dihydro-l,3,5-triazines from a resin-bound amine component has been reported <01JCO278>. The synthesis of thirteen lris(azol-l-yl)-13,5-triazines, as a new class of multidentatc ligands, has been described <01H(55)905>. Tris(pyrazolyl-13,5-triazincs) 14 have been prepared by cyclotrimerization of aromatic nitriles, in piperidine and in solvent-free conditions <01T4397>. 

Moderate yields of aromatic nitriles can be prepared by a process which consists formally of a metal-cyanide exchange reaction [106] but the mechanism of which differs fundamentally from that of metal-halogen exchange ... 

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