Condensation of nitriles

A new route to 4-substituted pyrimidines involves the condensation of nitriles with iV-vinyl amides which are activated by trifluoromethanesulfonic anhydride and 2-chloropyridine <2006JA14254>. The method is illustrated by the synthesis of 4-cyclohexyl-2,5-diphenylpyrimidine 627 from A-styrylbenzamide 625 and cyclohexanecarboni-trile 626 in 89% yield <2006JA14254>. 

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

In addition to the reaction of amino groups with carbonyl compounds, in another useful method for the preparation of imines the reduction or condensation of nitriles with other reagents is employed (Eq. 2). Other more specialized methods [lb] are described in Section 5. 

Condensation of nitriles (Thorpe) 9-33 Dimerization of cyano carbonyl compounds... 

N-Thioacylamidines (78), the starting materials required in this synthesis, are most readily accessible by the condensation of nitriles (75) and thioamides (76) in ethereal solution in the presence of hydrogen chloride. This reaction, first performed by Matsui101 and correctly... 

Ritter reactionThis reaction involves the condensation of nitriles with an alcohol in a strongly acidic medium to form an amide.J Yields are generally low with primary and secondary alcohols, which form relatively unstable carbocations. 

The cobalt(I)-catalyzed condensation of nitriles (1 mole) or isocyanates (1 mole) with alkynes (2 moles) gives pyridines and 2-pyridones, often in excellent yield (Scheme 72). 

It has been found that low-valent iridium hydride complexes are effective catalysts for activation of both the a-C-H bond and the CN triple bond of nitrile. Actually, the catalytic cross condensation of nitrile 27 and nitrile 28 in the presence of IrH(CO)(PPh3)3 catalyst (29) was performed under neutral conditions to give the... 

There are several preparations of cytosine 10.6 available, one of which is the condensation of nitrile 10.26 with urea 10.16. Propose a mechanism for this reaction. 

Pyridones can be made by the condensation of nitriles with dianions of -diketones or 3-iminoketones (e.g.,... 

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 / -ena-minonitriles formed in the classical Thorpe-Ziegler cyclization. For example, the base-catalysed dimerization of acetonitrile with sodium gives 3-amino-crotononitrile661. 

The synthesis starts with the condensation of nitrile 48 with the (/ )-2-methylcysteine compound 5 X HCl (Scheme 12). 

The Hiyama aminoacrylate synthesis " is the synthesis of alkyl ester of 3-aminoacrylic acids or derivatives by aldol-type condensation of nitriles with ester in the presence of a base such as (i-Pr)2NH. 

Trepanier DL, Wagner ER, Harris G et al (1966) 1,4,5,6-Tetrahydro-as-triazines I. Sulfuric acid catalyzed condensation of nitriles and hydrazino alcohols. J Med Chem 9 881-891... 

Aluminum chloride catalyzed condensation of nitriles with dlazoke-tones affords good yields of oxazoles. ... 

The formation of quinazolines by condensation of nitriles with imidoyl chlorides, or the cations derived from them, in the presence of a Lewis acid... 

Acetic hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. For example, a convenient and efficient one-step, base-catalyzed synthesis of 3,5-disubstituted-1,2,4-triazoles 161 is obtained from condensation of nitriles 159 and hydrazides 160 under microwave... 

Perhaps the most intensively studied synthesis of amino-1,2,3-triazoles is the base-catalyzed condensation of nitriles with azides and the following rearrangement discovered by Dimroth (Eq. 14). Lieber and Rao have made detailed studies of the relationship of cyclization to rearrangement and have shown the optimum conditions for the isolation of 6.1-7 and 6.1-S. ... 

Sml2 has been found to be an efficient catalyst for the condensation of nitriles with amines to form N,N-disubstituted amidines 204 under mild reaction conditions and in good yields (Scheme 31). The N,N-disuhstituted amidine alone cannot be transformed into r-triazine 205 whether Sml2 is used or not. r-Triazine 205 is obtained only in the presence of the corresponding nitrile and a catalytic amount of Sml2 <2002TL1867>. 

Another reported procedure consists of condensations of nitriles with glycols. The resultant poly (iminoether hydroxide)s hydrolyze to polyesters [32]. 

H. Baron, etal, J. Chem. Soc. 85, 1726 (1904) K. Ziegler er a/., Ann. 504,94 (1933). Base-catalyzed self-condensation of nitriles to yield imines which tautomerize to enamines ... 

Trivalent lanthanide inflates and Smta have been employed successfully as catalysts in the condensation of nitriles with primary amines and diamines into N,N -disubstituted and cyclic amidines, but monosubstituted... 

The Williams group has reported the use of cheaper, non-PGM catalysts for the condensation of nitriles with amines. With an excess of either the... 

Condensation of Nitriles and Dialkyl Sulphites. (Type C).—A novel isothiazole synthesis involves the interaction of phenylacetonitrile anion, generated in the presence of sodamide, and diethyl sulphite. The main product of the reaction, 4,5-diphenylisothiazol-3-ol (17) (47%), is accompanied by a-cyano-a-(4,5-diphenylisothiazol-3-yl)benzyl phenyl thione (18) (up to 15%). The use of other dialkyl sulphites produces the same isothiazolol (17), but in much reduced yields (9—18%). The reaction may possibly proceed by way of the sulphine intermediate (15), as outlined in Scheme 1, terminating with loss of hydrogen cyanide from (16). ... 

Condensation of nitrile (63) with 2-butanone gave pyridone (64). However, attempts to introduce an amino substituent into the 3-position of (64) by various electrophilic reactions gave only phenyl ring-substitution products (55, 58). This work clearly indicated the inherent difficulties associated with functionalization of pyridine C-ring precursor by electrophilic chemistry in the presence of a highly oxygenated D-ring. 

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