Subject nitrile synthesis

Hydroxyl Group. The OH group of cyanohydrins is subject to displacement with other electronegative groups. Cyanohydrins react with ammonia to yield amino nitriles. This is a step in the Strecker synthesis of amino acids. A one-step synthesis of a-amino acids involves treatment of cyanohydrins with ammonia and ammonium carbonate under pressure. Thus acetone cyanohydrin, when heated at 160°C with ammonia and ammonium carbonate for 6 h, gives a-aminoisobutyric acid [62-57-7] in 86% yield (7). Primary and secondary amines can also be used to displace the hydroxyl group to obtain A/-substituted and Ai,A/-disubstituted a-amino nitriles. The Strecker synthesis can also be appHed to aromatic ketones. Similarly, hydrazine reacts with two molecules of cyanohydrin to give the disubstituted hydrazine. 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

A.1.3. Syntheses of Natural Products and Related Compounds 1,3-Dipolar cycloaddition reactions of nitrile oxides in the synthesis of natural products and their analogs has been the subject of a recent review (458). 

This chapter mainly focuses on the latest achievements and recent developments in asymmetric hydroformylation. Since several reviews have been made in the last decade [9,14-16], the chapter discusses the contributions reported between 2000-2005 in particular, although the main diphoshites and phosphine-phosphite rhodium catalytic systems discovered since 1995 are also considered because of their significance in the subject. Particular attention is paid to mechanistic aspects and characterization of intermediates in the case of the hydroformylation of vinyl arenes because this is one of the most important breakthroughs in the area. The application of this catalytic reaction to different type of substrates, in particular dihydrofurans and unsaturated nitriles is the other main subject of this chapter because of their interest in organic synthesis and their industrial relevance. 

Primary amides can also be generated in situ from nitriles. Thus, one-pot synthesis of A -acyl-a-amino acids by Pd-catalyzed amidocarbonylation of alkyl- and arylnitriles has been developed.For example, acetonitrile was hydrolyzed to acetamide first and subjected to the reaction with cyclohexanecarbaldehyde in the same reaction vessel to give A-acetyl-2-cyclohexylglycine 13 in 92% yield (Equation (2)). This process is... 

Another example of oligomer preparation by C-C bond formation is outlined in Figure 16.30. In this synthesis, nitroalkyl phenyl selenides are converted into nitrile oxides in the presence of support-bound terminal alkenes, forming isoxazolines. Oxidative elimination of the selenide yields a new alkene, which can then be subjected to further 1,3-dipolar cycloaddition with a new nitrile oxide. Although this synthesis is short and easy to perform, the cycloadditions proceed with low diastereoselectivity... 

Whereas the subject of basicity of C=0 groups has already been covered by Palm and coworkers1, in this chapter we summarize more recent results and significant developments in the field of nitrones, nitriles and thiocarbonyls. This chapter is not exhaustive in scope, but rather consists of surveys of the most recent two decades of work in this still developing area. As indicated by the title of this contribution, we emphasize the more physical aspects such as acidity, basicity and proton affinity less attention is paid to synthesis, structure and bond theory which can be found in other specialized chapters of this book. 

The synthesis of a-alkylglutaric acids (e.g. 2-propylglutaric acid, Expt 5.136), is conveniently achieved by allowing an alkylmalonic ester to react with the a, / -unsaturated nitrile, acrylonitrile, in thfe Michael manner and then subjecting the product to vigorous acidic hydrolysis. 

The use of solid supported, recyclable catalysts, is a well-assessed technique in classic organic chemistry, and many exhaustive reviews dealing with this subject are available [105, 115]. The use of solid supported catalysts for library synthesis in solution has also been reported. Among others, Kobayashi et al. presented the use of a new supported scandium catalyst for 3CC reactions leading to solution libraries of amino ketones, esters, and nitriles (24-member model discrete library) [116], or to quinolines (15-member model discrete library) [117], and Jang [118] presented a polymer bound Pd-catalyzed Suzuki coupling of organoboron compounds with halides and triflates. This area was also briefly reviewed recently [119]. 

Dideoxynucleosides show potent anti-retroviral activity against HIV-specific reverse transcriptase80-83. In particular, 2, 3 -dideoxy-3 -C-cyano-2 -substituted thymidine derivatives (33 A and 33 B) with a free 5 -hydroxy function (R1 = H) are potential inhibitors of the HIV-reverse transcriptase-promoted c-DNA synthesis. As these compounds have yet to be prepared by another method, the 3 -ene-nitrile 3284 was subjected to conjugate addition reactions with ammonia, primary amines, secondary amines and carbon nucleophiles. Most of these nucleophilic amine addition reactions give either the trans-isomer 33 A as the sole product (e.g., reaction with pyrrolidine, piperidine, morpholine), or as the major product along with the c/s-isomer (e.g., reaction with methylamine, benzylamine), except for the reaction with ammonia where the cts-isomer 33B is formed as the major product84. 

The formation of olefinic nitriles from allylic halides is best accomplished with dry, powdered cuprous cyanide rather than with alcoholic alkali cyanides, with which side reactions such as isomerization and alcoholysis of the double bond are particularly bothersome. With cuprous cyanide the yields in the synthesis of allyl cyanide and methal-lyl cyanide are 84% and 86%, respectively. Higher allylic halides are subject to allylic rearrangements thus cuprous cyanide acts on crotyl halide (CH,CH CHCHjX) and methylvinylcarbinyl halide (CH,CHXCH = CH,) to produce the same mixture of isomeric nitriles (9 1) regardless of which halide is treated. Numerous cyanides of the allylic type (Cj-Ci4) have been prepared, although the possibility of an isomerization has not been considered. A similar isomerization has been observed in the reaction of sorbyl chloride and potassium cyanide. ... 

The second synthesis (398) is an extraordinarily simple and direct one, in which the protected tetracyclic indoloquinolizidine aldehyde 741, obtained as two C-14 epimers and prepared as shown in Scheme 113, was subjected to cleavage of the 3,A b-bond by reaction with benzyl chloroform-ate in aqueous tetrahydrofuran. The resulting C-3 alcohol was converted into the corresponding nitrile 742, which was again obtained as a mixture of C-14 epimers, regardless of whether the starting material 741 was either... 

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