And the Thorpe reaction

The formation of acetylenic carbinols from sodium acetylidos and carbonyl compounds,7 the addition of nitroparaffins to aldehydes,8 and the Thorpe reaction arc other transformations closely related to ahlol reactions. 

Until recently the products of all nitrile cyclizations by the Thorpe reaction had been formulated as imines, although the products were found in 1955 to be better written as the enamine structure. In order to verify the reaction mechanism of the Thorpe reaction, the solid-state reaction of 84 and Bu OK was monitored by measurement of IR spectra in Nujol mulls. As the reaction proceeds (Scheme 14), the CN absorption of 84 at 2250 cm" decreases and a new CN absorption of the imine intermediate (87) arises at 2143 cm As 87 is converted into 88 by a proton migration, the CN absorption of 87 at 2143 cm" disappears, and only the CN absorption of 88 at 2189 cm remains finally [13]. 

The use of classical condensation reactions is important. Thus, the Dieckmann reaction (equation 38) and the Thorpe-Ziegler cyclization (equation 39) have been used for almost a century for the preparation of a wide range of monocyclic and benzo-fused heterocycles. The aldol condensation and related reactions have also been fairly widely exploited, especially for the synthesis of 4-quinolones (the Camps reaction, e.g. equation 40), and various extensions of this general approach are described in the monograph chapters. 

The intramolecular iron-catalyzed Alder-ene reaction of enynes in the carbocy-clization reaction was recently reported by Furstner et al. (Scheme 9.8) [20], A low-valent cyclopentadienyliron catalyst, specifically the [CpFe(C2H4)2][Li(tmeda)] complex, is a reactive catalyst for enyne cydoisomerization reactions. Bicyclic products, also incorporating large ring systems, are thereby accessible, and the Thorpe-Ingold effect seems to be helpful for these types of reactions. 

The Dieckmann, Thorpe and Thorpe-Ziegler reactions all involve intramolecular cyclization of a stabilized anion to form a cyclic ketone. The Dieckmann reaction is the intramolecular equivalent of the Claisen condensation and yields cyclic 2-alkoxycarbonyl ketones as primary products, whereas the primary products of the Thorpe reaction are 2-cyanoenamines (Scheme 13). Sub quent hydrolysis affords cyclic ketones but the primary products, particularly those from the Dieckmann reaction, have a useful synthetic role (see Section 3.6.3.S.1). 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

Thorpe worked on the synthesis of polybasic organic acids with cyanoacetic ester, with Perkin on camphor derivatives (see p. 871), and on imino-com-pounds (1904-22), based on his discovery (1904) of the Thorpe reaction involving the condensation of cyanoacetic ester with its sodium compound. 

HNA was incorporated into many nuclear fuel reprocessing plants in the early 1970s replacing the ferrous sulfamate and hydroxylamine sulfate for plutonium reduction because it possessed the proper Pu(IV) to Pu(III) reduction attributes and the gaseous reaction products N2, N2O, and water contributed to the minimization of the volume of solid wastes produced. The French PUREX process at the La Hague site safely uses a mixture of HNA and nitric acid for the reductive stripping phase of plutonium. The British also used HNA in the thermal oxide reprocessing plant (THORP) for over several years (Barney, 1998). 

Scheme 9.160. A Thorpe-Ziegler reaction of 2,6-dicyano-2-methylhexane. First, base treatment allows the dinitrile to undergo acyloin-type condensation (Scheme 9.145) to an imino-nitrile. Hydrolysis of the imine (Scheme 9.65) generates a P-ketonitrUe, which, on further hydrolysis (Scheme 9.46), produces a P-ketocarboxylic acid, which then undergoes decarboxylation (vide infra). Interestingly, the intermolecular version of this reaction is the Thorpe reaction, while the intramolecular version is the Thorpe-Ziegler reaction. See Baron, H. Remfry, F. G. P. Thorpe, J. F. /. Chem. Soc., 1904,85,1726, as well as Ziegler, K. Eberle, H. Ohlinger, H. Liebigs Ann. Chem., 1933,504, 94, and Ziegler, K. Chem. Ber., 1934,67,139.

The successive condensation of compound (318) with tert-butyl cyanoacetate, hydrogen cyanide, and acrylonitrile, and pyrolysis to eliminate the tert-butoxycarbonyl grouping, led to the trinitrile (321). Its intramolecular condensation by the Thorpe reaction gave the bicyclic product (320) which was... 

More general processes rely on variations of the Guareschi-Thorpe reaction [14] where condensations between 1,3-dicarbonyls and cyanoacetamide yield functionalized monocyclic 2(lff)-pyridones (a and b. Scheme 2) [15, 16]. Unless the carbonyls are sufficiently different in reactivity, the reaction suffers from poor regioselectivity. The use of 3-alkoxy or 3-amino enones instead of 1,3-dicarbonyls has proven to be a versatile and reliable synthetic methodology where the 1,4-addition controls the regioselective outcome (c and d. Scheme 2) [17-19]. 

The intramolecular Thorpe reaction can also be carried out under solvent-free conditions. When a mixture of powdered adiponitrile (80) and Bu OK was kept at room temperature for 3 h, cyclization product 81 was obtained as a... 

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