Thorpe reactions

Thiurets — see 1,2,4-Dithiazolidines, diimino-Thonzylamine antihistamine, 3, 153 Thorpe reaction benzothiophenes from, 4, 876 Thorpe-Ziegler cyclization, 2, 74 Three-membered heterocyclic compounds basicity, 7, 23... 

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]. 

In the Thorpe reaction, the a carbon of one nitrile molecule is added to the CN carbon of another, so this reaction is analogous to the aldol reaction (16-38). The C=NH bond is, of course, hydrolyzable (16-2), so p-keto nitriles can be prepared in this manner. The Thorpe reaction can be done intramolecularly, in which case it is... 

It has been established that Thorpe reactions proceed efficiently under solvent-free conditions. For example, when a mixture of acetonitrile (71) and powdered Bu OK was kept at room temperature overnight, a 1 1 mixture of (E)- and (Z)-... 

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... 

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]. 

Thorpe reaction org chem The reaction by which, in presence of lithium amides, a,(rt-dinitriles undergo base-catalyzed condensation to cyclic iminonitriles, which can be hydrolyzed and decarboxylated to cyclic ketones. thorp re,ak-shan TMPC See tetrakis(hydroxymethyl)phosphonium chloride, thulia See thulium oxide. thu-le-a ... 

Problem 17.37 The C of the —C=N group is an electrophilic site capable of being attacked by a carbanion. Show how nitriles like CHjCH C N undergo an aldol-type condensation (Thorpe reaction) with hindered bases. M... 

Thorpe Reaction (If intermodular, known as the Thorpe-Ziegler Reaction.)... 

The Thorpe reaction is often better than the Diekmann Cvclization for ring sizes > 7. 

Ring closure by conventional methods (Thorpe reaction) is given in equation (7) (730S(53)98). An important route to the appropriate starting material employs a Michael addition of PhPH2 or MeOP(0)H2 to an a,j8-unsaturated nitrile, carbonyl compound, etc., e.g. equations (8) and (9). 

A Thorpe reaction scheme led to the synthesis of a benzo[( ]thiophene derivative (87) in 80% yield, when (86) was treated with sodamide in dry benzene (62JOC2821). While reactions are known to convert (87) into benzo[6]thiophene, this pathway has not yet been explored. 

In the anionic polymerization of rigorously purified acrylo-nitrile, studied in Du Pont Co. by Dr. E. F. Evans, there is apparently a termination if the reaction proceeds at higher temperatures (50°—70° C). This is shown by a decreasing yield at higher temperatures as compared with 100% conversion observed at lower temperatures. It has been proposed that the termination is due to an isomerization that resembles the Thorpe reaction, namely... 

Some general preparative aspects of cyclization, such as a choice of catalysts, solvents, etc., have been described earlier (1989MI2, 1992SR1). However, numerous new examples of the use of the Thorpe reaction in the synthesis of thienopyridine... 

Based on the structures of the starting reagents, several main pathways of formation (A-C) of the thiophene ring by the Thorpe reaction can be... 

The Thorpe reaction of 2-alkylthiopyridoquinuclidines 21 resulting in its isomerization to form the corresponding thienopyridoquinuclidines 22 (1989ZOR1980, 1994KGS122) is another example of the construction of the thieno[2,3-Z>]pyridine system according to method A. 

Recently, a method has been developed for the synthesis of thieno[2,3-Z>] indeno[2,l-< ]pyridine derivatives 23 by the Thorpe reaction starting from thiones 24 (2000SC3883). It should be noted that compounds 23 were synthesized according to the same procedure three years earlier (1997MI1). However, the latter study is... 

Nucleofuges, other than the chlorine atom, can be involved in these reactions. For example, 1,2-bipyridinium chloride 25 reacts with ethyl thioglycolate with elimination of pyridine to form sulfide 26, whose isomerization to thienopyridine 27 occurs under conditions of the Thorpe reaction (1998T5775). 

As mentioned above, amines of the thienopyridine series synthesized by the Thorpe reaction always contain an electron-withdrawing substituent (acyl, alkoxy-carbonyl, etc.) at position 2. The presence of the o-aminocarbonyl fragment in these compounds makes these compounds useful as synthons for pyridine ring construction in the Friedlaender synthesis. Generally, condensation occurs in the presence of a basic catalyst. The acid-promoted synthesis can be exemplified by the preparation of tetracyclic structure 59 from pyranothienopyridine 60 (1996RFP1417446). 

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