Thorpe reactions mechanism

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 Paris school included Robert Lespieau (18641947), Georges Dupont (18841958), Charles Prevost (18991983), and Albert Kirrmann (19001974). Principal figures in the London-Manchester school were Arthur Lapworth (18721941), Thomas Martin Lowry (18741936), Robert Robinson (18861975), Jocelyn Thorpe (18721940), and Christopher Ingold (18931970). A broadly defined German research school pursuing ionic and electronic theories of reaction mechanisms in organic chemistry does not enter into this history, because it did not exist. 

As is well known, Robinson became convinced that Ingold had not given him proper credit for his, and Lapworth s, role in the development of an electronic theory of organic reaction mechanisms. In reply to a furious letter from Robinson, Thorpe tried to reassure Robinson about Ingold. 

The present review covers the Thorpe-Ziegler syntheses of 3-aminofurans, 3-aminopyrroles, 3-aminothiophenes, 3-aminoselenophenes, and diverse aminoazoles as well as the corresponding annulated systems that appeared from 1983 to 1996 but excludes examples considered in the 3-cyanopyridine review (92MI1). Moreover, examples are included that do not report a separate Thorpe-Ziegler cyclization but are likely to involve this type of reaction (e.g., cases in which precursors 1 were not isolated and identified but directly formed in the reaction mixture). Special attention is paid to synthetic aspects, although some reaction mechanisms are discussed too. 

Onorato JM, Jenkins AJ, Thorpe SR, and Baynes JW (2000) Pyrldoxamlne, an Inhlhltor of advanced glycatlon reactions, also Inhibits advanced llpoxldatlon reactions. Mechanism of action of pyrldoxamlne. Journal of Biological Chemistry 275, 21177-84. 

Onorato JM, Jenkins AJ, Thorpe 8R, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. Mechanism of action of pyridoxamine. J Biol Chem 2000 275 21177-21184. 

The passage from (35) to (38) can be represented by two possible mechanisms (Scheme 4). One of them is the addition of the active methylene group of dimethyl succinate to the cyano group in the manner of a Thorpe reaction and the subsequent cyclization of (39) with the participation of the... 

Fu MX, Wells-Knecht KJ, Blackledge JA, Lyons TJ, Thorpe SR and Baynes JW (1994) Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. Diabetes 43, 676-683. 

The few thiophene syntheses reported in which the formation of the heterocycle is realized on an insoluble support (Entries 1-3, Table 15.10) are based on the intramolecular addition of C,H-acidic compounds to nitriles (Thorpe-Ziegler reaction), or on the Gewald thiophene synthesis. The mechanism of these cyclizations is outlined in Figure 15.6. In thiophene preparations performed on solid phase, the required a-(cya-... 

Figure 15.6. Mechanisms of thiophene formation by the Thorpe-Ziegler and Gewald reactions. X leaving group Z electron-withdrawing group.

A review of chemiluminescent and bioluminescent methods in analytical chemistry has been given by Kricka and Thorpe. A two-phase flow cell for chemiluminescence and bioluminescencc has been designed by Mullin and Seitz. The chemiluminescence mechanisms of cyclic hydrazides, such as luminol, have been extensively analysed. " Fluorescence quantum yields of some phenyl and phenylethynyl aromatic compounds in peroxylate systems have been determined in benzene. Excited triplet states from dismutation of geminate alkoxyl radical pairs are involved in chemiluminescence from hyponitrite esters. Ruorophor-labelled compounds can be determined by a method based on peroxyoxalate-induced chemiluminescence. Fluorescence and phosphorescence spectra of firefly have been used to identify the multiplicity of the emitting species. " The chemiluminescence and e.s.r. of plasma-irradiated saccharides and the relationship between lyoluminescence and radical reaction rate constants have also been investigated. Electroluminescence from poly(vinylcarbazole) films has been reported in a series of four... 

The original Thorpe conditions involved a catalytic amount of base, as the mechanism would imply. Later workers found that in certain reactions equivalent amounts of base were required or that catalytic and equivalent amounts of base gave different products. As shown in Scheme 84, the Michael dimer (177) is the major product when adiponitrile (175) is cyclized with a trace of sodium f-butoxide in f-butyl alcohol, whereas an equivalent of this base in toluene gave the monomer (176). 

On the surface it would appear that the mechanism of 4 and 5 formation arises by generation of equal molar amounts of acetonitrile and propionitrile from 1 by a metal catalyzed retro Thorpe-Ziegler Reaction (5) to generate equal moles of the two alkyl nitriles. These, in turn, are in-situ hydrogenated to their respective alkylideneamine intermediate (8) which in turn adds 1 to form the N-(aminoalkyl)-... 

When using cyanoacetic esters instead of aldehydes, the Guareschi-Thorpe pyridine synthesis assembles pyridines 155 by the condensation of acetoacetic esters 153 with cyanoacetic esters 154 in the presence of ammonia. A variation of this method involves the reaction of cyanoacetic ester 156 with 3-diketone 157 in the presence of ammonia to generate 2-hydroxypyridine 158." The mechanism of this reaction has been studied, and it was initiated by an ester/amide exchange on cyanoacetic ester 156 with... 

A mechanism for the piperazine-catalyzed formation of 4//-chromenes is complex cascade of reactions, starting with piperazine acting as a base which activates malononitrile, promoting Knoevenagel condensation, and also formation of an enamine, followed by Michael condensation, proton transfer, intermolecular cycliza-tion via a nucleophilic addition of the enolate oxygen to the nitrile group (hetero-Thorpe-Ziegler), and finally hydrolysis and tautomerization. 

Oxo-bridged metal complexes can be considered an extension of metal-aquo/hydroxo/oxo systems, and in fact these species often interconvert in the redox reactions of aqueous metal ions however, the pH-dependent reduction potentials of oxo-bridged complexes have enjoyed a special distinction because of their relevance to the proposed mechanisms for the oxidation of water by a tetramanganese oxo cluster in photosystem II.Thorp and co-workers characterized the pH-dependent redox mechanisms of mixed-valence manganese oxo-bridged complexes such as [(NN)2Mn (0)2Mn (NN)2], where NN represents bpy or phen. This family of complexes... 

Bach RD, Dmitrenko O, Thorpe C (2008) Mechanism of thiolate-disulfide interchange reactions in biochemistry. J Org Chem 73(l) 12-21.doi 10.1021/jo702051f... 

A library of novel 5-amino-2,7-diaryl-2,3-dihydrobenzo[l)]thiophene-4,6-dicarbonitriles was synthesized by a one-pot domino reaction of 5-aryldihydro-3(2H)-thiophenes, malonitrile, and aromatic aldehydes in the presence of morpholine (13BMCL2101). A mechanism was proposed that involves a sequence of Knovenagel condensation, Michael addition, intramolecular Thorpe-Ziegler cyclization, tautomerization, and elimination. The compounds were evaluated for their AChE (acetylcholinase) activity. The 5-amino-2,7-bis(4-methoxyphenyl)-2,3-dihydrobenzo[l)] thiophene-4,6-dicarbonitrile was found to be the most potent with IC50 4.16 xmol/L. 

---