Heterocyclic compounds elimination reaction

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

The importance of the penicillins as a class of heterocyclic compounds derives primarily from their effectiveness in the treatment of bacterial infections in mammals (especially humans). It has been estimated that, in 1980, the worldwide production of antibiotics was 25 000 tons and, of this, approximately 17 000 tons were penicillins (81MI51103). The Food and Drug Administration has estimated that, in 1979 in the U.S.A., 30.1 x 10 prescriptions of penicillin V and 44.3 x 10 prescriptions of ampicillin/amoxicillin were dispensed. This level of usage indicates that, compared to other methods of dealing with bacterial infection, the cost-benefit properties of penicillin therapy are particularly favorable. Stated differently, penicillin treatment leads to the elimination of the pathogen in a relatively high percentage of cases of bacterial infection at a relatively low cost to the patient in terms of toxic reactions and financial resources. 

Crozet and coworkers have used Sp l reactions followed by elimination of HNO for the synthesis of various new heterocyclic compounds substituted with alkenyl groups These compounds are expected to be important for pharmaceutical nse fsee Eq 7 139)... 

Halopyridines and other re-deficient nitrogen heterocycles are excellent reactants for nucleophilic aromatic substitution.112 Substitution reactions also occur readily for other heterocyclic systems, such as 2-haloquinolines and 1-haloisoquinolines, in which a potential leaving group is adjacent to a pyridine-type nitrogen. 4-Halopyridines and related heterocyclic compounds can also undergo substitution by nucleophilic addition-elimination but are somewhat less reactive. 

Phosphites and 2,2-bis(trifluoromethyl)-5(2//)-oxazolone 71 react with elimination of carbon dioxide to give 2-aza-4-phospha-l,l-bis(trifluoromethyl)-l,3-butadiene 72 that can be used as a synthon for the previously unknown hydrogen-substituted nitrile ylide 72a in [3 + 2]-cycloaddition reactions. Examples of cycloadditions of 72a with dipolarophiles to give heterocyclic compounds 12t-ll are shown in Scheme 7.18. 

The synthesis of heterocyclic group 13/15 compounds of the type [R2MER 2]jc has been investigated for many years [21]. General synthetic pathways such as dihydrogen, alkane and salt elimination reactions as summarized in Scheme 3... 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

Phase transfer catalysis (PTC), or more generally, applications of two-phase systems, is one of the most important recent methodological developments in organic synthesis. It is important because it simplifies procedures, eliminates expensive, inconvenient, and dangerous reactants and solvents, and also allows one to perform many reactions that otherwise proceed unsatisfactory or do not proceed at all. PTC has been reviewed,1-12 but only one review concerns the chemistry of heterocyclic compounds.13... 

In organo-fluorine compounds fluorine atoms can be eliminated by nucleophilic sulfur species to form C —S bonds. In principle, the fluorine to be eliminated can be bonded to aliphatic or araliphatic compounds, as well as to aromatic or heterocyclic compounds however, the replacement proceeds more efficiently the more the fluorine is activated. Therefore, the synthetic usefulness of these reactions is the broadest with fluoroaromatic compounds, including heteroaromatics, with which the reactions often proceed smoothly under mild conditions. The nucleophilic sulfur compound to be reacted is. in most cases, an aliphatic or aromatic thiol or a metal sulfide, but reactions with, for example, thiourea or ammonium thiocyanate have also been described. The sulfur introduced this way can be either oxidized or removed by reduction, opening additional possibilities for modifications of the original fluoro compounds. 

The second method employed for the synthesis of telluraxanthene is similar to that widely used for the preparation of various tricyclic heterocycles containing one or two heteroatoms. It is based on the interaction of 2,2 -dilithiodiphenylmethane with powdered tellurium, by which reaction telluraxanthene 82 has been prepared in 50% yield [81JOM(205)167]. The reaction apparently proceeds through the intermediate bis(telluro-phenolate) 86 which is oxidized to the heterocyclic ditelluride 87. The latter compound eliminates tellurium from its stericaily strained seven-membered ring and converts to telluraxanthene. This mechanistic scheme seems to be corroborated by the observation that the treatment of lithi-oarenes ArLi usually ends in the formation of diarylditellurides Ar2Te2 (74MI1 83MI2). 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

The ketodiester 31 was made from 32 by bromination and elimination. Reaction with 30 gave first the heterocycle 40 that was dehydrated and aromatised in dry HC1. Oxidation of this methoxy-compound with Ce(IV) was quite easy and methoxatin was synthesised. 

A reaction somewhat similar to this 1,1-elimination is that resulting in ring opening as observed for several heterocyclic compounds (Lilie, 1971 Schuler et al., 1973 Neta, 1972d), e.g. reactions (74)-(76). Some rate constants are given in Table 8 and the... 

A study of ketene A, O-acetals has shown that such compounds derived from lactam acetals may be used in the preparation of larger heterocyclic systems via reaction with a 1,3-dipolar species, the initial cycloadducts stabilizing their structures by aromatization. Pyrrolo[2,3-i/]-l,2,3-triazole derivatives, however, do not undergo such elimination reactions and stable cycloadducts may be obtained. Thus, the lactam acetals (133) give the ketene A,0-acetals (134), which on reaction with p-nitrophenyl azide yield substituted pyrrolo[2,3-d]-l,2,3-triazole derivatives (135) <86CB359l>. 

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