Condensation cyclocondensation

Aldol Condensation Claisen Condensation Claisen-Schmidt Condensation Cyclocondensation Friedlander Condensation Isay Condensation Knoevenagel Condensation Pechmann Reaction Ugi Condensation... 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

The original compound, maleimide (2,5-dioxo-A -pyrroline), is synthesized by the cyclo-condensation of ammonia and maleic acid. Similarly, primary amine is added to maleic anhydride, followed by cyclocondensation, to form N-substituted maleimide (Fig. 2). This reaction is applied to the preparation of bis-maleimides (BMl) [1]. At first, BMI was used as a crosslinking agent for natural rubber (NR). An o-dichlorobenzene solution of NR was crosslinked by BMI at I08-150°C in the presence of peroxides. The radicals generated from peroxides react with the double bonds of both BMI and NR [ 1 ]. 

Cyclocondensation reactions with perfluoroalkyl-subsbtuted CO and CN multiple bond systems can be divided into several subgroups, according to the charge pattern of both reactants On the basis of this simple concept, hetero-l,3-dienes should undergo two types of condensation reactions, classified by the number of skeleton atoms of the diene being incorporated into the ring system (equation 10). 

Available information on the mechanism of cyclocondensation is rather contradictory. According to one hypothesis, both the condensation of aryl halides with copper acetylides and the cyclization occur in the same copper complex (63JOC2163 63JOC3313). An alternative two-stage reaction route has also been considered condensation followed by cyclization (66JOC4071 69JA6464). However, there is no clear evidence for this assumption in the literature and information on the reaction of acetylenyl-substituted acids in conditions of acetylide synthesis is absent. 

Cyclocondensation of 2-aminopyridines with methyl 3-(A,A-dimethyla-mino)-2-(benzyloxycarbonylamino)acrylate in boiling AcOH for several hours gave 3-(benzyloxycarbonylamino)-4//-pyrido[l, 2-n]pyrimidin-4-ones 370 (99CCC177, 00MI33). 2-Amino-6-methylpyridine afforded only condensation product 371. 

Hydrazinotriazine 749 was prepared by the condensation of the respective quinone with thiosemicarbazide followed by sequential cyclization, chlorination with phosphorus oxychloride, and reaction with hydrazine (88JHC1139). Cyclocondensation of 749 with formic acid or carbon disulfide gave triazolotriazines 750 (88JHC1139) (Scheme 156). 

Monocyclic 2H-[ 1,2,3 Idiazaphospholes (B) are easily accessible from the condensation of the four-membered chain incorporated in hydrazones or azoalkanes with phosphorus trichloride making available a large number of representatives that have been intensively studied [2, 4, 7], In contrast, their 1//-isomers (A) are less known and are obtained only as second minor product during the synthesis of 2//-[l,2,3]diazaphospholes in some cases. A facile synthesis for pyrido-anellated azaphospholes has been developed in our group by making use of 1,2-disubstituted pyridinium salts for condensation with phosphorus trichloride [8, 13-15], Accordingly, cyclocondensation of 2-alkyl-1-aminopyridinium iodides (1) with phosphorus trichloride in the presence of triethylamine affords pyrido-anellated l//-[l,2,3]diazaphospholes, i.e. l,2,3]diazaphospholo 1,5-a] pyridines (2) (Scheme 1) [16],... 

A variety of anellated 1H- and 4//-[l,4,2]diazaphospholes could be obtained by our research group via [3+2] cyclocondensation and [4+1] cyclocondensation routes [7-9], Condensation of 2-aminoazines (68) with chloromethyldichlorophosphine (65) proceeds with complete regioselectivity to afford 3-unsubstituted [4,5]-anellated... 

The only publication on the angularly condensed benzologues, pyrimido[2,l-tf]quinoxalines, describes the synthesis of 161 by formation of both the pyrimido and the pyrazino ring from [6+0] atom fragments. Compound 160, the targeted cyclocondensation product of the propanediamine derivative 159, spontaneously cyclized to the pyri-mido[2,l- ]quinoxaline A-oxide 161 (Equation 17) <2002S2687>. 

The final step to 46 is cyclocondensation of 3,7-diazabicyclo[3.3.1]nonane (51), bispidine70, with formaldehyde. There are two different approaches to 51 (i) a pyridine is converted to a piperidine and (ii) the double Mannich or Robinson-Schopf condensation of ketone 52 with formaldehyde and primary amines affords 1,5-disubstituted 3,7-dazabicyclo[3.3.1]nonan-9-one (53), bispidone, from which 5,7-disubstituted l,3-diazaadamantan-6-one (61) is derived. Route (i) is adopted by Galinovsky and Langer,71 Stetter and... 

Several 3-mercapto-l,2,4-trizines have been synthesized through the condensation of thiosemicarbazide with diketones under microwave irradiation in a solventless system <06PS87>. The synthesis and cyclocondensation reactions of 3-substituted-5-(2-aminobenzyl)-l//-[l,2,4]triazin-6-ones have been reported <06JHC613>. 

Cyclocondensation of 2-aroylbenzoic acid 223 with hydrazine gave the phthalazine derivative 224, which was alkylated with ethyl chloroacetate in aqueous sodium hydroxide or pyridine to give the N-substituted derivative 225. Condensation of the latter with hydrazine afforded the hydra-zide 226, which could be cyclized to give the 2//[l,2,4]triazino[3,4-a]phthalazin-3(4tf)-one 227 (91MI3). 

Compound 642, obtained by condensation of glyoxal with benzotriazole and morpholine undergoes interesting [2+3] cyclocondensation with 2-aminopyridine to give imidazo[l,2- ]pyridine 643 (Equation 15) <2003JOC4935>. Similar derivatives of piperidine and pyrrolidine are also described. 2-Amino- and 6-aminopyrimidines react similarly to give imidazo[l,2- ]- and imidazoll - pyrimidines, respectively. 

Condensation of diazonium salts 1152 with activated nitriles provides hydrazones 1153. Treatment of hydrazones 1153 with hydroxylamine affords amidoximes 1154 in high yield. Upon heating with anhydrous sodium acetate in refluxing DMF, compounds 1154 undergo intramolecular cyclocondensation to provide 5-substituted 4-amino-2-aryl-277-1,2,3-triazoles 1155 in 75-85% yield (Scheme 190) <2006ARK(xv)53>. 

The synthesis of 4,5-disubstituted triazoles shown in Scheme 208, carried out on a polymer support with microwave assistance, is based on a similar principle. In the first step, sulfinate 1248 is converted to sulfone 1249. Condensation with aldehydes provides vinyl sulfones 1250. Cyclocondensation of sulfones 1250 with sodium azide generates corresponding triazoline intermediates that eliminate sulfinate 1248 to provide triazoles 1251 in moderate to good yield <2006OL3283>. 

The cyclizations to obtain cyclic thioureas have been performed using thiocarbonyldiimidazole.232 Reaction of methyl acetoacetate, thiourea and an aliphatic aldehyde in the presence of the zinc iodide (Znl2) was studied. Under the normal pressure, reaction has not been occurred whereas at high pressure (300 MPa) conditions 3,4-dihydropyrimidine-2-thione was obtained only in 10% yield.233 The same one-pot three-component cyclocondensation reaction in the presence of iodide (I2) provides a variety of 3,4-dihydropyrimi-dine-2-thione in high yields.234 Condensation reaction of thioureas with a,p-unsaturated ketones in the presence of the sodium methoxide in methanol affords 3,4-dihydropyrimidine-2-thione derivatives.235,236 Acylation of N,N -disubstituted thioureas with methyl malonyl chloride followed by base-catalysed cyclization leads in the formation of l,3-disubstituted-2-thiobarbituric acids (Scheme 78).237... 

Apart from some special cases, the ring-closure step in the course of the synthetic pathway is often condensation reaction and, thus, these transformations can be considered as cyclocondensations . Reactions following a few other mechanisms like cycloaddition, electrocyclization, and intramolecular nucleophilic addition of electron pair of an atom to a multiple bond also occur relatively often. Because of the fairly large complexity of the ring systems belonging to this chapter, the treatment according to the heteroatomic combinations seemed the most straightforward. Thus, the fused... 

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