Heterocycles cyclocondensation reaction

Abstract Controlled microwave heating has foimd many important applications in the synthesis of heterocycles. Almost all kinds of heterocycles have been prepared (or their preparation attempted) with the aid of microwaves. Many examples of cyclocondensations, reactions where two or more fimctional groups combine with the loss of another small molecule (usually water), have been described. Moreover, microwave irradiation successfully induces cycloaddition reactions, especially in the cases where high temperatures are required. This review collects the most representative examples of the application of microwaves to these two kinds of transformations. Except for a few examples, all the reactions selected have been carried out imder controlled microwave irradiation using dedicated instruments. 

Keywords Cycloaddition reactions Cyclocondensation reactions Heterocycles ... 

The heterocycle formed in the cyclocondensation reactions of 2-acetylenyl-l-chloro-9,10-anthraquinones or 5-acet-yleneyl-3-(diethylamino)-l,4-naphthaquinones with hydrazine is influenced by the presence of a heterofunctional OH group in the acetylenic substituent. This directive effect was used in the synthesis of naphtha [2,3- ]cin noline-4,7,12-triones and 4//-naphtho[ 1,8-z/7]-l, 2-dia/cpin-8-oncs <2000MC188>. 

Monocyclic and fused 1,3,5- and 1,3,6-oxadiazepines are accessible either by one-component cyclization (see Scheme 22), [1+6] cyclocondensation, [3+4] condensation (substitution) reaction, heterocyclic ring rearrangement (see also CHEC(1984) and CHEC-II(1996)), or multicomponent reactions (Scheme 37). The 1,3,5-oxadiazepine heterocyclic ring is also present in iminonucleosides, such as compounds 142 (Scheme 29), which are available via one-component cyclization and [1+6] cyclocondensation reactions. 

Surprisingly, the synthetic potential of this heterocycle synthesis remained unexplored for quite some time. In the 1970s and 1980s interest for the original Biginelli cyclocondensation reaction slowly increased and... 

Known from the literature are the heterocycle formation reactions from the interaction of 1,2-diamines with synthetic precursors of unsaturated ketones, i.e., the ones which contain an activated methyl or methylene group (Scheme 4.17). Since such cyclocondensations are obviously related to... 

A related intramolecular N-alkylation leading to saturated nitrogen heterocycles 99 can proceed via dehydration of intermediates 98 (Eq. 39) [96]. Unsaturated nitrogen heterocycles such as pyrroles [97], indoles [98], benzo-azoles [99], 2,3-dihydroimidazol-2-ones [100], and imidazo[l,2-a]pyridines [101] were obtained through similar cyclocondensation reactions. Interesting ruthenium-catalyzed syntheses of quinolines have been achieved by means of cyclocondensations of aniline derivatives with propanediols, aminoalcohols, or... 

As shown in Equation (4), the sensitized irradiation of a mixture of 4,6-dimethyl-2-pyrone and maleic anhydride, or of 4,6-dimethyl-5-ethoxycarbonyl-2-pyrone and maleimide, gives the mixed photoadducts (23) and (24) in ca. 20% yields (90BCJ3456, 92BCJ354). As with many other [2 + 2] cyclocondensation reactions involving heterocycles, these are thought to proceed via biradical intermediates. 

III. Introduction of Fluorine and Perfluoroalkyl Groups into Five-Membered Heterocycles via Cyclocondensation Reactions... 

Sausins A, Duburs G (1988) Synthesis of 1,4-dihydropyridines by cyclocondensation reactions. Heterocycles 27 269-289... 

Cyclocondensation reactions of benzodioxole diester 166 with ethylenediamine and hydrazine to give spiro heterocycles have been reported <1996AKZ124>. 

The second general type of cyclocondensation reactions is the interaction of iV-aminoazoles with bifunctional electrophilic-nucleophilic syn-thons. Evidently, the ring carbon atom in such heterocyclic substrates must carry an effective positive charge. Since loss of a hydride ion is unfavorable, thio- or alkylthio derivatives of N-aminoazoles 360 are usually used. 

Most information on cyclocondensation reactions of ZV-aminoazoles is concerned with vicinal N.C-diaminoazoles. In most cases, reactions were carried out with various carbonyl-containing compounds carboxylic acids and their derivatives, aldehydes and ketones, 1,2- an 1,3-dicarbonyl compounds, etc. Depending on the structure of these synthons, cyclocondensations lead to the formation of five-, and six- or seven-membered heterocycles. 

The reaction between secondary enediamines and propiolic acid esters has been studied in detaiP. In aprotic solvents such as benzene and dioxane, 8 adds to methyl propiolate at ambient temperature to give almost quantitatively product 118 with a tron -configuration of the new double bond, as indicated by a Jhh coupling constant of around 16 Hz in the NMR spectrum. It appears that the reaction proceeds via an ene-addition mechanism. In refluxing ethanol, the C-adducts 118 are converted to the heterocyclic compounds 119. The direct transformation of 8 to 119 is easily achieved in alcoholic solvents. 1,1-Enediamines with jS-nitro, ester and acetyl substituents undergo analogous addition and cyclocondensation reactions to give heterocyclic compounds jj5(39,i2o A -Ethynylcarbonyl imidazole behaves similarly to propiolic acid esters ° (equation 41). 

An additional heterocyclic ring fused to a (6 5 6) system can be constructed by a cyclocondensation reaction of an appropriately substituted tricyclic derivative with an external reagent. The NH2-CN functionality of (177) was transformed into a pyrimidine by the reaction with formamide <91H(32)895>, and cyclocondensation of the Ac-OH functionality in (178) with phenyl-hydrazine gave a pyrazole <9lH(32)90l>. A hydrazino derivative (179) was condensed with a carboxylic acid to give a 1,2,4-triazole in the reaction that involves an N-2 atom of (179) <88Ci(L)785>. 

Pyrimidines are an interesting class of nitrogen-containing heterocycles which display a broad range of useful properties.Based on a novel cyclocondensation reaction between acetylenic ketones of type 339 and polymer-bound isothiourea 338, Obrecht et developed a versatile and efficient solid-phase synthesis of polymer-bound 2-(alkylthio)-4,6-disubstituted pyrimidines 340, and combined this protocol with the nucleophilic displacement reaction of the 2-sulfonyl group of pyrimidines 47 j gy dgavage reaction. In addition, simple... 

A general and practical method for synthesis of aryl-substituted five-membered heterocycles was developed. In the presence of KOH (30 mol%), l,4-diaryl-l,3-butadiynes undergo a cyclocondensation reaction with water in dimethyl sulfoxide at 80 °C to afford 2,5-diarylfurans in good-to-exceUent yields (14T8252). 

Martins et al. [66] described the role of IL in synthesis of various heterocycles. IL is used in cyclocondensation reactions and three-membered heterocycles such as aziridines. It is used in the synthesis of five-membered heterocycles such as pyr-... 

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