HETEROCYCLES

Review | Regular issue | Vol. 83, No. 11, 2011, pp. 2451-2488
Received, 25th January, 2011, Accepted, 25th July, 2011, Published online, 11th August, 2011.
DOI: 10.3987/REV-11-696

■ Microwave Assisted Synthesis of Fused Heterocyclic Compounds

Kumar V. Srinivasan,* Pratip K. Chaskar, Satish N. Dighe, Dhanashri S. Rane, Pranav V. Khade, and Kishor S. Jain

Sinhgad College of Pharmacy, Vadgaon (Bk.), Pune-41, India

Abstract

Microwave assisted heating under controlled conditions has been proved beneficial for medicinal chemistry and drug discovery process since it dramatically reduces reaction times, from days or hours to minutes or even seconds. Also, microwave synthesis provides higher yields, lower cost, easy workups and greater purity as compared to lower yields, tedious workups, longer reaction times, lesser purity and termination of many by-products in the conventional thermal methods.

CONTENTS
1. Introduction
2. Microwave assisted synthesis of fused pyrimidine derivatives
3. Microwave assisted synthesis of fused pyridine derivatives
4. Microwave assisted synthesis of fused quinoline derivatives
5. Microwave assisted synthesis of fused quinazoline derivatives
6. Microwave assisted synthesis of fused indole derivatives
7. Microwave assisted synthesis of fused triazine derivatives
8. Microwave assisted synthesis of fused azepine derivatives
9. Microwave assisted synthesis of fused chromene derivatives
10. Microwave assisted synthesis of fused imidazole derivatives
11. Microwave assisted synthesis of fused pyrazole derivatives
12. Microwave assisted synthesis of fused triazole derivatives
13. Microwave assisted synthesis of fused thiazole derivatives
14. Microwave assisted synthesis of fused pyrrole derivatives
15. Microwave assisted synthesis of fused benzofuran derivatives
16. Conclusions
17. References

1. INTRODUCTION
In the new millennium, the concept of “Green Chemistry” will be forcing greater demands to meet the fundamental scientific challenges of protecting the health as well as environment, while maintaining the commercial viability. Exploration of alternative reaction conditions and media with minimal side products or waste and elimination of the use of hazardous solvents will be the main thrust area. Microwave technology has made greater residues now-a-days because of non-pollution, higher yields, lower cost, lesser time, easy workups and greater purity of final products.1 Microwave assisted chemical synthesis has proved successful in remarkably cutting the required reaction time and improving the yields and purity of the desired products. It has emerged as a powerful technique to promote a variety of chemical reactions.2 Microwave synthesis has the potential to influence medicinal chemistry efforts in at least three major phases of New Drug Discovery Research i.e. Generation of a discovery library, Hit-to-lead efforts and Lead optimization. On the other hand, it has become widely accepted that many classical reactions under microwave irradiation perform better than reactions under conventional heating.3-7 Microwaves have a variety of applications such as in synthetic chemistry, degradation of natural products, quantitative analysis, etc. microwave assisted synthesis has become a powerful synthetic tool for rapid synthesis of a variety of organic compounds.8-11 Microwave heating differs fundamentally from conductive heating. Microwaves couple directly with molecules within a reaction mixture, leading to rapid rise in temperature. The process is not dependent on the thermal conductivity of the vessel material resulting in instantaneous localized superheating of anything that will react to dipole rotation or ionic conduction, the mechanisms of energy transfer in microwave heating. The use of microwave energy reduces the heat-up and cool-down time for reactions and employs 50% less power than equivalent electric appliances.

This review details the synthesis of a variety of fused heterocycles (R/R1/R2/R3/R4 = alkyl/aryl, X/Y = C/N/O/S/Halogens and Ar = aryl) under microwave assisted conditions and the results are compared with those carried out under conventional methods in the form of reaction times, temperature, reaction conditions and product yields.

2. MICROWAVE ASSISTED SYNTHESIS OF FUSED IMIDAZOLE DERIVATIVES
2.1. Imidazo[1,2-a]annulated pyridines, pyrazines and pyrimidines
Aldehydes (1) and pyridine (3) were irradiated in a microwave oven by Varma et al.1 for 1 min (900 W) in the presence of montmorillonite K 10 clay (Scheme 1). After addition of isocyanide (2), the reaction mixture was further irradiated followed by a cooling period of 1 min to give the final product (4).

2.2. Fused 3-aminoimidazoles
The reaction of heterocyclic amidines (5) with aldehydes (1) was carried out by the Ireland et al.2 in methanol as solvent (Scheme 2). Immediate addition of the isocyanide (2) followed by microwave irradiation gave the product (6).

2.3. 2-Aryl-1-arylmethyl-1H-1,3-benzimidazoles
Perumal et al.3 obtained 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles (8) in good yields by the reaction of o-phenylenediamine (7) with various aldehydes (1) in the presence of montmorillonite K-10 under microwave irradiation (Scheme 3) in the absence of solvent.

2.4. Pyrazino[1,2-a]benzimidazol-1(2H)ones
Alen et al.4 refluxed substituted 3,5-dichloropyrazinone derivatives (9) and o-bromoanilino derivatives (10) in presence of i-propanol (11) for 48 h giving o-bromoanilinopyrazinone compounds (12). Using a power of 150W, precursors (12) were stirred at 150 °C for 25 min with 10% Pd(PPh3)4 (14) and anhydrous potassium carbonate (13) in DMF (15) in a microwave in 61-74% yields (Scheme 4) to give 16.

2.5. Fused imidazo-pyridine and -azepine derivatives
Beebe et al.5 condensed an fused aldehyde (17) with an amine (19) and then treated with phenylTosMIC (18) in the presence of base to give imidazole (20) which was converted to the imidazo[1,5-a]pyridines (21) (Scheme 5).

2.6. Substituted imidazo[2,1-b]benzothiazoles
A series of substituted imidazo[2,1-b]benzothiazoles (24) have been synthesized by Jakhar et al.6 by irradiating 3-(2’-bromoacetyl)-6-substituted coumarins (22) with 6-substituted-2-aminobenzothiazoles (23) by microwave irradiation in good yields (Scheme 6).

2.7. Substituted imidazo[2,1-b]-1,3,4-thiadiazoles
Rani et al.7 synthesized 2-alkyl/aryl-6-benzofuranylimidazo[2,1-b]-1,3,4-thiadiazoles (27) by the condensation of 5-alkyl/aryl-2-amino-1,3,4-thiadiazoles (26) with 2-(2-bromoacetyl)benzofurans (25) (Scheme 7).

2.8. Pyrimidoimidazoles and pyrroloimidazolones
Rahmouni et al.8 irradiated neat benzimidazole (29) and N-acylimidate (28) in an open vessel to give the product (30) (Scheme 8).

Irradiation of diamine (32) with keto-ester (31) in the presence of aluminium trioxide (33) led to the isolation of product (34). The reaction was carried out by supporting the reagents onto alumina and irradiating in an open vessel (Scheme 9).

2.9. Thiazolobenzimidazole and benzylbenzimidazole derivatives
Rao et al.9 carried the one-pot synthesis of 1H,3H-thiazolo[3,4-a]benzimidazoles (38) by the condensation cyclization reaction between the appropriate o-phenylenediamine (7) in the presence of toluene (37), substituted aromatic aldehyde (36) and 2-mercaptoacetic acid (35) (Scheme 10).

The same workers synthesized 2-aryl-1-benzylbenzimidazoles (41) by reacting a o-phenylenediamine (7) with an excess of 2,6-difluorobenzaldehyde (39) in the presence of a catalytic amount of p-toluenesulfonic acid (40) (Scheme 11).

2.10. Xanthine derivatives
Burbiel et al.10 irradiated 5,6-diaminouracils (42) for 5 min with triethoxymethane (43) at 160 °C giving xanthine derivatives (44) in 76-90% yields (Scheme 12).

3. MICROWAVE ASSISTED SYNTHESIS OF FUSED PYRAZOLE DERIVATIVES
3.1. Pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives
A series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives (51) were synthesized by Zhang et al.11 by the reaction of ethyl 3-aryl-1-(2-bromoethyl)-1H-pyrazol-5-carboxylate (45) with dibromoethane (46) in presence of potassium carbonate (13) and methyl cyanide (47), giving intermediate (48) which reacts with amine (49) in presence of potassium iodide (50) and methyl cyanide (47) (Scheme 13).

3.2. Tetrahydropyrazol[3,4-c]pyrazoles and thiazolo[5,4-c]-2,3-dihydropyrazoles
Pande et al.12 reported the synthesis of 1-(2-hydroxybenzoyl)-3-methyl-4-aryl-1,3a,4,5-tetrahydropyrazol- [3,4-c]pyrazoles (57) by the condensation of hydrazine hydrate (56) with 4-alkylidene-2-(2-hydroxybenzoyl)-5-methyl-2,4-dihydropyrazol-3-ones (55) which is obtained from 2-(2-hydroxybenzoyl)-5-methyl-2,4-dihydropyrazol-3-ones (52) and aldehyde (1) in presence of acetic acid (57) and sodium acetate (54) (Scheme 14).

3.3. Benzopyrano[2,3-c]pyrazol-3(2H)-ones
Borisov et al.13 reacted 1.50 mmol of 2-iminocoumarin-3-carboxamide (58) and 5% excess of the hydrazine (56) in acetic acid under microwave irradiation at 190 °C for 5 min to yield the benzopyrano[2,3-c]pyrazol-3(2H)-one library (60) via an intermediate (59) (Scheme 15).

4. MICROWAVE ASSISTED SYNTHESIS OF FUSED TRIAZOLE DERIVATIVES
4.1. Triazolo[3,4-c]-1,2,4-triazine derivatives
Shaaban et al.14 coupled 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione (61) with diazonium salt of 1,2,4-aminotriazole (62), in pyridine (64), to give the corresponding hydrazone (63) which undergoes intramolecular cyclization in pyridine under microwave irradiation to give 6-thienoyl-5-(trifluoromethyl)-[1,2,4]triazolo[3,4-c][1,2,4]triazine (65) (Scheme 16).

4.2. 3,6-Ddisubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues
Mathew et al.15 reported condensation of the triazoles (66) with heteroaromatic aldehydes (67, 69) (Scheme 17), giving a series of 5,6-dihydrotriazolothiadiazoles (68, 70) in presence of DMF (15) and p-TsOH (40) in 52-62% yields.

Condensation of the triazoles (66) with heteroaromatic acids (71, 73, 75) in the presence of phosphorous oxychloride produced a series of triazolothiadiazoles (72, 74, 76) in 49-64% yields (Scheme 18).

4.3. Triazolo[4,3-b][1,2,4,5]tetrazines and triazolo[3,4-b][1,3,4]thiadiazines
Gomha et al.16 reported a novel approach to the synthesis of triazolo[4,3-b][1,2,4,5]tetrazines (79) via reactions of 4-amino-5-methyl-1,2,4-triazole-3(2H)-thione (66) with hydrazonoyl halides (77) in 78-88% yields using chitosan and ethanol (78) as a basic catalyst under microwave irradiation (Scheme 19).

4.4. Substituted triazolo[3,4-b][1,3,4]thiadiazoles
Rani et al.17 prepared substituted triazolo[3,4-b][1,3,4]thiadiazoles (81) by the condensation of 3-akyl/aryl-4-amino-5-mercapto-s-triazoles (66) with chromon-3-carboxyaldehyde (80) in the presence of p-TsOH (40) (Scheme 20).

5. MICROWAVE ASSISTED SYNTHESIS OF FUSED THIAZOLE DERIVATIVES
5.1. 20-Amino-5a-cholest-6-eno[6,7-d]thiazole derivatives
The synthesis of steroidal[6,7-d]thiazoles (85) was done by Khan et al.18 under microwave irradiation using neutral alumina in anhydrous media in good yield. A slurry of steroidal ketones (82) (1 mmol), phenylthiourea (83) (1 mmol), iodine (84) (2 mmol) in isopropanol (11) (1 ml) was added to neutral aluminium oxide. The contents were then mixed thoroughly. The mixed contents were kept under microwave oven and irradiated (Scheme 21).

5.2. 2-Thioxopyrano[2,3-d][1,3]thiazoles by Diels-Alder reaction of arylidene rhodanines
The reactions of 5-arylidene-1,3-thiazolidin-2,4-dithiones (86) with maleic anhydride or maleimide (90), dimethylacetylene dicarboxylate (87) and acrylonitrile in acetic acid (88) at room temperature have been reported by Yarovenko et al.19 to yield thiopyrano[2,3-d]thiazolidin-2-thiones (91, 89) (Scheme 22).

5.3. Benzthiazoles
Chandra Sheker Reddy et al.20 reacted o-substituted anilines (92) with butenones (93) to give benzthiazoles (94) in presence of toluene (37) under microwave conditions (Scheme 23).

5.4. Substituted thiazoles
Varma et al.21 reacted α-tosyloxyketones (95) with ethylenethioureas (96) in a microwave oven to give thiazoles (97) (Scheme 24).

6. MICROWAVE ASSISTED SYNTHESIS OF FUSED PYROLLE DERIVATIVES
6.1. Hexahydrochromeno[4,3-b]pyrroles by cycloaddition
The cycloaddition reaction between aldehyde (98) and amine (99) was carried out by Pospisil et al.22 to give 100 (Scheme 25) using toluene as a solvent (37).

6.2. Nazarov cyclization of pyrrole derivatives
The Nazarov cyclization8,23,24 is a very versatile process for the synthesis of cyclopentanones. Bachu et al.25 treated 101 with 20 mol% TsOH at 80 °C. The enone underwent Nazarov cyclization to furnish 102 in low yields. The reaction at higher temperature with extended hours of heating resulted in the formation of a significant amount of decarboxylated compound of 4-phenyl-4,5-dihydrocyclopenta[b]pyrrol-6(1H)-one (103) (Scheme 26).

6.3. Pyrrolo[1,2-b]pyridazine derivatives
Butnariu et al.26 reacted pyridazine (104) with 2-bromo-1-phenylethanone (105) to give ylide (106) which reacts with N-phenylmaleimide (107), maleic esters (109i) and fumaric esters (109ii) to give cycloadducts (108, 110, 111) (Scheme 27).

6.4. Bicyclic pyrrolidines
Rajendra Prasad et al.27 synthesized, by microwave irradiation of an amine (112), aldehyde (36) and maleimide (106) in the presence of DMF (15) in one pot (Scheme 28) to give the desired product (113).

7. MICROWAVE ASSISTED SYNTHESIS OF FUSED BENZOFURAN DERIVATIVES
7.1. Cyclocondensed synthesis of benzofuran derivatives
The condensation of diacids (114) to anhydrides (115) and p-TSA (116) has been reported by Villemin et al.28 (Scheme 29) to form 117.

7.2. Diaurones
Ashok et al.29 synthesized diaurones (121) by the oxidation of 4,6-dicinnamoyl resorcinols (118) using cupric bromide (119) or mercury (II) acetate (120) in DMF (15) in microwave (Scheme 30).

7.3. 2-Aroylbenzofurans
Varma et al.21 obtained 2-aroylbenzofurans (123) from α-tosyloxyketones (95) and salicylaldehydes (122) in the presence of aluminium trioxide (33) using microwave irradiation (Scheme 31).

8. MICROWAVE ASSISTED SYNTHESIS OF FUSED PYRIMIDINE DERIVATIVES
8.1. Pyrano[2,3-d]pyrimidines
Hren et al.30 synthesized pyrano[2,3-d]pyrimidines (125) from β-(4-hydroxypyrimidyl)-α,β-didehydro-α- amino acid derivatives (124) in ethanol (78) in a single step using microwave irradiation (Scheme 32).

8.2. Fused bicyclic 2,3-diarylpyrimidin-4(3H)-ones via Lewis acid
Yang et al.31 carried out the synthesis of 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones (129) from various amides (126), titanium (IV) chloride (127) and thionyl chloride (128) (Scheme 33).

8.3. Pyrazolo[3,4-d]pyrimidines
Quiroga et al.32 reported a versatile synthesis of N4-substituted-4,6-diaminopyrazolo[3,4-d]pyrimidines (134) using microwave in the absence of solvent from 2-amino-4,6-dichloropyrimidin-5-carbaldehyde (130) with secondary amine (132) with hydrazine hydrate (56) proceeding through 133 with good yields (Scheme 34).

8.4. 2-Amino-6,7-disubstituted-5-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-4-(3H)-one
The reaction was carried out by Tu et al.33 using diaminopyrimidines (135), aldehydes (1) and acyclic 1,3-dicarbonyl compound (136) and glycol (137) to afford dihydropyridopyrimidine derivatives (138) under microwave irradiation (Scheme 35).

8.5. Pyrimido[4,5-d]pyrimidines
Prajapati et al.34 placed a mixture of 6-[(dimethylamino)methylene]amino-1,3-dimethyl uracil (139) with an equimolar amount of ethyl glyoxylate (140) and aniline (49) in a reaction vessel which is irradiated in microwave at 110 °C, which gave, after elimination of dimethylamine, the pyrimido[4,5-d]pyrimidine (141) (Scheme 36) as the only product.

8.6. Pyrimido[1,2-a]pyrimidines
Pyrimido[1,2-a]pyrimidines (144 or 145) were worked on by Eynde et al.35 and synthesized by reacting dihydroaminopyrimidines (142) and chromone-3-aldehydes (143) as is shown in Scheme 37.

8.7. β-Pyrimidyl-α,β-didehydro-α-amino acid derivatives and pyrano[2,3-d]pyrimidines
The reaction of 2H-pyran-2-one (146) with a slight excess of acetamidine hydrochloride (148) and haloacid (147) in the presence of a base was carried out by Hren et al.30 to give pyrano[2,3-d]pyrimidines (151). Applying DBU as a base, the product was obtained (Scheme 38).

8.8. 1,2,4-Triazolo[1,5-a]pyrimidine derivatives
Shaaban et al.36 reacted 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione (61) with 3-amino-5-substituted-1,2,4-triazole (154) and triethylorthoformate (43) to give 6-thienoyl-7-(trifluoromethyl)benzimidazo[1,2-a]pyrimidine (155). The same workers also reacted 61 with 2-aminobenzimidazole (152), under the same experimental conditions to afford only 6-thienoyl-7-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyrimidine (153) (Scheme 39).

8.9. Pyrido[2,3-d]- and pyrimido[4,5-d]- pyrimidines
Devi et al.37 reported the reaction of N,N-dimethyl-6-amino-5-formyluracil (156) with 1-phenyl-1H-pyrrole-2,5-dione (106) giving pyrido[2,3-d]pyrimidines (158) (Scheme 40).

8.10. Dihydropyridopyrimidinones
Quiroga et al.38 synthesized dihydropyridopyrimidinones (161) by ring annulations of aminopyrimidinones (154) with phenylpropanenitrile (160) and aldehydes (1) (Scheme 41).

8.11. Triazolopyrimidines
A Biginelli-like reaction of arylpyruvic acids with urea and aldehydes in the presence of catalytic amounts of acid to yield dihydropyrimidine carboxylic acids has also been reported in the literature.39 Sakhno et al.40 synthesized 5-aryl-7-hydroxy-6-phenyl-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]-pyrimidine-7-carboxylic acids (164) from the reaction mixture after refluxing (~120 °C) equimolar amounts of aminotriazoles (152), phenylpyruvic acid (162) and aldehydes (163) in HOAc (164) for 2–3 min (Scheme 42).

8.12. Hexahydropyridopyrimidine–spirocyclohexanetriones
The synthesis of pyrimido[4,5-b]quinolines in a three-component reaction from 6-aminopyrimidines, dimedone and aromatic aldehydes was reported by Quiroga et al.41 A facile one pot cyclocondensation takes place between 6-aminopyrimidines (159), dimedone (165) and aldehydes (1) affording pyridopyrimidinspirocyclohexanetriones (166) (Scheme 43).

8.13. 8-Arylmethyl-9H-purin-6-amines
The synthesis was carried out by Tao et al.42 consisting of irradiating 2-(benzo[d][1,3]dioxol-5-yl)acetic acid (168) (1.0 eq.) and pyrimidine-4,5,6-triamine (167) (1.2 eq.) at 220 °C for 15 min in the presence of P(OPh)3 (169) (1.2 eq.) in pyridine (64), to give 8-(benzo[d][1,3]dioxol-5-ylmethyl)-9H-purin-6-amine (170) as the product (Scheme 44).

When the triamine pyrimidine substrate was replaced with its tetramine equivalent (171) and irradiated with dioxoloacetic acid (172) in presence of pyridine (64), the product (173) was formed in 62% isolated yield (Scheme 45).

9. MICROWAVE ASSISTED SYNTHESIS OF FUSED PYRIDINE DERIVATIVES
9.1. Multicomponent approaches to pyrazolopyridines
The three component reaction of 3-substituted 5-aminopyrazoles (174) with pyruvic acid (175) and aldehydes (1) was carried out in ethanol (78) by Chebanov et al.43 using microwave to give pyrazolopyridines (176) (Scheme 46).

9.2. 2-Substituted oxazolo[4,5-b]pyridines
Myllymaki et al.44 synthesized 2-phenyloxazolo[4,5-b]pyridines using palladium catalyzed C-2 arylation of oxazolo[4,5-b]pyridine. Condensation reaction of 3-hydroxybenzoic acid (177) and 2-aminopyridin-3-ol (178), shown in Scheme 47 also gives 2-phenyloxazolo[4,5-b]pyridines (179).

9.3. Pyrazolo[3,4-b]pyridine derivatives
Zou et al.45 developed a synthetic method of pyrazolo[3,4-b]pyridines (183) by the reaction of aminopyrazole (180) with chalcones (181) in one step under microwave irradiation in the presence of ZnCl2 (182) leading to higher yields and shorter reaction times (Scheme 48).

9.4. Thiazolo[3,2-a]pyridine derivatives
Shi et al.46 carried out the synthesis of thiazolo[3,2-a]pyridines (186, 187) via microwave assisted three component reactions of malononitrile (184) (2mmol), aldehydes (1) (1mmol) and 2-mercaptoacetic acid (185) (1mmol) in water with molar ratio of 2:1:1 (Scheme 49).

9.5. Pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives
Pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives were prepared in very low yields (20-35%), after long reaction time (48 h), through hetero Diels-Alder cycloaddition between the formamidine and the corresponding N-phenylmaleimide, under conventional heating, using AcOH or DMSO as solvent.47 The same product (Scheme 50) was synthesized by Nascimento-Junior et al.48 using pyrazol-5-amine (180) and N,N-dimethylmethanamine (188) to give an intermediate (189) which when reacted with pyrrole-2,5-dione (106) gives pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives (190).

9.6. Dipyrazolopyridines
A new series of dipyrazolopyridines (193) has been synthesized by microwave irradiation by Thakre et al.49 by the reaction of 2-pyrazolin-5-ones (191) with 4-aminoazobenzene (192) and aldehydes (1) (Scheme 51).

9.7. Pyrazolo[1,5-a]pyridines
The Stille coupling between 2-tributylstannylpyridine (194) and 2-chloro-3-nitropyridine (195) was carried out by Nyffenegger et al.50 and nitro bicycles (197) were synthesized. From this bicycle, 199 was formed (Scheme 52).

9.8. Pyrido[1,4]thiazinones based on the S–N type Smiles rearrangement.
Thiazinone fused pyridine derivatives (203) were synthesized via an intermediate (202) by Ma et al.51 using N-substituted chloroacetamides (200) with 2-bromopyridin-3-thiol (201) (Scheme 53) in one pot.

10. MICROWAVE ASSISTED SYNTHESIS OF FUSED QUINOLINE DERIVATIVES
10.1. Polysubstituent Pyrimido[1,2-a]quinolines
Using ethylene glycol (2.0 ml) as a solvent and 120 °C temperature, Tu et al.52 carried out the reactions of different aldehydes (1), various enaminones (204) and malononitrile (184) to give pyrimido[1,2-a]quinolines (205) (Scheme 54).

10.2. Poly-substituted indeno[1,2-b]quinolines assisted by p-toluene sulfonic acid (p-TsOH)
Tu et al.53 reacted indane-1,3-dione (206), aldehyde (1) and substituted 3-amino-cyclohex-2-enone (207) in presence of p-TsOH (40) to give substituted indeno[1,2-b]quinolines (209) (Scheme 55).

10.3. 4-Methoxy-1-methyl-2-quinolinone and its analogs
In the presence of a catalytic amount of p-toluenesulfonic acid (40), Nadaraj et al.54 isolated quinolinone (212) in 84-96% yields in 6-11 min from a mixture of aniline (210) and diethylmalonate (211) (2:1 molar ratio) by irradiating under the microwave (Scheme 56).

10.4. 1H-Pyrazolo[3,4-b]quinolines
Danel et al.55 heated aromatic amine (210) (0.02 mole), pyrazole (213) (0.01 mole), and anhydrous ZnCl2 (182) (0.02 mole) in ethylene glycol in a microwave (800W) to give pyrazolo[3,4-b]quinolines (214) (Scheme 57).

10.5. Poly-substituted quinolines
Jia et al.56 reacted 2-amino-4’-fluorobenzophenone (215) and ethyl acetoacetate (216) to afford quinoline (217) under microwave conditions (Scheme 58).

The same workers tried library synthesis of quinoline (220) from 2-aminoacetophenone (218) and various carbonyl compounds (219) under microwave conditions (Scheme 59).

10.6. 2,9-Diaryl-2,3-dihydrothieno[3,2-b]quinolines
The synthesis of a series of 2,9-diaryl-2,3-dihydrothieno[3,2-b]quinolines (224) was initially investigated under thermal conditions.57,58 Balamurugan et al.59 heated a mixture of 5-aryldihydro-3(2H)-thiophenone (221), 2-aminobenzophenone (222) and trifluoroacetic acid (223) (Scheme 60) under microwave conditions to give 224.

10.7. Indeno[1,2-b]quinoline-9,11(6H,10H)-dione derivatives by Michael addition
A series of aldehydes and enaminones were applied under microwave irradiation conditions by Tu et al.61 to afford a newtype of heterocyclic compounds, the indeno[1,2-b]quinoline-9,11(6H,10H)-dione derivatives (225) from indane-1,3-dione (206), aldehyde (1) and cyclohexenone (204) (Scheme 61).

11. MICROWAVE ASSISTED SYNTHESIS OF FUSED QUINAZOLINE DERIVATIVES
11.1. Synthesis of triazoloquinazolinones and benzimidazoquinazolinones
A general route to prepare 5,10-dihydro[1,2,4]triazolo[5,1-b]quinazolines (226) (Scheme 62) included the reaction of triazolamine (152), aldehydes (1) and cyclohexane-1,3-dione (165) in DMF (15) was reported by Mourad et al.62

The same workers tried a microwave assisted synthesis of benzimidazoquinazolinones (227) from aldehydes (1), cyclohexane-1,3-dione (165) and benzoimidazol-2-amine (154) completed in 1-5 min and gave 90-96% yields (Scheme 63).

11.2. Quinazolines by Niementowski reaction
The most common synthetic method of the 3H-quinazolin-4-one ring (231) is based on the Niementowski reaction.63 Alexandre et al.64 fused anthranilic acid (229) with formamide (228) proceeding via an o-amidine intermediate (230) (Scheme 64).

11.3. Quinazolin-4(3H)-one derivatives
Li et al.65 reacted anthranilic acids (232) and anthranilamides (233) to give 2-substituted quinazolin-4(3H)-ones (234) (Scheme 65).

The same workers tried to react different benzamides (235) with carbonyl compounds (236) to give 2,2-disubstituted-2,3-dihydroquinazolin-4(1H)-ones (237) (Scheme 66).

The same workers tried to react different benzoyl chlorides (238) with urea (239) giving 1H,3H-quinazolin-2,4-dione (240) (Scheme 67).

11.4. 8H-Quinazolino[4,3-b]quinazolin-8-ones via two Niemen-towski condensations
Novel tetracyclic 8H-quinazolino[4,3-b]quinazolin-8-ones were prepared from anthranilic acids, by fusing the quinazolinone and the quinazoline rings. The synthesis of various congeners was performed via two Niementowski condensations.63 Alexandre et al.66 condensed amide (233) with various anthranilic acids (241) to afford substituted quinazolinones (242) (Scheme 68) in the first step.

The second step involves the preparation of 8H-quinazolino[4,3-b]quinazolin-8-ones (246) consisting of microwave irradiation of a mixture of the 4-(thiomethyl)quinazoline (243) with an excess of anthranilic acid (244) (6 eq.), adsorbed on graphite (Scheme 69). This procedure led to the cyclised compounds (246) in good yields and in a shorter time.

The same workers tried 4-chloroquinazoline (247) with an excess of anthranilic acid (244) (6 eq.) to get adsorbed on graphite (Scheme 70). This procedure led to the cyclised compounds (248) in good yields and in a shorter time.

11.5. Quinazolinones and quinazolines
Rad-Moghadam et al.67 performed the condensation of anthranilic acid (249), ammonium acetate (250) and the orthoesters (251), which gives access to the 2-substituted-4(3H)-quinazolinone (252) (Scheme 71) under microwave conditions.

A microwave promoted synthesis of 4-aminoquinazolines (256) by reacting cyanoaromatic compounds (253) with anthranilonitrile (254) in a microwave oven was carried out by Seijas et al.68 (Scheme 72).

11.6. Polysubstituent Quinolino[1,2-a]quinazolines
Under the optimal conditions of ethylene glycol (2.0 ml) as a solvent and 120 °C, Tu et al.52 performed the reactions of different aldehydes (1), various enaminones (257) and malononitrile (184) (Scheme 73) to give quinolino[1,2-a]quinazolines (258).

12. MICROWAVE ASSISTED SYNTHESIS OF FUSED INDOLE DERIVATIVES
12.1. Indole derivatives
Sridar et al.69 synthesized indoles (261) from an aryl hydrazine (259) and a ketone (260) in acetic acid (88) (Scheme 74).

12.2. Carbazole derivatives
The Abrarnovitch group70 have irradiated 262 in formic acid in a Parr bomb and produced the product (263) in excellent yields (Scheme 75).

Villemin and co-workers71 have illustrated the utility of this procedure in the synthesis of 265 from cyclohexanone (264) and phenyl hydrazine (259) (Scheme 76).

12.3. Imidazo[1,2-f]pyrimidine derivatives
Rahmouni et al.72 have synthesised 2,3-dihydroimidazo[1,2-c]pyrimidines (268) under microwave irradiation in moderate yields from N-acylimidates (266) and activated 2-benzimidazoles (267) (Scheme 77).

12.4. γ-Carboline and Pyrido[4,3-b]indole derivatives
Molina et al.73 converted 1-arylbenzotriazoles into carbazoles or their heterocyclic analogs under microwave conditions (Scheme 78) where the 1-(4-pyridyl)benzotriazole (269) reacts with 4-chloropyridine (270) to give γ-carboline (273).

12.5. Pictet–Spengler reactions for preparation of 1,1-disubstituted tetrahydro-β-carbolines
Kuo et al.74 reacted tryptophan (274) with ketones (275) by microwaves to produce 1,1-disubstituted tetrahydro-β-carbolines (277) in much shorter reaction times with good to excellent isolated yields (Scheme 79).

13. MICROWAVE ASSISTED SYNTHESIS OF FUSED TRIAZINE DERIVATIVES
13.1. Synthesis of pyrazolo[5,1-c]triazine and benzimidazo[5,1-c]-1,2,4-triazine derivatives
Shaaban et al.14 coupled thiazole compound (61) with the diazonium salt of aminopyrazole derivatives (278) and 2-aminobenzimidazole (280) under same conditions. In each case, 6-thienoyl-4-(trifluoromethyl)pyrazolo[5,1-c][1,2,4]triazines (279) and 3-thienoyl-4-(trifluoromethyl)-benzimidazo[2,1-c][1,2,4]triazine (281) was obtained (Scheme 80).

13.2. Triazino[4,3-a][1,8]naphthyridines
Mogilaiah et al.75 reported a rapid and efficient protocol for the synthesis of novel triazino[4,3-a][1,8]naphthyridines (284) by the reaction of 3-Aryl-2-hydrazino-1,8-naphthyridines (282) with ω-bromoacetophenones (283) in the presence of catalytic amount of DMF (15) in solvent free conditions under microwave irradiation (Scheme 81).

14. MICROWAVE ASSISTED SYNTHESIS OF FUSED AZEPINE DERIVATIVES
14.1. Fluorine containing benzopyranotriazolothiadiazepines
Dandia et al.76 developed the reaction of 3-arylidene flavanones (285) with 4-amino-5-alkyl-3-mercaptotriazole (66) involving the formation of intermediate followed by condensation of the carbonyl group with the aromatic primary amine to give a seven membered ring system leading to the formation of a new class of tetracyclic ring system (286) (Scheme 82).

14.2. 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines
Insuasty et al.77 irradiated an equimolar mixture of 4,5,6-triaminopyrimidine (167) and chalcones (287, 289) in presence of catalytic amounts of DMF (1 ml) to afford the desired products (288, 290) (Scheme 83).

14.3. 1,5-benzodiazepine derivatives
A very few methods for the preparation of 1,5-benzodiazepines are reported in the literature.78-80 Pozarentzi et al.81 synthesized 2,3-dihydro-1H-1,5-benzodiazepines (292) by condensation of ketones (291) with o-phenylenediamines (7) in acetic acid (88) (Scheme 84) by microwave irradiation.

15. MICROWAVE ASSISTED SYNTHESIS OF FUSED CHROMENE DERIVATIVES
15.1. Synthesis of 5-nitrofurfurylidine
Villemin and Martin82 have synthesized 5-nitrofurfurylidine by the condensation of 5-nitrofurfuraldehyde with active methylene compounds under microwave irradiation using K 10 and ZnCl2 as a catalyst. Singh et al.83 developed solventless systems wherein salicylaldehydes (293) undergo Knoevenagel condensation with a variety of ethyl acetate derivatives (294) piperidine (295) to afford coumarins (296) (Scheme 85).

15.2. α-Lapachone derivatives
A new class of α-lapachone derivatives (298) with diversed structure in one pot was developed by Wei et al.84 (Scheme 86). The reaction of a variety of substituted aldehydes (1), dioxandione (165) and naphthalenedione (297) as reactants using AcOH (88) as a solvent was performed in a microwave.

15.3. Aryl-14H-dibenzo[a,j]xanthenes
Kantevari et al.85 reacted β-naphthol (299) and TBAB (300) (10 mol%) with various aldehydes (1) to yield various aryl-14H-dibenzo[a,j]xanthenes (301) (Scheme 87).

16. CONCLUSIONS
This review deals with microwave assisted synthesis of a variety of five membered fused heterocycles like imidazoles, pyrazoles, triazoles, thiazoles, pyrroles and benzofurans. The review also deals with microwave assisted synthesis of a variety of six and seven membered fused heterocycles like pyrimidines, pyridines quinolines, quinazolines, indoles, imidazoles, pyrazoles, triazoles, triazines, azepines, thiazoles, pyrolles, benzofurans and chromenes. Deliberate attempts were made to compare the microwave assisted synthesis with those of the conventional conditions. Microwave assisted conditions proved to be faster in terms of reaction times, dramatically decrease the reaction times and improve the product yields and purity as compared to the conventional conditions.

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