Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis

Abstract

Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from their respective precursors (typically imines and hydrazones) under a variety of conditions, can both react with a wide range of substrates in many kinds of reactions. Most of these reactions discussed here include nucleophilic additions, Michael-type reactions, cycloadditions, Diels-Alder, inverse electron demand Diels-Alder, and aza-Diels-Alder reactions. This review focuses on the reports during the last 10 years employing 1,2-diaza-, 1,3-diaza-, 2,3-diaza-, and 1,4-diaza-1,3-butadienes as intermediates to synthesize heterocycles such as indole, pyrazole, 1,2,3-triazole, imidazoline, pyrimidinone, pyrazoline, -lactam, and imidazolidine, among others. Fused heterocycles, such as quinazoline, isoquinoline, and dihydroquinoxaline derivatives, are also included in the review.

Keywords: diaza-1,3-butadienes; heterocycles; synthesis.

Scheme 1

Structure and synthesis of diaza-1,3-butadienes.

Scheme 2

Synthesis of tetrahydroberberine derivatives 5.

Scheme 3

Multicomponent sequential cyclization for the synthesis of 5-arylamino thiophenes derivatives.

Scheme 4

Synthesis of indole derivatives 24 using 1,2-diaza-1,3-dienes and anilines.

Scheme 5

Synthesis of 3-alkyl- and 3-aryl 2-unsubstituted indoles 27 using 1,2-diaza-1,3-dienes.

Scheme 6

Synthesis of 1,2,3-triazole derivatives from 1,2-diaza-1,3-dienes and sodium azide.

Scheme 7

Triazole synthesis from bifunctional amino reagents and 1,2-diaza-1,3-dienes generates in situ.

Scheme 8

Triazole synthesis from amines and 1,2-diaza-1,3-dienes generates in situ.

Scheme 9

Triazole synthesis from amines and 1,2-diaza-1,3-dienes generates in situ from dichloro-N-tosylhydrazones.

Scheme 10

Synthesis of pyrazoles 50 from conjugated hydrazones and 1,2-diaza-1,3-dienes.

Scheme 11

Pyrazolones synthesis from 1,2-diaza-1,3-dienes by a sequence Michael-type nucleophilic attack/cyclization/[2,3]-Wittig rearrangement.

Scheme 12

Synthesis of 1-aminopyrrole derivatives 58 from catalyzed cycloaddition of 1,2-diaza,1-3-dienes.

Scheme 13

Synthesis of thienodolin alkaloid 64 from indoline 2-thiones and 1,2-diaza-1,3-dienes.

Scheme 14

Synthesis of Pyrrolo-pyridines derivatives 73.

Scheme 15

Tandem synthesis of benzo[4,5]imidazo[1,2-b]pyridazine derivatives 80.

Scheme 16

Reaction mechanism for synthesis of pyridazone derivatives 82 from 4,4-dichloro-1,2-diazabuta-1,3-dienes, with malonate ester or cyanoacetic esters.

Scheme 17

Pyridazone synthesis from 4,4-dichloro-1,2-diazabuta-1,3-dienes and ethyl acetoacetate.

Scheme 18

Dihydropyridazinones synthesis by [4+2] annulation of 1,2-diaza-1,3-dienes with N-acyl amino acids.

Scheme 19

Synthesis of 3,7-diaryl-6,7-dihydro-5H-6-substituted thiazolo[3,2-a]pyrimidin-5-ones 97.

Scheme 20

[4+2] Cycloaddition of 1,2-diaza-1,3-dienes with 3-phenacylideneoxindoles (aza-Diels-Alder reaction).

Scheme 21

Aza-Diels–Alder reaction between electron-deficient 3-methyleneoxindoles and 1,2-diaza-1,3-dienes.

Scheme 22

Synthesis of bicyclo[4.1.0]tetrahydropyridazine derivatives 109 from sulfur ylides and 1,2-diaza-1,3-dienes generated in situ.

Scheme 23

Synthesis of dihydropyridazines 112 or pyridazines 115 by [4+2] cycloaddition of enaminones with in situ generated 1,2-diaza-1,3-dienes.

Scheme 24

Aza-Diels–Alder reaction between 3-tetrazolyl-1,2-diaza-1,3-diene 116 with methyl vinyl ketone.

Scheme 25

Synthesis of tetrahydropyridazine derivatives 123 from enamides and 1,2-diaza-1,3-dienes.

Scheme 26

Tetrahydropyridazines derived 127 from 3-vinylindoles.

Scheme 27

Tetrahydro-1,2,4-triazine synthesis from 1,3,5-triazinanes and 1,2-diaza-1,3-diene generated in situ.

Scheme 28

[4+2] Inverse aza-Diels-Alder reaction of α,β-unsaturated thioesters with 1,2-diaza-1,3-dienes.

Scheme 29

[4+2] Cycloaddition reaction of 1,2-diaza-1,3-dienes with indoles catalyzed by ZnCl₂.

Scheme 30

Synthesis of 2-imidazoline 146.

Scheme 31

Groebke–Blackburn–Bienaymé reaction.

Scheme 32

Isocianide synthesis in situ from N-formamide 155 and its use in the Groebke–Blackburn–Bienaymé reaction.

Scheme 33

Use of different 2-aminoazines in the Groebke–Blackburn–Bienaymé reaction.

Scheme 34

Complex heterocycles derived from imidazo[1,2-a]-heterocycles.

Scheme 35

Synthesis of 2-imidazoline derivatives 160.

Scheme 36

Synthesis of pyrimidine derivatives 169 and 170.

Scheme 37

Synthesis of benzothiazolopyrimidine derivatives 173.

Scheme 38

Synthesis of dihydropyrimidine derivatives.

Scheme 39

Synthesis of pirimidinones 184.

Scheme 40

Synthesis of pyrimido[5,4-b][1,4]thiazin-8-ium iodide 193.

Scheme 41

Synthesis of 3,7-diaryl-6,7-dihydro-5H-6-substituted thiazolo[3,2-a]pyrimidin-5-ones 195.

Scheme 42

Synthesis of 4- susbstituted 2-(trichloromethyl) quinazolines 203.

Scheme 43

Synthesis of perhydro [1,2,4] triazolo [1,2-a] [1,2,4] triazole-1,5-dithiones 204.

Scheme 44

Intramolecular cyclization of 2,3-diaza-1,3-butadienes 207 catalyzed by FeCl₃.

Scheme 45

Intramolecular cyclization of 2,3-diaza-1,3-butadienes 209 catalyzed by Cu.

Scheme 46

Intramolecular cyclization of 2,3-diaza-1,3-butadienes 211 catalyzed by I₂.

Scheme 47

Synthesis of (N′-substituted)-hydrazo-4-aryl-1,4-dihydropyridines 217.

Scheme 48

Synthesis of isoquinoline derivatives 218.

Scheme 49

Synthesis of mono β-lactams 218 and bis-β-lactams 219.

Scheme 50

Synthesis of 1,4-diazabicyclo[4.2.0]octan-8-ones 224.

Scheme 51

Synthesis of imidazolium salt 225 by mechanochemical one-pot two-step procedure.

Scheme 52

Synthesis of chiral imidazolium salt 227.

Scheme 53

Synthesis of unsymmetrical imidazolium salts 229.

Scheme 54

Mechanism reported for the synthesis of the unsymmetrical imidazolium salts 235.

Scheme 55

Synthesis of the unsymmetrical imidazolium salts 236.

Scheme 56

Synthesis of bulky imidazolium salts 239 containing an acenaphthylene element.

Scheme 57

Synthesis of higher steric hindrance imidazolium salts 242.

Scheme 58

Synthesis of zwitterionic imidazolium salt 243.

Scheme 59

Synthesis of heteroatom-functionalized imidazolium salts.

Scheme 60

Synthesis of 2-formylimidazolium salt 254 and reaction of decarbonylation.

Scheme 61

Synthesis of 4,5-bis(arylimino)-2-(alkylimino)imidazolidines 258.

Scheme 62

Synthesis of 1,3-thiazolidine-2-thiones 262.

Scheme 63

Synthesis of thiazolidines derivatives 264.

Scheme 64

Synthesis of 1,3-thiazolidine-2-thiones 267 and 271.

Scheme 65

Synthesis of 1,3,2-Diazaphospholenes P-substituents derivatives.

Scheme 66

Reaction of cyclic 1,4-diazadiene 223 with diketone 276.

Scheme 67

Synthesis of N,N-disubstituted exo-2-imidazolidinone dienes 282 and cycloaddition reactions.

Scheme 68

Synthesis of pyrrolo[3,2-b]pyrrole- 1,4-diones (isoDPP) derivatives 287.

Scheme 69

Examples of iso DPP derivatives 287.

Scheme 70

Synthesis of 1,4,diaza-2,3-diborinine derivatives.

Scheme 71

Synthesis of dihydroxyquinoxaline derivative 297 by an NHC-catalyzed α-carbon amination of α-chloroaldehyde with cyclohexadiene-1,2-diimine.

Scheme 72

Synthesis of dihydroxyquinoxaline derivative 301 in a one-pot reaction.

Scheme 73

Synthesis of dihydroxyquinoxaline derivative 305 by hetero-Diels–Alder reaction of ketene enolates and ortho-benzoquinone diimides 302.