Vakhid a mamedov quinoxalines synthesis, reactions, mechanisms and structure springer (2016)

In this book the author describes thesynthesis, and the chemical properties of an important class of heterocyclicchemistry, the quinoxalines.Chapter1describes some properties of the Quin

Vakhid A Mamedov

QuinoxalinesSynthesis, Reactions, Mechanisms and Structure

Quinoxalines

A.E Arbuzov Institute of Organic and

Library of Congress Control Number: 2016931837

© Springer International Publishing Switzerland 2016

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Heterocycles form a fundamental basis for the development of pharmaceutical andagricultural products with wide applications In this book the author describes thesynthesis, and the chemical properties of an important class of heterocyclicchemistry, the quinoxalines.

Chapter1describes some properties of the Quinoxaline–As a Parent Heterocycle.Chapter2covers recent advances in the Synthesis of Quinoxalines involving themethods based on the (a) condensation of 1,2-diaminobenzenes and derivativeswith various two-carbon unit suppliers, (b) condensation of o-benzoquinonediimines and diimides with various two-carbon unit suppliers, (c) condensation ofN,N-dimethyl(dibenzyl)ethylenediamine with 1,2- and 1,4-dihydroxybenzenes,(d) synthesis of quinoxalines from aniline and its derivatives, (e) synthesis ofquinoxalines from heterocyclic systems and (f) synthesis of quinoxalines based onthe carbocyclic system

From the data presented in this chapter many original and interesting methodsrecently appeared for the synthesis of quinoxalines, which are difficult to obtain or

in general are unobtainable These new methods by Kaufmann, Tanimori, Kalinskiand Shaabani are based on the reactions of a wide variety of compounds thatdeserve further attention

Chapter3describes two methods of the Synthesis of Pyrrolo[l,2-a]quinoxalinesbased both on quinoxalines and pyrroles Chapter 4 captures the Synthesis ofImidazo[1,5-a]- and Imidazo[1,2-a]quinoxalines Chapter5discusses the Synthesis

of Quinoxaline Macrocycles through (a) introduction of the quinoxaline system intomacrocycles, (b) the closing of 1,n-bis(quinoxalin-1-yl)alkanes and (c) from bothresorcin[4]arenes and quinoxalines Chapter 6 demonstrates all knownRearrangements of Quinoxalin(on)es in the Synthesis of Benzimidazol(on)es and theinteresting new rearrangements discovered by Mamedov, the author of this book,comprising (a) the acid catalysed conversion of “any of the spiro-derivatives of1,2,3,4-tetrahydrtinquinoxalin-3-one with at least one mobile hydrogen atom in theirspiro-forming component into benzimidazole derivative with the spiro-forming

component at position 2” and (b) the acid catalyzed rearrangement of “any of thespiro-derivatives of 1,2,3,4-tetrahydroquinoxalin-3-one without any mobile hydro-gen atom in their spiro-forming component are on their way to the benzimidazolonederivative with the spiro-forming component at position 1”.

Henk van der Plas

The book gives equal weight to each of the fundamental aspects of quinoxalinechemistry: synthesis, reactions, mechanisms, structure, properties, and uses Thefirst four chapters present a survey of the developments in quinoxaline chemistrysince the publication of the monograph on“Condensed Pyrazines” by Cheesemanand Cookson in 1979 These chapters give a comprehensive coverage of theimportant quinoxaline-containing ring systems such as thiazolo[3,4-a]-, pyrrolo[1,2-a]-, imidazo[1,5-a]-, pyrano[2,3-b]quinoxalines, etc Chapter five describesmany new methods for the construction of quinoxaline macrocycles, which areimportant because of their application to optical devices and materials Theremaining sixth chapter gives a review of all the previously known rearrangements

of heterocyclic systems that lead to benzimidazole derivatives A critical analysis

of these transformations reveals novel acid-catalyzed rearrangements of alinones giving 2-heteroaryl benzimidazoles and 1-heteroaryl benzimidazolones inthe presence of nucleophilic reactants The Appendix gives X-ray crystallographicdata for a number of quinoxaline derivatives (41 samples) synthesized in theLaboratory of the Chemistry of Heterocyclic Compounds of the A.E ArbuzovInstitute of Organic and Physical Chemistry, Kazan Scientific Centre of the RussianAcademy of Sciences The literature has been covered up to the end of 2013, withsome additional data from publications in 2014 and 2015

quinox-This book is the result of a collective effort Ifind it necessary to acknowledgethe assistance rendered by the compilers of this book Dr Nataliya A Zhukova, whocontributed to thefinal version of the manuscript and also Dr Elena A Hafizova,

Dr Liliya V Mustakimova and the authors of the dissertations Dr A.A Kalinin (inChap.6), Dr D.F Saifina (in Chap.6), Ph.D O.G Isaykina (in Chap.6), Ph.D A

M Murtazina (in Chap.6) and Ph.D V.R Galimullina (in Chap.6) as well as all

my co-workers whose names appear in the references My profound thanks are due

to Ida H Rapoport for her invaluable assistance in reading thefirst English version

of the manuscript Special acknowledgments are due to Prof Aidar T Gubaidullinfor X-ray structural analyses of all the compounds and the X-ray structural analysesdata in the Appendix I take this opportunity to express my special thanks to the

administration and mainly to the director of the A.E Arbuzov Institute of Organicand Physical Chemistry of the Kazan Research Center of the Russian Academy ofSciences Prof Oleg G Sinyashin for his interest in our research and to the RussianFoundation for Basic Research for funding (Grants No 07-03-00613-a,10-03-00413-a, 13-03-00123-a) The completion of this endeavor would have neverbeen possible without the consent of Prof Bert U.W Maes from the University ofAntwerp, whom I am extremely grateful to And last, but no means least, I considermyself indebted to Profs Yakov A Levin and Ildus A Nuretdinov of the A.E.Arbuzov Institute, Eugene A Berdnikov of the Kazan University and Sadao Tsuboi

of the Okayama University (Japan) Their dedication and skill taught me how toteach I thank them

Finally, I should like to thank Prof John A Joule from the University ofManchester, who has constantly provided me with helpful advice and criticism asregards the grammatical and editing aspects while the manuscript was in prepara-tion I am particularly grateful to my wife Dr Vera L Mamedova and my son Javidand daughter Sevil They endured with patience and understanding the many daysand nights of my staying at the Institute and the endless hours on the computer.They helped me in so many ways that are too numerous to mention

1 Quinoxaline–As a Parent Heterocycle 1

References 3

2 Synthesis of Quinoxalines 5

2.1 Introduction 5

2.2 Condensation of 1,2-Diaminobenzenes (1,2-DABs; Ortho-Phenylenediamines) and Derivatives with Various Two-Carbon Unit Suppliers 14

2.2.1 With Pyruvates (2-Oxopropanoates) 14

2.2.2 Withα-Diketones (1,2-Diketones) 22

2.2.3 With Ketones 29

2.2.4 With Hexane-1,3,4,6-tetraones 32

2.2.5 With Haloketones 32

2.2.6 Withα-Hydroxy Ketones 37

2.2.7 With Vicinal Diols 37

2.2.8 With Dimethyl (DMAD) and Diethyl (DEAD) Acetylenedicarboxylates 37

2.2.9 With Nitroolefins 40

2.2.10 With 1,2-Diaza-1,3-butadienes 42

2.2.11 With Ketones(Aldehydes) and Isocyanide 43

2.2.12 With Aldehydes and NaCN 46

2.3 Condensation ofo-Benzoquinone Diimines and Diimides with Various Two-Carbon Unit Suppliers 48

2.3.1 With Allylstannane 48

2.3.2 With Aldehydes 50

2.3.3 With 1,2-DAB 51

2.4 Condensation ofN,N-Dimethyl(dibenzyl)ethylenediamine with 1,2- and 1,4-Dihydroxy Benzenes 52

2.5 Synthesis of Quinoxalines from Aniline and Its Derivatives 57

2.5.1 From Anilines 57

2.5.2 From Benzil-α-arylimino Oximes and α-Nitroketene N,S-Anilinoacetals 58

2.5.3 From 2-Haloanilines 60

2.5.4 From Nitroanilines 66

2.5.5 From 2-Fluoro-1-nitrobenzenes 68

2.5.6 From 4-Bromo-5-nitrophthalonitrile 71

2.5.7 From N-Aryl-2-nitrosoanilines and Alkylated Cyanoacetic Esters 71

2.6 Synthesis of Quinoxalines from Heterocyclic Systems 73

2.6.1 Synthesis of Quinoxalines from Various Fused Nitrogen-Containing Heterocycles Without a Pyrazine Fragment 74

2.6.2 Synthesis of Quinoxalines from Various Heterocyclic Systems, Containing Neither a Pyrazine ring nor a Benzofragment 84

2.6.3 Synthesis of Quinoxalines from Heterocyclic Systems with a Pyrazine Ring 102

2.7 Synthesis of Quinoxalines Based on the Carbocyclic System 102

2.7.1 From 3,3,6,6-Tetrachloro-1,2-cyclohexanedione 102

2.7.2 From Ninhydrin 103

2.7.3 From 1,2-Difluorobenzene 104

2.8 Conclusion 104

References 105

3 Synthesis of Pyrrolo[l,2-a]quinoxalines 135

3.1 Pyrrolo[1,2-a]quinoxalines Based on Quinoxalines 135

3.1.1 Introduction 135

3.1.2 Possible Variants of the Construction of the Pyrrolo [1,2-a]quinoxaline System on the Basis of Quinoxalines 135

3.1.3 Production Methods of Type QA (Version QA1) 137

3.1.4 Production Methods of Type QB (Version QB1) 141

3.1.5 Production Methods of Type QB (Version QB3) 142

3.1.6 Production Methods of Type QC (Version QC1) Cycloaddition Reactions 142

3.1.7 Production Methods of Type QC (Version QC2) 146

3.1.8 Production Methods of Type QD 150

3.1.9 Production Methods of Type QE1 151

3.1.10 Production Methods of Type QE2 151

3.1.11 Other Methods of Synthesis 152

3.1.12 Conclusion 158

3.2 Pyrrolo[l,2-a]quinoxalines Based on Pyrroles 159

3.2.1 Introduction 159

3.2.2 Type PA1 Production Methods 159

3.2.3 Type PA2 Production Methods 163

3.2.4 Type PA3 Production Methods 165

3.2.5 Type PA4 Production Methods 166

3.2.6 Type PB1 Production Methods 166

3.2.7 Type PB2 Production Methods 187

3.2.8 Type PD Production Methods 188

3.2.9 Other Methods of Synthesis 190

3.2.10 Conclusion 200

References 200

4 Synthesis of Imidazo[1,5-a]- and Imidazo[1,2-a]quinoxalines 211

4.1 Introduction 211

4.2 Synthesis of Imidazo[1,5-a]quinoxalines on the Basis of Quinoxaline Derivatives 212

4.2.1 Methods of Formation of the N(10)–C(1) Bond (Variant A1Q) 213

4.2.2 Method of Formation of the C(1)–N(2) Bond (Variant A2Q) 217

4.2.3 Method of Formation of the N(2)–C(3) Bond (Variant A3Q) 218

4.2.4 Methods of Formation of the N(10)–C(1) and C(1)–N(2) Bonds (Variant B1Q) 218

4.2.5 Methods of Formation of the N(10)–C(1) and N(2)–C(3) Bonds (Variant C1Q) 220

4.2.6 Methods of Formation of the N(10)–C(1) and C(3)–C(3a) Bonds (Variant DQ) 223

4.2.7 Method of Formation of the N(10)–C(1), C(1)–N(2), and N(2)–C(3) Bonds (Variant E1Q) 228

4.3 Synthesis of Imidazo[1,5-a]quinoxalines Based on Imidazole Derivatives 229

4.3.1 Method of Formation of the C(3a)–C(4) Bond (Variant A1I) 229

4.3.2 Methods of Formation of the C(4)–N(5) Bond (Variant A2I) 230

4.3.3 Methods of Formation of the C(9a)–N(10) Bond (Variant A4I) 232

4.3.4 Methods of Formation of the C(3a)–C(4) and C(4)–N(5) Bonds (Variant B1I) 233

4.4 Other Methods of Synthesis of Imidazo[1,5-a]Quinoxalines 237

4.5 Synthesis of Imidazo[1,2-a]quinoxalines Based on Quinoxaline Derivatives 239

4.5.1 Methods of Formation of the N(10)–C(1) Bond

(Variant A1Q) 239

4.5.2 Method of Formation of the C(2)–N(3) Bond (Variant A3Q) 244

4.5.3 Method of Formation of the C(2)–N(3) and N(3)–C(3a) Bonds (Variant B3Q) 244

4.5.4 Methods of Formation the N(10)–C(1) and C(2)–N(3) Bonds (Variant C1Q) 244

4.5.5 Method of Formation of the N(10)–C(1) and N(3)–C(3a) Bond (Variant DQ) 245

4.5.6 Method of Formation of the N(10)–C(1), C(1)–C(2) and C(2)–N(3) Bonds (Variant E1Q) 246

4.6 Synthesis of Imidazo[1,2-a]quinoxalines on the Basis of Imidazole Derivatives 247

4.6.1 Method of Formation of the C(3a)–C(4) Bond (Variant A1I) 248

4.6.2 Methods of Formation of the C(4)–N(5) Bond (Variant A2I) 248

4.6.3 Methods of Formation of the C(9a)–N(10) Bond (Variant A4I) 250

4.6.4 Methods of Formation of the C(3a)–C(4) and C(4)–N(5) Bonds (Variant B1I) 251

4.6.5 Methods of Formation of the C(4)–N(5) and C(9a)–N(10) Bonds (Variant D1I) 252

4.7 Other Methods of Synthesis of Imidazo[1,2-a]quinoxalines 254

4.8 Biological Activity of Imidazo[1,5-a]- and Imidazo[1,2-a] quinoxalines 255

4.8.1 Kinase Inhibition 255

4.8.2 Phosphodiesterase Inhibition 257

4.8.3 Antimicrobial and Antifungal Activity 258

4.9 Conclusions 258

References 261

5 Synthesis of Quinoxaline Macrocycles 271

5.1 Introduction 271

5.2 The Introduction of the Quinoxaline System into Macrocycles 272

5.2.1 N,N′-Polymethylene-1,2-Diaminobenzenes 273

5.2.2 Crown Ethers with Diaminobenzene and Benzofuroxane Moieties 273

5.2.3 Macrocyclic Diketones 275

5.2.4 Porphyrins 276

5.2.5 Resorcin[4]arene Cavitands 285

5.3 Quinoxaline Derivatives in the Synthesis of Macrocycles 287

5.3.1 Quinoxalin-2,3(1H,4H)-dione, 2,3-Dichloroquinoxaline and Quinoxalin-2,3 (1H,4H)-dithione 288

5.3.2 2,3-Dibromomethylquinoxaline 291

5.3.3 Diphenylquinoxalines 295

5.3.4 2,3-Di(pyrrol-2-yl)quinoxalines 297

5.3.5 2,3- and 6,7-Dicyanoquinoxalines 302

5.4 1,n-Bis(quinoxalin-1-yl)alkanes in the Synthesis of Macrocycles 308

5.4.1 1,n-Bis(3-acetylquinoxalin-2-on-1-yl)alkanes 308

5.4.2 1,n-Bis(3-benzoylquinoxalin-2-on-1-yl)alkanes 310

5.4.3 Bis(3-indolizinylquinoxalin-2-on-1-yl)alkanes 314

5.5 Both Resorcin[4]arenes and Quinoxalines in the Synthesis of Macrocycles 317

5.6 Other Methods of Synthesis 323

5.6.1 Pyran 1,4-Diazaphenanthrenes 323

5.6.2 Quinoxaline-2,3-dicarboximide 324

5.6.3 Macrocyclic Quinoxaline Compounds as Anticancer Drugs and Inhibitors of Hepatitis C Virus 325

5.7 Conclusion 330

References 331

6 Rearrangements of Quinoxalin(on)es for the Synthesis of Benzimidazol(on)es 343

6.1 Introduction 343

6.2 Synthesis of Benzimidazoles 346

6.2.1 Rearrangement of Quinoxalines (Historical Background) 346

6.2.2 Principles of the Method 351

6.2.3 Advantages of the Method 352

6.3 Synthesis of 2-(Benzimidazol-2-yl)quinoxalines with no Use Rearrangements 356

6.3.1 Gold Catalysis for Synthesizing 2-(Benzimidazol-2-yl) quinoxaline Derivatives from Glycerol and 1,2-Diaminobenzenes 356

6.3.2 Synthesis of Quinoxalines and 2-(Benzimidazol-2-yl)quinoxalines via the Isocyanide Based Multicomponent Reactions (IMCRs) 360

6.4 Synthesis of 2-Hetarylquinoxalines via Rearrangements (Use of 3-Aroyl-, 3-Alkanoyl- and 3-Hetaroylquinoxalin-2(1H)-ones as Analogues of α-Diketones) 363

6.4.1 Synthesis of 2-(Benzimidazol-2-yl)quinoxalines

and Their Aza-Analogues 3636.4.2 Synthesis of 2,3-Bis(benzimidazol-2-yl)

quinoxalines 3676.4.3 Synthesis of 2-(Pyrazin-2-yl)benzimidazoles 3746.4.4 Synthesis of 2-(Imidazol-4-yl)benzimidazoles 3786.5 Synthesis of 2-(3-Arylindolizin-2-yl)benzimidazole

via the Rearrangement (Use of 3-

α-Chlorobenzyl-andα-Chloroalkylquinoxalin-2(1H)-ones as Analogues

ofα-Haloketones) 3826.6 Synthesis of 2-(Pyrazol-3-yl)benzimidazoles via the

Rearrangement (Use of

3-Arylacylidene-3,4-Dihydroquinoxalin-2(1H)-ones as Analogues

ofβ-Diketones) 3846.7 Synthesis of 2-(Pyrrol-3-yl)benzimidazole via the

Rearrangement (Use of 3-

α-Aminobenzylquinoxalin-2(1H)-ones as Analogues of α-Aminoketones) 3876.8 Synthesis of 2-(Benzimidazol-2-yl)quinolines

via the Rearrangement (Use of

3-Methylquinoxalin-2(1H)-ones as Analogues of Usual Ketones) 3896.9 Synthesis of 4-(Benzimidazol-2-yl)quinolines via the

Rearrangement (Use of

3-(2-Aminophenyl)quinoxalin-2(1H)-ones as Aromatic o-Aminoaldehydes (or Ketones) 3916.9.1 Synthesis of Structurally Diverse Quinoline

Derivatives with Benzimidazole Moieties 3916.9.2 Synthesis of Benzimidazolo[2,1-a]pyrrolo[3,4-c]

quinolines 3956.9.3 Synthesis of 1-(1H-Indazol-3-yl)-1H-benzimidazol-2

(3H)-one 3966.10 Synthesis of 1-Pyrrolylbenzimidazolones via the New

Rearrangements (Use of 3-Aroyl-,

3-Alkanoyl-and 3-Hetaroylquinoxalin-2(1H)-ones as Analogues

ofα-Diketones) 3976.10.1 Synthesis of 2,3-Di(1H-benzimidazol-2-yl)-1-

(1H-benzoimidazol-2-on-1-yl)pyrrolo[1,2-a]

quinoxalin-4(5H)-one 3976.10.2 Synthesis of 3-[(3,5-Disubstituted-4-(1H-

benzimidazol-2-on-1-yl)-12(1H)-ones 3996.10.3 Synthesis of 1-Pyrrolylbenzimidazolones

H-pyrrol-2-yl]quinoxalin-from Quinoxalinones and Enamines Generated

In Situ from Ketones and Ammonium Acetate 400

6.10.4 A Reaction for the Synthesis of Benzimidazol-2-ones,

Imidazo[5,4-b]- and Imidazo[4,5-c]pyridin-2-ones from Quinoxalinones and Their Aza-Analogues

When Exposed to Enamines 405

6.11 Conclusion 409

References 410

Appendix 423

Chapter 1

Quinoxaline–As a Parent Heterocycle

N N

Quinoxaline

1 2 3 4 5 6 7 8

Quinoxalines are products of the spontaneous condensation of1,2-diaminobenzene (1,2-DAB) with 1,2-dicarbonyl compounds (Scheme1.1) Thereaction was independently discovered many years ago by Hinsberg (1884) and

Körner (1884)

Hinsberg suggested calling this series of compounds quinoxalines to point outtheir relationship with quinolines and the glyoxal—the dicarbonyl compound, fromwhich the first representative of the series was obtained Quinoxaline: [Quin(oline) + (gly)oxal + ine] (Hinsberg1884)

Quinoxaline is a bicyclic heterocycle consisting of a benzene ring fused to apyrazine, hence a quinoxaline is also called Benzo[a]pyrazine, Benzopyrazine,Benzoparadiazine, 1,4-Benzodiazine, Phenopiazine, Phenpiazine, Quinazine, andChinoxalin It is isomeric with quinazoline, phthalazine, and cinnoline

N

N

N N

NNquinazoline phthalazine cinnoline

At least five methods are currently used for the synthesis of quinoxaline 3(R = H) The first and the principal method is based on the condensation of1,2-DAB with two-carbon suppliers, such as glyoxal (Mirjalili and Akbari2011;Rahmatpour 2012; Chandra Shekhar et al 2014) (Scheme 1.2, Eq 1),ethane-1,2-diol (Climent et al 2012; Tang et al 2015) (Scheme 1.2, Eq 2),2-aminoethanol (Tang et al 2015) (Scheme 1.2, Eq 3), 1,4-dioxane-2,3-diol(Venuti1982) (Scheme1.2, Eq 4) The second method is based on the reaction of

2-nitroaniline with ethane-1,2-diol (Nguyen et al.2015) (Scheme1.2, Eq 5) Thethird is the self-condensation of aniline derivatives, such as N-ethyl-2-nitroaniline(Walczak et al 2015) (Scheme 1.2, Eq 6) and N-[2-(2-phenylhydrazono)ethyli-dene]aniline (McNab 1980; Duffy et al 2004) (Scheme 1.2, Eq 7) The fourthmethod is based on the condensation of benzofurazan (benzo[c][1,2,5]oxadiazole)with 2-aminoethanol (Samsonov2007) (Scheme1.2, Eq 8), and thefifth method isbased on the redox processes of various quinoxaline derivatives (Hirasawa et al.

2008; Karki et al.2013; Chelucci and Figus 2014; Cui et al 2015; Jeong et al

2015) (Scheme1.3)

Quinoxaline 3 (R = H) is a light yellow to brown crystalline, water-solublepowder, with the molecular formula C8H6N2and the molar mass 130.15 g/mol The

R O

R O

H Ph

pKa (Albert 1963) of quinoxaline in water at 20 °C is 0.60: it is therefore siderably a weaker base than the isomer diazanaphthalenes namely, cinnoline(pKa2.42), phtalazine (pKa3.47), and quinazoline (pKa1.95) Quinoxaline has thefollowing physical properties: mp 29–32 °C, bp 220–223 °C, density 1.124 g/mL at

con-25 °C and flash point 209 °F TCC (98.33 °C) and is used mainly in organicsynthesis

The1H NMR spectrum of quinoxaline3 (R = H) has been measured in

DMSO-d6 The signal for H(2) and H(3) of quinoxaline appears as an AA′BB′ system Thelow-field half of the AA′BB′ multiplet is assigned to the protons H(5) and H(8) andthe high-field half to the protons H(6) and H(7) Some broadening of the signalsfrom protons 5 and 7 is attributed to long-range coupling with protons 2 and 3 Thechemical shifts for protons 2 and 3, 5 and 8, and 6 and 7 are 8.97, 8.13–8.09, and7.90–7.86 ppm (our result), respectively As compared with the 8.85 (s, 2H),8.17–8.05 (m, 2H), 7.84–7.72 (m, 2H) in CDCl3(Cui et al.2015) and 8.83 (s, 2H),8.10 (dd, J = 4.2, 2.3 Hz, 2H), 7.76 (dd, J = 4.2, 2.3 Hz, 2H) in CDCl3(Tang et al

iii iv

i = In, water, reflux, 5.5 h (44%)

ii = Pd(OAc) 2 , PPh 3 , NaBH 4 , TMEDA, THF (72%) iii = Cu(OTf)2, 1,2-DCE, MS 4Å, 60 o C, 12 h (81%)

iv = FeOx@NGr-C (cat), heptane, 15 bar air, 100o C, 12 h (93%)

Cheeseman GWH, Cookson RF (1979) Condensed pyrazines In: Weissberger A, Taylor EC (eds) The chemistry of heterocyclic compounds (a series of monographs) John Wiley and Sons, New York, p 835

Chelucci G, Figus S (2014) NaBH4-TMEDA and a palladium catalyst as ef ficient regio- and chemoselective system for the hydrodehalogenation of halogenated heterocycles J Mol Catal A Chem 393:191 –209 doi: 10.1016/j.molcata.2014.06.012

Climent MJ, Corma A, Hern ández JC, Hungría AB, Iborra S, Martínez-Silvestre S (2012) Biomass into chemicals: one-pot two- and three-step synthesis of quinoxalines from biomass-derived glycols and 1,2-dinitrobenzene derivatives using supported gold nanoparticles as catalysts.

J Catal 292:118 –129 doi: 10.1016/j.jcat.2012.05.002

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in a flash vacuum pyrolysis (FVP) experiment Org Biomol Chem 2:2677–2683 doi: 10.1039/ b410786c

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Hirasawa N, Takahashi Y, Fukuda E, Sugimoto O, Tanji K-I (2008) Indium-mediated dehalogenation of haloheteroaromatics in water Tetrahedron Lett 49:1492 –1494 doi: 10 1016/j.tetlet.2007.12.116

Jeong J, Lee D, Chang S (2015) Copper-catalyzed oxygen atom transfer of N-oxides leading to a facile deoxygenation procedure applicable to both heterocyclic and amine N-oxides Chem Commun 51:7035 –7038 doi: 10.1039/c5cc01739d

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Venuti MC (1982) 2,3-Dihydroxy-1,4-dioxane: a stable synthetic equivalent of anhydrous glyoxal Synthesis 1:61 –63 doi: 10.1055/s-1982-29701

Walczak C, Payne TJ, Wade CB, Yonkey M, Scheid M, Badour A, Mohanty DK (2015) The thermal instability of 2,4 and 2,6-N-alkylamino-disubstituted and 2-N-alkylamino-substituted nitrobenzenes in weakly alkaline solution: sec-Amino effect J Heterocyclic Chem 52:681–687 doi: 10.1002/jhet.2154

The synthesis and chemistry of quinoxalines have attracted considerable tion in the past 10 years (Porter 1984; Horton et al.2003; Sherman et al 2007;Patidar et al.2011) The quinoxaline moiety is present in a large variety of phys-iologically active compounds, with applications varying from medicinal to agri-cultural Various quinoxalines exhibit biological activities including antiviral(Westphal et al.1977; Fonseca et al.2004), in particular, against retroviruses such

atten-as HIV (Loriga et al.1997; Balzarini et al 2000; Rosner et al 1998; Patel et al

2000), antibacterial (Griffith et al 1992; El-Sabbagh et al 2009), antimicrobial(Sanna et al.1999; Ali et al.2000; Carta et al.2001; Seitz et al.2002; Badran et al

2003; Singh et al.2010), anti-inflammatory (Wagle et al 2008; El-Sabbagh et al

2009), antiprotozoal (Hui et al.2006), anticancer (Monge et al.1995a; Loriga et al

1997; Lindsley et al.2005; Carta et al.2006), (colon cancer therapies) (LaBarberaand Skibo2005), antidepressant (Sarges et al.1990), antifungal (Loriga et al.1997;El-Hawash et al.1999; Carta et al.2001), antituberculosis (Waring et al.2002; Jaso

et al.2003; Ancizu et al.2010), antimalarial (Rangisetty et al.2001; Guillon et al

2004), antihelmintic (Sakata et al.1988), antidiabetic (Gupta et al 2005), and askinase inhibitors (Levitzki2003; Lindsley et al.2005) Additionally, they are used

in the agricultural field as fungicides, herbicides, and insecticides (Sakata et al

1988) Quinoxaline moieties are also present in the structure of various antibioticssuch as echinomycin, levomycin, and actinoleutin, which are known to inhibit the

growth of gram-positive bacteria and are active against various transplantabletumors (Dell et al.1975; Kim et al.2004) In addition, quinoxaline derivatives havefound applications as dyes (Katoh et al 2000; Sonawane and Rangnekar 2002;Jaung2006), efficient electroluminescent materials (Thomas et al.2005), in organiclight-emitting devices (Fukuda et al.1996; O’Brien et al.1996; Wang et al.2002;Kulkarni et al 2005; Thomas et al 2005), asfluorescent materials (Ahmad et al.

1996; Hirayama et al.2005; Tsami et al.2007), organic semiconductors (O’Brien

et al 1996; Dailey et al 2001), chemically controllable switches (Crossley andJohnston2002), building blocks for the synthesis of anion receptors (Sessler et al

2002), cavitands (Castro et al 2004), dehydroannulenes (Sascha and Rudiger

2004), and DNA-cleaving agents (Yamaguchi et al.1998; Kazunobu et al.2002;Hegedus et al.2003; Patra et al.2005) They also serve as useful rigid subunits inmacrocyclic receptors in molecular recognition (Elwahy2000; Mizuno et al.2002;Kumar et al.2008)

Besides these, quinoxalines have been identified as platforms fordiversity-oriented synthesis on a solid phase (Lee et al 1997; Zaragoza andStephensen1999), and they are established as inhibitors of aldose reductase (Sargesand Lyga1988), agonists of theγ-aminobutyric acid A (GABAA)/benzodiazepinereceptor complex (TenBrink et al.1994; Jacobsen et al 1996), antagonists of theAMPA and angiotensin II receptors (Kim et al.1993), antagonists of the selectivehuman A3 adenosine receptor (Catarzi et al.2005), antagonists of 5-HT3 receptors(Monge et al.1993), growth inhibitors of Trypanosoma cruzi (Aguirre et al.2004),

in the growth inhibition of Escherichia coli (Takeda et al.2005), in cyclooxygenase(COX-2) inhibitory activity (Singh et al.2004), and as inhibitors of cholesteryl estertransfer protein (Jones et al.2005; Eary et al.2007)

A number of selected examples of biologically active quinoxalines chosen from

an impressive list (Negwer and Scharnow2001) are depicted in Fig.2.1 Note:‘R’indicates the salt form of the drug;‘S’ indicates the synonyms under which the drug

is known;‘U’ indicates its medicinal use; and ‘P’ indicates the page in reference(Negwer and Scharnow2001)

As can be seen from the below data (Fig.2.1) quinoxalines belong to a class ofexcellent heterocyclic scaffolds owing to their wide biological properties anddiverse therapeutic applications in medicinal research They are complementary inshapes and charges to numerous biomolecules they interact with, thereby resulting

in increased binding affinity The pharmacokinetic properties of drugs bearingquinoxaline cores have shown them to be relatively easy to administer either asintramuscular solutions, oral capsules, or rectal suppositories Below (Figs.2.2,2.3,

2.4,2.5,2.6,2.7,2.8,2.9,2.10,2.11,2.12,2.13,2.14,2.15,2.16,2.17and2.18) therecent advances in the synthesis (see papers referred to under the structures) andpharmacological diversities of quinoxaline motifs which might pave ways for noveldrugs development are given

N N

U Antiviral (P.962)

N N

N NH O

REV 3164, RHC 3164, Antiallergic, Antiasthmatic (P.663)

MeO

S AG-1296

U Protein tyrosine kinase inhibitor (P.1214)

N N

N N N

F 3 C

Cl

CP 68247 Adenosin A 1

receptor antagonist (P.1060)

N N

O

N OMe

R also monohydrochloride,

S Calmaverin, Calmaverine, Caroverine, Delirex, Espasmofibra, P201-1, Spadon, Spasmium,

"Donau-Pharmazie", Tinnitin, U Spasmolitic (P.2293)

U Anticonvulsant, neuroprotectant (AMPA receptor antagonist) (P.782) R also monohydrate

N N O

O N

O OH

S Bayo-Nox, Va9391 Celbar, Enterodox plus, Fedan, Neo-Iccadox, Olaquindox

U Antibacterial growth stimulant (veterinary) (P.687)

N N O

O O

O OH

S CP 22341, Temodox

U Antibacterial growth stimulant (veterinary) (P.677)

N N O

O OH

S GS-7443-Mequidox

U Antibacterial (P.434)

Fig 2.1 Quinoxaline containing drugs and their synonyms

N

O

O NHMe O

S Bamaquimast, L 004

U Anti-asthmatic

(P.1303)

N N O

O N

H OMe O

S Anticarb 100, Carbadiar 2, Carbadox, Carbamix, Enterodox, Enterosuis, Fortigro, Getroxel, GS-6244, Mecadox

U Antibacterial (P.546)

N N

N CN

NH

S VC 501

U Anti-emetic (P.806)

N

H S

Cl

O O

H 2 C

S 2720

U Antiviral (P.942)

O Cl

N H

O CN

S Ciadox, Cyadox, VUFB-11502

U Antibacterial growth promotor (veterinary) (P.655)

N

H O

U Neuroprotectant (AMPA receptor antagonist) (P.944)

N

H O

O Cl

CO 2 H

S MCD-819

U Antibiotic from Streptomyces ambofaciens MA2870 (P.317)

N

H O

O Cl

NO 2

Cl

S ACEA 1021, Glystatine, Licostinel

U NMDA receptor antagonist (neuroprotective) (P.233)

N

H O

CO 2 H N

S H

CO 2 H O

S Chinacillina, Quinacillin R.D 13962

U Antibiotic (P.1535)

S Dazoquinast P.

Anti-allergic (P.533) N

CO 2 H

N N

O H

S Ataquimast, Tinamast

U Tumor necrosis factor antagonist (P.581)

Fig 2.1 (continued)

O N

O CN

S CGA 56766 Cinoquidox

U Antibacterial growth promotor (veterinary) (P.800)

N N O

O N

O

NH 2

S Drazidox

U Antiseptic (P.437)

N N

N NH N Br

R D-Tartrate (1:2)

S AGN 190342-LF Alphagan Brimonidine tartratr UK-14304-18

U Antihypertensive Antiglaucoma agent (α2-adrenoceptor agonist) (P.542)

N

O Cl

O

N N O OH

N N N

O Cl

N O N

S U-80447

U Antidepressant Anxiolytic (P.1191)

N N N

O

CO 2Bu-t

N O N

S U 97775

U Anxiolytic (GABA A receptor ligand) (P.2442)

N

S

NH 2

R also monosodium salt,

S Anticox, Apokina, Avicocid, Aviochina, Benachinossalina, Biococcid, Biocrin S, Chinovit L, Chinoxal, Coccidione, Coccidioxal, Coccistop, Coccisulfa, Compound 3-120, Coxine 200, Deidrochin L, Embazin, Italquina, Izochinossal, Kinocond, Kokozigal S, Liquicox, Med-Solvimix, Nococcin, Oxalin 100, Quinoxal, Quinoxipra-C,

Solaquin Un Comm Lombarda, Solucoccid, SQX,

Sulfabenzpyrazinium, Sulfachinossalina, Sulfachinoxalin, Sulfox, Sulfoxin, Sulfaquinoxaline, Sul-Q-Nox, Sulquin, Ursokoxalin, U Coccidiostatic (P.916)

O N

O O O

N O NH N

O N

O

O

O

N N

S

O

Fig 2.1 (continued)

Thus quinoxaline derivatives are crucial structural scaffolds found in diverselibrary of compounds which are therapeutically useful agents in medicinal chem-istry research A constant analysis into chemistry and biodiversity relevance ofquinoxaline is inevitable for its pharmacological influence Above data unveilednumerous biological applications of quinoxaline-based scaffolds offering excellentpathways to new biomolecular targets which qualify them to be excellent precursors

in drug design and future candidates in therapeutic research It also demonstratedthat a continuous explorative study into the world of quinoxaline cannot beoveremphasized, if mankind wants to stay healthy and live free of infection This isbecause it provides resourceful tool of information for synthetic modifications ofold existing quinoxaline-based drugs in order to tackle drug resistance bottlenecks

in therapeutic medicine

This diversity of useful synthetic quinoxaline derivatives accounts for theappearance of modifications of the classical synthetic methods and for the search fornew methods ensuring the availability of the corresponding functionalizedquinoxalines

N

O N

O 2 N

N

H O

N

N

N

S N N

N N

N

S N N Cl

7

N

N NH

NH

9

(Abid and Azam 2006)

(Abid and Azam 2006) (Budakoti et al 2009)

(Duque-Montano et al 2013) (Lopez-Vallejo et al 2011)

In this chapter, a comprehensive overview of the different synthetic ologies leading to functionalized quinoxalines and their di-, tetra-, and hexahydroderivatives will be given These methodologies are based on the five mainapproaches to the synthesis of quinoxalines: condensation of 1,2-diaminobenzenes(1,2-DABs) with various two-carbon unit donors, cyclization of aniline derivatives,

method-N

N F

10

N N H H

OH O

O

11

N N H H

OH O

O

12

OH

N N O

13

N N N

O

N Cl

14

N

N NC

17

N N

20

N

O S O

N NH O

22

I I

23

N H

S N

N

N O

24

O

(Reddy and Reddy 2010) (Tandon et al 2006) (Tandon et al 2006)

(Hassan 2013) (Kalinin et al 2013)

(Aravind et al 2013)

(Ishikawa et al 2013)

(Parhi et al 2013)

(Morales-Castellanos et al 2012) (Waly et al 2012) (Al-Hiari et al 2007)

N

N N N F

+

+

Fig 2.4 Some quinoxaline motifs with antibacterial activity

and reactions of various heterocyclic systems devoid of a pyrazine fragment andwith heterocyclic systems containing a pyrazine fragment.

The synthesis of fused and polycyclic derivatives of quinoxalines will not bedealt with in this chapter, except those cases where the formation of these systemsoccurs in one pot This implies either the condensed parent compounds or thecompounds capable, besides constructing a quinoxaline system, to annulate sepa-rate rings on various sides under the reaction conditions

N N

Cl

27

N N O

O H

29

N

N F

OMe

N H

N OMe

N

N

N O

H N N I

N H

O N H

O

36

N

N N

(Lee et al 2010a)

(Karki et al 2009) (Tanimori et al 2009) (Lee et al 2010a)

NNCl Cl

Ni Ni Cl

NH NH

O O

HN

+1

.H 2 O

45

(Wagle et al 2009) (Wagle et al 2009) (Alswah et al 2013)

(Bayoumi et al 2012) (Ibrahim et al 2013) (Sahu et al 2012)

(Ghadage and Shirote 2011)

F 3 C N O

O O P O OH OH

47

N N

O O

N O N

48

N N

N N

N

H O

(De Sarro et al 2005)

Fig 2.7 Some quinoxaline motifs with antiepileptic activity

2.2 Condensation of 1,2-Diaminobenzenes

(1,2-DABs; Ortho-Phenylenediamines) and Derivatives with Various Two-Carbon Unit Suppliers

2.2.1 With Pyruvates (2-Oxopropanoates)

The reaction of pyruvates with 1,2-DABs, first discovered by Hinsberg (1884,

1887) and Körner (1884) many years ago, independently of one another, is still themost appropriate method for the synthesis of 3-substituted quinoxalin-2(1H)-ones(Abasolo et al.1987; Piras et al 2006; Eller et al 2007; El-Sabbagh et al.2009;Yuan et al 2009; Singh et al 2010) A kinetic study of the Hinsberg reactioninvolved reacting unsymmetrical 1,2-DABs with pyruvates and the formation of

56

F

Cl Cl

N N

N

N N O

O N

62

(Ajani et al 2010) (Ajani and Nwinyi 2009)

(Ajani and Nwinyi 2009)

(Gupta et al 2013)

(Carta et al 2004) (Carta et al 2004)

(Xu and Fan 2011)

isomeric quinoxalin-2(1H)-ones (Abasolo et al 1987) Some related compoundswere synthesized in acetic acid to improve the regioselectivity (Lumma et al.1981).The reaction of N-methyl-1,2-DAB with pyruvic acid, unlike the reactions ofunsymmetrical 1,2-DABs, proceeds with the formation of 1,3-dimethylquinoxalin-2(1H)-ones as the sole products (Lawrence et al.2001) Recently, a one-pot synthesis

of polyfunctionalized dihydroquinoxalinone derivatives via the anti-Michael tion has been developed (Ballini et al.2009) Six quinoxalinone and three benzo-quinoxalinone derivatives were obtained by using S cerevisiae as a biocatalyst andalso by means of microwave-assisted approaches (Gris et al.2008) In general, most

reac-of these methods involve the use reac-of toxic/volatile organic solvents with longreaction times, poor yields, and tedious product isolation procedures

Nageswar and coworkers developed a facile and expeditious synthesis of3-substituted quinoxalin-2(1H)-ones in water under catalyst-free conditions(Murthy et al.2010) 3-Substituted quinoxalin-2(1H)-ones 158 are obtained whenthe pyruvic esters 156 or the phenylglyoxylate 157 are used in reaction with1,2-DABs155a–c (Scheme2.1) (Murthy et al.2010)

While ethyl glyoxalate 159 and terminal alkynes 160 were used instead ofpyruvic esters 156, or phenyloxalate 157, a novel and efficient protocol for thecopper(II) catalyzed synthesis of furoquinoxalines161–163 from readily available1,2-DABs155a–h has been developed (Naresh et al.2014) (Scheme2.2)

N

H N

N HN

N

H O

O N N O

NH HN S

66

N N N N O

NH HN S

67

(Pelletier et al 2009) (Pelletier et al 2009)

(Pelletier et al 2009)

(Pelletier et al 2008) (Pelletier et al 2008)

Fig 2.9 Some quinoxaline motifs with GnRH antagonist activity

A possible reaction mechanism for the formation of furoquinoxalines appears to

be the tandem C–C bond formation followed by a 5-endo-dig cyclization reaction

as outlined in Scheme 2.3 Generally, in A3-coupling reactions, the amine155areacts with aldehyde 159 and forms the imine which is further transformed toiminium ion A; at the same time the in situ generated copper acetylide B fromterminal alkyne and copper(II) trifluoromethanesulfonate attacks the intermediate

A to produce the propargylamine C (Peshkov et al 2012) The resulting gylamineC further attacks the ester functionality intramolecularly, leading to thegeneration of intermediateD Since intermediate D is easily enolizable in an acidicmedium, it provides the cyclized intermediate 3-(alkynyl)-3,4-dihydroquinoxalin-2(1H)-one E and a further cleavage of the metal π-complex occurs followed byoxidation furnishing the target furoquinoxaline

propar-This novel method involves the formation of four new bonds (2C–C, C–N, and

C–O) in a cascade pathway

A new and effective procedure was developed for the synthesis of3-ethylquinoxalin-2(1H)-one from 1,2-DAB 155a and ethyl 2-oxobutanoate

S N N O

NH 2

69

N N

S N N O

O

71

N N

O H

O N

Cl O

CO 2 H

N N

OMe

77

(Abu-Hashem et al 2010) (Abu-Hashem et al 2010) (Abu-Hashem et al 2010)

(Achutha et al 2013) (Achutha et al 2013)

(Guirado et al 2012) (Guirado et al 2012) (Ingle and Marathe 2012)

Fig 2.10 Some quinoxaline motifs with anti-inflammatory and analgesic activities

(Mamedov et al.2005) The latter was prepared by the Grignard reaction of diethyloxalate with ethylmagnesium bromide or iodide 3-Functionally substitutedquinoxalin-2(1H)-ones can also be synthesized by the functionalization of an alkylgroup at C(3) of quinoxalin-2(1H)-ones For example, the functionalization ofquinoxalinone165 was performed via the substitution of the bromine atom in α-bromoethyl derivative166 when acted upon by various nucleophiles (Scheme2.4)(Mamedov et al.2005) Compound 166 is readily obtained by the treatment of asuspension of165 in 1,4-dioxane with bromine at 12–15 °C The bromine atom in

166 is readily replaced by such nucleophiles as KSCN, PhNH2, and NaN3 inDMSO to give the corresponding 3-(α-ethyl)quinoxalines 167–169 Both thetreatment of 3-(α-azidoethyl)quinoxaline 169 with a 70 % aqueous acetic acid andthe direct oxidation of quinoxalinone165 with chromic anhydride in 95 % aceticacid proceed with the formation of ketone170 as the major product (Scheme2.4)(Mamedov et al.2005)

O 2 N

80

N N

F 3 C

84

CN

N N O

(Vicente et al 2008) (Zarranz et al 2006)

+ +

+

+

+ +

Fig 2.11 Some quinoxaline motifs with antimalarial activity

Later the same strategy, using Cr2O3in AcOH, was applied for oxidizing themethylene group of three 3-benzylquinoxalin-2(1H)-ones (Piras et al.2006).The cyclocondensation of equimolar amounts of 1,2-cyclohexanediamine(1,2-DACH) 171a and ethyl pyruvate 156a in a hot EtOH solution containing acatalytic amount of AcOH proceeds with the formation of 3-methyl-4a,5,6,7,8,8a-hexahydro-2(1H)-quinoxalinone 172 (Scheme2.5) (El-Sabbagh et al 2009) Thecoupling of the latter with an equimolar amount of diazonium salts173 at 0 °C inAcOH, buffered with NaOAc, provided the novel hydrazones174 A good yield ofester 175 was obtained through the reaction of 1,2-DACH 171a with diethyloxaloacetate156d in EtOH containing AcOH at 80 °C and then at room temperature.

F 3 C

CF3

N N O

O

87

Cl

O OMe

N

H O O

NNHO

91

N

H O

O

90

Cl

N CN

F H

N N O

O

88

Cl

O N Cl

N N O

O

94

CN

F N

N O

O

N N O N O

O Cl

N

98

N

H N N

(Ramalingam et al 2010) (Ramalingam et al 2010)

(Silva et al 2009) (Torres et al 2011) (Villar et al 2008)

(Rao et al 2010) (Puratchikody et al 2011) (Puratchikody et al 2011)

+

+

+ +

+ +

+

+

+ +

+ +

+ +

+ +

Fig 2.12 Some quinoxaline motifs with antitubercular activity

N

O O

Cl

100 (XK-469)

N N

N

CN Cu

N

N NC

103 R = H

104 R = OH

N N

O

OMe OMe

N H

O N N

O

O

O

(Polin et al 2002; Zheng et al 2002;

Hazeldine et al 2005; Undevia et al 2008)

(Urquiola and Gambino 2008)

Fig 2.13 Some quinoxaline motifs with antitumor activity

N N

111

N

N

N N

HN NH

O O

112

HN

N N

O

N

N N

O N O

Ni Ni Cl

H

H 2 O

H N

H 2 O NH N

O

113

N N O O Cl

CF 3

O

114

(Toshima et al 2004) (Metry et al 2010) (Aggarwal et al 2011)

(Alper et al 2003) (Budagumpi et al 2010) (Junnotula et al 2010)

Fig 2.14 Some quinoxaline motifs with DNA-cleavage properties

The hydrazide 176 was obtained through condensation of the ester 175 withhydrazine hydrate by heating the reactants in EtOH at reflux Hydrazide 176 wasused for synthesizing other functionalized derivatives of hexahydroquinoxalin-2(1H)-one 175 (El-Sabbagh et al.2009).

Diethyl ketomalonate (diethyl mesoxalate)177 reacts with 1,2-DAB 155a in thesame way as do pyruvates to provide 3-ethoxycarbonyl quinoxalin-2(1H)-one 178(Scheme2.6) (Mahesh et al.2011)

O

O

O O

116

N

N

N N

121

N N

N N O

120

N

N

N N O

118

N N

N

N N N

123

N N

N OH O

F 3 C

124

N

N MeO

MeO

OH

128

N N

N N HN

126

(Park et al 2011) (You et al 2011) (Gavara et al 2010) (Gavara et al 2010)

(Szekelyhidi et al 2005) (Lindsley et al 2005) (Dolle et al 2006)

(Li et al 2013b)

Fig 2.15 Some quinoxaline motifs with kinase inhibitory activity

N

O

OMe OMe

OMe

N O

OMe

OMe OMe

N N O

134

S

N N O

N N O

O Cl

137

N O

O

Cl

N O

N N O

O

Cl

N

O Cl

N

CF 3

N N O

O O O

O O O

142

N H

S

H

H 2 C

N N H

O O

143

N N

N O

145

CN

CN

CN CN

CN

Cl

(Estevez et al 2011) (Estevez et al 2011) (Benitez et al 2011)

(Benitez et al 2011) (Lavaggi et al 2008) (Vicente et al 2010) (Romeiro et al 2009)

(Ancizu et al 2009) (Aguirre et al 2004) (Barea et al 2013)

+

Fig 2.16 Some quinoxaline motifs with trypanocidal properties

2.2.2 With α-Diketones (1,2-Diketones)

There are many examples of quinoxalines being prepared from α-diketones(1,2-diketones) usually involving the reaction of 1,2-DABs in refluxing ethanol oracetic acid (Carta et al.2003; Fonseca et al.2004; Hui et al.2006; Wang et al.2006;

N N

F

N N

N

O HO

HO

152

N N

O

S

S O OMe F

N S N

(Xu et al 2009) (Xu et al 2009)

Fig 2.18 Some quinoxaline motifs with anti-HIV activity

NH 2

NH 2

H 2 O,

50 o C, 15 min O

R 2

O

OEt

N N

Tingo li et al.2011; Xu et al.2011a; You et al.2011) Various catalysts, such asgraphite (Kadam et al 2013), bismuth(III) triflate (Yadav et al 2008), metalhydrogen sulfates (Niknam et al 2008), gallium(III) triflate (Cai et al 2008),molecular iodine (Bhosale et al.2005; More et al 2005), cerium(IV) ammoniumnitrate (More et al 2006), stannous chloride (Shi et al 2008), manganese(II)chloride (Heravi et al.2008), zirconium tetrakis(dodecylsulfate) (Hasaninejad et al.

N OEt O H