PRACTICAL HETEROCYCLIC CHEMISTRY

A. O. Fitton and R. K. Smalley University of Salford, Lancs, England

ACADEMIC PRESS

London and New York

1968

CONTENTS

Page

Introduction . . . . . . . . . . v

Preface . . . . . . . . . . . vii

C H A P T E R l : Five-membered Systems Containing One Hetero-atom . . . . . . . . . . . 1

M e . X 0 2 E t 2,4-Diethoxycarbonyl-3,5- p "~T| ^

dimethylpyrrole E t 0 2 C ^ N - ^ M e H

2,5-Dimethylpyrrole M e ^ K T ^ M e 2

H

Ph-. ^ C 0 2 H 4,5-Diphenyl-2-methylfuran-3-carboxylic acid I I 3

P h ^ N ) ^ M e

2,5-Dimethylthiophen I II 5

C H A P T E R 2: Benzoderivatives of Five-membered Systems Containing One Heteroatom . . . . . . . 7

Carbazole ^ ^ , „ H

1,2,3,4-Tetrahydrocarbazole ^ ^^

H

0 2,3-Dioxoindoline (isatin) I II I 11

H (ix)

X CONTENTS

^ ^° H Indigotin (indigo) -^ ^^A 1 ,

H 0S

12

2-Phenylindole ^ . J ^ T J V ™ 1 3

\ - N Ph H

2-Benzoylbenzofuran (2-benzoylcoumarone) I | | 15 > ^ - O ^ C O P h

HO 5-Hydroxycyclo-octano[&]coumaran [ j! | 15

2-Methylcoumaran [ X I 1 6

5-Chloro-3-methylbenzo[ö]thiophen [ ]| j| 17

C H A P T E R 3 : Five-membered Systems Containing More Than One Heteroatom . . . . . . . . . 19

° S NH 2,4-Dioxoimidazolidine (hydantoin) [ ^L 19

H

4,5 -Diphenylimidazole (4,5 -diphenylglyoxaline)

2-Methyl-A2-imidazoline

3,5 -D imethylpyrazole

P h - ^ N H

P h - ^ S T

| NH

1 * H

21

22

23

CONTENTS

3-Methyl-l-phenyl-5-pyrazolone

Me

N-

I Ph

24

1,3,5 -Triphenyl-A2-pyrazoline

-Ph

P h ^ ] s r N

I Ph

25

3,5 -Dimethylisoxazole M E

11 1 28

3 -Phenyl-5 -isoxazolone f Ph

i1 29

4-Benzylidene-2-phenyl-5-oxazolone

Cyclohexanespiro-2'-(l',3'-oxazoiidine)

°Y-o P h C H ^ N ^ - p h

-O/

30

31

2-Methyl-A2-oxazoline -O I

^ N ^ - M e 32

2,4,5-Triphenyloxazole Ph O

33 P h ^ N ^ P h

^-Chlorophenylsydnone N - O

-CVC6Hi-N~®J%0

H 34

3,4-Dimethyl-l,2,5-oxadiazole (3,4-dimethylfurazan)

M e N / M e 1 II 36 N. 0 .N

2,5 -Diphenyl-1,3,4-oxadiazole N N

1 X P h ^ C T ^ P h

37

Xl l

2,4-Dimethylthiazole

2-Methyl-A2-thiazoline

CONTENTS

( 1 — s

M e ^ N ^ M e

1 S

39

40

C H A P T E R 4: Benzoderivatives of Five-membered Systems Containing More Than One Heteroatom . . . . 42

r i—N

Benzimidazole H

f ^ \ NH

kAAo 43 H

1,2-Dihydro-2-oxobenzimidazole (benzimidazolone)

6-Nitroindazole „ I S T ^ - W / V N ^ N 44

H

N

1 -Aminobenzotriazole ^^v^-N' ' 45 I

NH,

f^\ N

Benzotriazole W / \ >-N ^7 H

-N

l-(/)-Nitrophenyl)-4,5,6,7-tetrahydrobenzotriazole ' \ / ^ N ' ' N 48 I

/>-N02C6H4

3-Methyl-S-nitrobenzisoxazole ( || II 51 v O"^

3-Phenylbenzo-2,l-isoxazole i ^ ^ l f (3-phenylanthranil) [. L ^ 5 3

CONTENTS

r ^ i — o 2-Methylbenzoxazole I I 55

0 2 N ^ \ 0

2-Methyl-6-nitrobenzoxazole I II I 56

Benzo-2.1,3-oxadiazole 1-oxide (benzofuroxan) I 57

5(6)-Chlorobenzo-2,l,3-oxadiazole r ^ ^ j = N ' ^ 1-oxide [S(6)-chlorobenzofuroxan] I - I ^ S S ^ W M ' - O °

a—NH

N X B \ D , 61 H

a—NH D«5* 62

H

I II 1 A ^

2-Phenylbenzo-l,3-oxaza-2-borole ks. J k - . ^ i u 0 J

r ^ — o

^Ph H

2-Phenylbenzothiazole I | I 64 N ^ P h

Benzo-2,l,3-thiadiazole [ I y 65 kANi

C H A P T E R 5: Six-membered Systems Containing One Hetero-atom . . . . . . . . . . . 67

3-Chloro-2,6-dimethylpyridine || 67 M e - ^ N ^ M e

XIV CONTENTS

3,5-Diethoxycarbonyl-2,6-dimethyl-4-(wj-nitrophenyl)pyridine

m-N02-C6H4

E t 0 2 C v ^ L ^ C 0 2 E t 68

M e A N A M e

4-Nitropyridine iV-oxide

N O ,

70

Me A^CN

3-Cyano-4,6-dimethyl-2-pyridone: Method 1 jj | 71

H

3-Cyano-4,6-dimethyl-2-pyridone: Method 2

3,5-Diacetyl-l,4-dihydro-2,4,6-trimethylpyridine

Me

^ v CN

Me' '

A c \

Me-"

H

Me

r\ V1 H

^ O

^Ac

x M e

72

72

4-Pyridone-2,6-dicarboxylic acid (chelidamic acid)

O

74 H02CT ^Nr ^ C 0 2 H

H

3-Acetyl-3,4-dihydro-6-methyl-4-oxo-a-pyrone (dehydroacetic acid)

O

75

Me-^Cr^o

2,6-Dimethyl-y-pyrone

O

76

M e ^ ^ O - ^ M e

CONTENTS XV

6-Isobutenyl-4-methyl-a-pyrone

Me

\ Me, C=CH ^ 0 ^ * 0

77

C H A P T E R 6: Benzoderivatives of Six-membered Systems Containing One Heteroatom . . . . . . . 79

3 -Methyl-1 -phenylisoquinoline

Ph

6-Chloroquinoline Ck

82 -N*

4-Methyl-2-phenylquinoline

Me

83

N T x P h

2,4,6 -Trimethylquinoline

2-Methyl-4-quinolone

Me Me

84 •N-^Me

O

•KT^Me H

86

4-Methyl-2-quinolone

Me

87

H O

4-Phenyl-2-quinolone

Ph

N ^ o

CONTENTS

9-Acridone 90

Phenanthridine 91

6-Phenanthridone 93

Chromone-2-carboxylic acid

O

* * % > 94

O ^ C 0 2 H

2-Methyl-5,6,7,8-tetrahydrochromone

O

O-^-Me 95

7-Hydroxy-4-methylcoumarin (4-methylumbelliferone)

Me

H C K ^ - ' ^ O ' ^ o 97

Benzo[/]chroman-4-one O 98

B enzo [/ ] chromone 99

CONTENTS

O

Xanthone [ |T \\ 1 101

C H A P T E R 7: Six-membered Systems Containing More Than One Heteroatom . . . . . . . . . 103

4-Cyano-2,3-dihydro-5,6-diphenyl- 1 1^ ..„,, P h ^ N . N H

ro-5,6-diphenyl-3-oxopyridazine

CN

H

2,4-Dioxo-6-methyl-l,2,3,4- i ; 1 0 4

tetrahydropyrimidine (6-methyluracil) " \ - N H

O

H O ^ N o

Hexahydro-2,4,6-trioxopyrimidine j ' (barbituric acid) \ / N H

O

105

H

2,5-Dioxopiperazine [ 107

H

^ N ^ C 0 2 H Pyrazine-2,3-dicarboxylic acid U J ^ 108

-N^^COzH

Hexahydro-l,3,5-tri-j>-tolyl- />-Me-C6H4-N N—C6H4.p-Me s-triazine ^1V^

I £-Me-C6H4

C H A P T E R 8: Benzoderivatives of Six-membered Systems Containing More Than One Heteroatom . . . 1 1 1

O

4-Cinnolone y |j |] 111

H N-N

xvm CONTENTS

Quinazoline

3-Amino-3,4-dihydro-2-methyl-4-oxoquinazoline

C O »2

O

N / N H 2

114 N ^ M e

Quinoxaline 115

3,4-Dihydro-l-hydroxy-4-oxophthalazine

O

NH

N

OH

116

3,4-Dihydro-l-methyl-4-oxophthalazine

O

NH I

^ N

Mc

117

Dibenzo[a,c]phenazine 118

3,4-Dihydro-4-oxo-l,2,3-benzotriazine: Method 1

O

N H

^ / ^ N ^ N 118

3,4-Dihydro-4-oxo-l,2,3-benzotriazine: Method 2

O

NH I

N*N 120

2-Ethyl-4-oxo-3,l-benzoxazine

O

O

N * ^ E t

121

CONTENTS XIX

2,3 -Dihydro-3 -oxo-1,4-benzoxazine (benzo-3-morpholone): Method 1

O

N H X. 123

O

2,3-Dihydro-3-oxo-1,4-benzoxazine (benzo-3-morpholone): Method 2

O 124

g~o

2,4-Dinitrophenoxazine 0 ^ / ^ / N 0 2

NO,

125

Phenothiazine 127

2-Oxo-l ,4-benzodioxan O ^

128

Phenoxathiin o-

128

C H A P T E R 9 : Miscellaneous Systems . 130

Cyclohexa-2,5-diene-4-one-spiro-2'-oxetano[3',4']cyclo-octane 130

4,6-Dinitrobenzimidazo[l,2-a]pyridine NO,

% ^ N -

131

NO,

2-Phenylimidazo[l,2-a]pyridine N

Ph 132

XX CONTENTS

2,3)4,5-Tetrahydropyrido[l,2-a]- f ^ \ ^ ' ^ 133 benzimidazole ^ / ^ N ^ \ /

l,4-Dihydro-erarfo-l,4-oxanaphthalene [I Q II I 135

Bibliography . . . 137

Subject Index 139