RODD'S CHEMISTR Y

OF CARBON COMPOUND S

A modern comprehensive treatis e

SECOND EDITION

Edited byS. COFFEY

M.Sc . (London), D.Sc. (Leyden), C .Chem., F.R.I .C.formerly of

I. C.I. Dyestuffs Divison, Blackley, Manchester, Great Britai nand

MARTIN F. ANSELLPh.D., D .Sc . (London) F .R.S .C., C .Chem .

Reader Emeritus, Department of Chemistry, Queen Mary College,University of London, Great Britain

VOLUME IV PART IJ

HETEROCYCLIC COMPOUND S

Edited byMARTIN F. ANSELL

Six-membered heterocyclic compounds with two hetero-atoms from Group V of th ePeriodic Table : the Pyridazine and Pyrimidine groups, the Pyrazine group . Pheno-xazine, phenothiazine, phenazine and sulphur dyes . Six-membered heterocylic com-

pounds with three or more hetero-atoms

Heterocyclic Compounds : Six-membered heterocyclic compounds with two hetero-atoms fromGroup V of the Periodic Table : the Pyridazine and Pyrimidine groups, the Pyrazine group .Phenoxazine, phenothiazine, phenazine and sulphur dyes . Six-membered heterocyclic com-pounds with three or more hetero-atom s

PREFACE VI I

OFFICIAL PUBLICATIONS ; SCIENTIFIC JOURNALS AND PERIODICALS XVI I

LIST OF ABBREVIATED NAMES OF CHEMICAL FIRMS MENTIONED IN PATENT REFERENCES

XVII I

LIST OF COMMON ABBREVIATIONS AND SYMBOLS USED XI X

Chapter 42. Pyridazines, Cinnolines, Benzocinnolines and Phthalazinesby R .N . HUNSTON, J . PARRICK and C .J .G. SHAW

1 . Pyridazines 1a. Introduction 1b. Methods of synthesis 1c. Pyridazine and its alkyl and aryl derivatives 6

(i) Pyridazine, 6 - (ii) Spectra, 8

(iii) Chemical reactivity, 9 - (iv )Alkyl- and aryl-pyridazines, 1 0

d. Halogenopyridazines 1 2e. Nitropyridazines 1 4f. Aminopyridazines and related compounds (nitroamines, hydrazines, azides) 1 5g. Pyridazine-N-oxides 1 8h. Pyridazinones 22i. Pyridazinecarboxylic acids 26j. Pyridazine sulphur compounds 2 8k. Reduced pyridazines

30(i) Dihydropyridazines, 30 - (ii) Tetrahydropyridazines, 33 - (iii) Hexa-hydropyridazines (piperidazines), 34 -

2 . Cinnolines 3 5a. Introduction 3 5b. Methods of synthesis 3 6c. Cinnoline and its alkyl and aryl derivatives

3 9(i) Cinnoline, 39 - (ii) Spectra, 41 - (iii) Chromatography, 45 - (iv )Reactions, 45 - (v) Alkylcinnolines, 47 - (vi) Arylcinnolines, 4 8

d. Cinnoline-N-oxides 49e. Halocinnolines 5 4f. Nitrocinnolines 5 9g. Aminocinnolines

6 1(i) Hydrazinocinnolines, 68

h. Hydroxycinnolines

7 0(i) 3- and 4-Hydroxycinnolines, 70 - (ii) 5-, 6-, 7- and 8-Hydroxycinnolines ,80 - (iii) Phenyl ethers, 82 ,

I . Cinnolinecarboxylic acids and derivatives 83

J . Reduced cinnolines 9 2(i) Reduction of cinnolines, 92

(ii) From cyclisation reactions, 96 - (iii )Reactions and biological properties, 98 -

3 . Benzocinnolines 9 9a. Introduction 9 9b. Benzo[c]cinnolines

100(i) Synthesis, 100 - (ii) Physical and chemical properties, 102 - (iii)Methylated benzo[c]cinnolines, 105 - (iv) Halogeno-, nitro-, and othe rsubstituted benzo[c]cinnolines, 106 - (v) Reduced benzo[c]cinnolines, 10 9

c. Other benzocinnolines 11 04 . Phthalazines 11 4

a. Methods of synthesis 11 4b. Phthalazine, its alkyl and aryl derivatives

11 9(i) Phthalazine, 119 - (ii) Spectra, 120 - (iii) Reactivity, 121 -- (iv) Alkyl-and aryl-phthalazines, 122 -

c. Phthalazine-N-oxides and -N-aminoazolium salts 123d. Halogenophthalazines 124e. Aminophthalazines and related compounds 12 6f. Phthalazinones, hydroxyphthalazines and oxidophthalazinium betaines

13 0(i) 1(2H)-Phthalazinones, 130 - (ii) 3-Alkyl(or aryl)-1(2H)-phthalaziniu msalts and 3-alkyl(or aryl)-1-oxidophthalazinium betaines, 133 - (iii) 4-Hy-droxy-1(2H)-phthalazinones, 136

(iv) Chemiluminescence, 139 -g. Phthalazinethiones and mercaptophthalazines 141h. Phthalazine quinones 142i. Phthalazinecarboxylic acids and their derivatives 144J . Reduced phthalazines 145

(i) 1,2-Dihydrophthalazines, 145 - (ii) 1,4-Dihydrophthalazine, 150 - (iii )1,2,3,4-Tetrahydrophthalazines, 150 - (iv) 5,6,7,8-Tetrahydrophthalazines,151 - (v) Other reduced phthalazines, 15 3

Chapter 43 . Pyrimidines and Quinazolines

by R .T . WALKER

1 . Introduction 1552 . Physical properties of pyrimidine 15 8

a. Structure and geometry 15 8b. The ionisation constant of pyrimidines 159c. Spectroscopy

16 2(i) Nuclear magnetic resonance, 162 - (ii) Infrared and ultraviolet spectra ,163 - (iii) Mass spectra, 163 -

d. Tautomerism 16 43 . Synthesis 16 5

a. The principal method

16 6(i) From ß-dialdehydes, 166 - (ii) From ß-aldehydo-ketones, 168 - (iii )From ß-diketones, 170 - (iv) From ß-aldehydo esters, 172 - (v) Fromß-keto esters, 173 - (vi) From /3-diesters, 175 - (vii) From ß-aldehydo-

nitriles, 177 - (viii) From /3-keto-nitriles, 179

(ix) From ß-ester nitrites ,179 - (x) From ß-dinitriles, 180 -

b. Primary syntheses

18 1(i) Involving the formation of one bond, 181 - (ii) Involving the formationof two bonds, 181 - (iii) Involving the formation of three bonds, 184

(iv )Involving the formation of four or more bonds, 18 5

c. Syntheses of the pyrimidine ring from other heterocycles

18 6(i) From pyrroles, 186 - (ii) From imidazoles, 186 - (iii) From mixed 5- or6-membered heterocycles, 187 - (iv) From purines and related heterocycles ,188 - (v) Miscellaneous examples, 189 -

d. Some factors governing the synthesis of substituted pyrimidines 1904. Chemical reactivity and properties of pyrimidine derivatives 19 3

a. General properties 19 3b. Reactivity of the ring positions

194(i) To electrophiles, 194 - (ii) To nucleophiles, 197 - (iii) Photochemicalreactions, 197 - (iv) Oxidation and reduction, 198 -

c. Properties of various pyrimidine types

199(i) Pyrimidine, alkyl- and aryl-pyrimidines, 199 - (ii) Halogenopyrimidines ,201 - (iii) Nitro- and nitroso-pyrimidines, 208 - (iv) Pyrimidinamines, 20 9- (v) Hydroxy- and alkoxy-pyrimidines, 213 - (vi) Carboxylic acids an dderivatives, 218 - (vii) Sulphur-containing pyrimidines, 221

(viii) Metal-lopyrimidines, 225 - (ix) Pyrimidine-N-oxides, 227 -

5 . Quinazolines 227a. General chemical and physical properties 229b. Synthesis of quinazolines 23 1c. Chemical reactions of quinazolines 23 4d. Chemical reactivity of substituted quinazolines 23 5

Chapter 44. Pyrazines and Related Ring Structuresby K .J. MCCULLOUG H

1 . Pyrazines, 1,4-diazines 24 1a. Introduction 24 1b. Physical and spectroscopic properties 24 3c. General methods of synthesis

24 5(i) Self-condensation of a-aminocarbonyl compounds, 245 - (ii) Con-densation of a,ß-diamines with a,ß-carbonyl compounds 247

(iii) Miscel-laneous condensation and dimerisation procedures, 249 - (iv) Dehydrogena-tion of piperazines, 251 - (v) Cleavage of quinoxalines and pteridines, 25 2

d. Pyrazine, its homologues and derivatives

25 2(i) Pyrazine, alkyl- and aryl-pyrazines, 252 - (ii) Halopyrazines, 257 - (iii )Aminopyrazines, 259 - (iv) Hydroxypyrazines, 261 - (v) Pyrazinecarbo-xylic acids, 270

e. Reduced pyrazines

27 5(i) Dihydropyrazines, 275 - (ii) Tetrahydropyrazines, 283 - (iii) Pipera-zines (hexahydropyrazines), 287 - (iv) Piperazinones (ketopiperazines), 294

2 . Quinoxalines (benzopyrazines) 30 1a . Introduction 30 1b . Physical and spectroscopic properties 30 1C . Methods of synthesis 302d . Quinoxaline, its homologues and derivatives

31 0(i) Quinoxaline and its alkyl and aryl derivatives, 310 - (ii) Halogenate dquinoxalines, 319 - (iii) Nitroquinoxalines, 323 - (iv) Aminoquinoxalines ,324 - (v) Hydroxyquinoxalines (quinoxalin-2(111)-ones), 327 - (vi)Quinoxaline-N-oxides, 334 - (vii) Polyhydroxyalkylquinoxalines, 342 -(viii) Quinoxalinecarboxaldehydes, 344 - (ix) Quinoxaline-2-carboxyli cacids, 345 -

c . Reduced quinoxalines

34 9(i) Dihydroquinoxalines, 349 -- (ii) Tetrahydroquinoxalines, 350 - (iii )Decahydroquinoxalines, 353 -

3 . Phenazines (dibenzopyrazines) 354

a. Introduction 35 4b. Physical and spectroscopic properties 35 6c. General methods of synthesis 35 7d. Phenazine, its homologues and derivatives

36 3(i) Phenazine, alkyl- and aryl-phenazines, 363 - (ii) Benzo- and dibenzo-phenazines, 367 - (iii) Phenazine-N-oxides, 369 - (iv) Halogenated phcna-zines, 375 - (v) Nitrophenazines and phenazinesulphonic acid, 378 - (W )Aminophenazines, 381 - (vii) Hydroxypbenazines (phenazinols), 384 -(viii) Phenazinecarboxylic acids, 390 - -

e. Reduced phenazines

39 1(i) 5,10-Dihydrophenazines, 392 - (ii) 1,2,3,4-Tetrahydrophenazines, 397 -(iii) Octahydrophenazines, 398 - (iv) Decahydrophenazine, 400 - (v )Tetradecahydrophenazines,401 -

Chapter 45 . Phenazine, Oxazine, Thiazine and Sulphur Dyesby N . HUGHE S

1 . Introduction 40 32. Phenazine dyes 40 4

a. Eurhodines and eurhodols 405b. Aposafranines 407c. Safranines 409d. Fluorindines 41 2e. Indulines and nigrosines 41 4

f. Aniline black (C .1 . Pigment Black 1, 50440)

41 63 . Phenoxazine dyes 41 7

a. Basic type 41 7

b. Gallocyanines 420

c. Triphendioxazines 4224 . Phenothiazine dyes 4275 . Sulphur dyes 430

a . Constitution of the sulphur dyes 433

Chapter 46. Quinazoline Alkaloidsby A . MCKILLOP, M . SAINSBURY AND B .P. SWAN N

1. Simple quinazolines . . . .

;., n .,. T.: : ..

. 43 7

2. Vasicine and related alkaloids 44 0

3. Febrifugine and isofebrifugine 44 94. The indoloquinazoline alkaloids 45 1

Chapter 47. Compounds Containing a Six-Membered Ring with more than Two Hetero-Atomsby D .G . NEILSON AND D. HUNTER

1 . Triazines :; 457a . 1,2,3-Triazines a :r. :. . . .~a »r :: 457

(i) Simple derivatives, 457

(ii) Fused 1,2,3-triazines, 459 -b . 1,2,4-Triazines

46 1(i) Amino-1,2,4-triazines, 462 - (ii) 1,2,4-Triazinecarboxylic acids, 462 -(iii) Halogen-substituted 1,2,4-triazines, 463 - (iv) Hydroxy-1,2,4-triazine s(triazinones), 463

(v) 1,2,4-Triazine-N-oxides, 464 - (vi) Triazinethiones ,464 (vii) Reduced 1,2,4-triazines, 465 - (viii) 1,2,4-Benzotriazines (a-phe-notriazines), 465 - (ix) 1,2,4-Benzotriazines and related species with reduce dring systems, 467 - (x) Compounds containing 1,2,4-triazines fused t opolycyclic and heterocyclic systems, 467 -

c . 1,3,5-Triazines :; . ~• 46 8(i) Synthesis, 468 - (ii) 1,3,5-Triazine and its alkyl- and aryl-substitutedderivatives, 471 - (iii) Amino-substituted 1,3,5-triazines (melamines), 472(iv) Carbonyl derivatives and carboxylic acids, 472 - (v) Cyanuric aci d(2,4,6-trihydroxy-1,3,5-triazine) ; trithiocyanuric acid, 473 - (vi) Halogen-substituted 1,3,5-triazines - cyanuric halides, 473 - (vii) N-oxides an dazides, 475

(viii) Compounds with a fully reduced 1,3,5-triazine ring, 47 5- (ix) Fused ring 1,3,5-triazines, 475 -

2. Thiadiazines ; ;.; 47 6(i) 1,2,3-Thiadiazines, 476 (ii) 1,2,4-Thiadiazines, 476 - (iii) 1,2,5-Thia-diazines, 476 - (iv) 1,2,6-Thiadiazines, 476 - (v) 1,3,4-Thiadiazines, 477 -(vi) 1,3,5-Thiadiazines, 477 -

3. Oxadiazines

47 8(i) 1,2,3-Oxadiazines, 478 - (ii) 1,2,4-Oxadiazines, 479 - (iii) 1,2,5 -Oxadiazines, 479 - (iv) 1,2,6-Oxadiazines, 479 - (v) 1,3,4-Oxadiazines, 47 9- (vi) 1,3,5-Oxadiazines, 480 -

4. Dithiazines and dioxazines :. . .

„ ., . . 48 1(i) Dithiazines, 481 - (ii) Dioxazines, 48 2

5. Oxathiazines w ..; 48 3(i) 1,2,3-Oxathiazines, 483

(ii) 1,3,5-Oxathiazines, 484

(iii) Otheroxathiazine systems, 485

6 . Trithianes, trioxanes, oxadithianes and dioxathianes v 48 57 . Tetrazines 48 6

a. 1,2,3,4-'Tetrazines xx •~ .` _~

(i) General preparations and properties, 489

(ii) Reduced 1,2,4,5-tetra -zines, 491 - (iii) Properties of 1,2,4,5-tetrazines, 492 - (iv) Verdazyls, 494

8 . Thiatriazines and oxatriazines

49 5(i) 2H-1,2,3,6-Thiatriazines, 495 - (ii) 1H-1,2,4,6-Thiatriazines, 496 - (iii )2H-1,2,4,6-Thiatriazines, 496

(iv) Other systems, 497 - (v) Oxatriazines ,498 -

9. Dithiadiazines, oxathiadiazines, dioxadiazines and dioxathiazines

49 8(i) Dithiadiazines, 498 - (ii) Oxathiadiazines, 498 - (iii) Dioxadiazines ,499 - (iv) Dioxathiazines, 500 -

10.Tetrathianes 50011 .Pentazines 50112.Other ring systems with five hetero-atoms (N, 0, S) 501

Index 503

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