RODD'S CHEMISTR Y

OF CARBON COMPOUND S

A modern comprehensive treatise

SECOND EDITIO N

Edited by

S . COFFE YM .Sc . (London), D .Sc. (Leyden), C.Chem., F.R.I .C .

formerly ofI.C.I. Dyestuffs Division, Blackley, Mancheste r

VOLUME IV PART H

HETEROCYCLIC COMPOUND S

Six-membered heterocyclic compounds with (a) a nitrogen atom commonto two or more fused rings ; (b) one hetero-atom in each of two fused rings .Six-membered ring compounds with two hetero-atoms from Groups VI B,or V B and VI B of the Periodic Table, respectively . Isoquinoline, lupinane

and quinolizidine alkaloids

Heterocyclic Compounds : Six-membered heterocyclic compounds with (a) a nitrogenatom common to two or more fused rings ; (b) one hetero-atom in each of two fuse d

rings. Six-membered ring compounds with two hetero-atoms from Groups VI B, o r

V B and VI B of the Periodic Table, respectively . Isoquinoline, lupinane and quinolizidin ealkaloids .

PREFACE VI I

OFFICIAL PUBLICATIONS ; SCIENTIFIC JOURNALS AND PERIODICALS XV I

LIST OF ABBREVIATED NAMES OF CHEMICAL FIRMS MENTIONED IN PATENT REFERENCES XVI I

LIST OF COMMON ABBREVIATIONS AND SYMBOLS USED XVII I

Chapter 36. The Isoquinoline Alkaloidsby S . F . DYK E

1 . Derivatives of isoquinoline and tetrahydroisoquinoline 2a. The simple tetrahydroisoquinolines

2

(i) Structure determination and synthesis, 3 - (ii) Biosynthesis, 5 -

b. 1-Phenyltetrahydroisoquinolines

7

(i) The cryptostylines, 7 - (ii) Cherylline, 8 -

c. The 1-benzylisoquinolines

1 0

(i) Structure determination and synthesis, 11 - (ii) Absolute configuration, 23 -

(iii) Biosynthesis, 24 -

d. The cularines

2 8

(i) Structure determination, 28 - (ii) Absolute configuration, 30 - (iii) Bio-synthesis, 31 - (iv) Synthesis, 31 -

2 . The dibenzopyrrocoline alkaloids

3 5

(i) Structure determination, 35 - (ii) Synthesis, 35 - (iii) Biosynthesis, 38 -

3 . Pavinanes and isopavinanes 3 8a. Pavinane alkaloids

4 0

(i) Configuration, 44 - (ii) Synthesis, 45 -

b. Isopavinane alkaloids

47

(i) Configuration, 52 - (ii) Synthesis, 52 - (iii) Biosynthesis of pavinanes and iso-pavinanes, 53 -

4 . The bisbenzylisoquinolines 5 5a. Structure determination 5 9b. Biosynthesis 68c. Chemical synthesis 68

5 . Aporphinoids 72a. Aporphines

7 3

(i) Structure determination, 73 - (ii) Chemical synthesis, 83 - (iii) Biosynthesi sof aporphines, 92 -

b. The proaporphines 100c. The oxoaporphines

10 6

(i) Structure determination, 106 -

6 . The ptolobcrbcrincs 11 0a. Occurrence and structural variations I I 1b. Structure determination 11 3c. Sonic reactions of proloberberine derivatives 124d. Synthesis

12 7Cr) Tyne 1 syntheses . 128 - ] Tyne 2 syntheses, 136 -• (iii) Type 3 syntheses . 139 -liV) Type 4 syntheses . 141 -

e. Biosynthesis 14 1

7 . The protopinc alkaloids 14 5a. Structure determination 14 7b. Synthesis

14 9(i) Chemical synthesis . 149 - (ii) Biosynthesis, 151 -

8, The phtltalideisogttinoline alkaloids 15 2a. Structure determination

15 3(i) (-) -Narcotine . 153 - (ii) (-)fl-Iiydraslinc, 154 -

b. Absolute configuration 154c. Synthesis

158(i) Chemical synthesis . 158 -- fill Biosynthesis. ISO -

9 . The rhoeadincs and papaverrubines 163a. Structure determination

1630) Relative configuration, 164 - (ii) Absolute configuration . 167 -

b. Some rearrangement reactions 16 8C. Synthesis 16 8

(il Chemical synthesis, 168 -

Biosynthesis . 173 -10 . The benzo[c]pIicnanthridines 17 3

a. Structure and stercochemistry 17 8b. Spectral characteristics 18 4c. Synthesis

18 6(i) Chemical synthesis, Itid - (ii) Biosynthesis . 194

11 . The spirobenrylisoquinolittcs 197a, Structure determination

199(r1 Ochotcnsinc and related alkaloids. 199 •• (ii) Other alkaloids, 203 -

b . Synthesis

20 5(i) Biosynthesis, 205 - (ii) Chemical synthesis, 205 -

12 . The lpecacuanha alkaloids 21 5a. Configuration of cnictinc and related compounds 21 9

Emetinc,219-(ii) [melinenalo g ues,224--(iii)Structurcof rubremetinc .227- -b. Synthesis of crnctirte 22 7

(i) Chemical synthesis. 227 - (ii) Biosynthesis, 231 -13 . Colchicine 232

a. Structure determination 23 3b. Optical properties

24 1(i) Rotation . 241 - (ii) Nuclear magnetic resonance, 242 - -

c. Colehicine-like alkaloids 242d. The synthesis of coichicine

244(i) Chemical syntheses, 244 - (ii) Biosynthesis . 249 -

14. 1-Phenethylisoquinolines 25 4a. Simple 1-phenethyltetrahydroisoquinolines 254b. Bisphenethyltetrahydroisoquinolines 25 5c. The homoproaporphines and homoaporphines 25 5

Chapter 37 . Fused Heterocyclic Systems having a Nitrogen Atom in Common to Two o rMore Ring s

by NEIL CAMPBEL L

1 . Indolizines 25 9a. Indolizine and its derivatives 25 9b. Benzoindolizines 26 2

2 . Quinolizines and their derivatives 26 4a. Quinolizines 264b. Quinolizidine and its derivatives 26 7

(i) Quinolizidine and the quinolizidones, 267 - (ii) Benzoquinolizinium ions ,269 -

3 . Azepine derivatives containing a bridge nitrogen atom 27 0

4 . Tricyclic compounds with nitrogen common to all three rings 27 2a . Cyclazines 272

(i) Cycl[3 .2 .2lazine, oyrrolo[2,1,5-cd]indolizine, 272 - (ii) Cycl[3 .3 .2]azine ,273 - (iii) Cycl[3 .3 .3]azine, 274 - (iv) Julolidine and lilolidine, 276 -

5 . Bridged ring compounds 27 8a. Compounds with nitrogen common to two rings 27 8b. Bicyclic systems having a nitrogen bridge 27 9c. Compounds with nitrogen common to three rings

28 1(i) Quinuclidine, 281 -

Chapter 38 . Lupinane and Quinolizidine Alkaloidsby H . C . S. WOOD AND R . WRIGGLESWORT H

1 . Lupinane alkaloids 28 6a. Bicyclic lupinane alkaloids 28 6b. Phenanthronorlupinane alkaloids 29 0c. Tricyclic lupin alkaloids

29 2(i) StereochemistrY, 294 -

d. Tetracyclic lupin alkaloids 29 9(i) Anagyrine, lupanine and sparteine alkaloids, 299 - (ii) Matrine-like alkaloids ,319 -

2 . Nuphar alkaloids 32 8

3 . Ormosia alkaloids 33 4

4 . Lythraceae alkaloids 33 8

Chapter 39 . Compounds Containing Two Fused Five- and Six-Membered HeterocyclicRings each with One Hetero Atom

by NEIL CAMPBEL L

1 . Compounds containing two hetero rings fused to an aromatic system 34 3a. Bz-Pyrroloquinolines 34 3b. Phenanthrolines 344

2 . Compounds containing two hetero rings fused through adjacent carbon atoms 34 7a. Furopyridines 34 7b. Furoquinolines 34 8c. Pyranopyridines 35 2

(i) 2H-Pyrano[2,3-b]pyridine and derivatives, 352 - (ii) 1H-Pyrano[4,3-b]pyri-dines, 353 - (iii) 2H-Pyrano[3,2-c]-pyridines, 354 - (iv) 1H-Pyrano[3,4-clpyri-dines, 354 -

d. Pyrrolopyridines or azaindoles 35 5e. Carbolines or pyridindoles 35 9f. Dihydro-furoquinolines and -pyranoquinolines 362g. Naphthyridines or diazanaphthalenes 366

Chapter 40 . Compounds Containing a Six-Membered Ring having two Hetero-atoms fro mGroup VI B of the Periodic Table : Dioxanes, Oxathianes and Dithianes

by MALCOLM SAINSBUR Y

1 . Dioxanes and related compounds 37 5a. 1,2-Dioxanes, 1,2-dioxins and related structures 37 6b. 1,3-Dioxanes and related compounds 37 7

(i) 1,3-Dioxanes, 377 - (ii) 1,3-Dioxins, 380 - (iii) 2,4-Dihydro-1,3-benzodioxi nand related compounds, 380 -

c. 1,4-Dioxanes and 1,4-dioxins 38 2

(i) 1,4-Dioxanes, 382 - (ii) 1,4-Dioxins, 385 - (iii) 1,4-Benzodioxin and itsderivatives, 385 - (iv) Lignan derivatives, 387 - (v) Polychlorinated dibenzo-1,4-dioxins, 387 --

2 . Dithanes, dithiins and their benzo derivatives 38 9a. 1,2-Dithianes, 1,2-dithiins and their benzo derivatives 389

(i) 1,2-Dithianes, 389 - (ii) 1,2-Dithiin and derivatives . 390 - (iii) Benzoditbiins .392 -

b. 1,3-Dithianes, 2,4-dihydro-1,3-dithiins and their benzo derivatives . . . .

39 3

(1) 1,3-Dithianes, 393 - (ii) 2,4-Dihydro-l,3-dithiins, 399 -c. 1,4-Dithiane, 1,4-dithiin and their benzo derivatives 40 0

(i) 1,4-Dithiane and simple derivatives, 400 - (ii) 1,4-Dithiins, 403 - (iii) Benzo -1,4-dithiins, 406 - (iv) Thianthrene and its derivatives, 407 -

3 . Oxathianes and oxathiins 41 1a. 1,2-Oxathianes and oxathiins

41 1

(i) 1,2-Oxathianes, 411 - (ii) Dihydro 1,2-oxathiins and 1,2-oxathiins, 412 -b. 1,3-Oxathianes 41 4c. 1,4-Oxathianes, 2,4-dihydro-1,4-oxathiins and 1,4-oxathiins

41 5

(i) 1,4-Oxathianes, 415 - (ii) Dihydro-l,4-oxathiins and 1 .4-oxathiins, 418 -d. Benzoxathiins 420

(i) 1,2-Bcnzoxathiin derivatives, 420 - (ii) 2,1-Benzoxathiin derivatives, 421 -(iii) 2,3-Benzoxathiin derivatives, 421 - (iv) Dihydro-l,3-benzoxathiins, 422 -(v) 2,4-Dihydro-3,l-benzoxathiin derivatives, 422 - (vi) 1,4-Benzoxathiin, 423 -(vii) Phenoxathiin (phenothioxin or dibenzo-l,4-oxathiin), 424 -

4. Miscellaneous compounds containing selenium or tellurium atoms 425

Chapter 41 . Compounds Containing a Six-Membered Ring with Two Hetero Atoms fromGroups V and VI respectively, of the Periodic Table . Oxazines, Thiazines and their Analogues

by MALCOLM SAINSBUR Y

1 . Oxazines 42 7a. 1,2-Oxazines 42 7

(i) 6H-1,2-Oxazines, 427 - 2H- and 4H-1,2-Oxazines. 429 - (iii) Dihydro- an dtetrahydro-l,2-oxazines, 430 -

b. 1,3-Oxazines 43 2(i) 4H-1,3-Oxazines, 433 - (ii) 1,3-Oxazin-l-ium salts, 434 - (iii) Hydro-l,3 -oxazines, 437 -

c. 1,4-Oxazines and related compounds 44 6(i) 1,4-Oxazines, 446 - (ii) Dihydro-l,4-oxazines, 447 - (iii) Tetrahydro-l,4 -oxazines : morpholines, 448 - (iv) Oxomorpholines (morpholones), 453 -

2. Benzoxazines 45 5a. 1,2-Benzoxazines 45 6b. 1,3-Benzoxazines and their hydro derivatives 45 6

(i) 2H-1,3-Benzoxazines, 456 - (ii) 4H-1,3-Benzoxazines, 460 -c. 1,4-Benzoxazines and their hydro derivatives 46 1

(i) 1,4-Benzoxazines, 461 - (ii) Dihydro-l,4-benzoxazinones, 462 - (iii) Dihydro -1,4-benzoxazines, 463 - (iv) 1H-2,3-Benzoxazines, 465 - (v) 4H-3,1-Benzoxazinesand related compounds, 467 -

3 . Phenoxazines 47 1a. Methods of synthesis 47 2b. Phenoxazine and its simple derivatives 47 4

(i) Nitrophenoxazines, 475 - (ii) Aminophenoxazines, 475 - (iii) 3-Methoxy-phenoxazines, 476 - (iv) Phenoxazinecarboxylic acids, 476 - (v) Halogenophenox -azines, 477 - (vi) N-Alkylphenoxazines and N-arylphenoxazines, 477 - (vii )Acylphenoxazines, 479 -

c. Oxidation products of phenoxazines

479(i) Phenoxazinones and phenoxazonium salts, 479 -

d. Naturally occurring phenoxazine derivatives 482e. Benzophenoxazines and benzophenoxazinones 484

4. Thiazines and related compounds 486a. 1,2-Thiazines and their hydro derivatives 486b. 1,3-Thiazines and related compounds 48 8

(i) 4H-1,3-Thiazines, 488 - (ii) 1,3-Thiazinium salts, 489 - (iii) Dihydro-2H-1,3 -thiazines, 490 - (iv) 5,6-Dihydro-4H-1,3-thiazines and tetrahydro-l,3-thiazines ,493 -

c. 1,4-Thiazines and their hydro derivatives 49 5

(i) Thiazines, 495 - (ii) Dihydro-l,4-thiazines, 496 - (iii) Tetrahydro-l,4-thiazines ; 1,4-thiazanes, 498 -

5 . Benzothiazines 50 1a. 1,2- 2,1- and 2,3-Benzothiazines and their hydro derivatives 50 1

(i) 2H-1,2-Benzothiazines, 501 - (ii) 1H-2,1-Benzothiazines, 503 - (iii) 1H-2,3-Ben -zothiazine derivatives, 503 -

b. 1,3- and 3,1-Benzothiazines and their hydro derivatives

504(1) 1,3-Benzothiazines, 504 - (ii) 4H-3,1-Benzothiazine derivatives, 506 -

c. 1,4-Benzothiazines and their hydro derivatives 50 9(i) 2H-1,4-Benzothiazines, 509 - (ii) 2H-1,4-Benzothiazinium salts, 511 - (iii )2H-1,4-Benzothiazin-3(4H)-ones, 512 - (iv) Phenothiomorpholines, 514 - (v)4H-1,4-Benzothiazines, 514 -

6 . Phenothiazines 51 6a. Methods of synthesis 51 7b. Physical properties 52 0c. Chemical properties 52 1

(1) Oxidation . phcnothiazinyl radical cation and phenothiazonium (phcnaza-thionium) salts, 521 - (ii) F.!ectrovhilic substitution . 524 -

d. Phenothiazine derivatives 527(i) 1'henothiazine homologues . 527 - (ii) Halogenovhcnothiazines . 528 - (iii)Nitrophenothiazines, 529 - (iv) N-Alkyl- and N-acy!-derivatives . 529 - (v)Aminophenothiazines, 531 - (vi) Hydroxynhenothiazines, 532 - (vii) 3f o-thiazinc derivatives, 532 - (viii) Desulphurization of phenothiazincs

. 534534 -

(Ix) Azaphenothiazines, 534 -

Index 537