Identification

CHAPTER 2

Identification The evidence for the structures of the naturally occurring quinones is given in the succeeding chapters of this book, and this is necessarily a mixture of the old and the new. Modern investigations rely very heavily on the interpretation of spectral information whereas older work, going back to the structural elucidation of alizarin a hundred years ago, was mainly dependent on the preparation of derivatives and on degradative experiments. This chapter, in consequence, is mainly concerned with spectra but other methods of identification still in use are considered briefly. Isolation and purification The methods employed are common to natural products chemistry and not peculiar to quinones. Normally these pigments are isolated by sequential extraction with solvents of increasing polarity, and the appropriate fractions are purified by column and/or thin layer chromato­ 79 (p.l.c). Ultrasonic graphy (t.l.c.) or preparative layer chromatography extraction may offer some advantage. As some quinones are photolabile, unknown pigments should preferably be stored out of light and occasionally they require handling in the dark. I t is not possible to recommend any particular procedure as quinones vary so much in polarity and solubility, for example, the bioquinones are easily taken into non-polar solvents whereas xylindein is extracted with phenol, and obviously the chromatographic behaviour of polyhydroxyquinones may be very different from that of hydroxyl-free analogues. Original papers should be consulted for details. As the majority of quinones are relatively involatile, and t.l.c. is so efficient, preparative g.l.c. has rarely been used but undoubtedly many quinones could be 1separated in this way, using, where appropriate, trimethylsilyl ethers. Quinones usually occur in the free state but hydroxy quinones, especially in the anthraquinone series, are frequently present in the plant in glycosidic combination, some naphthaquinones occur as glycosides of the corresponding quinols, and on occasion hydroxyquinones may exist in vivo as metal salts (spinochromes), O-sulphates (fusarubinogen) or in association with protein (namakochrome). Appropriate treatment is required in each case.

40

NATURALLY OCCURRING QUINONES

Chemical methods are avoided as far as possible but may be useful in the separation of hydroxylated quinones. Hydroxybenzoquinones and 2(3)-hydroxynaphthaquinones are vinylogous carboxylic acids and hence can be extracted into aqueous sodium bicarbonate; naphtha­ quinones and anthraquinones /3-hydroxylated in a benzenoid ring dissolve in aqueous sodium carbonate (some pass into bicarbonate solution), whereas the chelated a-isomers require aqueous sodium hydroxide. Similar considerations apply to other types of quinones and alkaline extraction, used with 2caution, can be very helpful in the separation of complex mixtures. Colour reactions Although colour reactions are much less important than formerly they are still useful, particularly at the beginning of an investigation when crude extracts or even natural tissue may yield information of 82 reactions may be carried value. Very little material is required and the out, i f desired, by spraying chromatograms. These rough tests should preferably be supplemented later by spectrophotometric measurements on purified material. The most useful diagnostic tests depend upon the 78 redox properties of quinones and the presence of hydroxyl groups. Leucomethylene b l u e is a useful spray for the detection of benzo­ quinones and naphthaquinones on paper or thin layer chromatograms, the quinones appearing as blue spots on a white background. Reduction to a colourless (or much less highly coloured) product, and easy restora­ tion of the original colour on oxidation, is characteristic and distin­ guishes quinones from nearly all other natural compounds. Re-oxidation can usually be effected simply by shaking the solution in air, but the leuco compounds of non-hydroxylated benzoquinones and naphtha­ quinones do not oxidise so readily. Reduction is easily effected with neutral or alkaline sodium dithionite but many other reducing agents may be used. Catalytic hydrogenation can be employed quantitatively and sodium borohydride is convenient when reductions are to be followed spectrophotometrically. F o r hydroxy quinones the colour changes are more striking in alkaline solution and re-oxidation (by air) is more rapid. Anthraquinones can be distinguished from benzoquinones and naphtha­ quinones as they usually give red solutions on reduction in alkaline solution (zinc or dithionite in aqueous sodium hydroxide). A yellowbrown colour is ambiguous however, as some hydroxynaphthaquinones (e.g. lawsone) may behave in the same way, but generally anthraquinols, in contrast to benzoquinols and naphthaquinols, absorb > 4 0 0 nm in alkaline solution. Reductions in aqueous alkaline dithionite can be followed spectrophotometrically i f a layer of dioxan is added to the

41

2. IDENTIFICATION

3 or i f tetraethylenepentamine is solution to prevent aerial oxidation, used in place of sodium hydroxide. The characteristic colours given b y hydroxyquinones in alkaline solution are useful aids to structure determination. Those listed in Table I are obtained with excess sodium hydroxide although compounds TABLE I

Colour of hydroxyquinones in alkaline solution

/HO

Quinone

Colour

AJ^°" ~ nm

Benzoquinones 2-hydroxy-5-methyl2,3-dihydroxy-5,6-dimethyl2,5-dihydroxy-

Red Bluish-purple Bluish-Red

493 522 505

Naphthaquinones 2-hydroxy5-hydroxy6-hydroxy2,3-dihydroxy2,5-dihydroxy3,5-dihydroxy5,6-dihydroxy5,7-dihydroxy5,8-dihydroxy-

Orange Violet Violet-red Blue Violet-red Red Blue Violet Blue

459 538 520 650 490 435 571 542 655

Anthraquinones 1-hydroxy2-hydroxy1,2-dihydroxy1,3-dihydroxy1,4-dihydroxy1,5-dihydroxy1,8-dihydroxy1,2,3-trihydroxy1,2,4-trihydroxy1,4,5-trihydroxy1,4,5,8-tetrahydroxy-

Red Orange-red Violet-blue Red Violet Red Red Green Violet-red Violet Blue

500 478 576 485 560 496 513 668 544 561 630

containing more than one hydroxyl group may show more than one indicator change. Obviously too much reliance should not be placed on these colour changes which may be modified by cross-conjugation and 4 hydroxyquinones are now other structural features. Many older tests for obsolescent but the zirconium nitrate t e s t (a red-violet precipitate in acid solution) for vicinal hydroxyl groups (as in alizarin) is useful, and 5 methanolic magnesium acetate reagent. This was originally so is Shibata's introduced for hydroxy anthraquinones, the colour obtained being

42

NATURALLY OCCURRING QUINONES

indicative of the orientation of the hydroxyl groups, but it appears to be of wider utility and a positive colour reaction with magnesium acetate 6 7, 6 is a general test for a hydroxy quinone. Peri-hydroxyquinones form boro-acetates (1) with boro-acetic a n h y d r i d e resulting in a significant bathochromic shift in the visible region. «(OAc)

v

2

'

(1)

v

Non-hydroxylated quinones having a free quinonoid position, that is, 8 and naphthaquinones, can be recognized by principally 7 benzoquinones the Craven or R e s t i n g test. I n this reaction the quinone is treated in alcoholic solution with a reagent containing a reactive methylene group

9 (aceto-acetic ester, malononitrile, etc., also nitromethane )62 and ammonia; the anion so formed then undergoes Michael addition. The blue-green or violet-blue colour which appears is that of the mesomeric anion [e.g. (3)] derived from the addition product [e.g. (2)]. I f a hydroxyl group is present the Kesting-Craven colour may be masked or sup­ 63 pressed, and a free quinonoid position is not, in fact, essential, as alkoxyl and halogen groups can be displaced by the reagent. The mesomeric

O (4)

2. IDENTIFICATION

43

anion64(3) is similar to that (4) given b y allylquinones in the D a m - K a r r e r t e s t which is responsible for a transient blue-violet colour obtained 1 0 potassium hydroxide. when such quinones are treated with alcoholic Other colour reactions with bases (e.g. indole ) designed to detect free quinonoid positions are limited in scope, and again nucleophilic dis­ placement of substituents can occur. Derivatives The only derivatives routinely prepared are leuco-acetates, and the acetates, methyl ethers and trimethylsilyl ethers of hydroxyquinones, and frequently these are made solely in order to obtain a more soluble or more volatile form of the parent compound for spectroscopic study (their n.m.r. spectra give a convenient "count" of the number of hydroxyl groups). Some indication of the orientation of hydroxyl groups can be gained from R¥ values, and b y the use o f selective reagents. Only j8-hydroxyl groups are readily methylated with diazomethane; chelated a-hydroxyl groups are normally resistant but they succumb to methyl iodide-silver oxide-chloroform or methyl sulphate-potassium carbonate-acetone. I t is sometimes possible to methylate one hydroxyl group in a 1,8-dihydroxyanthraquinone using diazomethane. All 65 nuclear hydroxyl groups can be esterified b y reaction with acetic anhydride but selective j3-acetylation can be achieved using k e t e n e 66 followed or acetic anhydride in the presence o f boro-acetic anhydride, by hydrolysis of chelated(a) boric esters with cold w a t e r . Reductive acetylation is extremely useful as the electronic spectrum o f the leuco11 to that of the parent hydrocarbon, bathoacetate is very similar chromically shifted. The main group to which the quinone belongs can thus be determined in most cases. Quinoxaline derivatives are 2 frequently prepared from o-quinones but it should be 1 remembered that some p-quinones also react with o-phenylenediamine. Degradation reactions Most new quinones can be identified without recourse to degradation but it is often necessary when novel structures are encountered. I f the basic polycyclic system is not recognizable from the ultraviolet spectrum 3 other ways, zinc dust distillation or the less of the leuco-acetate or 1in 14 drastic zinc dust fusion can be used to obtain the parent hydrocarbon 15 (or heterocycle). The disadvantages are well-known but milder methods of reduction eliminate only the quinone oxygen functions 15 obtained, for example leaving substituents intact. However, the yields by reduction of anthraquinones with diborane, are vastly superior to

44

NATURALLY OCCURRING QUINONES

those available by degradation with zinc and such methods might repay further study. Oxidative degradation is used mainly to establish the structure of a side chain attached to a quinone ring or to obtain an iden­ 16 I n the former case, usually tifiable fragment containing a benzenoid ring. effected with alkaline hydrogen peroxide, the group R in (5) is isolated as the acid (7). Under similar, or more vigorous, conditions, naphtha-

+

(5)

(6)

H0 C—R

2

(7)

quinones yield phthalic acids (6), but anthraquinones and more highly condensed compounds where the quinone ring is protected on both sides by benzene rings, are much more difficult to degrade. However, methoxylated anthraquinones can be cleaved to form benzoic acids by heating with 31 t-butoxide and water (molecular ratio 3:1) and this recent potassium m e t h o d may be useful.

SPECTRA

Ultraviolet-visible Spectra Benzoquinones The spectrum of ^-benzoquinone is characterized b y intense absorp­ 17 band ~ 2 8 5 nm ( e tion near 240 nm ( e m .a 26,000), a medium x m >a~x3 0 0 ) attributed to an electron-transfer ( E . T . ) transition, and much weaker absorption (n - > 7r*) in the visible region (Fig. 1) (Table I I ) . The spectrum is modified by the introduction of substituents, and spectroscopically nearly all the natural compounds can be regarded as alkyl, hydroxyl, and alkoxyl derivatives o f the parent quinone [see structures (8) to (21)]. Exceptionally, aryl groups may also be present. The electronic 18 spectra of ^-benzoquinones have been discussed and analysed in a 19 number of papers but for organic chemists concerned only with empirical interpretations, that o f Flaig et al. is the most useful. Much of the information in Table I I is drawn from their work while the spectra of a representative group of natural quinones are listed in Table I V . The great majority of natural quinone spectra have been determined in ethanol solution although this is not the ideal spectroscopic solvent. The 1 81these , 2 possible presence of basic impurities must be borne in mind since will ionise hydroxyquinones resulting in misleading s p e c t r a ; this

2 . IDENTIFICATION

45

4-0

cn 3 5

30

2-5 300

400

500

600

Wavelength (nm)

F I G . 1. Electronic absorption spectrum (in E t O H ) of: 1,4-benzoquinone ( ); 2,5-dihydroxy-l,4-benzoquinone ( ) ; 2-hydroxy-5-methyl-l,4-benzoquinone ( ) ; 2-hydroxy-5-methyl-1,4-benzoquinone (EtOH/HO) ( ).

can be avoided b y running spectra in acidified ethanol. F o r simple synthetic compounds most information is available for chloroform 19 solutions (Table I I )f and when comparing spectra run in different media the solvent shifts recorded b y F l a i g should be consulted. Chloroform is not suitable, however, for measuring alkali shifts, etc., and much of the information in Tables I V - X , and the spectra in Figs 1 - 6 , were ob­ tained in ethanolic solution. Introduction of a substituent of the usual type into the benzoquinone nucleus produces a small bathochromic displacement of the first band in the spectrum ( < 1 0 nm) but the second band undergoes a more significant red shift in the order Me ( 2 7 nm), MeO ( 6 9 nm), HO ( 8 1 nm) in chloroform solution. The visible band is little affected and is frequently obscured under the envelope of band 2 . Introduction of a second -j- For a short list of spectra measured in ethanol see ref. 20.

46

NATURALLY OCCURRING QUINONES TABLE I I

Ultraviolet-visible absorption of 1,4-benzoquinones

A Quinone Parent

2-Methyl2-Ethyl2,3-Dimethyl2,5-Dimethyl2,6-DimethylTrimethylTetramethylMethoxy2,3-Dimethoxy2,5-Dimethoxy2,6-DimethoxyTrimethoxyHydroxy2,5-Dihydroxy2 -Hydroxy - 3 -methyl -h 2-Methoxy-3-methyl 2 -Hydroxy - 5 -methyl 2-Methoxy-5-methyl2 -Hydroxy - 6 -methyl - b 2-Methoxy-6-methyl2-Hydroxy-3,6-dimethyl- b 2-Methoxy-3,6-dimethyl2-Hydroxy-3,5,6-trimethyl2 -Methyl - 5,6 -dimethoxy3-Hydroxy thymo quinone ° 3,6-Dihydroxythymoquinone

3

\CHC1, max.

246 (4-42) 242° (4-26) 249 (4-33) 255(sh) (4-27) 248 (4-30) 256(sh) (4-29) 250 (4-26) 257(sh) (4-20) 254 (4-37) 261(sh) (4-32) 255 (4-29) 258 (4-30) 263 (4-27) 262 (4-30) 269 (4-31) 254 (4-26) 254 (4-17) 278 (4-37) 284 (4-38) 287 (4-38) 291 (4-29) 256 (4-14) 279 (4-35) 286(sh) (4-34) 255 (4-17) 254 (4-12) 264 (4-28) 264 (4-32) 268 (4-21) 263 (4-23) 266 (4-24) 265 (4-15) 272 (4-29) 280 (4-30) 264 (4-16) a267 (4-16) 293 (4-31)

nm (loge)

315 (2-80)

439 a(1-35) 4 3 4 (1-26) 454° (1-22) 436 (1-38)

318 (2-95)

437 (1-53)

337 (3-05)

425 (1-55)

316 (2-42)

430 (1-43)

319 (2-54) 340 (2-61)

429 (1-45) 425 (1-53) 430(sh) 430(sh) (1-5)

288 (2-50) 285''(sh) (2-6)

342 (2-34) 357 (3*21) 398 (3-17) 370 (2-48) 377 418 369 393

(2-78) (2-65) (3-07) (2-43)

396 374 382 365 380 355 402 376 409

(3-16) (3-13) (2-82) (2-88) (2-87) (2-97) (2-94) (2-89) (2-65)

402 (2-94) 404 (3*01) 435 (2-36)

b EtOH. «In In CC14. substituent has much less effect on band 2 than the first and may be negligible; it is always greatest in 2,3-disubstituted derivatives. Further substitution results in further bathochromic displacements but the

48

NATURALLY OCCURRING QUINONES

shifts are not particularly useful for empirical calculations of A m >a x Since model compounds are available for most of the natural structures which are likely to appear, an unknown may be best identified by spectral comparison with known compounds. F o r example shanorellin (14), a recent addition to the list of fungal benzoquinones, shows A m #a x 272 and 406 nm, and may be regarded as a trialkylhydroxybenzoquinone; 2-hydroxy-3,5,6-trimethylbenzoquinone absorbs at 272 and 409 nm. Note, however, that plastoquinones and ubiquinones show only one maximum. I n alkaline alcoholic solution there is a marked shift of the visible absorption (Fig. 1) (Table I ) . I n this respect only instantaneous shifts, reversible on acidification, are important; on keeping, other changes may take place more slowly, notably hydroxylation of the ring or nucleophilic replacement of methoxyl by hydroxyl. Addition of sodium borohydride to an ethanolic solution of a benzoquinone affords the a quinol caccompanied by a sharp change to benzenoid absorption with ^max. - 290 nm and marked reduction in € m #a Spectrophotometric x assays18of plastoquinone and ubiquinone have been developed on this basis. Only two natural o-benzoquinones have been found, both highly 1 82 , 2 substituted (Table I V ) ; relatively few o-benzoquinone spectra (Table I I I ) have been r e c o r d e d . They show triple absorption peaks and are easily distinguished from the ^-isomers b y the relatively low intensity and marked bathochromic displacements. B a n d 2 is frequently shifted TABLE I I I

Ultraviolet-visible absorption of 1,2-benzoquinones Quinone

b Parent 4-Methyl-

fl

3,5-Dimethyl- fl 4,5-Dimethyl-

5 3,4,5-Trimethyl3-Methoxy-

Amax. nm (log c)

b

a

b 4-Methoxya 4,5-Dimethoxy5-Ethyl-3-methoxya bIn CHC1 . 3 In CH2C12.

249(sh) (3-32)

375 (3-23) 387 (3-23)

260 (3-19) 260 (3-46)

410 (3-20) 400 (3-12)

265 (3-33) 269(sh) (2-66)

425 (3-11) 465 (3-26)

255(sh) (3-75) 283 (4-09)

406 (3-21) 406 (2-82) 470 (3-19)

568 (1-48) 544(sh) (1-48) 570 (1-52) 558 (1-66) 555 (1-48) 570 (1-48) 545 (1-75) 545(sh) (1-78) 575(sh) (1-56) 538(sh) (1-66) 504(sh) (1-60) 570(sh) (2-60)

2. IDENTIFICATION

49

into the visible region and the low intensity n - > 77-* absorption may extend as far as 600 nm. TABLE I V

Ultraviolet-visible absorption of some naturally occurring benzoquinones Quinone Lagopodin A (8) Plastoquinones (9) a-Tocopherolquinone (10)

/ (11) Primin 4,4 -Dimethoxydalbergione (12) Perezone (13; R = H ) Hydroxyperezone (13; II = OH) Shanorellin (14) Ardisiaquinone A (15) Fumigatin (16) Ubiquinones (17) Spinulosis (18) Polyporic acid (19) 0-Benzoquinones Mansonone A (20) Phlebiarubrone (21)

A S ™ nm (log*) 257 (4-25) 254 262(sh) 261 (4-38) 269 (4-29) 267 (4-33) 258 (4-14) 266 (4-05) 295 (4-26) 272 (4-05) 289 (4.60) 265 (4-14) 275 297 (4-35) 256 (4-63) 262 (4-63) 260(sh) (3-5) 280(sh) (3-1) 268 (4-48)

310 (2-55)

435 (1-55)

365 (2-54) 333 (3-23) 412 (3-01) 425 (2-41) 406 (2-07) 420 (2.83) 450 (2-96) 405 460 (2-29) 330(sh) (4-06)

465 (2-60)

432 (3-2) 332 (3-64)

465 (3-54)

"In CHCI3.

Naphthaquinones These spectra are inevitably more complex than those o f benzo­ quinones since both benzenoid and quinonoid absorption is involved, and either or both rings may be substituted. I n the natural compounds the principal substituents can be regarded as alkyl, hydroxyl, and alkoxyl groups, but in addition acyl groups and conjugated double bonds may be present and the quinonoid ring may be fused to a furan or 1 8 ,692 3 pyrone ring system [see structures (22) to (34)]. The spectra of numerous * 24 simple 1,4-naphthaquinones have been measured and a n a l y s e d , the most useful compilation being t h a t of Scheuer and his co-workers from which many of the data in Table V are taken. Illustrative spectra for some natural quinones are given in Table V I I . The spectrum of the parent compound (Fig. 2) comprises intense benzenoid and quinonoid electron-transfer absorption in the region

2-Methoxy-3-isopentyl

5-Hydroxy5-Methoxy6-Hydroxy-

2-Methoxy-

2-Hydroxy-

5-Methyl2,3-Dimethyl-

2-Methyl-

Parent

Quinone

242 (4-22) 248 (4-25) 253-5 (4-19) 247 (4-24) 254 (4-30) 261 (4-29)

245 (4-34) 251 (4-37) 245-5 (4-27) 251 (4-30) 252 (4-29) 243 (4-26) 249 (4-26) 249 (4-20)

252 (4-41) 279 (4-32)

260(sh) (4-07) 260 (4-28) 269 (4-28) 275-5 (4-23) 282 (4-24) 274 (4-21) 280 (4-21)

258-5 (4-22)

257(sh) (4-12)

3 ( g <0

m ln o

333 (3-66)

337 (3-15) 324(sh) (3-10) 344(sh) (3-24)

333 (3-47)

339 (3-53)

355 (3-59) 330 (3-8)

335-5 (3-43)

335 (3-48)

K£™

Ultraviolet-visible absorption of 1,4-naphthaquinones

TABLE V

382(sh) (3-10)

429 (3-64) 396 (3-52) 388 (3-38)

02

o

a


Q

M

g

o

Q Q cl

©

270 (4-20) 249 (4-19)

2,3,5,7-Tetrahydroxy2,3,5,8-Tetrahydroxy-

In MeOH.

a bIn EtOH.

262 (4-12) 292 (3-91)

6

2,5,7-Trihydroxy2,5,8-Trihydroxy-

5,8-Dihydroxy-

240 (3-89)

240 (4-00)

2,5-Dihydroxy-

3,5-Dihydroxy- fl 5,6-Dihydroxy5,7-Dihydroxy-

262 (4-25)

2 -Hydroxy - 3 -iso - a-pentenyl 2,3-Dihydroxy-

320 (3-89) 288 (3-66) 302 (3-66)

308 (3-93) 390(sh) (3-06)

283 (4-15) 263 (4-01) 249(sh) (4-04) 263 (4-10) 269 (3-87)

265 (4-41) 274(sh) (4-23) 288(sh) (4-16) 286 (4-10)

387 (3-45) 463 (3-74) 488 (3-80)

403 (3-30) 481 (3-74)

338 (3-00)

371(sh) (3-35)

316 (3-51) 335 (3-36) (3-56) (3-56) (3-64) (3-51) (3-57)

490 (3-73) 547 (3-56) 452 (3-35) 496(sh) (3-79) 528 (3-67) 470 (3-16) 478(sh) (3-77) 511 (3-65)

418 430 419 461 436

419 (3-30) 439 (3-17)

524 (3-64)

506 (3-80) 543 (3-60)

524 (3-78) 564 (3-57)

Cn I—»

O

«

1

M

to

52

NATURALLY OCCURRING QUINONES

17 240-290 nm and a medium intensity benzenoid E . T . band at 335 nm. A broad weak local excitation ( L . E . ) band at 425 nm (e 32) is dis­ cernible in iso-octane solution but not in more polar solvents. The shoulder at 257 nm is ascribed to a quinonoid E . T . transition, and is shifted bathochromically by + 1 and + M substituents in the quinone ring whereas the benzenoid absorption at 245 and 251 nm is usually

—i

300

1

1—*

400

\

i

500

>

i

600

Wavelength (nm)

F I G . 2 . Electronic absorption spectra (in E t O H ) of: 1,4-naphthaquinone ( ); 1,2-naphthaquinone ( ) ;2-hydroxy- 1,4-naphthaquinone ( ; 2-hydroxyl,4-naphthaquinone (EtOH/HO~) ( ).

scarcely affected. A visible band in the spectrum of, for example, 2,3-dihydroxy-l,4-naphthaquinone is attributed to a quinonoid E . T . transition usually obscured b y the broad benzenoid band at ~ 3 3 5 nm except in derivatives which have powerful electron-donating groups at positions 2 and 3. I n bz-substituted 1,4-naphthaquinones the benzenoid and quinonoid E . T . bands in the region 240-290 nm frequently coalesce, and the prominent benzenoid absorption near 335 nm is shifted towards the red. Pen-substitution b y a hydroxyl group is exceptional, the benzenoid band shifting almost 100 nm into the visible to give a peak at 429 nm

2. IDENTIFICATION

53

Wavelength (nm)

F I G . 3. Electronic absorption spectra (in EtOH) of: 5-hydroxy-l,4-naphthaquinone ( ); 5-hydroxy-l,4-naphthaquinone (EtOH/HO~) ( ); 5-methoxy 1,4-naphthaquinone ( ); 5-acetoxy-1,4-naphthaquinone ( ).

Wavelength (nm)

F I G . 4. Electronic absorption spectra (in EtOH) of 5,8-dihydroxy-1,4-naphthaquinone. (neutral); (+HO~); · (+A1C13).

(34)

(35) (36) Representative naturally occurring naphthaquinones

(37)

GO

O %

Q <©

I

3

Q Q

o

55

2. IDENTIFICATION

(422 nm in MeOH) characteristic of simple juglones (Fig. 3). The effect is less marked in juglone methyl ether ( A mxa396 nm), while in the acetate (5-acetoxy-l,4-naphthaquinone) the —M effect of the ester carbonyl group inhibits transfer of an oxygen # electron into the juglone IT system and the spectrum reverts to that of the parent 1,4-naphthaquinone. Acetylation is thus a useful way of observing the spectrum of a hydroxyor polyhydroxyquinone uninfluenced b y the hydroxyl group(s). An TABLE V I

Ultraviolet-visible absorption of 1,2-naphthaquinones Quinone

^max.

6

fl Parent f 3-Methyl- l 4-Methyl5-Hydroxy-*c 6-Hydroxy- 0 7-Hydroxy-c 4-Methoxy- a a 8-Methoxy8-Methoxy-6-methyl- a c 5 -Methoxy- 7 -methyl3,8-Dimethoxya bIn ethanol. c In dioxan.

255 253 252 250 276 265 250 242 244 262 261

(4-36) (4-40) (4-40) (4-26) (4-18) (4-47) (4-41) (4-22) (4-27) (4-26) (4-16)

343 (3-37) 340 (3-30) 345 (3-40) 350(sh) (3-23) 375 (3-79) 335 (3-11) 335 (3-30)

376 (3-24) 290(sh) (3-46)

nm

(loge)

406 (3-33) 490(sh) (2-20) 430 (3-67) 425(sh) (3-20) 455 (3-36) 400 (3-35) 422 (3-82) 420 (3-87) 472 (3-64) 450 (3-55)

490(sh) (2-20)

In chloroform.

24 acetyl group directly attached to a ring has little effect on the spectrum. Scheuer et al. tentatively ascribe the weaker band at ca. 340 nm in juglone and some related compounds to a quinonoid E . T . transition. The benzenoid E . T . band at 429 nm in the juglone spectrum is not significantly changed b y further benzenoid substitution with the exception of further o- and ^-hydroxylation. Naphthazarins, with two ^en-hydroxyl groups, are characterised b y a combined benzenoid and quinonoid E . T . band in the region 2 7 0 - 3 5 0 nm (e < 1 0 , 0 0 0 ) which is to be expected from such a tautomeric system, and multibanded benzenoid absorption centred around 525 nm (e 6000-9000). These bands often engulf a weak quinonoid E . T . band observed in some derivatives in the region 330-500 nm. The combination band is susceptible to substitution, and it has been noted in polyhydroxynaphthazarins that each jShydroxyl group produces a bathochromic shift of ca. 20 nm. The sub­ stitution pattern in such compounds is associated with the fine structure of the visible absorption band.

56

NATURALLY OCCURRING QUINONES TABLE V I I

Ultraviolet-visible absorption of some naturally occurring naphthaquinones

n m Quinone Menaquinone-1 (22) Chimaphilin (23) a-Lapachone (24) Dehydro-alapachone (25) Plumbagin (26) Eleutherin (27) Frenolicin (28) a Dianellinone ( 2 9 ) Mollisin (30) Lambertellin (31)

^m£? 245 (4-46) 249 (4-44) 248 (4-19) 254-5 (4-19) 251 (4-45)

246 (4-13) 234 (4-26) 259 (4-26)

Alkannin (32)

(l°g e)

262 (4-34) 273 (4-31) 265(sh) (4-02)

331 (3-58)

282 (4-22)

332 (3-44) 375(sh) (3-15) 333 (3-40)

267 (4-35) 276(sh) (4-17) 266 (4-12) 269(sh) (4-07) 284(sh) (3-54) 275(sh) (4-29) 280(sh) (3-9) 284(sh) (4-08) 290 (4-10) 280 (3-84)

338 (3-19)

418 (3-61) 393 (3-58) 362 (3-71) 429 (3-89) 420 (3-52)

a Solaniol ( 3 3 )

304 (3-97)

Maturinone (34)

251 (4-39)

266 (4-00) 287(sh) (3-74)

355 (3-58)

o -Naphthaquinones j8-lapachone (35) Mansonone G (36) Biflorin (37) 8-Methoxy-3-methyl-

256 244 234 241

282 (4-01) 274 (4-40)

330 (3-28)

a

(4-44) (4-25) (4-50) (4-29)

434 (3-21)

340 (3-75)

430 (3-68) 480 (3-74) 510 (3-78) 546 (3-60) 472(sh) (3-84) 500 (3-91) 536(sh) (3-72)

431 407 555 427

(3-26) (3-95) (3-76) (3-78)

In dioxan. The alkali shifts shown b y hydroxynaphthaquinones are of diagnostic value (Figs 2 - 4 ) . T h e anion o f 2-hydroxy-1,4-naphthaquinone is orange, t h a t of 5-hydroxy-1,4-naphthaquinone is violet, while those o f 2 , 3 - , 5 , 6 - and 5,8-dihydroxy-l,4-naphthaquinones are blue (see Table I ) . Addition of anhydrous aluminium chloride to an ethanolic solution of a naphthazarin gives 68 a visible spectrum showing characteristic triplet absorption (Fig. 4 ) ; this is not shown by juglones. 1,2-Naphthaquinones are comparatively rare in Nature and, with two exceptions, are a t least partly terpenoid in origin, structures ( 3 5 ) - ( 3 7 ) being representative (see Table V I I ) . Only two possess phenolic

2. IDENTIFICATION

57

2 85 groups. No1 extensive study of 1,2-naphthoquinone spectra has been p u b l i s h e d ' and the selection listed in Table V I is drawn from various sources. As the parent quinone itself contains two different carbonyl groups and a substituent in any position will be conjugated with one of these, a detailed analysis of a larger number of 1,2-naphthaquinones might yield some useful structural correlations. The parent quinone shows intense absorption near 250 nm and bands of medium intensity near 340 and 400 nm (Fig. 2). A weak longwave band > 5 0 0 nm is only observed in non-polar solvents. Substitution in the quinonoid ring has relatively little effect on the spectrum whereas substitution in the benzenoid ring produces marked changes which clearly depend upon the position of substitution.

A nthraquinones This large group of pigments consists almost entirely of polyhydroxy or alkoxy derivatives, and the influence of these substituents dominates the spectra. Table V I I I lists the spectra of some of the more common synthetic compounds while formulae (38)-(56) illustrate the diversity of hydroxyl substitution found among the natural pigments (spectral 1 82 given 26 876- in Table I X ) . Several surveys have been pub­ data are 30 lished, *29 » the most useful analyses being those of Morton and E a r l a m , and Peters and S u m n e r although unfortunately these are limited to mono- and disubstituted derivatives. Anthraquinone shows intense benzenoid absorption at ca. 250 nm and medium absorption at 322 nm, strong quinonoid E . T . bands are seen at 263 and 272 nm and there is weak quinonoid absorption at 405 nm. These areas of selective absorption are characteristic and the pattern in the ultraviolet region is not seriously affected by substitution, the benzenoid bands appearing fairly regularly within the range 2 4 0 - 2 6 0 and 320-330 nm and the quinonoid band(s) at 260-290 nm (see Table V I I I ) . I n addition hydroxy anthraquinones show an absorption band in the region 2 2 0 - 2 4 0 nm, 27 the parent compound. This is frequently ignored although not shown by Ikeda et al. consider that the A mxaand e mx avalues depend upon the number and orientation of the hydroxyl groups. B y regarding the 29 arising 81 spectrum of anthraquinone as a combination of the absorptions from partial acetophenone and benzoquinone chromophores, S c o t t has shown that the ultraviolet spectra of simple derivatives can be calculated empirically by the addition of increments, appropriate to the substituent and its position, to the relevant absorption bands of the parent quinone. Rough agreement with the observed values for A mxa can be obtained but unfortunately such predictions are not applicable

255 (4-65)

252 (4-46)

254 (4-52) 241 (4-31)

246 (4-21)

247 (4-45) 251 (4-46)

1-Methyl-

2-Methyl-

1-Hydroxy-

1-Methoxy2-Hydroxy-

2-Methoxy-

1,2-Dihydroxy1,2-Dimethoxy-

Parent

243 (4-52) 252 (4-71) 252 (4-66)

Quinone 263 272 263 272 265 274 266 277 262 270 271 283 267 280 278 270 280

(4-31) (4-31) (4-26) (4-16) (4-32) (4-24) (4-18) (4-44) (4-36) (4-18) (4-55) (4-46) (4-51) (4-38) (4-13) (4-30) (4-28)

(l°ge)

330 (3-46) 330 (3-50)

329 (3-56)

328 (3-46) 330 (3-55)

327 (3-52)

324 (3-66)

331 (3-68)

322 (3-75)

^mS^

nm

Ultraviolet-visible absorption of anthraquinones

TABLE V I I I

434 (3-70) 374 (3-71)

363 (3-60)

378 (3-72) 378 (3-55)

402 (3-74)

415 (2-18)

405 (1-95)

0Q

O

Q <©

a S

o Q Q

w

— ia

Or 00

241 (4-28) 245 (4-30) 255 (4-46)

250 (4-21)

253 (4-31)

1,2,3-Trihydroxy-

1,4,5-Trihydroxy-

l,3,8-Trmydroxy-6-methyl-

In CHC13.

fl

1,3,6,8-Tetrahydroxy-

l,4,5,8-Tetrahydroxy-

253 (4-17) 262 (4-17)

251 (4-27)

1,8-Dihydroxy-

a

253 (4-33)

1,5-Dihydroxy-

1,2,4-Trihydroxy-

246 (4-43) 248 (4-23) 254 (4-26)

1,3-Dihydroxy1,4-Dihydroxy-

291 (4-48)

477(sh) (3-81) 509 (4-07) 546-5 (4-14) 601(sh) (3-25) 372 (3-47)452 (4-01)

436 (4-14)

266 (4-29) 289 (4-36) 287 (3-81) 299(sh) (3-79)

452(sh) (3-83)

414 (3-81)

418 (4-00) 432 (4-00) 429 (3-98)

420 (3-65) 452(sh) (3-87) 480 (3-91)

459(sh) (4-02) 489 (4-12)

318 (3-96)

330 (3-30) 325 (3-36)

284 (3-94)

295(sh) (3-98)

275(sh) (4-05) 284-5 (4-03) 273(sh) (4-00) 283 (3-99) 287 (4-49)

284 (4-36) 279 (3-95)

M «

to

487(sh) (3-91) '1) 521 (4-14) 560 (4-19)

5©

o

g

'«) a

483 (3-93) 518(sh) (3-81) 478(sh) (4-08) 510(sh) (4-00) '0) 523 (3-93)

465(sh) (3-89) 499-5 (3-76) 512 (3-67)

Representative naturally occurring anthraquinones

1

:e

02

O

Q

1

Q

o

I

g

61

2. IDENTIFICATION

to the longwave quinonoid absorption band which is of most value in the structural elucidation of the natural anthraquinones. Substitution b y hydroxyl or alkoxyl invariably intensifies this band, and in general there is a bathochromic shift. However, there is no shift in the case of 1T

300

400

500

600

Wavelength (nm)

- ( F I G . 5 . Electronic absorption spectra (in E t O H ) of: anthraquinone hydroxyanthraquinone ( ) ; 1-hydroxyanthraquinone ( E t O H / H O ) ( 1 -methoxyanthraquinone ( ).

); );

hydroxyanthraquinone and on methylation the hydrogen bond contri­ bution is eliminated and the peak at 402 nm is moved hypsochromically to 378 nm (Fig. 5). Exceptionally 2-hydroxyanthraquinone absorbs at 378 nm and its methyl ether at 363 nm. Absorption above 360 nm is dominated by the number of a-hydroxyl 28 groups, the influence of /3-hydroxyls being much weaker except when adjacent to an a-hydroxyl (Fig. 6). The visible absorption is of medium intensity (e ~ 10,000) and may obscure the benzenoid band at 3 2 0 - 3 3 0 n m ; tri- and tetra-a-hydroxylated derivatives frequently display fine structure in the longwave band. Quinones possessing one a-hydroxyl

62

NATURALLY OCCURRING QUINONES

group normally absorb in the range 4 0 0 - 4 2 0 nm but this may extend as far as 436 nm i f an adjacent hydroxyl or a ^ m - m e t h o x y l group is also present. The spectra of 1,8-dihydroxyanthraquinones show a peak at ca. 4 3 0 - 4 5 0 nm (still higher in the 1,3,6,8-tetrahydroxy series), 1,5dihydroxy compounds usually display two maxima in the region 418-440 nm (again shifted bathochromically b y an adjacent j8-hydroxyl), while

300

400

500

600

Wavelength (nm)

F I G . 6. Electronic absorption spectra (in E t O H ) of: 1,2-dihydroxyanthraquinone ( ) ; 1,4-dihydroxyanthraquinone ( ) ; 1,5-dihydroxyanthraquinone ( ) ; 1,8-dihydroxyanthraquinone ( • ).

the 1,4-dihydroxy quinones absorb at 4 7 0 - 5 0 0 nm with a peak (or shoulder) above 500 nm (Fig. 6). Additional a-hydroxylation results in a further red shift of the longwave absorption. 1,4,5-Trihydroxyanthra­ quinones show two or more maxima in the range 485-530 nm, and the 1,4,5,8-tetrahydroxy compounds show multibanded absorption in the 540-560 nm region. Excellent examples of poly-a-hydroxylated anthra­ quinones can be found in the anthracyclinone series (Chapter 6). Most of the natural anthraquinones contain at least four substituents which modify the absorption spectra and irregularities will be found which do not fit in with the above generalisations (Table I X ) . Further information

Aurantio-obtusin (55) Ventimalin (56)

Rhodocomatulin 6-methyl ether (52) Catenarin (53) Cynodontin (54)

Erythrolaccin (49) Alaternin (50) Averythrin (51)

226 (4-20) 227 (4-23)

231 (4-51)

228 (4-26) 229 (4-32) 223 (4-46)

225 (3-60) 222 (4-46)

Macrosporin (46) Emodin (47)

Kermesic acid (48)

232 (4-50)

220 (4-45) 225 (4-59)

219 (4-56)

224 (3-74)

Morindone (44) Coelulatin (45)

Pachybasin (38) Digitolutein (39) Nordamnacanthal (40) 2-Methylquinizarin (41) Soranjidiol (42) Aloe-emodin (43)

Quinone

H

256 263 257 241

(4-24) (4-25) (4-19) (4-56)

252 (4-11) 255 (4-12)

253 (4-31)

259 (4-53) 247 (4-23)

252 (4-01) 242-5 (4-27) 262 (4-73) 250 (4-59) 245 (4-04) 254 (4-34)

286 (4-58) 272 (4-39)

281 (4-21) 295 (4-06)

281 (3-65) 274 (4-40) 292 (4-57) 286 (4-06) 271-5 (4-46) 276-5 (4-01) 287 (4-03) 292 (4-16) 270 (4-28) 285 (4-30) 284 (4-80) 266 (4-29) 289 (4-36) 292 (3-73) 266 (4-18) 295 (4-13) 283-5 (4-40) 266 (4-18) 294 (4-45) 293 (4-42)

314 (3-94) 312 (4-03)

300 (4-01)

317 (3-96)

317-5 (4-06) 324 (4-02)

305 (4-40)

301 (4-18) 320 (4-30)

322 (3-48) 337-5 (3-17)

388 (3-82)

366 (3-46)

381 (4-15)

411 (3-80)

403 (3-02) 386 (3-52)

A*'a° nm (log e)

418 (3-62) 468 (3-95) 495 (4-06)

491 (4-13) 512 (4-05) 525 (3-99) 471 (4-06) 483 (4-14) 503 (4-31) 514 (4-38) 539 (4-37) 552 (4-42)

456 (4-05)

466 (3-74) 430 (4-01) 453 (3-95)

436 (4-14) 436 (4-14) 498 (3-04) 538 (2-94)

448 (4-07) 437 (3-54)

430 (4-04)

421 (4-09) 482 (4-29)

Ultraviolet-visible absorption of some naturally occurring anthraquinones

TABLE I X

CO

O

M

s

M

to

64

NATURALLY OCCURRING QUINONES

concerning the number and arrangement of a-hydroxyl groups can be obtained by measuring the bathochromic shift of the longwave absorp­ tion which occurs on ionization, accompanied always by an increase in intensity (see Table I ) . Infrared

spectra

The carbonyl frequencies of quinones are useful diagnostic aids in structure determination and have been studied extensively. Ideally spectra should be run in dilute solution but many natural quinones are poorly soluble in suitable solvents and in practice most spectra are now measured in potassium bromide discs. I t should be noted that many symmetric £>-quinones show multiple absorption in the carbonyl region, even in 37dilute solution, which is attributed mainly to Fermi resonance effects. I n published spectra minor peaks or shoulders in the 6 JJL region 3 332 cited. Useful are frequently ignored, only the principal band(s)2,0being 3 45 are , 3 available for benzoquinones 36 compilations ' and anthra­ quinones, but naphthaquinones are less well served and the -1 information is more scattered. The carbonyl absorption of ^-benzoquinone falls at 1669 c m (in solution) which is normal for an a/3: a'/?' di-unsaturated ketone, and the - 1 number of linear fused rings increases - 1 frequency rises as the (1,4-naphtha1 38 quinone 1675 c m , 9,10-anthraquinone 1678 c m , naphthacene-5,12quinone 1682 c m ) . The carbonyl frequency is lowered by hydrogen bonding, by substitution either in the quinonoid ring or an adjacent benzenoid ring with -f-I or + M groups, and by separation of the carbonyl functions so that quinonoid conjugation extends through more than one ring (extended quinones). The carbonyl frequency is raised by —M substituents and by steric strain, both of which are relatively rare in natural quinones. The commonest substituents are alkyl, hydroxyl and alkoxyl, and the shift to lower frequencies can be appreciable in highly -1 substituted quinones [for example, a-tocopherolquinone (10) shows v co 1641 c m (CC1 4)], particularly if they are chelated (see below). Consequently it is difficult to give a meaningful range of v co values for any large group of quinones (Tables X - X I I ) . I t follows that v co alone is insufficient to classify a quinone and additional information is required. o-Quinones normally exhibit two carbonyl bands, usually at somewhat 39 higher frequency than expected for the ^p-isomers. There is very little information available for o-benzoquinones j but o-naphthaquinones -1 can often be distinguished from the ^-quinones by the presence of a medium band (or shoulder) in the range 1700-1680 c m (Table X ) . t o-Benzoquinone samples should not be prepared in K B r disc as the heat generated causes 85 decomposition. Even in Nujol the spectra may show several bands in the carbonyl region.

2. IDENTIFICATION TABLE

X

Carbonyl absorption of various quinones

e

v

0 1,4-Benzoquinones Parent 0 d MethylEthyl2,3-Dimethyl-°fl 2,5-Dimethyl- a 0 2,6-DimethylTrimethyl- 0 b Tetramethylb Methoxy2,3-Dimethoxy- b 2,5-Dimethoxy- b fl 2,6-Dimethoxy2-Methyl-3-methoxy2-Methyl-5-methoxy-° 0 1,2-Benzoquinones c Parent 3,4-Dimethyl-

-1

cm

c o

1669, 1653 1661 1661 1656, 1626 1661, 1637 1656 1647 1653, 1639 1678, 1645 1664, 1637 1658 1695, 1645 1669, 1653 1681, 1653 1680, 1658 1675, 1646

0 1,4-Naphthaquinones Parent 2-Methyl-°b 5-Methyl- b b 6-Methyl2,3-Dimethylb 2,7-Dimethyl-° 2-Methoxy- b b 5-Methoxyb 2,3-Dimethoxy5-Acetoxy- b 6-Hydroxy-

1675 1670 1669, 1662 1661 1660 1673 1678, 1645 1667(sh), 1657 1680, 1650 1760, 1669(sh), 1661 1664

1,2 -Naphthaquinones 5 Parent* 3-Methoxy- b' 4-Methoxy-b ' 6-Methoxy- b ' 7-Methoxy- b 8-Methoxy- b 5-Hydroxy- b' 6-Hydroxy- b' b 7-Hydroxy - ' b 5-Methoxy-7-methylb 8-Methoxy-6-methyl' 3,5-Dimethoxy- b 4,7-Dimethoxy-b 3,8-Dimethoxy- '

1678, 1661 1700, 1665, 1645 1700, 1667, 1648 1685, 1655 1695, 1660 1683(sh), 1653 1689, 1637 1680, 1645 1685, 1645 1695, 1653 1681, 1659 1690, 1670 1696, 1661(sh), 1644 1690, 1670, 1660

66

NATURALLY OCCURRING QUINONES T A B L E X—continued

e v

c 9,10-Anthraquinones c Parent 2-Methyl- a l-Methoxy- c 1 - Acetoxy-c c 2-Hydroxyc 2 -Hydroxy - 3 -methyl 2,3-Dihydroxy- c 2,6-Dihydroxy- c l,2,3-Trimethoxya 6CC1 . 4

KBr. *' KC1.

c ocm

-l

1675 1675 1675 1764, 1678 1667 1658 1675 1656 1664

c dNujol. eC S . 2

Bold numerals = principal band.

Chelated quinones are numerous, and can be recognised by their displaced carbonyl absorption (see Tables X I and X I I ) together with the downward shift in hydroxyl frequency (o-hydroxyquinones) or the complete absence of hydroxyl absorption in the 3 /x region (perihydroxyquinones).| In all cases acetylation eliminates the effect of the chelating group and vco is restored to approximately that of the parent quinone. Thus 2- and 5-hydroxy-1,4-naphthaquinones can be dif­ ferentiated from the 6-isomer, and likewise 1- from 2-hydroxyanthra­ quinones. 2,5- and 3,5-Dihydroxy-l,4-naphthaquinones can be dis­ -1 the former show doublet carbonyl absorption tinguished (in CHC1 3) as near 1660 and 1620 c m whereas-1the spectra of the latter have only one carbonyl peak near 1630 c m (ignoring unimportant shoulders). Juglones generally -1show two carbonyl peaks in the regions 1675-1650 1 and- 1645-1620 c m while naphthazarins absorb strongly at ~ 1 6 2 0 - 1 5 9 0 35 a study of fifty-nine anthraquinones Briggs and his co­ c m . From workers found the following correlations (see also ref. 34). Some

Number of a-HO groups None 1 2 (1,4- and 1,5-) 2(1,8-) 3 4

v

,-1

co (Nujol) cm"

1678-1653 1675-1647 and 1637-1621 1645-1608 1678-1661 and 1626-1616 1616-1592 1592-1572

f Obviously this only applies in the absence of other non-chelated hydroxyl groups.

2. IDENTIFICATION

67

TABLE X I

Carbonyl absorption of chelated hydroxyquinones

1

v coc m " Benzoquinones Monohydroxy-* b b 2,5-Dihydroxy3,5-Dimethyl-2,6-dihydroxy-

1669, 1658 1646(sh), 1620(br) 1660, 1641

b Naphthaquinones 2-Hydroxy- b b 5-Hydroxy2,3-Dihydroxy- b 2,5-Dihydroxy- b 3,5-Dihydroxy- a 5,8-Dihydroxy-

1674, 1640 1666, 1645 1672, 1638 1658, 1614 1645, 1625b 1623 (1613 )

Anthraquinonesc c 1 -Hydroxyl,2-Dihydroxy- c l,3-Dihydroxy- c 1,4-Dihydroxy- c l,5-Dihydroxy- c l,6-Dihydroxy- c l,8-Dihydroxy- c l,2,3-Trihydroxy- c l,2,4-Trihydroxy- c 1,4,5-Trihydroxy- c c l,2,8-Trihydroxy1,3,5,7 -Tetrahy droxy - c l,3,6,8-Tetrahydroxy- c l,4,5,8-Tetrahydroxy-

1667, 1658, 1675, 1626 1634 1664, 1678, 1650, 1621 1605 1661, 1608 1669, 1592

a bCC1 . cK B r 4.

1631 1634 1637

1634 1621 1626

1621 1624

Nujol

exceptions were noted and the ranges quoted should now be slightly extended for K B r measurements. 1,4,5-Trihydroxy anthraquinones can be further distinguished from the 1,4- and 1,5-dihydroxy derivatives as the latter normally show a strong doublet in the 6 /x region not seen in the spectra of the former. Anthraquinones having no a-hydroxyl groups j* show only one carbonyl peak and its position is little affected by sub­ - 1 in the case of j8-hydroxylation but the maxi­ stitution except (usually) mum shift is < 2 0 c m . All the naturally occurring extended quinones are chelated. The simplest example, diphenoquinone (no natural •j* Aminoanthraquinones are ignored in this discussion.

68

NATURALLY OCCURRING QUINONES TABLE X I I

Carbonyl absorption of some naturally occurring quinones

1

v co cm" Benzoquinones Plastoquinone (9)fl b Lagopodin A ( 8 ) c Perezone (13; R = H ) Hydroxyperezone (13; R = O H ) Ardisiaquinone cA (15) ° c Spinulosin ( 1 8 ) Mansonone A ( 2 0 )

1647 1745, 1658 1650, 1628 1640(sh), 1615 1655(sh), 1633 1655(sh), 1637 1685, 1670

Naphthaquinones c a-Lapachone ( 2 4c) Plumbagin ( 2 6 )c Eleutherin ( 2 7 ) c Dianellinone ( 2 9 ) c Alkannin (32)° c Solaniol ( 3 3 ) /?-Lapachone ( 3 5 )

1678, 1640 1659, 1637 1662 1695, 1667, 1623 1603 1602 1690, 1640

c Anthraquinones Digitolutein ( 3 6 c) Soranjidiol ( 3 9 ) c Kermesic acid (47) c) Morindone (41 Emodin ( 4 6 ) Catenarin (52) b Cynodontin ( 5 3 )

1666 1664, 1634 1670, 1623 1634 1675, 1631 1598 1572

a bIn CC1 . 4 c In Nujol. In KBr.

-1

-1

-1 which shifts to 1650 c m derivatives), shows v co 1639 c m (Nujol) in perylene-3,10-quinone, and to 1631 c m in its 4,9-dihydroxy deriva­ tive, the simplest natural quinone in this class. I n other regions of the spectrum substituent groups reveal their characteristic absorption independently of the quinone chromophore but one or two correlations have been noted which are of some diagnostic -1 value for certain types of quinone. Most anthraquinones have an intense absorption band in the region 1600-1575 c m but this overlaps35 the carbonyl peak in highly chelated derivatives as already noted. I n benzoquinones and naphthaquinones a corresponding band, attributed to a C = -C 1vibration, usually appears at higher wave numbers ( ~ 1 6 2 0 1590 c m ) . Benzoquinones which have an isolated ring hydrogen atom

- 1 69

2. IDENTIFICATION

usually show a strong or medium band between 910 and 880 c m , and - 132 medium to strong if two adjacent ring hydrogen atoms are present, -1 occurs between 40 840 and 805 c m . Bands at 1299 and absorption 714 c m are considered to be characteristic for menaquinones but are 41 not found regularly in other naphthaquinones with an unsubstituted benzenoid ring. Whiffen and co-workers have published useful correla­ tion tables relating the in-plane and out-of-plane C—H deformation frequencies of a large number of naphthalene derivatives with their substitution pattern, and these correlations appear to be equally valid for naphthaquinones. Little attention has been paid to these empirical data but it could be helpful in cases where insufficient material is available for n.m.r. determination. N.m.r. spectra The quinonoid protons in ^-benzoquinone resonate at T 3-28 and in 4 , 2 4, 47, 38 at r 3*03. The effect of substitution (Tables X I I I 1,4-naphthaquinone and X I V ) is analogous to that observed in comparable cisvinyl compounds, and for benzoquinones the chemical shift of Q—H

2

3

4

5

6

7

8

9

I0r

F I G . 7 . N.m.r. spectrum ( 6 0 MHz in C D C 1 ) of 2-methyl-1,4-naphthaquinone.

3

42

is very similar to that found in cyclohex-2-ene-l,4-diones. On reduction to a quinol (leuco-acetate formation is usually most convenient) the signal shifts downfield to the aromatic region, frequently with a reduction in multiplicity, and this is a useful criterion for a quinonoid structure. The signal from an alkyl substituent undergoes a corresponding shift and reduction in multiplicity. Thus in 2-methyl-1,4-naphthaquinone the quinonoid proton at C-3 gives rise to a quartet at r 3-16 ( J , 1-5 Hz) coupled to a doublet from the ally lie methyl protons at r 7-81 (Fig. 7).

a 6Narrow multiplet. c In C C 1 . 4 I n CHCI3.

b Parent b 2-Methyl6 2,6-Dimethylc 2-Methyl-5-isopropylb 2,6-Dimethoxyb 2-Methoxy-5-methyl2,3-Dimethoxy-5-methyl-

6

Benzoquinone

—

— — —

—

—

3-28

H-2

—

3-28 3-42(m) 3-50(m) 3-45(q) 4-14(m) 4-26

H-3

— —

4-14(m)

—

3-28 3-30° 3-50(m)

H-5

3-60(q) 3'74(q)

—

3-53(d)

—

3-28 3-30"

Others

Me, 7-93(d) Me, 7-97(d) Me, 7-98(d); Pr, 7-00(m) MeO, 6-16 Me, 8-02(d);MeO, 6-26 Me, 8-05(d); MeO, 6 1 0 , 6-12

(r values)

H-6

N.m.r. spectra (60 MHz) of some p-benzoquinones

TABLE X I I I

^1

02

o

M

a

<©

O

M

a

Q Q

o

Hi

o

a

J , 10 Hz.

fl bIn CDC1 . cJ , 7 Hz. 3

8 -Methoxy - 6 -methyl -

1,2 -Naphthaquinone Parent

Parent 2-Methyl2-Hydroxy 2-Methoxy2-Acetoxy2-Acetyl5-Hydroxy5-Hydroxy-7-methyl 5 -Hydroxy - 3,7 -dimethoxy 5,8-Dihydroxy5,8 - Dihy dr oxy - 2 -methoxy 5,8-Dihydroxy-2-ethyl5,8 -Dihydroxy - 2,7 -dimethoxy -

1,4-Naphthaquinone

0

2-60 2-71 c 2-62 2-78

H-3 6

303 309 3-92 2-87 — — —

— — — —

305 —

H-2

H-4 3-49* 3-65 c 3-56 3-73

3-83 3-16(t) 3-60

— 2-87

305 3-21(q) 3-63 3-83 3-24 2-94 303 3-09

H-3

3-14(d)

H-5

—

— — —

— —

— —

— —

— — — —

3-27(d)

H-7

2-75(m) 2-92(d) 3-40(d) 2-87 2-77 2-80 3-60

—.

—

2-23(m)

—•

H-6

l-93(m)

H-5

—

2-87 2-77 2-80

— —

2-40(m)

— — — — —

2-23(m)

H-7

—

—

— —

—. — 2-30(m) 2-59(d) 2-92(d)

—

l-93(m) —

H-8

N.m.r. spectra (60 MHz) of some naphthaquinones (r values)

TABLE X I V

-1-93 - 1 - 8 3 ; Me, 7-58 - 1 - 9 7 ; MeO, 3-91 -2-43 - 2 - 6 3 , —2-17; MeO, 6 0 '8» -2-45, -2-60 - 3 1 2 , - 2 - 7 0 ; MeO, 6-06

MeO, 6 04; Me, 7-60

HO, HO, HO, HO, HO, HO, HO,

MeO, 6 1 1

Me, 7-87(d)

Others

O

Hi

Q

O

M

to

72

NATURALLY OCCURRING QUINONES

In the spectrum o f the leuco-acetate (Fig. 8) the C-3 proton and the ring-methyl protons are revealed as singlets at r 2-87 and 7-70, respec­ tively. Note that in unsymmetrical bz-substituted 1,4-naphthaquinones (Table X I V ) the adjacent protons at C-2 and C-3 frequently give a singlet rather than an A B quartet, and this is also true for some monosubstituted benzoquinones. The nuclear protons in simple benzo­ 4 23 , 4 quinones give rise to multiplets which originate from long range inter­ actions. The following coupling constants have been o b s e r v e d :

F I G . 8. N.m.r. spectrum (60 MHz in CDC1 3) of 2-methylnaphthaquinone leucodiacetate. ^aiiyiic

( C # 3— G = G — H ) ii

1-5-1-7 Hz,

II

1-3 Hz, J (H—C—C—C—H)

e/

h

.

a o

3) c lm l o(GH y 3—C=C—CH l i

2-2-2-5 Hz. Other long range spin-spin

couplings, i f present, are much smaller, and the coupling constants for 44 angle between the C = C allylic and homo-allylic systems vary with the double bond and the relevant C—H bonds. Very little information is available on the n.m.r. spectra o f o-quinones but 1,2-naphthaquinones with no quinonoid substituents can be distinguished from 1,4-isomers by virtue of the A B quartet given by the non-equivalent quinonoid protons (Table X I V and Fig. 9). The other signals observed in the n.m.r. spectra of quinones, arising from aromatic and side chain protons, are not peculiar to these com­ pounds and little comment is needed. I n 1,4-naphthaquinone and 9,10anthraquinone the a- and /S-protons give A 2B 2 multiplets centred at T 1-93 and 2-33 respectively, and these are modified b y substitution in the normal way. I n naphthaquinones the benzenoid substitution pattern 4 90 , 5 can usually be deduced from the aromatic proton signals without difficulty but the situation is more complex in anthraquinones. In

2. IDENTIFICATION

73

practice, however, certain types of substitution predominate and some representative examples are given in Table X V . I n this connection, as 45 many quinones are phenolic, the substituent constants compiled by Ballantine and Pillinger for phenols can be used to predict the chemical shift of the aromatic protons and hence the orientation of substituents. Chelated a-hydroxyl groups are easily recognized as their protons resonate at very low field (~r —2 to —3). F o r methyl and methoxyl groups, which are common substituents, additional information can be obtained from solvent shifts. Relative to deuterochloroform solution,

F I G . 9 . N.m.r. spectrum ( 6 0 MHz in C D C 1 ) of 8-methoxy-6-methyl-l,2-naphtha3 quinone.

the chemical shift of anthraquinonoid /3-methyl protons moves upfield 0-52-0-60 ppm in benzene solution, that of an a-methyl group is little 4 6 attached to a affected (+0-06-0-17 ppm)f while for methyl groups 3 a e r quinone ring the upfield shift is 0-29-0-51 p p m . J F o r methoxyl substituents the solvent shifts A%P£l again upfield being ~ 1 ppm when the group is attached to a quinone ring,f 0-65-0-74 ppm for perimethoxyls, and ~ 0 - 8 ppm for /3-methoxyl groups (in anthraquinones J ) . However when two methoxyls occupy ortho- or meta-positions the shifts may be considerably modified and difficult to interpret. D a t a of this 7 other solvents might be explored with sort are still limited and the use 4of advantage. I t has been s h o w n recently that isomeric compounds of the rhodoquinone type can be distinguished by their solvent shifts in benzene and pyridine (relative to carbon tetrachloride), the protons of the methyl and methylene groups attached to the quinone ring being chiefly affected. The location of O-methyl and O-glycosyl substituents in 1,8-di80 hydroxyanthraquinones is a common structural problem. Steglich and L o s e l 3 have found a solution by measuring the acylation shift (AAc ) of t Jg>£i = S C D C I — S C H PPm. 3 66 X Only a few compounds have been studied.

—

3-20

303 2-83

— — — — — —• — — — — — —

2-79(d) 3-44 2-60

— — —

2-97 d 3 02 2-92 2-90 3-49(d) 3-58(d) 3-30(d)

H-3

H-2

—

2-56

—

2-70 2-40 2-36 2-96(d) 3-08(d) 2-76(d) 2-12 2-71

d

—

—•

2-44(d)

H-4

2-84 2-75(d) 2-83(d) 2-76(d)

— — 2-61(d)

—

3-02(d) 2-65(d) 2-67(d)

l-85(m)

H-5 H-7

—

— —

—

— — 3-49(d) — — — —

1-9 2-9(m)-

3-30(d) 3-25(d)

— 3-26(d)

303 3-28(d)

— 317

3-54(d) 3-33(d) 3-23(d)

1-7 2-3(m) 1-7 2-3(m) 2-23(m) 1 2-23(m)

H-6

—

—

— — — —

—

— — — 2-96(d)

l-85(m)

H-8

7-28 7-25 7-63 7-62 7-63

7-58 7-65 7-52 7-63

Me

a

O O

O

M

c w w

«In DMSO. c"In CDC1 . 3 dIn C H N. 5 5 9 and H-4 in a 1 -hydroxy(methoxy) -3-methyl system may show broadened but unsplit singlets. The methyl signal is Meta-protons at 4 H-2 also broadened.

l,2-Dihydroxy-° l,2,4-Trihydroxy-° 1,2,4-Triacetoxy-" b 1,2,4-Trimethoxyl,8-Dihydroxy-3-methyl- fl b l,6,8-Trihydroxy-3-methylb 1,8 -D ihy dr oxy - 3 -methyl - 6 -methoxy • a 1,6,8 -Tr imethoxy - 3 -methyl l,3,5,7-Tetrahydroxyl,3,5,6-Tetrahydroxy-8-methyl-°b l,3,5,6-Tetramethoxy-8-methyl- b l,2,6,8-Tetramethoxy-3-methyl-a l,6,7,8-Tetrahydroxy-3-methyl- & l,4,6,8-Tetramethoxy-3-methylft b 2 -n -Hexanoyl -1,3,6,8 -t etramethoxy4-n-Butyryl-l,3,6,8-tetramethoxy-

Anthraquinone

X V

N.m.r. spectra (60 MHz) of some1 anthraquinones (Tvalues)

TABLE

75

2. IDENTIFICATION

nuclear protons, this being the difference in chemical shift observed on comparison of pertrimethylsilyl ethers and per-acetates. Significant differences are found for protons in different environments (see examples below) which are of diagnostic value. Glycosidic substituents may be

HO

O 11

8 -

°

'

r

Acylation Shifts ( ^ A) tc

HO

V

-0-4-0-5

i

MeO" 0

-0-4 -0-5

O

O

-0-8 MeO

[A

f^A^.

HO'VV-0-5

_o-3-0.fi

s

Me

O

0

-0-35 -0-5

similarly located using AAc values; figures for emodin 1- and 8-glucoside are shown below. Acylation Shifts (A'Aq )% HO -0-83

O

O—Glu -0-55

Glu—O - 0 - 8 5 ^

O ^yT

OH "V"

^i-0-43

HO

HO

The tautomeric naphthazarin system is a special case. Hitherto redox potentials have been used to assess the equilibrium position since electron releasing substituents attached to a quinone ring lower the potential, and vice versa. Thus [(57a); R = Me] has a lower redox potential than [(57c); R = Me)] and hence a lower energy, and con­ sequently will predominate in solution. (It does not necessarily follow that this is the tautomeric form adopted in the crystalline state, nor that which preferentially takes part in chemical reactions.) I n naph­ thazarin systems 1,5-quinone structures [see (57)] must also be considered although their contribution to the equilibrium is normally 7 the 1,5-quinone structure small. However, the parent compound 7has [(57b); R = H)] in the crystalline s t a t e . The predominant tautomeric 73 form in solution can now be conveniently determined by n.m.r. spectro­ scopy, and Moore and S c h e u e r have done this for a large number of f A =S Ac H t ^AC = ^ H

m a (per-trimethylsilylanthraquinone—S ro Haro m(per-acetylanthraquinone. A M(per-trimethylsilyl-aglycone)—S R O Haro m(per-acetyl-glycoside).

76

NATURALLY OCCURRING QUINONES

naphthazarins carrying up to four of the substituents normally encountered in natural quinones of this type. The n.m.r. spectrum of naphthazarin consists of two singlets; one at T —2-43 arising from the peri-hydroxyl protons and the other, at T 2-87,f is the signal from both the aromatic and the quinonoid protons which results from the rapid inter conversion of the tautomers. I n naphtha­ zarins (57) where R = OH, OMe, OAc, E t , structure (a) predominates.

o (d)

This is evident from the chemical shift of the C-3 proton, which is essentially the same as that for the corresponding 2-substituted-1,4naphthaquinone or -juglone (cf. Figs 7 and 10), and from the downfield shift of the C-6 and C-7 proton signals. (In juglone the C-6 proton resonates at r 2-75.) Moreover, in [(57); R = E t ] , the C-3 proton signal is a sharp triplet ( J , 1-5 Hz) clearly coupled with the methylene protons, confirming that a double bond is localized between C-2 and C-3. On the other hand where R = Ac (in 57) the predominant tautomer is (c) as the singlet signal for the two vinyl protons has shifted upfield to r 2-92, and the C-3 proton resonates at r 2-44 (whereas the C-3 proton in 2acetyl- 1,4-naphthaquinone resonates at r 2-94). Similar data for 72 | Unchanged at - 6 0 ° .

77

2. IDENTIFICATION

naphthazarins with one substituent in each ring lead to the conclusion that substituents promote quinonoid properties in the ring to which they are attached in the order OH > OMe > OAc > E t > H > Ac, and for two adjacent substituents the order is OH, Ac > OH, OMe > OMe, OMe > CHCI3

111111111111111111111111111111111

2

3

4

5

1,,

6

111111111111111

7

8

1111111111111111111

9

IOT

F I G . 10. N.m.r. spectrum (60 MHz in CDC1 3) of 2-methylnaphthazarin.

OMe, E t > OMe, Ac. The position of the pair OH, Ac, at the head of the second list, is attributed to increased stabilisation arising from the tautomeric forms (58) and (59) which involve enolic structures.

(59)

Mass spectra Features common to the mass spectra of all quinones are peaks 5 15 , 7 to the loss of one and two molecules of carbon monox­ corresponding ide. Benzoquinones and naphthaquinones also eliminate an

78

NATURALLY OCCURRING QUINONES

acetylenic fragment from the quinone ring, and i f the latter is hydroxyl ated breakdown is accompanied by a characteristic hydrogen rearrange­ ment. Benzoquinones These compounds normally form abundant molecular ions which 52 fragmentation frequently give rise to the base peak. The principal processes are shown in (60) for the parent compound. I n addition loss C, m/e 80

A, m/e 82

B, m/e 54

°

(60)

of two molecules of carbon monoxide gives an important peak at m/e 5 2 . This necessarily requires the formation of at least one carboncarbon bond and the fragment is most simply represented as ionised

1

i

+r

I36(M )

100 -C0(*)

^

80

c

60

-C0(*)

-H(*)

—C0(*)

-2H(*)

-C0(*)

40

107 20 h

108

39

40

100

120

140

F I G . 11. Mass spectrum of 2,3-dimethylbenzoquinone. From Bowie et al. J. Chem. Soc. (B) (1966), 335.

cyclobutadiene. F o r unsymmetrical quinones fragmentation A always leads to the elimination of the most highly substituted acetylene, for example, 2,3-dimethylbenzoquinone gives an ion m/e 8 2 (M—MeC—CMe) but no M — H C = C H fragment (Fig. 11). Similarly in fragmentation B ,

79

2. IDENTIFICATION

the most highly substituted neutral moiety is eliminated. Appropriate metastable peaks show that this breakdown is frequently a two-step 52 process, elimination of an acetylene being followed b y loss of carbon monoxide. Scheme 1 shows the p o s t u l a t e d fragmentation path for tetramethylbenzoquinone (Fig. 12). The formation of a hydroxytropylium ion (a) is supported by evidence from other spectra which

100 8

80h

o

60

>

39

+

-COW

-CO

o

-a I

-CH,W

-COW -2H(*)

I64(M ) 136

93(d)

o 40 CD

135

108

20

40

60

100

159 ( M |CH3) 120 140

1

I

!

I

160 180

m/e

F I G . 12. Mass spectrum of 2,3,5,6-tetramethylbenzoquinone. From Bowie et al. J. Chem. Soc. (B) (1966), 335.

indicates that the presence of at least two methyl (or larger) groups is necessary to allow an M—CO ion to break down by loss of a radical with formation of a relatively stable carbonium ion, and also by the sub­ sequent decomposition of (a) into (6) and (c) which is exactly analogous O

IOC

-co

..Me

s

Me

CO

Me s

•Me

s Me'

Me m/e 108

HO (a) m/e 121

(b) m/e 93 Scheme 1

(c) m/e 91

80

NATURALLY OCCURRING QUINONES

to the fragmentation of the hydroxytropylium ion in the spectrum of benzyl alcohol. A distinguishing feature of the spectra of hydroxybenzoquinones arises from the fact that fragmentation C is accompanied by hydrogen

100

a)

40

140 m/e

F I G . 13. Mass spectrum of 2-hydroxy-5-methylbenzoquinone. From Bowie et al. J. Chem. Soc. (B) (1966), 335.

52

rearrangement. This has been established by deuteriation s t u d i e s + of 2-hydroxy-5-methylwhich show, for example, in the breakdown benzoquinone (Pig. 13), that the ion C 4H 50 ( 6 0 % of m/e 69) shifts to

02 OH o=c—CH=C=O {d) m/e 69 (40%)

CH

-co (e)

O H Me^

H ^H

(g) m\e 70 Scheme 2

J

x Me

H

(/) m/e 69 (60%)

81

2. IDENTIFICATION

m/e 70 in the spectrum of the monodeuteriated derivative which means t h a t the hydroxyl group is the principal source of the rearranged hydrogen. The transfer most probably+ occurs in the M — C O ion (e) (Scheme 2) to give ( / ) while the C 4H 60 peak at m/e 70 (Fig. 13) must be associated with a double hydrogen transfer and is plausibly + rep­ H02 (d) resented by (g). The remaining part ( 4 0 % ) of m/e 69 is due to C3 which is commonly encountered in the spectra of compounds containing the — 0 — C = C H — C = 0 system. The mass spectra o f methoxybenzoquinones are rather more complicated but ions (d) appear regularly, and

Me

(61)t

(62)t

M-71 peaks are also prominent. They correspond to the formal loss of two molecules of carbon monoxide and a methyl group from the molecular ion, and further decompose by loss of carbon monoxide to give M-99. These fragments may be represented by (h) and (i), respec­ tively.

Me

Me

100

140

220

197

260

235

300

340

xlOO

380

420

f460

111, k h, m/e

500

J , »

540

1 V*• >r

r *• 580 I

H ,

620

fl c -X660

700

740

780

820

860^900

M = 862

n—i—i—r

F I G . 1 4 . Mass spectrum of ubiquinone 1 0 . From Muraca et al. J. Amer. Chem. Soc. ( 1 9 6 7 ) , 89, 1 5 0 5 .

180

liit

n — i — i — r

03

tzj O

M

<© a

Q

M

a

Q Q

o

W

00 to

83

2. IDENTIFICATION

1 R3.

+ /R

O (h)

53 but very characteristic 54 Somewhat different behaviour is shown by the plastoquinones and ubiquinones under electron bombardment. B o t h groups show strong molecular ion peaks, and base peaks at mje 189 and 235, respectively, attributed to the pyrylium ions (61) and (62), formed by cleavage of the bond S to the ring and cyclisation. Between the molecular ion peak and the base peak, a series of weak peaks appears at [M-69-(68) n], due to successive loss of prenyl units (Fig. 14). Significant M + 2 peaks are frequently observed in the mass spectra of benzoquinones, sometimes increasing in intensity with time. Introduc­ tion of deuterium oxide into the ionisation chamber along with a quinone results in the appearance of M + 3 and M + 4 peaks in the mass spectrum, 5 5 65 that the M + 2 peaks originate from a reaction involving indicating water. * The intensity of the M84+ 2 peak can be correlated with the redox potential of the quinone. However in some cases the M + 2 ion may arise by hydrogen transfer from a side chain. No systematic study of the mass spectra of o-benzoquinones has been 56 gave M + 2 peaks comparable in reported but in three examples they intensity with the molecular i o n . Naphthaquinones

51

The fragmentation processes of 1,4-naphthaquinone and its simple 57 similar to those of the benzoquinones. derivatives are essentially Scheme 3 is illustrative. Usually the molecular ion forms the base peak. The appearance of an abundant ion mje 104 (j) and its decom­ position products mje 76 (k) and mje 50 are characteristic for naphtha­ quinones with no benzenoid substituents. On the other hand substitution in the benzenoid ring causes these peaks to shift to the appropriate higher mje values. As in the polyprenylbenzoquinones, phylloquinone (63) shows a base peak at mje 225 ascribed to a pyrylium ion (64) while O

o

o

(63)

(64)

(65)

84

NATURALLY OCCURRING QUINONES

59 to (65) arising by cleavage of an intense M-15 peak may be attributed the C—Me bond § to the quinone r i n g . Again, as in the benzoquinone series, a 2-hydroxynaphthaquinone undergoes a characteristic hydrogen rearrangement which results in a partial or almost complete replacement O

mje 128 Scheme 3

57 benzoyl ion (I) at mje 1 0 5 in the case of of the ion mje 1 0 4 (j) by the 58 in hydroxynaphthazarins this lawsone (see Scheme 4 ) . However, rearrangement may be suppressed. Naphthazarin itself is very stable and undergoes remarkably little fragmentation. Comparison of the spectra of 2 , 5 - and 5,7-dihydroxy-1,4-naphthaquinone (Figs 1 5 and 1 6 ) illustrates the differences which arise from substitution in different rings,

85

2. IDENTIFICATION

OH

C=0+

CH

-CO

(I) m/e 1 0 5 -CO -2C0 m/e 77 •OH

-CHO

m/e 1 1 8

m/e 89 Scheme 4

the "doublet" at M-54 (mje 136) and M-56 (m/e 134) (Fig. 16) being characteristic for a 1,4-naphthaquinone with no quinonoid substituents. In methoxynaphthaquinones the initial fragmentation tends to involve n — r

i

n — r

"i—i—r

r

100

+ 190 ( M

80 HO 60

+

Hhc-o

40

120^ 105

69(C,H0t)

20

162 (M-CO) I34(M-2C0)

92 il I.I !• 40

60

i 80

II I

, 1 r

100

120

140

160

i — r 180

200

m/e

F I G . 1 5 . Mass spectrum of 2,5-dihydroxy-1,4-naphthaquinone. From Bowie et al. J. Amer. Chem. Soc. ( 1 9 6 5 ) , 8 7 , 5 0 9 4 .

the methoxyl groups, the naphthaquinone skeleton being broken subsequently. 2-Methoxy-1,4-naphthaquinone affords abundant M—Me and M — C H 20 ions while the 5-methoxy isomer shows an M—CHO

86

NATURALLY OCCURRING QUINONES

peak at m/e 159 represented as (m). Elimination of a second formyl radical leads to m/e 130 (n) which breaks down in the usual way. The same spectrum contains an M — H 20 peak (11%) which is characteristic

( m ) m / e 159

( n ) m/e

130

of ^en-methoxyquinones, the water originating from the70 carbonyl 71 oxygen and the hydrogen atoms of the methoxyl group. (A periethoxyquinone fragments initially by loss of Me- followed by * C H 0 . ) 1

1

1

1

1

1 1

1

1

1

1

1

1

100

1

1

l90(/tf

+ )

\l S 4 ( M - 2 C 0 I36[M-(HC = 5

"ill1 40

i

6 3(C HO£)

1

3

1 li.i.J ill,. Jit II »i 1 1 1 60 80

Id 1 mill) 1 L*i 1 1 1 1 1 100 120 140 m/e

inl i

1

CH+C0)1

32(A/-CO)

|C) 8

1

1 i, 1, 1 1 I 160

180

2 0 0

F I G . 1 6 . Mass spectrum of 5,7-dihydroxy- 1,4-naphthaquinone. From Bowie et al. J. Amer. Chem. Soc. ( 1 9 6 5 ) , 8 7 , 5 0 9 4 .

The presence58of a C-acetyl group has a marked effect on the fragmen­ tation pattern. 2-Acetyl-1,4-naphthaquinone breaks down b y loss of a methyl radical followed b y carbon monoxide to give a peak at M-43, and also by elimination of ketene to give M-42. Further losses of carbon monoxide and acetylene from these two peaks gives a characteristic series of "doublets" (Fig. 17). This behaviour is considerably modified if a hydroxyl group is adjacent to the acetyl group (Fig. 18). Elimination of ketene is now largely suppressed, the major decomposition being loss

87

2. IDENTIFICATION

of carbon monoxide followed by a methyl radical to give the base peak at mje 173 (p). A minor fragmentation involving loss of water from (o)

+ 200(M ) -CH-

100-co -co ? 60H =5 o ~ 40a Ql 20-\

-CH^CH

50

751 76

„5I

—CO

—CO

-CO

L - C H = CH

101

*

-CHo=C0

157 158

185

102

104 I29||I30 144 172 l li , I ill lL 80 100 120 140 160 180 2 0 0 2 2 0 m/e F I G . 1 7 . Mass spectrum of 2-acetyl-1,4-naphthaquinone. From Becher et al. J. Org. Chem. ( 1 9 6 6 ) , 31, 3 6 5 0 . I, ,111, „.l r 0 40 60

173

100 cu 8 0 60

+ 2\6(M )

"53 4 0 20 0 40

77

76

43 ll.H.I

,iil,,n

60

I,

-CO 89 9 104 0

.lllli |I , . ! ! h,lli 80

100

'P^ng 170 l.l/

.J

174

i

120 140 m/e

160

180

-HoO

|4*200 220

F I G . 1 8 . Mass spectrum of 3-acetyl-2-hydroxy- 1,4-naphthaquinone. From Becher et al. J. Org. Chem. ( 1 9 6 6 ) , 31, 3 6 5 0 .

to give (q) is diagnostic for vicinal acetyl and hydroxyl groups. These 58 and related fragmentations have been applied extensively by Djerassi and his co-workers to the highly substituted spinochrome pigments.

88

NATURALLY OCCURRING QUINONES COMe

COMe

-CO

OH

-Me

€=0

+

OH

0H (p) mje 173

C=0 CH, (q) m/e 170

The behaviour of 1,2-naphthaquinones under electron impact is similar to that of the 1,4-isomers except that the ion m/e 104 (j) does not arise. The o-isomers can usually be distinguished by the fact that their 5 660and the M + 2 peaks are of similar or greater molecular ions are weak intensity (cf.ref. 8 6 ) . ' A nthraquinones

61 I n this series the molecular ion almost invariably forms the base peak. Anthraquinone i t s e l f undergoes successive elimination of two molecules of carbon monoxide to give strong peaks at m/e 180 (M—CO) and 152 + 208(/tf )

100

-C0(*)

80

180 -C0(*)

r

60

76

40

152

20

20

40

60

80

100

120

140

160

180

200

220

(m/e)

F I G . 19. Mass spectrum of anthraquinone.

(M—2CO) (and strong doubly charged ions at m/e 90 and 76) which correspond to the molecular ions of fluorenone and biphenylene, respec­ tively. Otherwise there is very little fragmentation (Fig. 19). The

89

2. IDENTIFICATION

5 174 spectra of derivatives follow the same pattern with additional peaks appropriate to the substituents and to their a- or /?-orientation. ' 2-Hydroxyanthraquinone shows more intense M—CO and M—HO peaks than does the chelated 1 -isomer and both spectra have a peak at mje 140 corresponding to the loss of three molecules of carbon monoxide, the third arising from the phenolic group in the normal manner. A very stable ion at mje 139 (M—2CO—CHO) may be (66) or (67). Dihydroxy-

(66)

(67)

anthraquinones behave similarly and a peak at M—4CO (mje 128) may be the molecular ion of naphthalene. As in the naphthaquinone series, a ^en-methoxy group gives rise to M—HO70and M — H 20 peaks which are not observed in /?-methoxy derivatives, and 1,8-dimethoxyanthra­ 71 quinone can be distinguished from the 1,5-isomer by virtue of its abundant M—Me ion. Both a- and j8-methoxy compounds eliminate a 51 but again this fragmentation is only signi­ formyl radical (M—CHO) ficant for peri-isomers. REFERENCES

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