New Reactions in Organoselenium Chemistry Andrew George Brewster

Home , Selenenic acid, Selone

NEW REACTIONS IN ORGANOSELENIUM CHEMISTRY

a thesis presented by

ANDREW GEORGE BREWSTER

in partial fulfilment of the requirements

for the award of the degree of

DOCTOR OF PHILOSOPHY

OF THE

UNIVERSITY OF LONDON

WHIFFEN LABORATORY) CHEMISTRY DEPARTMENT, IMPERIAL (ALLEGE)

LONDON SW7 2AY AUGUST) 1977, 2.

ACKNOWLEDGEMENTS

I thank Professor Sir Derek Barton, F.R.S., for his encourage- ment, guidance and tolerance throughout the course of this work.

I also thank Dr. S.V. Ley for his enthusiasm and assistance,

Mr. K.I. Jones and his staff for the microanalytical service, Mrs. Lee for the mass-spectrometry service, Mr. T. Adey for technical assistance,

Mrs. Day for her kindness and cooperation in the stores and Miss

Maria C. Serrano for her patience and helpfulness during the typing of this Thesis.

Finally, I wish to thank the Science Research Council for a student- ship for the period of this research.

Andrew G. Brewster,

Whiffen Laboratory,

August, 1977.

ABSTRACT

Reviews of some interesting new reactions in organoselenium chemistry and of the synthesis of ortho-quinones are presented and the properties and reactions of benzeneseleninic anhydride are summarised.

Benzeneseleninic anhydride has been used to oxidise simple phenols, the major products being the para-hydroxydienones, eg. (A)

(A)

Reaction of the anhydride with the phenolate anion did not noticeably affect the results.

Oxidation of many phenols with benzeneseleninic anhydride at 50° gives ortho-quinones in yields of 50-70%. The procedure is almost exclusively ortho-selective and represents the best method yet developed for the conversion of phenols to o-quinones. The previously unreported compound, 3-methyl-6-isopropyl-1,2-benzoquinone (B) was prepared in this manner but some simple phenols, eg. 2,4-xylenol, give complicated mixtures of products from which no quinones can be isolated. 4.

OH OSePh

(B) (C)

Attempts to isolate or trap likely intermediates of type (C) were unsuccessful.

Treatment of some catechols and quinols with the anhydride at 50° gave the corresponding quinones in high yield.

The reaction of phenols with hexamethyldisilazane and the anhydride to give selenoimines, (D), has been examined. Several selenoimines have been prepared and the mildness of the procedure has been demonstrated.

Compound (D) has also been the subject of an X-ray crystallographic study.

NSePh 0 SiMe / 3 Ph —Se —N Si Me3

(o) (E)

The mechanism of selenoimine formation has been studied but attempts to synthesise potential reactive intermediates, eg. (E), have failed.

A redox titration study of benzeneseleninic anhydride oxidations has enabled the relative rates of reaction to be qualitatively estimated 5.

and has given support to mechanistic conclusions reached previously.

A series of benzylic alcohols was smoothly oxidised to the corresponding carbonyl compounds in high yield using benzeneseleninic anLydride. 6.

CONTENTS Page

Acknowledgements 2

Abstract 3

Review 7

New Reactions in Organoselenium Chemistry 7

The Synthesis of Ortho-Quinones 27

References 34

Benzeneseleninic Anhydride; Previous Work 38

References 47

Results and Discussion 49

(1)Hydroxylation of Phenols with Benzene- 49 seleninic Anhydride

(2)Conversion of Phenols to Quinones 55

(3)Conversion of Catechols and Quinols to 65 Quinones

(4)Formation of Selenoimines 66

(5)Mechanism of Selenoimine Formation 81

(6)Redox- Titration Study of Benzeneseleninic 84 Anhydride Oxidations

(7)Oxidation of Benzylic Alcohols with 93 Benzeneseleninic Anhydride

Experimental 95

References 125

NEW REACTIONS IN ORGANO-SELENIUM CHEMISTRY

1 An exhaustive review of organoselenium chemistry, covering the literature up to the end of 1972 was recently published. This section examines some of the more significant work which has appeared since that date, but is not meant to be a comprehensive survey.

1- Selenoxide Eliminations

Selenoxides are preparedby oxidation of selenides2, usually with ozone or peracid. The products are stable at room temperature unless there is a s-hydrogen atom present in the molecule, in which case a facile elimination of the selenenic acid takes place to yield the olefin.

0 ,c t. ,/ H Se 13 RCH==CH2+ RSeOH RCH2CH2SeR ------+ R--CH--CH2 ----4

3 This elimination process was first observed by Jones et al. who found that both diastereomers of the 6-phenylseleninocholestane derivative (1), which were separable at low temperature (-500), gave A6-cholestene on warming to room temperature. At 0°C however, one isomer was inert whilst the other gave the olefin after four hours.

0.) 8.

It was deduced that a syn-elimination process was taking place and

the rate difference between the two isomers was attributed to steric

crowding in the transition-state. Thus in transition-state (A), from the

(S)-isomer, there is less compression so the elimination is rapid. In the

case of the (R)-isomer the steric factor makes the cyclic transition-state

(B) harder to attain, so the elimination is slower.

Ph Me

.E--/ H [(B) as for (A) with Ph and lone pair of • (A) electrons reversed]

Further evidence for the syn-nature of the elimination was obtained 4 from a study of the ratios of olefins produced by selenoxide elimination

after oxidation of selenides (2) and (3). As shown below, formation of the

2-phenyl-2-butenes occurred by stereospecific syn-elimination. The erythro-

isomer (2) gave only the (Z)-olefin and the threo-isomer (3) gave only the

(E)-olefin, while the major product in both cases was the 3-phenyl-1-butene.

PRODUCTS Ph> P h Ph

N 0(21.1 3 (z) (E) PhSe Ph 15% 42% H H 3 (2) H202/THF

25°, 2.5 h ,Ph PhSe 13% 45% C H H 3 C H 3 (3) 9.

The ease with which selenoxides undergo hydration has also been demonstrated Treatment of selenide (4) with aqueous hydrogen peroxide solution at room temperature gave only 6% of the olefin after sixteen hours. On addition of anhydrous magnesium sulphate, however, the olefin was produced in 77% yield after only two and a half hours. It would appear that, in this case, the hydrate is actually the predominant species in solution.

1:111

THF RCH CH RCH CH SePh----R RCH CH SePh 2 21 2 21 2 2 70% H202 -0 (4) OH (R = n-decyl)

The phenomenon of selenoxide fragmentation at, or below, room temp- 5 erature was applied to the introduction of a,6-unsaturation into ketones.

Thus treatment of the enol acetate of cyclohexanone with silver trifluoroacetate and benzeneselenenyl bromide in ether at 0°, followed by hydrolysis, gave the a-phenylselenoketone in 70% yield. Oxidation with sodium periodate

gave the enone in 92% yield.

Ac (1)Ag0 2CCF3 o IllithSeBr,Et20, 0

(2)Hydrolysis

6 Sharpless and Lauer developed a route to allylic alcohols via the

nucleophilic action of the benzeneselenolate anion on an epoxide to give

6-hydroxyalkyl phenylselenides. Oxidation and elimination then gave the

(E)-alcohol in high yield. It was noted that the elimination always

10.

appears to occur away from the hydroxyl group.

0 HO-_,./\,/ EtOH 1)H2 2'0-25° 2h, RT Se Ph SePh

B-HydroXyalkyl phenylselenides have also been obtained by the addition of benzeneselenenyl trifluoroacetate to olefins, followed by hydrolysis.7

PhSeOCOCF3 0 KOH 0 EtOH SePh

The reaction is not highly regioselective for unsymmetrical olefins but in all cases studied the addition was stereospecific. Cis and trans- butenes gave different products while cyclohexene gave a single adduct with both substituents in an equatorial environment.

Benzeneselenenyl bromide and acetate undergo electrophilic trans- 8 1,2-addition to olefins and this has been used as a basis for a new route to allylic acetates and ethers. For example, oxidation of the adduct (5) gave predominantly the allylic derivative since, as noted previously, elimination shows a marked preference for occurring away from the functional group, (Interestingly, when X = Cl,elimination occurs equally in both directions.) Solvolysis of the adduct (5) followed by oxidation gave the allylic ethers.

11.

SePh ROM + PhSeX CI: 'X (5)

X = Br, Cl, OAc 02/THF

+ OR

(MAJOR)

Treatment of ketones and aldehydes with benzeneselenenyl chloride 9 has been shown to give the a-phenylseleno-derivatives in high yield.

Methods for the introduction of the selenide function a-to an ester group were also developed and oxidation of the product yielded the a,8-unsaturated compounds.

R SePh R\ X = H, alkyl or

0 o 0-alkyl

10 a-Phenylseleno-carbonyl compounds have been obtained by the low temperature (-78°) reaction between benzeneselenenyl bromide and lithium enolates. Oxidation of the product yielded the unsaturated compounds by an even milder procedure. In this manner, 1,4-dipheny1-1-butanone (6)

12.

'was converted to (7) in 84% yield. Less than 0.5% of the more stable

phenyl-conjugated isomer (8) was formed.

0 0 Ph Ph Ph

Ph Ph \ Ph

(6) (7) (8)

11 Reich recognised that the necessity for achieving a cyclic transition-

state in the selenoxide elimination may impose conflicting conformational

demands on cyclic systems and an investigation was carried out into why

only a limited range of cyclic enones (five and six membered rings) had

been prepared. It was concluded that in many cases a Pummerer-type reaction

was occurring to give unwanted byproducts.

t0H 1)K 0 t_0 1-1 €Ph SePh SePh SePh H+ 6H2 +0 H2

This reaction depends on the acidity of proton Ha. If this is a-

to a carbonyl group the reaction is facile. Thus in the oxidation of

selenide (9) the desired product (10) is obtained in low yield and the

byproducts (11) and (12) may be directly attributable to the Pummerer

reaction. 13.

Se Ph ePh (iii) (iv)

(10),48%. (11),17% (12),9% (i)LiNR 2 ( 9) (ii)PhSeBr (iii)03, -78° (iv)25°

However the ketal (13) undergoes oxidation and elimination to give enone ketal (14) in good yield, since the ketal function does not enhance the acidity of the a-proton.

1---\ 0 o 0 ■„;>< Se Ph ((i; 0H )2 SePh H 0 2 2 2 Ts0H

(9) (13),81% (14),80%

Using this procedure 8-dicarbonyl compounds may be converted to 11 enediones , a transformation which is difficult using classical methods.

Thus 2-carboethoxycyclohexanone gave the alkenone in 78% overall yield.

14.

Owing to the mild reaction conditions the non-enolised ft-dicarbonyl enones were formed exclusively in all cases even though a number of these systems are known to be significantly, or even predominantly, enolic at 12 eLyilibrium .

13 Grieco et al. developed a route to a-methylene lactones involving the stereospecific alkylation of the lactone enolate. In the case of the trans-fused y-butyrolactone (15), conversion to the trans-a-methylene-y- butyrolactone (16) was readily achieved with complete exclusion of the endo- cyclic isomer (17).

(15) (17)

This example provides further support for the involvement of a cyclic transition-state during selenoxide elimination.

14 A study of the nucleophilic action of anions a- to a selenoxide showed that two different reactions were possible (pathway (a) or (b), below) depending on the direction of elimination.

15.

0 0 Ha H6 b/ PhSe PhSe x Ha Li b

In order to block one of these pathways it was necessary to choose systems containing either no Ha or no Hb. Thus with benzaldehyde, anion

(18) gave the path (a) product, the net reaction being therefore equivalent to the operation of a vinyl anion.

Reaction of anion (19), which contains no 8-hydrogen atom, with cinnamyl bromide gave the path (b) type product only.

0 II (b) PhSe + Ph Br ,N^ Ph (19) 75%

16.

Since the selenide precursor to (19) is prepared from the halide, this reaction is equivalent to a coupling of two halides to give an olefin.

15 In a full paper, Reich has summarised his work on the conversion of ketones to enones using selenoxide elimination. The best methods for initial phenylselenenylation are discussed and several procedures for subsequent oxidation and elimination are also presented.

In addition to the Pummerer-type byproducts, a further side reaction was detected involving the reaction between the enolate (or enol) of a-phenylselenino ketones and selenenylating species formed during the disproportionation of benzeneselenenic acid. Hence the selenide (21) was shown by means of cross-over experiments to be derived from (20).

PhSeX

(21)

(20)

The most likely selenenylating agent was thought to be PhSeOSePh but this could not be isolated.

Direct introduction of the benzeneseleninyl group a- to the carbonyl function, followed by syn-elimination in one step was possible but the yields were variable and frequently lower than those obtained by the two- step procedure,

17.

01 0

v,c.,Se Ph II 0

Since benzeneseleninyl chloride is extremely hygroscopic it is recommended that this method only be used when the normal selenide oxidation procedure fails because of competing or preferential oxidation elsewhere in the molecule.

16 A study has been made of the effect of electron-withdrawing substituents on the rate of selenoxide decomposition, and this showed that such groups increase both the rate and the yield of olefin produced.

A route to terminal olefins was developed but although the final step was efficient, the initial alkylation step suffered due to the decreased nucleophilicity of the selenium anion.

Se(CH ) CH Et0H 2 11 3 + CH (CH 3 2)11Br NO THE 2 2

CH (CH )CH==CH 3 2 9 2 91% The overall yield was 76%, compared with 59% obtained when diphenyldiselenide was used as a source of phenylselenolate anion.

The mildness of the selenoxide elimination process makes this an attractive method for the introduction of unsaturation into complex molecules.

The synthesis of the important natural product vernolepin17 involved the

18.

following transformation:

NO2 OMe

DAC NN,/d//,, sON 50% H 0 2 2 H THE

OAc Me02C 02Me

89%

18 The final step in the synthesis of the naturally occurring lactone

(±) -diplodialide-A also utilised selenoxide fragmentation:

NaI0 o 4

SePh (±)-diplodialide-A

19 Nicolaou has developed a route to cyclic ethers which utilises the high electrophilicity of selenenyl halides combined with the facile fragmentation of selenoxides. 19.

H 0 PhSeC1 2 2 CH C1 THF "H,\ (1E)2 2 o -78° 0-25 ,...... , .2 SSePh +Se...'' * 0 \ Ph Raney Ni THF, 25° I

20 This method has also been used to synthesise an analogue of prostacyclin, (below) CO2Me

CO2Me OH SePh

HO'' HO%s OR OR

1)H 0 2 2 2)Li0H/Me0H 20.

21 A similar procedure was also developed for the preparation of lactones.

CO2H

cl,) PhSeC1 -Et N 3 H202 > -78° THF, 90% CH2C12' 100% SePh

Raney Ni, THF, 25° , 85%.

030

2. Selenone Esters

22 Earlier work utilised the action of pyridine and hydrogen selenide

on the imidate ester hydrochloride to give moderate yields of selenonesters

e.g. methylselenonebenzoate (22)

OPh

(22)

23 Recently, 0-cholesterylselenonebenzoate (24) has been obtained in good yield by treating the salt (23) with sodium hydrogen selenide, prepared by the borohydride reduction of elemental selenium. 21.

Et0H + NaHSe Se + NaBH4 --). (Et0)3B + 3H2

1 ROH + Ri Cl R....Thr, OR NaHSe Nt - N+ / \C1 / \C1

(23)

,-- OR (24)R 1=Ph,R=cholesteryl (78%)

(25)R 1=H,R=cholesteryl (44%)

The selenone formate (25) was prepared in lower yields and decomposed rapidly in air.

Aryl or alkylethynylthiolates were known to react with alcohols under 24 certain conditions to give thionesters . Recently in a similar reaction 25 it was found that in very dilute solutions the corresponding selenium analogues (26) reacted with solvent alcohol to give selenoesters. In more concentrated solutions, however, the diselenafulvene was formed. The latter reaction was catalysed by traces of acid.

Se 1 R OH II 1 R--CEEC--Se- K+ > R-- CH dilute 2-- C-- OR H+ (26) base 1 fe- 1 R---CH=C---OR

R = PhCH 2 R1= Me

The selenonesters were formed in only moderate yield and were not

22.

submitted for microanalysis. On treatment with base a bathochromic shift

was observed in the ultraviolet spectrum and this may be attributed to

enolisation, as shown above.

3. Selenoketones

26 In 1927, Lyons and Bradt claimed to have prepared monomeric aliphatic

selenoketones but their products were poorly characterised and the claim

was almost certainly unjustified. Barton et alr,28 heated a mixture of

the phosphoranylidene hydrazone (27) and selenium powder in the presence of

a trace of.butylamine and obtained the selone (28) as a blue liquid in 35%

yield. Use of the fenchylidene hydrazone derivative (29) gave the corres-

ponding selone (30) as blue crystals in 28% yield.

trace iN.C."1H, --—N=PPh + Se N 3 o = Se )).-= 120 20h `). (27) (28)

(29) (30)

These selones were thermally stable, being recovered after prolonged

heating at 150° under a nitrogen atmosphere. Oxidation with mCPBA at -80°

caused loss of the blue colour, but warming to room temperature gave only

the ketone and selenium. It was thought that the selenine (31) was formed

at low temperatures but that this species decomposes, possibly via the three-

membered cyclic transition state (32) on warming.

mCPBA __Se --.) )== Sepn e-----0' , 0 + Se 7 (31)

23.

Treatment of the selone (28) with tributylphosphine or sodium- potassium alloy gave 2,2,4,4-tetramethylpentane.

Bu P 3 )—Se or Na/K

Reduction with ethanolic borohydride however, gave the diselenide

(33).

Se Se (33)

The addition of radicals to di-t-butyl selone (28) shows it to be an 29 extremely good radical trap .

R M + Se R MSeBut n n 2

(34) (28) (35)

RnM = CH3, CF3, Me3Sn, Me3C0

The radicals (34) add rapidly to the selone and the adducts (35) are fairly persistent. The addition of Me3C0• is so fast that it competes with its attack on good H-donors, such as trimethylsilane, even when the latter are present in one hundred-fold excess.

4. Episelenides

Although episelenides have not been isolated, evidence for their exis- 30 tence continues to accumulate. Clive and Denyer published a general route to olefins involving the reaction of triphenylphosphine selenide and trifluoroacetic acid with epoxides. It was believed that an episelenide was formed but that this underwent spontaneous breakdown to the olefin and

24.

elemental selenium.

AoPhn

Ph3P=Se 0 r- Se- Se

\ cF3co2 Pq Pe Fr Ri R' Fe 14 Ize

The reaction was rapid at room temperature and the conversion was

stereospecific. Thus trans-stilbene oxide gave trans-stilbene in 71%

yield. Chan and Finkenbine31 reported the same reaction and they claimed

that n.m.r. studies further demonstrated the intermediacy of an episelenide.

The reaction mixture showed complete absence of epoxide at low temperature,

no selenium was precipitated and a new signal at 3.66 was observed. On

warming to room temperature, this signal vanished, selenium was precipitated

and the olefin was formed.

32 Olefins can also be obtained by treating epoxides with selenocyanate

ion in neutral or slightly alkaline conditions. An intermediate episelenide

was again implicated.

Fe t Se

25,

In this way, trans-stilbene and cyclohexene were formed quantitatively from their epoxides, but the cyclooctene and cyclopentene systems failed to react, probably because steric factors prevented the selenocyanate nucleophile from attacking from the rear of the epoxide-ring.

Since epoxides are readily opened under acidic conditions, the selectivity of this procedure affords a potential method for the protection of double bonds which are in different environments.

Perhaps the most striking example of the use of episelenides in 27,28 olefin synthesis was provided by Barton et al. who synthesised hexa- methy1-2,21-binorbornylidene (36), the most highly hindered olefin yet prepared, by the reaction of the selone (30) with the phosphoranylidene hydrazone (29). The mechanism involves nitrogen and selenium extrusion from the isolable 1,3,4-selenadiazoline (37), and an episelenide is thought to be an intermediate.

( Se N-N=PPh3

(30) (29) (37) q'A (36), 24% 26.

33 A recent conversion of either epoxides or episulphides to olefins utilises the novel reagent 3-methyl-2-selenooxobenzothiazole (38). Once again the reaction is stereospecific and is thought to proceed via the episelenide.

Me N S

Y = 0 or S

+ Se

In this way, trans-stilbene oxide afforded trans-stilbene in 97% yield.

27.

THE SYNTHESIS OF 0-QUINONES

34 As the synthesis of quinones was the subject of an extensive review in 1974, this section will summarise only those methods which are specific for the preparation of o-quinones from non-quinoid precursors and will also include a survey of the more recent literature.

Most of the known syntheses of ortho-quinones involve oxidative procedures, the typical precursors being phenols, phenolic ethers or, in some cases, hydrocarbons. However, by far the most general route to o-quinones involves oxidation of catechols by a variety of oxidants. The oxidation of monohydric phenols by either one- or two-electron oxidants is also a common process although this generally shows a marked preference for

2:quinone formation.

The use of hydrocarbons as substrates is limited owing to the general severity of the reaction conditions.

1. Oxidation of Catechols

Treatment of catechols with fresh silver oxide in dry ether or benzene 35 in the presence of anhydrous sodium sulphate gives the o-quinones in high yield. A recent improvement36 of this reaction uses silver carbonate and celite as the mild oxidant.

OH Ag20 or

Ag2CO3/Celite OH 28.

37 The rather unstable o-benzoquinone can also be prepared (86% yield) by the reaction of a chloroform solution of catechol with ceric sulphate in aqueous sulphuric acid.

38 Oxidation of catechols with tetrachloro- or tetrabromo-o-benzoquinone gives o-quinones provided that the redox potential of the catechol is lower than that of the oxidant.

pcOH OH

OH OH

X = CI or Br 39 40 38 o.-Quinones prepared in this way include (39) , (40) , and (41) .

However, the method fails with alizarin and related compounds.

(39), 84% (40), 94%

(41), 85% (42) 29.

High potential quinones of type (42) are usually made by oxidising 41 alizarin, etc. with lead tetraacetate .

Many other oxidants are suitable for o-quinone preparation including 42 44 45 dichlorodicyanoquinone , iiodate 43, potassium ferricyanide and periodate .

2. Oxidation of Catechol Ethers

45 . Treatment of monoethers of catechols with sodium periodate in either water or aqueous acetic acid gives o-quinones in good yield. The reaction is regarded as a nucleophilic attack by water on a periodate ester to give a hemi-ketal which subsequently yields the quinone.

H2O:

OMeID e OMe OMe

OH 0 0 17 -I 030 H

Oxidation of catechol dimethyl ethers is of little synthetic importance unless there are substituents at positions 4 and 5, when treatment" with silver oxide in cold aqueous dioxan acidified with nitric acid affords o-quinones in moderate yields.

3. Fremy's Salt

The oxidation of monohydric phenols to quinones using Fremy's salt

(potassium nitrosodisulphonate (43)) proceeds rapidly and efficiently under very mild conditions. In general, however, the major product is the p-quinone and o-quinones are only formed in special cases. The mechanism for the

30.

formation of o-quinones (p-similar) is shown below.

+ (K03S)2N0' + (K038)2NOH (43)

(43)

+ HN(S03K)2

(44)

If the 4-position is unblocked then the -quinone is the exclusive product. This result may be due to the large steric requirement of the intermediate dienone (44) in the case of o-quinone formation. Certain a-naphthols give a mixture of o- and p-quinones

(5-hydroxy-1,2- and 1,4-naphthoquinone from 1,5-dihydroxynaphthalene47) which may be ascribed to steric restriction of -dienone formation by the peri-substituent.

If the para-position is occupied by alkyl (or alkoxy) groups, 48 simpler phenols are converted to o-quinones in 70-90% yield. More complex phenols such as (45) can also be selectively oxidised49 and, in general, substituents and side chains are not attacked by Fremy's salt. 31.

(45) 75%

4. Other Reagents

Hydrocarbons provide a relatively unfavourable substrate for oxidation to quinones and the method is limited in practice to those few hydrocarbons which are readily available and form stable quinones.

50 Treatment of 1-bromonaphthalene with ceric ammonium sulphate in a mixture of dilute sulphuric acid and acetonitrile gave a mixture containing a 30% yield of the o-quinone (46). However, this method is of limited application and, generally, p-quinones are formed wherever possible.

500 + 5 h

0 (46), 30% 0 Br +

0 0

10% 18% 32.

Many other procedures afford o-quinones but they are not general. 51 Thus lead tetracetate oxidation of phenols gives varying yields of, inter alia, o-quinones, and 3-methyl-l-tetralone has been oxidised 52 with selenium dioxide to a mixture of the o- and p-quinones.

When the oxidation of phenols by molecular oxygen is accomplished, in the presence of cupric ions and a secondary amine such as morpholine, 53 amino-substituted o-quinones are rapidly produced. Thus 1- and 2-naphthol are converted to 4-morpholine-.1,2-naphthoquinone, whereas phenol affords

4,5-dimorpholino-1,2-benzoquinone.

R2NH 2+ 0 Cu 37%

OH 2+ NR 2 2' + R2NH 84%

OH 2+ 02' Cu + 2R NH 2 64% R2N

R2N H = 0 NH 33.

In conclusion, therefore, it is apparent that the only good general synthesis of o-'quinones is via oxidation of catechols. Monohydric phenols give, wherever possible, the p-quinones, and oxidation of hydrocarbons requires vigorous conditions and usually gives complex mixtures of products. 3'4.

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2. idem, ibid, p. 207.

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25. F. Malek-Yazdi and M. Yalpani, J. Org. Chem., 1976, 41, 729.

26. R.E. Lyons and W.E. Bradt, Ber., 1927, 60, 824.

27. T.G. Back, D.H.R. Barton, M.R. Britten-Kelly, and F.S. Guziec Jr., J.C.S. Chem. Comm., 1975, 539.

28. T.G. Back, D.H.R. Barton, M.R. Britten-Kelly, and F.S. Guziec Jr., J.C.S. Perkin I, 1976, 2079.

29. J.C. Scaiano and K.U. Ingold, J.C.S. Chem. Comm., 1976, 205.

30. D.L.J, Clive and C.V. Denyer, J.C.S. Chem. Comm., 1973, 253.

31. T.H. Chan and J.R. Finkenbine, Tetrahedron Letters, 1974, 2091. 36.

32. J.M. Behan, R.A.W. Johnstone, and M.J. Wright, J.C.S. Perkin I, 1975, 1216.

33. V. Calo, L. Lopez, A. Mincuzzi, and G. Pesce, Synthesis, 1976, 200.

34. S. Patai, (Ed.), "The Chemistry of the Quinoid Compounds", Wiley and Sons, 1974.

35. J. Cason, Org. Reactions, 1948, 4, 305.

36. V. Balogh, M. Fetizon, and M, Golfier, J. Org. Chem., 1971, 36, 1339.

37. R. Brockhaus, Ann., 1968, 712, 214.

38. L. Horner and W. DUrckheimer, Z. Naturforsch., 1959,24b, 741.

39. L. Horner, W. DUrckheimer, K-H, Weber, and K. Dolling, Chem. Ber,, 1964, 97, 312.

40. L. Horner and K-H. Weber, Chem. Ber., 1967, 100, 2842.

41. M.V. Gorelik, Zh. Org. Aim., 1968, 4, 513.

42. P. Boldt, Chem. Ber., 1966, 99, 2322.

43. L. Horner and K-H. Weber, Chem. Ber., 1965, 98, 1246.

44. Review; H, Musso, Angew.Chem., 1963, 75, 965; Angew. Chem. Internat. Edn., 1963, 2, 723.

45. E. Alder and R. Magnusson, Acta. Chem. Scand., 1959, 13, 505.

46. C.D. Snyder and H. Rapoport, J. Amer. Chem. Soc., 1972, 94, 227.

47. H,J, Teuber and N. Getz, Chem. Ber., 1954, 87, 1236. 37.

48. F.R. Hewgill and B.S. Middleton, J. Chem. Soc., 1965, 2914.

49. H.J. Teuber, Chem. Ber., 1953, 86, 1495.

50. M. Periasamy and M. Bhatt, Synthesis,1977, 330.

51. F. Wessely and J. Kottan, Monatsh., 1953, 84, 291.

52. F. Weygand and K. Schr8der, Ber., 1941, 74, 1844.

53. W. Brackmann and E. Havinga,Rec. Tray. Chim., 1955, 74, 1937, 1021, 1070, 1100, and 1107. 38.

BENZENESELENINIC ANHYDRIDE: PREVIOUS WORK

1 2 Benzeneseleninic anhydride (1) has recently been shown ' to be a versatile reagent for the oxidation of organic substrates. In this section some of the properties and reactions of this compound are described and other related work performed in these laboratories is discussed.

1. Synthesis

3 Benzeneseleninic anhydride has been known since 1909 but an efficient synthesis was not devised until 19624, when it was found that ozonolysis of diphenyldiselenide gave the anhydride quantitatively. It was postulated that three intermediates were involved:

0 0 I 0 0 H PhSeSePh---02- -> PhSeSePhc-----> PhSe0SePh4,----PhSeSePh --PhSe-O-SePh (1)

However, these intermediates could not be prepared when the calculated amounts of ozone were used and, to date, they are still unisolable, despite current interest5 in their properties.

The large scale preparation of benzeneseleninic anhydride is most conveniently achieved by the nitric acid oxidation of diphenyldiselenide.

The resulting seleninic acid hydronitrate6 (2) may be converted quantitatively to the anhydride by heating at 130° in vacuo for several hours.

0 HNO 0 0 3 II A U II PhSeSePh ------*PhSe0H.HNO ------4 3 vac PhSeOSePh

(2)

2. Properties and Reactions

Benzeneseleninic anhydride has a molecular weight of 360.12.

39.

No molecular ion is apparent in the mass spectrum, and peaks are recorded at 314(38.7), 234 (37.1), 174 (42.0), 157 (85.5), 154 (75.8), 93 (27.4),

77 (100) and 65 (22.5).

This fragmentation pattern is similar to the aromatic solenoxide 7 fragmentation investigated by Rebane , and the following scheme may be proposed,

[phseor [Phol+

m/e 174 m/e 93 m/e 65

[PhSe0SePh [ph] Ephse] +

m/e 157 m/e 77

[PhSePhil [Ph-Phj÷

[PhSeSePhi + m/e 234 m/e 154

m/e 314

The selenium atom gives a characteristic group of peaks in the mass spectrum which results from the typical distribution of the six major natural isotopes': 74Se (0.87%), 76Se (9.02%), 77Se (7.58%), 78Se

(23.52%), 80Se ( 49.82%), and 82Se (9.19%). The peak arising from the 80 most abundant Se isotope is generally chosen to represent a selenium- containing fragment.

Use of infra-red and nuclear magnetic resonance spectroscopy has helped to confirm that, in contrast to the sulphur analogue, benzeneseleninic anhydride is a true anhydride with the symmetrical structure (1) shown above, The so-called sulphinic anhydrides are actually sulphinyl sulphones9 (3). 40.

0 0 II II R--S--S--R (3) 11 0

Analysis of the vibrational spectrum was particularly useful in demonstrating the presence of the Se-O-Se bridge within the molecule. 10 The data obtained by Paetzold et al. are summarized below.

Benzeneseleninic Wave Numbers anhydride (cm-1)

PhSe 687 vs

vas SeOSe 590 vs v SeOSe 557 m s

= valency vibrations

vs = very strong,

m = medium

The equivalence of the two phenyl groups was shown by nuclear magnetic 11 1 resonance spectroscopy . Thus the H spectrum showed only two signals,

T1 2.167 (2H, ortho) and 2.350 (2H, meta and 1H, para), while the 13C spectrum showed only four signals due to Cl, C2 and C6, C3 and C5, and C4.

0 0 II II Ph Se 0 Se

Benzeneseleninic anhydride is a white powder melting at 164°, It is hydrolysed by moist air giving benzeneseleninic acid but this process is slow and no special precautions are needed when handling the reagent.

41.

0 0 0 H H2O PhSeOSePh 2PhSe0H

The anhydride may be recovered unchanged after prolonged heating at

1600, although some sublimation occurs. It is unaffected by solvents such as benzene, tetrahydrofuran and carbon tetrachloride at room temperature but reacts rapidly with ethanol to give the ester (4) and benzeneseleninic acid.

0 0 0 0 II II II iI PhSeOSePh + EtOH PhSeOEt + PhSeOH

(4)

The reagent is only slightly soluble in tetrahydrofuran, dimethyl- formamide and dimethylacetamide and does not dissolve in benzene, dichloromethane and diethyl ether. Consequently, the anhydride is most commonly used as a suspension, and vigorous stirring during the reaction is required.

During the course of studies on the synthesis of tetracycline carried out in this department, it became necessary to introduce a hydroxyl group into the 12a position of the derivative (5):

OH OH OH OH

COR COR HO 0 0 0 OH HO 0 0___/ 0

R=OMe or NH (5) (6) 2 42.

12 As standard methods, such as treatment with periodate ,failed,

a new hydroxylation procedure was required.

13 Rosenfeld examined the effect of benzeneseleninic anhydride on the simple phenols (7)-(9). Treatment of a solution of the phenols in dichloromethane with excess benzeneseleninic anhydride gave mixtures of ortho- and para-hydroxylated products. Thus 2,4-xylenol (7) gave the dimer of the o-hydroxydienone (10) in 40% yield and the p-hydroxydienone (11) in

15% yield. Similarly, mesitol (8) gave the o-hydroxydienone dimer (12),

(48%) and the E:hydroxydienone (13), (30%). 2,6-xylenol (9) gave

2,6-dimethylbenzoquinone (14), (25%), 3,3',5,5'-tetramethylbiphenoquinone

(15) (40%) and a trace of the o-hydroxydienone dimer (16).

OH (7) (10) (11)

OH + 0 OH (8) (12) (13) OH

(9) 0 (14) (16)

(15) 43.

However, when the phenols were first converted to the phenolate

anions (using sodium hydride), hydroxylation occurred specifically in the

ortho-position and only traces of a-isomer could be detected. Thus,

2,4-xylenol, (7) gave compound (10) in 45% yield, mesitol (8) gave compound

(12), (55%) and 2,6-xylenol (9), gave compound (16) in 44% yield.

Reaction of benzeneseleninic anhydride with the monoanions of the

tetracycline ring-A model compounds (17) gave the o-hydroxydienones (18)

in high yield.

OH A OH OH

COR COR COR HO OH 0 R=NH (68%) (17) 2 (18) (19) R=OMe (75%) The hydroxylated products (18) were sufficiently acidic to be

extracted into aqueous sodium bicarbonate solution, and subsequent acidi-

fication afforded the hydroxydienones, free from the quinones (19) and

other impurities. However, treatment of the tetracyclic derivative (5)

failed to yield the desired product (6) and a complex mixture of

products was obtained.

Hydroxylation of phenolate anions appeared therefore to exhibit much

greater ortho-selectivity than did the reaction with free phenols. In

the hope that increased yields of o-hydroxylated products might result,

the effect of generating the anions using a different base was examined.

When 2,4-xylenol (7) was treated first with sodium hexamethyldisilazide

and subsequently with benzeneseleninic anhydride a dark red compound was

rapidly produced. This material was isolated by chromatography and shown

to be the phenylselenoiminoquinone ((20), selenoimine).

44.

OH 0 Na N SePh NaN(SiMe3)2

(7) (20)

The first examples of this class of compound, (21) and (22), were 14 15 recently prepared ' by the reaction of selenenyl and seleninyl halides with 1,1-di-ptolylmethenimine in the presence of triethylamine.

O C=--N H + PhSe(0)C1 C=N-Se(0)„Ph 2 2

(21) n=0

(22) n=1

The selenoimines obtained by Rosenfeld show similar spectral features to the sulphur analogues (23) which result from the reaction of triben- 16 zenesulphenamide with phenols .

OH N SPh + (Ph S)3N

(23)

Benzeneseleninic anhydride has also been used for the oxidation of primary amines to carbonyl compounds17. Thus 2-adamantylamine was converted quantitatively to adamant-2-one and 1-phenylbenzylamine gave benzophenone in 97% yield.

45.

NH2 0

100%

Ph Ph ›.-NH2 XO Ph Ph

97%

When the procedure was applied to amines which could form enamines however, only unrecognisable products were isolated.

Treatment of ketone hydrazones, oximes and semicarbazones with benzeneseleninic anhydride affords the parent carbonyl compounds in good yield.18 Some examples are shown below. Significantly, cholesta-1,4- dienone was smoothly regenerated from the 27nitrophenylhydrazone derivative, a transformation which could not be achieved using standard reagents.

Ph. 11/Ph Derivative 0

Phenyl Hydrazone 90 57

Oxime 89 96

Semicarbazone 89 85

1\1-N H 86%

46.

The 1,3-dithiolane and 1,3-dithiane protecting groups may be removed from aldehydes and ketones by treatment with benzeneseleninic anhydride at room temperature19. In the case of the tetracyclic carbinol (24), the carbonyl compound was formed in 78% yield; all the standard methods tried failed to achieve this conversion.

OH OH

(24)

In other examples, the method is comparable or exceeds the literature procedures. 47.

REFERENCES

1. D.H.R. Barton, P.D. Magnus, and M.N. Rosenfeld, J.C.S. Chem. Comm., 1975, 301.

2. D.H.R. Barton, P.D. Magnus,S.V. Ley, and M.N. Rosenfeld, J.C.S. Perkin I, 1977, 567.

3. H.W. Doughty, Amer. Chem. J., 1909, 41, 326. (Chem. Abs., 1909, 3, 1749.)

4. G. Ayrey, D. Barnard) and D.T. Woodbridge, J. Chem. Soc., 1962, 2089.

5. H.J. Reich, J.M. Renga, and I.L. Reich, J. Amer. Chem. Soc., 1975, 97, 5434.

6. M. Stoecker and K. Krafft, Ber., 1906, 39, 2197.

7. E. Rebane, Acta. Chem. Scand., 1970, 24, 717.

8. L.B. AgenUs, Acta. Chem. Scand., 1968, 22, 1763.

9. H. Bredereck, A. Wagner, H. Beck, and R.-J. Klein, Chem. Ber., 1960, 93, 2736.

10. R. Paetzold, S. Borek, and E. Wolfram, Z. Anorg. Chem., 1967, 353, 53. R. Paetzold, A. Chem., 1964, 321.

11. M.N. Rosenfeld, Ph.D. Thesis, London, 1976, 46.

12. E. Adler, L. Junghahn, U. Lindberg, B. Berggren, and G. Westin, Acta. Chem, Scand,, 1960, 14, 1261.

13. M.N. Rosenfeld, Ph.D. Thesis, London, 1976, 48.

14. F.A. Davis and E.W. Kluger, J. Amer. Chem. Soc., 1976, 98, 302. 48.

15. C.O. Meese, W. Walter, and H. Schmidt, Tetrahedron Letters, 1976, 3133. C.O. Meese, W. Walter, and H-W. Muller, Tetrahedron Letters, 1977, 19.

16. D.H.R. Barton, I.A. Blair, P.D. Magnus, and R.K. Norris, J.C.S. Perkin I, 1973, 1031.

17. M.R. Czarny, J.C.S. Chem. Comm., 1976, 81. idem, Syn. Comm., 1976, 6, 285.

18. D.H.R. Barton, D.J. Lester, and S.V. Ley, J.C.S. Chem. Comm., 1977, 445.

19. D.H.R. Barton, N.J. Cussans, and S.V. Ley, J.C.S. Chem. Comm., in press. 49.

RESULTS AND DISCUSSION

1. Hydroxylation of Phenols with Benzeneseleninic Anhydride

1 Earlier results indicated that treatment of phenolate anions with

benzeneseleninic anhydride afforded ortho-hydroxydienones in high yield,

with only traces of the para-isomers detectable. Further study of these

reactions, however, has shown that, in some cases, the selectivity is less

general than was at first recognised.

Thus, treatment of 2,4-xylenol with sodium hydride in tetrahydrofuran

followed by addition of one equivalent of benzeneseleninic anhydride gave

the p:hydroxydienone (1) as the major product (31%), identified by comparison 2 with an authentic sample . No o-hydroxydienone dimer (2) could be detected,

but at least three other products were formed in low yield, and 34% of the starting material was recovered.

OH 0 Na OH

NaH

(1) (2)

When the reaction was performed using three equivalents of the anhydride only 21% of 2,4-xylenol was recovered and the major product was again the para-'isomer (1), (34%), with no o-hydroxylation being observed.

50.

Increasing the reaction time from two to twelve hours did not significantly affect the result, and the same product distribution was obtained when the reaction was carried out in glyme or benzene.

Reaction of 2,4-xylenol, without prior formation of the phenolate, with the anhydride gave the same products in similar yields. It therefore appears that use of the phenolate az substrate was without advantage.

An authentic sample of the o-hydroxydienone dimer (2) was prepared by the periodate oxidation of 2,4-xyleno13.

OH OH

10 - 4

(2)

This compound exhibited characteristic peaks in the n.m.r, spectrum at T: 8.3 (3H, s), 8.6 (6H, s) and 8.7 (3H, s) which were clearly not present in the spectra of the crude products from the reaction of 2,4- xylenol with benzeneseleninic anhydride.

When the sodium salt of 2,6-xylenol was treated with one equivalent of the anhydride in tetrahydrofuran, the o-hydroxydienone dimer (3) was isolated as an oil in 15% yield. Although a crystalline sample could not be obtained, the spectral data were in good agreement with those previously 4 reported , Other products isolated included 2,6-dimethylbenzoquinone (5%) and 3,3',5,5'-tetramethylbiphenoquinone (4), (8%); 50% of the starting material was also recovered.

51.

•-• 4- 0 Na OH

(3 ) 0 (4)

Attempts to increase the yield of the hydroxylation product either by using three equivalents of oxidant or by heating the reaction mixture merely increased the amount of quinone formed. Once again, essentially the same result was obtained using the free phenol as substrate.

Oxidation of the sodium salt of mesitol with three equivalents of the anhydride in tetrahydrofuran gave predominantly the 2.-hydroxydienone (5),

(48%) together with 17% of recovered starting material. A further product

(17%) melting at 111-112°, which gave T: 0.2 (1H, s), 2.5 (2H, s) and 7.7

(6H, s) in the n.m.r. spectrum, appeared to be the aldehyde (6) (lit.5 m.p.

113.5 - 1140 ). This conclusion was supported by mass spectral and infrared spectroscopic data (141- = 150, 3600 (br) and 1702 cm-1). vmax.

- 0 Na OH

Ph Se 2 203

OH HO

(5) (6)

52.

There is some precedent for this observation, since benzeneseleninic anhydride also oxidises the side chain methyl group of the xylenes in 6 boiling chlorobenzene.

CHO

When the monosodium salt of the tetracycline ring-A model ester (7) was similarly treated with one equivalent of benzenseleninic anhydride the o-hydroxydienone (8) was obtained in 42% yield after chromatography. The major byproduct was the quinone (9), (25%). Rosenfeld7 claimed that chromatography was unnecessary since the pure hydroxydienone could be extracted with aqueous sodium bicarbonate solution; however, it was found that appreciable amounts of quinone (9) and benzeneseleninic acid were also extracted.

1)NaH OH 2)Fh2se2o3 OH

CO Me -71/`CO Me CO Me 2 HO 2 2 OH 0

(7) (8) (9)

7 Use of one third of an equivalent of the anhydride reagent, reported to give complete reaction, gave only 20% of the hydroxydienone.

The most plausible mechanism for the reaction of the phenolate with benzeneseleninic anhydride is shown below. Initial nucleophilic attack by the phenolic oxygen at the selenium atom of the reagent is followed by a sigmatropic shift and subsequent cleavage of the Se-0 bond by, for 53.

example, water or benzeneseleninate anion.

OH OH

C 0 Me CO e 2 0 2M 0) %1,‘,0 PhSel- Ph Nu Ph Se-0 Se(0)Ph (8)

If the anion is instead formed on the 3-hydroxyl substituent then the quinone may arise as follows:

0 Me CO2Me OH 2 0 (9) H OSePh step 1 0

C 02Me step 2/ 0 H

Ph (10) 0= Se5 OSePh Ph Se° OSePh \ -'41 0 OH 0 1)step 1 2)step 2' CO2Me CO Me CO2Me 2 OH OH OH

Although pathway (a) involves less steps there would be a strong driving force for rearomatisation of intermediate (10) so path (b) cannot be discounted.

The initial step in these proposed mechanisms would be 54. expected to be strongly influenced by the nature of the substituents ortho- to the phenolate anion. When a mixture of mesitol and the more hindered 2,6-di-t-butyl-4-methyl phenol was treated with one equivalent of benzeneseleninic anhydride at room temperature in tetrahydrofuran, recovery of unreacted starting material after twenty minutes ohowed that

50% of the mesitol had been consumed compared with 5% of the 2,6-di-t- buty1-4-methylphenol. This result suggests that mesitol reacted approximately ten times faster than the more hindered phenol. By comparison, treatment of the same mixture of phenols with benzoyl chloride and pyridine followed by recovery of the unreacted starting materials. showed that mesitol was consumed approximately fifteen times as fast as the 2,6-di-t-butyl-

4-methyl phenol.

Reactivity

OH OH Ph Se 10 : 1 2 203

PhCOC1/py 15 : 1

The reaction between benzeneseleninic anhydride and 2,6-di-t-butyl-

4-methyl phenol at room temperature gave a red oil as major product (11%).

N.m.r. spectroscopy showed peaks at T: 3.40 (1H, br.s.), 3.85 (1H, br.s.),

7.86 (3H, s) and 8.74 (9H, s) which are in good agreement with the reported 8 8 data for the quinone (11), (lit. T: 3.37, 3.82, 7.84, and 8.74).

However, the sample could not be purified for further characterisation.

No hydroxydienones could be isolated from the reaction mixture. 55.

Loss of a t-butyl group suggests that the reaction might proceed

via a radical mechanism.

Attempts to prepare o-hydroxydienones by the reaction of benzene-

seleninic anhydride with thymol (12) or carvacrol (13) failed. The reactions Un were complex, giving a number ofkidentifiable products.

(12) (13)

2. Conversion of Phenols to Quinones

Consideration of the proposed mechanism for formation of the quinone

(9) from the tetracycline ring A model ester (7) suggested that treatment

of unblocked phenols with excess benzeneseleninic anhydride might provide

a general route to o-quinones, given suitable conditions.

When -naphthol was treated with three equivalents of the anhydride

at room temperature a slow reaction took place to yield o-naphthoquinone

(35%) and 1-phenylseleno-2-naphthol (14), (23%). 56.

(14)

On stirring the selenated naphthol (14) with the anhydride at room temperature no reaction was observed. However, on warming the

mixture to 50° the quinone was formed in 85% yield. Accordingly when oxidation of the naphthol was carried out at 50° no byproduct (14) was observed and the quinone was formed in 63% yield.

The phenylseleno-naphthol (14) is probably formed by reaction of the free phenol with an electrophilic phenylselenating agent. It is

possible that the seleninyl-selenenate (15), formed by attack of benzeneseleninate anion on intermediate (16), or others, is capable of being the selenating species. 0 c0-5e-Ph PhSe 0') OrSe Ph 0 0 0 + Pi-de OSePh

(16) (15) 0 fr Ph Se0 SePh

,rb H

(14 ) 57.

Alternatively the free naphthol may be phenylselenated directly

by reaction with species such as intermediate (16).

It has been suggested that compound (15) may be an intermediate formed 9 during the ozonolysis of diphenyldiselenide , but to date it has not been isolated. Evidence for the existence of compound (15) has been obtained

by the reaction of the lithium salt of benzeneseleninic acid with benzeneselenenyl chloride in tetrahydrofuran at 0°. The orange colour of the halide disappeared to leave a pale yellow solution. No major product could be isolated but treatment of the reaction mixture with 0-naphthol gave the

1-phenylseleno-derivative in 62% yield.

0 - ti 1 0-naphthol Li + PhSeC1 [PhSe0SePhj PhSe02

(15) (14)

Also, treatment of diphenyldiselenide with two equivalents of m- chloroperbenzoic acid (mCPBA) gave a similar pale yellow solution which gave compound (14) in 32% yield, on treatment with a-naphthol. SePh 0 OH PhSeSePh 222EL, [PhSe0SePh) 0-naphthol

(15) (14)

However, the possibility that the same transformation could be achieved by an intermediate such as

0 II PhSeSePh

0 cannot be discounted. 58.

Isolation of the ~-naphthoquinone from the reaction mixtures involved initial dilution with chloroform followed by rapid washing with aqueous sodium bicarbonate solution to remove benzeneseleninic acid. Finally, passage through a short silica gel column removed diphenyldiselenide

(eluting with petrol) and the quinone was eluted with chloroform/petrol.

10 In this manner, several phenols were converted to ~-quinones in good yield.

Phenol Quinone Yield (%)

rQCr0H o 63

OH (12)

OH 60 (17)

OH o

68 59.

As l,2-thymoquinone (17) was not previously reported in the literature it was fully characterised by spectroscopy and microanalytical data.

Mechanistic considerations suggested that a likely intermediate in the conversion of phenols to quinones might be compound (18) which could subsequently undergo nucleophilic attack by benzeneseleninate anion to give quinone. r-02SePh ,H OH -SePh

(18)

It was hoped that in the absence of benzeneseleninate anion this intermediate would be sufficiently stable to permit isolation. However, the room temperature reaction of 2,4-di-t-butylphenol with benzeneseleninyl chloride, where the only nucleophile present would be chloride ion, gave none of the expected product (18). The quinone (22%) and unreacted starting material (54%) were the only identifiable components of the reaction mixture.

SePh OH OSePh OH 0 OSePh 0 Ph SeCl

(18)

22%

60.

In an attempt to trap intermediate (18) the phenolate anion was

treated with benzeneseleninyl chloride at -78°, allowed to warm to room

temperature and mixed with excess benzene thiol, (a soft nucleophile), in

the hope that attack on selenium would occur to give catechol-type products.

0 Ph 0— 05e Ph OH sie OH 0 11 PhSeC1 RT "0 S/111Ph

-78°

(18)

However, no catechol could be isolated after hydrolytic work-up.

Attempts to trap intermediate (18) in a similar way using lithium cyanide

were also unsuccessful, possibly due to solubility problems.

Although quinone formation was known to be slow at room temperature

it was hoped that the reaction of 2,4-di-t-butylphenol with benzeneseleni-

nic anhydride at room temperature would afford compound (18). Reaction at

the other ortho-position was thought to be unlikely due to steric factors.

Unfortunately, the reaction gave a mixture of unidentifiable products and

intermediate (18) could not be detected.

When the reaction was carried out in the presence of either lithium cyanide or benzenethiol no catechol-type products were formed at room temperature, whilst at 50°, the quinone was formed as normal, the added nucleophiles apparently having no effect.

OH OH OH O Se Ph Ph2Se203 >

(18) 61.

A further attempt to prepare intermediate (18) by the reaction of the monoanion of 3,5-di-t-butylcatechol (formed using sodium hydride) with benzeneselenenyl chloride gave 3,5-di-t-butyl-o-benzoquinone as the only identifiable product (38%). This may have been formed by attack of the unreacted phenolate anion on the intermediate (18) as shown. r- OAr 1H OH OH OH /-4 0 PhSeCl

(18) To counter this possibility, the reaction was repeated using the free catechol in the presence of excess pyridine. However, the quinone was formed in even higher yield (78%) and no intermediate (18) could be detected.

It seemed likely that the proposed intermediate (18) could act as a phenylselenating agent towards unreacted phenol. When 2,4-di--t-butylphenol was stirred for two hours with one equivalent of benzeneseleninic anhydride and the resulting solution treated with -naphthol, 1-phenylseleno-

2-naphthol (14) was isolated in 18% yield. No di-t-butylcatechol was detected however,

OH OH SePh 0- SePh OH

(18) (14)

62.

When, instead of treating with 0-naphthol, the reaction mixture

was concentrated and reductively acetylated with zinc, acetic anhydride,

acetic acid and pyridine, no catechol diacetate (19) was obtained although

this would have been expected if intermediate (18) had been present.

OH OAc OSePh OAc Zn/HOAc Ac20/ py

(18) (19)

In conclusion, it appears that although quinone formation almost

certainly occurs via the proposed intermediate (18), this species is too

unstable to be isolated or trapped under the conditions employed.

The major advantage offered by this new method of oxidation is the high degree of o--selectivity of quinone formation. In cases where

2.-quinone formation was possible, e.g. a-naphthol, only ca 10% was detectable and only traces of para-products were observed in the oxidations of thymol (12) and carvacrol (13). No other methods are able to convert

phenols to o-quinones with this selectivity.

However, there are limitations; when the simple phenols (20)-(25) were similarly treated with the anhydride, complex mixtures of products were obtained and no o-quinones could be isolated.

OH OH OH OH NO2

(20) (21) (22) (23)

63.

OH OH OH PhSe

OH HO OH

(24) (25) (26) (27)

Presumably, the quinones are formed but further oxidation takes place. Use of less anhydride or lower reaction temperatures failed to give any o-quinones.

With 4-t-butylphenol (26), benzeneseleninic anhydride gave a mixture of products from which the dark purple phenylselenated quinone (27) could be isolated in 4% yield. The structure of this compound was eluci- _ 7 dated by Rosenreld . Another member of this class of quinone was compound

(28), formed when 3-naphthol was stirred with the anhydride for twenty four hours, again in low yield.

OH Ph2Se,

SePh

(28)

The phenylselenoquinones appear to be produced after initial o-quinone formation. Possible mechanisms for this reaction are summarised below.

64.

Path (A)

Ph Se— SePh SePh

Path (B)

Path (A) involves Michael addition of phenylselenolate anion to the quinone followed by oxidation and path (B) involves attack by the quinone at an electrophilic Se atom. Since the presence of such electrophilic species had already been indicated, path (B) therefore appeared more likely. In an attempt to prepare the phenylselenoquinone (28) by this type of process,• 1,2-naphthoquinone was treated with several phenylselenating agents, as shown in the Table.

In all cases, the phenylselenating agent was present in five-fold excess. Little useful information was gained from these results. 65.

Quinone Selenating agent Yield of (28)

PhSeSePh, 24h, RT 0

0 Li0 SePh + PhSeCl, 24h, RT 4% 2 (PhSe)2 + 2mCPBA, 24h, RT 0

Ph S 24h, RT 2 e203' 3%

3. Conversion of Catechols and Quinols to Quinones

Benzeneseleninic anhydride was also used to smoothly convert many catechols to o-quinones and quinols to p-quinones. Thus, treatment of

3,5-di-t-butylcatechol with one equivalent of the anhydride at room temperature in tetrahydrofuran gave the quinone (29) in 88% yield.

OH OJ 0 - Se Ph

(29) (30)

The mechanism probably involves attack by the phenolic oxygen at the selenium atom of the oxidant to give intermediate (30), which breaks down to give quinone as shown.

Although catechol gave a rapid reaction, no identifiable products could be isolated, even at lower temperatures (0°).

Treatment of 2,6-dimethylhydroquinone with one equivalent of benzeneseleninic anhydride at room temperature gave the p-quinone (31) in 88% 66.

yield. Hydroquinone and 1,4-dihydroxynaphthalene were also converted to the £-quinones (32) and (33) in high yield.

Quinol Product Yield (%)

OH o (31)

OH 0 0 84 OH o (32)

OH o

o (33)

This new method of converting catechols and quinols to quinones is 11 very mild and compares favourably with other procedures .

4. Formation of Selenoimines

Rosenfeld had reported 7 that reaction of benzeneseleninic anhydride with 2,4-xylenol and either the sodium or lithium salt of hexamethyldisilazane gave the selenoimine (34) in 91% yield.

67.

OH N Se Ph 1)MN(SiMe ) 3 2 2)Ph Se 0 2 2 3

(34)

M = Na or Li

This interesting discovery prompted further investigations. When the experiment was repeated using sodium hexamethyldisilazide only a 38% yield of the selenoimine (34) was obtained. However, use of hexamethyldisilazane instead of the salt gave the selenoimine in 61% yield, in an equally rapid reaction.

The reaction conditions were varied to optimise the yield although little improvement could be made. Thus at lower temperatures the reaction was slower but the yield of selenoimine remained constant. Below -10°C no reaction occurred. The reaction was equally fast in all solvents employed, e.g. benzene, tetrahydrofuran and glyme. Different proportions of the reagents were used and the results are summarised in the Table.

2,4-xylenol HN(SiMe3) Ph Se 0 Yield (34) 2 2 2 3

1 equivalent 1.1 equivalents 0.3 equivalents 23%

II tt II 1 1.1 1.0 61%

1 t, 1.1 11 2.0 it 64%

1 I, 2.1 II 1.0 I/ 64%

1 it 2.1 It 2.0 II 70%

It is clear that little advantage may be gained by use of excess reagents. Neither performing the reaction under nitrogen nor passing 68.

oxygen through the reaction mixture affected the results. Also the reaction gave a similar result when carried out with the strict exclusion of laboratory light.

A number of other phenols ~-'lere converted to selenoirnines in compa- 12 rable yields (Table)

Phenol Selenoimine Yield (%)

OH o NSePh 64

(34) OH o NsePh I . 45 © Cr~ (35)

OH o

58 NSePh

(36)

NSePh 56 OH

(37)

The selenoimines were characterised spectroscopically and gave satisfactory microanalytical data. These new compounds are dark red 69.

250-275 and 460-490 nm in the and show distinctive absorptions at Xmax. ultraviolet spectrum. The carbonyl group resonates at a surprisingly low frequency in the infrared spectrum. Thus selenoimine (34) absorbs at 1605 cm-1 and it appears likely that there is a significant contribution from the cyclic selenoxazoline structure (38).

(38)

13 In accordance with this, X-ray crystallography showed that the selenoimine group adopts a syn-conformation (39) with the Se...0 distance only 45% greater than that of a formal Se-0 bond. The data are summarised overleaf.

/Ph Ph / Se S N.

(39) (40)

This finding is in direct agreement with the analogous thioimine case where the syn-conformation is again adopted.

It was hoped that the selenoimine might be induced to flip to the anti-conformation by the action of heat. However, on cooling a melt of selenoimine (34), the resulting crystals did not appear to have X-RAY STRUCTURAL STUDY OF SELENOIMINE (34)

Bond Lengths (R)

Se...0 2.575 Se--N 1.805 Se--C 1.924 N=C 1.308 C==0 1.240 71.

undergone any change in properties.

The selenoimines were further characterised by conversion to the aromatic N,0-diacetates by reduction with zinc, acetic anhydride, acetic acid and pyridine. As the diacltates of 2-aminothymol and 2-aminocarvacrol were previously unreported in the literature, authentic samples were prepared by nitration and subsequent acetylation.

OH OAc

NHAc

NO2

OH NHAc

OH OAc 72.

The ease with which selenoimines are reductively acetylated suggested that it might be possible to convert them to aminophenols, thus achieving a mild, two-step ortho-amination procedure for phenols. Treatment of selenoimine (34) with five equivalents of benzenethiol in benzene gave

85% of the crude aminophenol, isolated by chromatography. These products are unstable to air and decompose rapidly during work-up. Use of thioglycollic acid as reducing agent, a reagent easily removed from the reaction mixture by washing with aqueous sodium bicarbonate solution, gave the aminophenol in 40% yield. These reaction conditions were not optimised.

OH NSePh NH2 PhSH or thioglycollic acid

(34)

Hydrogen sulphide did not react with selenoimine (34).

It is apparent that, as in the case of quinone formation, selenoimine formation is extremely ortho-selective. When selenoimine (35) was prepared from phenol, only 3% of the pTisomer (41) was isolated. This 14 was converted directly to the N,0-diacetate, mpt 148-1500 (lit. 150-1510).

OH OAc Zn/Ac20 HN(SiMe3)2 (35) Ph Se 0 2 2 3 AcOH/py NSePh

(41)

73.

In all other cases, however, no ETselenoimines could be detected, although many coloured compounds were formed in trace amounts.

Treatment of 2,6-xylenol with hexamethyldisilazane and benzeneseleninic anhydride gave the p--selenoimine (42) in 48% yield.

HN(SiMe ) 3 2 Ph Se 0 2 2 3

Rosenfeld had been unable to obtain this selenoimine using the 7 sodium salt of hexamethyldisilazane , but claimed that the product was obtained in 85% yield by reaction of the cathylate (43) under the usual conditions.

NaN(SiMe3)2 Ph Se 0 2 2 3 0 OEt

0 (42) (43)

However, these results could not be reproduced and only a 28% yield of selenoimine (42) could be obtained.

When the unblocked cathylate (44) was treated with hexamethyldisilazane and benzeneseleninic anhydride the selenoimine (45) was formed in 45% yield,

74.

HN(SiMe3)2 NSePh

Ph Se 2 203 OEt

(45)

The mildness of selenoimine formation is underlined by the fact that the sensitive cathylate group remains unaffected during the reaction.

The mechanism of selenoimine formation is not clear. Since benzeneseleninic anhydride is known-to convert phenols to o-quinones, it appeared likely that this could be the first step. The reaction of quinones with sodium hexamethyldisilazide to give the silylated iminoquinones (46) 15 is known , and further reaction of these with an electrophilio phenylselenating agent would presumably give the selenoimines.

NSiMe3 NSePh NaN(SiMe3)2 PhSeX

N Si Me3 NSePh

(46)

However, several pieces of evidence suggest that this route is not followed:

(1)The formation of selenoimines occurs rapidly at room temperature whereas quinone formation is slower and often requires heating.

(2)Some simple substrates such as 2,4-xylenol and phenol, which readily give selenoimines, do not afford quinones when treated with

75.

benzeneseleninic anhydride alone. If quinones were intermediates in selenoimine formation, then very rapid trapping must occur to prevent the further oxidation that is usually observed, (see page 62).

(3) Treatment of o-quinones with hexamethyldisilazane and benzeneseleninic anhydride does not always give selenoimines. Thus 1,2-thymoquinone gave a mixture of unidentifiable products. Selenoimine (36) could not be detected.

X HN(SiMe ) 3 2 Ph Se 0 2 2 3 (36)

(4) Conversion of quinone intermediates to selenoimines should give a mixture of two isomeric compounds since attack on the quinone could occur at either of two sites.

N SePh N SePh 0

However, in the majority of cases only one selenoimine could be isolated.

When a-naphthol was treated with hexamethyldisilazane and the anhydride two selenoimines were isolated and characterisation as the

N,0-diacetates showed them to be isomers (47) and (48).

76.

OH N Se Ph HN(SiMe3)2

Ph Se 0 2 2 3

(47) (48)

7 Rosenfeld had only observed isomer (47) in this reaction. The total yield of selenoimine was 66% and the product ratio (47):(48) was 75:25.

Using 13-naphthol the same products were obtained in total yield of 61%.

Here the product ratio (47):(48) was 40:60. It appears likely that some selenoimine is formed via the quinone in this particular case, possibly

due to the high stability and ease of formation of o-naphthoquinone, but since a- and (3-naphthol do not give identical product ratios at least one other pathway must be operative. Under the same conditions o-naphtho-

quinone gave isomers (47) and (48) in total yield of 45%, in the ratio

77:23 respectively.

HN(SiMe3)2 (47) + (48) Ph2Se203

The use of other reagents to effect conversion of phenols to selenoimines has also been investigated.

Treatment of 2,4-xylenol with hexamethyldisilazane and one equivalent of benzeneselenenyl chloride gave selenoimine (34) in 40% yield.

The reaction was rapid at room temperature. Use of benzeneseleninic acid as oxidant gave a 25% yield of selenoimine.

The presence of trimethylsilyl leaving groups in the amine appears 77.

to be essential for efficient formation of selenoimines. When 2,4-xylenol

was treated with benzeneseleninic anhydride and excess liquid ammonia only

a trace of selenoimine (34) was detectable. No selenoimine was formed

using t-butylamine.

Tris-(trimethylsily1)-amine (49) was prepared by reaction of sodium

hexamethyldisilazine with trimethylsilyl chloride in the hope that this

compound would assist formation of selenoimines.

Me3SiCl + NaN(SiMe ) —411(SiMe 3 2 3)3 (49)

However, treatment of 2,6-xylenol with the anhydride and one equiv-

alent of tris-(trimethylsily1)-amine gave the selenoimine (42) in only

19% yield, The lower reactivity of the tris-substituted amine may be

attributed to the steric hindrance about the nitrogen atom and the possible

difference in basicity caused by the introduction of a third trimethyl-

silyl group.

Reaction of 2,4-xylenol with benzeneselenenylchloride and tris-

(trimethylsilyl)-amine gave a mixture of unidentifiable products. No

selenoimine could be detected. These results are summarised below.

Phenol Oxidant Amine Product Yield(%)

2,4-xylenol PhSeC1 HU (SiMe3)2 (34) 40 It PhSe0 H n n 2 25 n Se 0 n Ph2 2 3 NH3 trace tt IT tBuNH2 NONE 2,6-xylenol n N(SIMe3) 3 (42) 19 2,4-xylenol PhSeC1 I! (34) 0 78.

Since selenoimine formation had been shown not to occur via a

quinone intermediate, and hexamethyldisilazane does not react with

phenols, it appeared possible that benzeneseleninic anhydride could

react with disilazane to give a species of type (50) which would then

react with phenols to give selenoimines.

0 II SePh 0 a/ ,SiMe3 Ph — SiMe3 )2 Ph-- Se -- N \ 0 SiMe3

OSiMe 3 Ph— Se= N—SiMe3 PhSe = N (50)

However, treatment of benzeneseleninic anhydride with one equivalent

of hexamethyldisilazane in tetrahydrofuran gave no reaction after twelve

hours and the starting materials could be recovered quantitatively. When the mixture was heated at 100° in a sealed tube, a small amount of diphenyl-

diselenide was obtained, but the starting materials were recovered in

greater than 95% yield.

Other attempts to prepare potential reactive intermediates were also unsuccessful. Thus when tris-(trimethylsilyl)-amine was treated with

benzeneseleninic anhydride no reaction was observed after twelve hours.

Addition of benzeneselenenylchloride to either hexamethyldisilazane or sodium hexamethyldisilazide gave intractable mixture of products from which diphenyldiselenide could be isolated in yields of approximately

55%. Treatment of benzeneselenium trichloride with one equivalent of tris-(trimethylsilyl)-amine gave no reaction and both starting materials were recovered quantitatively.

79.

Reaction of benzeneseleninic anhydride with hexamethyldisilazane

might possibly be catalysed by the presence of the phenol. It was hoped

that a Lewis acid might exhibit a similar influence. However, when one

equivalent of boron trifluoride etherate was added to the anhydride, and the mixture treated with hexamethyldisilazane no reaction occurred.

Benzeneseleninyl chloride (51onveniently prepared by ozonolysis of 16 a solution of benzeneselenenyl chloride in carbon tetrachloride , would

be expected to behave similarly to benzeneseleninic anhydride towards nucleo-

philes. Attention was therefore turned to this reagent.

0 03 PhSeC1 -0-PhSeC1 (51)

Treatment of 2,4-xylenol with one equivalent of benzeneselenenyl chloride and hexamethyldisilazane gave selenoimine (34) in 18% yield.

OH 0 11 PhSeCl

HN(SiMe3)2

(34)

In an attempt to prepare the proposed reactive intermediate (50), benzeneseleninyl chloride was treated at 0° under N2 with one equivalent of lithium hexamethyldisilazide in THF. A white precipitate of lithium chloride was formed but attempted work-up of the mixture either by chromatography or crystallisation gave diphenyldiselenide (68%) as the only identifiable product.

0 it PhSeCl + LiN(SiMe ) -----s(PhSe) + LiCl 3 2 2

so.

The same reaction was performed in the presence of 2,6-di--t-butyl-

phenol which, it was hoped, would be a good trap for PhSeN, but the major

product was the biphenoquinone (52), (24%).

OH 0 II PhSeC1 LiN(SiNe3) + 2

(52)

The same product was obtained in 39% yield on treatment of 2,6-di- t-butylphenol with hexamethyldisilazane and benzeneseleninic anhydride and no selenoimine was observed. Formation of this type of product suggests that a radical mechanism is operative.

When benzeneseleninyl chloride was treated with excess liquid ammonia a white precipitate of ammonium chloride was rapidly produced. Fil- tration and evaporation of unreacted ammonia gave a clear, pale yellow solution which decomposed to a red oil on concentration. Attempts to isolate a major component from the yellow solution by crystallisation failed.

When the clear yellow solution was treated with 2,4-xylenol the selenoimine (34) was formed in 4% yield. With 8-naphthol the solution gave selenoimine (48) in 5% yield, free from positional isomer (47).

z 2,4-xylenol NH3 ---* intermediate Ph SeCI 0 \1-naphthole

(48), 5% 81.

This suggests that a small amount of a reactive intermediate may be formed from ammonia and benzeneseleninyl chloride and that this gives selenoimine (48) via a pathway which does not involve a quinone as intermediate.

These results are summarised in the Table below.

Reaction Product o 100 no reaction observed HN(SiMe3)2 + Ph2Se2'

II N(SiMe3)3 + Ph2Se203 RT (PhSe) ca 55% HN(SiMe3)2 + PhSeC1 RT 9 NaN(SiMe ) + PhSeC1 RT (PhSe)n ca 55% 3 2 L. N ( SiMe ) + PhSeC1 no reaction observed 3 3 3 RT HN(SiMe)+ PhSe0/BFRT II 32 2233 0 2,4-xylenol + HN(SiMe3)2 + PhSeC1 (34) 18%

-.0 LiN(SiMe)+ PhSe -..-% (PhSe)68% LiCl 32 N\ 2 Cl OH

+ PhSe(0)C1 + (52), 2L% LiN(SiMe3)2

HN(SIMe) ) + Ph2Se203 + 0 (52), 39% 3 2

NH + PhSe(0)C1 NH C1 3 4

NH3 + PhSe(0)C1 + 2,4-xylenol (34), 4% 11 + 8-naphthol (48), 5%

5, Mechanism of Selenoimine Formation

The high degree of o-selectivity observed during selenoimine formation suggests that the mechanism involves initial reaction of the phenolic

82.

oxygen with some species in the reaction mixture to give an intermediate

which is capable of delivering functionality into the ortho-position. A sequence of this kind was postulated above to account for the region specificity of quinone formation. Generation of the phenolate anion using sodium hexamethyldisilazide would be expected to increase the rate of the first step and thus improve the yield of selenoimine since undesirable side- reactions would be disfavoured. However, this was not found to be the case.

It must therefore be concluded that the first step is fast compared with subsequent steps and that increasing the electron-density on the phenolic oxygen does not affect the overall reaction. The most probable mechanism is shown below.

0 ,4 PhSelOX (Me3S0 NH Ph 2 t t0H Se ,SePh .0H 0' \`'l 1:Y \ 0— S Me3 (a) (a) , SiMe3 (a)

Ph Ph Se(0)-0X (Se SePh 0/ \\ OH f)(N-SiMe3 01 NSiMe3 ,SePh (a) , H _A„ S iMe3 (b)

( 5 3)

Ph (IS% 0 0 OSePh NSePh NSePh SiMe3 ,_N SePh

SiMe3 83.

0 SePh

(18a)

This type of pathway is analogous to that postulated by Corey and

Schaefer7 to explain the behaviour of selenium dioxide towards ketones.

The intermediate (53) need not be formed; instead sequence (b) could operate first to give intermediate (18a) which is then converted to selenoimine via sequence (a).

An alternative proposal is that the benzeneseleninic anhydride reacts on carbon instead of oxygen as shown below:

LO I-1 SePh ..7 > H.N(SiMe3)2 (54)

o CSePh N SiMe3 N Se Ph t N-SiMe3 ■..A Ph Se X SiMe 3 (55) 84.

18 (Sharpless has suggested that intermediates of type (54) arc involved in selenium dioxide oxidations). The regioselectivity is explained by assuming a weak associative interaction between the phenolic oxygen and the benzeneseleninic anhydride causing o-reaction to predominate. The final step involves attack of an electrophilic phenylselenating agent on the silylimine (55).

6. Redox Titration Study of Benzeneseleninic Anhydride Oxidations

The course of the reactions of benzeneseleninic anhydride with phenols to give, under varying conditions, hydroxydienones, quinones and selenoimines may be followed qualitatively by monitoring the disappearance of phenol by t.l.c. However, a quantitative study of the relative reaction rates of these three processes, which should provide valuable mechanistic evidence, was complicated by several factors. Whilst quinones (414 nm) and selenoimines (ca. 440 nm) have characteristic absorptions in the ultraviolet spectrum, the principal absorption maxima of the hydroxydienones 225, 270, and 315 nm) are masked by other (Amax: components of the reaction mixture. A similar argument may be constructed against the use of infrared spectroscopy, and an n.m.r. study would be uninformative. Furthermore, since the benzeneseleninic anhydride is used as a suspension, spectroscopic examination of the reaction mixture would require considerable manipulation and significant errors could result.

An attractive solution would be to observe the disappearance of oxidant by a redox titration method. It seemed likely that iodide ion should be oxidised by benzeneseleninic anhydride and other species which were possibly present in the reaction mixture, according to the equations below.

85.

— I + 2e Iodide 21 2

+ Benzeneseleninic Ph Se 0 + 611 + 6e r (PhSe)2 + 3H 0 2 2 3 2 anhydride

ie Ph2Se203 31 2

+ 2PhSe0 H + 6H + 6e ------4 (PhSe) + 4H 0 Benzeneseleninic 2 2 2 acid

ie PhSe0 H ER 3/2 1 2 2

+ Benzeneselenenic 2PhSe0H + 2H + 2e > (PhSe) + 2H 0 2 2 acid

ie PhSe0Ha--:- 1/2 1 2

0 + Reactive PhSeOSePh + 4H + 4e_ (PhSe)2 + 2H 0 2 intermediate

ie PhSe0 SePh 2 1 2 2

Thus, as the oxidation proceeds, the ability of the reaction mixture to oxidise iodide ion to iodine should decrease and this would be reflected in the titration results.

It was first necessary to show that benzeneseleninic anhydride would liberate three equivalents of iodine. Early experiments were unable to do this due to the low solubility of the anhydride, but when the reagent was warmed in dilute sulphuric acid and excess acidic potassium iodide solution was added, titration with N/10 aqueous sodium thiosulphate using starch as indicator showed that 2.98 equivalents of iodine had been liberated.

When the oxidising ability of a complete reaction mixture was to be determined it was found advantageous to quench with sulphuric acid as 86.

before but to subsequently extract the aqueous layer with ether to remove diphenyldiselenide and other organic components. The resulting extract would not oxidise iodide, and treatment of the aqueous phase with potassium iodide and titration with sodium thiosulphate then gave the oxidising ability of the reaction mixture. More consistent results were obtained when the titration was performed in the presence of ethanol (ca.

20% by volume) as this helped to solubilise the liberated iodine. The error due to aerial oxidation of the iodide was estimated to be ca 1% and not significant. The oxidation of several phenols was studied and in some cases the diphenyldiselenide produced was also recovered in order to determine whether the loss in oxidising ability was equal to the per- centage formation of diselenide. The titration data are shown in the

Table, and have been plotted as a function of time (graphs).

Titration Results

Reaction Time(min) Titre (ml) Oxidising Ability (%)

1. 2,4-xylenolate 0 14.9 99 + Ph S RT 5 2 e203' 12.7 85 20 11.5 78 120 10.2 68

2. 2,4-xylenolate 0 14.9 99 o + Ph Se 0 0 2 2 3' 120 13.2 88 overnight 12.0 80

3. 2,4-xylenol 0 14.9 99 + Ph S RT 2 e203' 5 13.8 92 120 13.2 88 120 8.6 58 87.

Titration Results/continued

Reaction Time(min) Titre(m1) Oxidising Ability (%)

. Mesitolate + 0 14.9 99 Ph S RT 2 e203' 20 13.1 88 60 12.5 83 120 12.3 82

5, 2,6-di-t-butyl- 0 14.9 99 4-methylphenolate 20 14.2 95 + Ph S RT 60 12.6 84 2 e203' 120 12.2 81

6. 2,4-xylenol + 0 14.9 99 Ph Se 0 + 75 2 2 3 5 11.2 HN(SiMe3)2, 41 RT 20 6.1 120 2.1 19

7. 2,4-xylenol 0 14.9 99 + Ph Se 0 13.2 88 2 2 3 + 120 HN(SiMe3)2, 00 overnight 12.1 81

8. Cathylate (43) 0 14.9 99 54 + Ph2Se203 + 120 8.1 HN(SiMe3)2' RT

. 2,4-di-t-butylphenol 0 14.9 99 + Ph Se 0 5 13.8 92 2 2 3' RT 20 12.3 82 120 10.4 69

10, 2,4-di-t-butylphenol 0 13.5 90 + Ph Se 0 6.9 46 2 2 3 5 A, 50° 20 6.8 45 120 4.8 32 88.

Diphenyldiselenide Recovery

Reaction Work-up Time(min) Yield PhSeSePh (%)

la Acidic 0 0 5 10 20 12 120 13

lb Phosphate 0 0 Buffer 5 15 20 25 120 27

10 Normal 0 0 5 31 20 59 120 72

6 Normal 0 0 5 24 20 47 120 55 89.

PLOTS OF TITRATION DATA OBTAINED FOR REACTIONS (1) - (10)

1. Hydroxylation conditions

100

O\0 TY ILI

B 50 . A NG ISI ID OX

0 10 20 30 60 120 TIME (mins)

2. Selenoimine and Quinone forming conditions

100

0\0 80

60 50

40 IDISING ABILITY

OX 30

10 20 30 60 120

TIME (mins) 90.

3. Diphenqldiselenide recovery

100

80 --, .,0\° 70 60 o w ri4 50 40

30 EU 20 10

0 10 20 30 60 120

TIME (mins) 91.

The reaction of 2,4-xylenolate anion with benzeneseleninic

anhydride at room te,Aperature appeared to be complete after about forty

minutes, by which time the oxidising ability of the reaction mixture had

dropped to 65%. When the reaction was performed at 0° the rate was very

slow and the oxidising ability had only dropped to 80% even after stirring

overnight. Reaction of the free phenol gave a similar titration curve which showed a decrease in oxidising ability to 58%. From these results,

it appears that there is little advantage to be gained by using the

phenolate anion as far as reaction rates are concerned.

The reaction between mesitolate anion and benzeneseleninic anhydride was slower (1 life: 9 min )than that of the less hindered xylenolate

(1 life; 6 min ) but similar to that of the anion of 2,6-di-t-buty1-4-

methyl phenol (1 life;10min). This suggests that the rate-limiting step is not significantly affected by steric factors.

The rate of formation of the selenoimine from 2,4-xylenol appeared to be slightly faster than hydroxylation (1 life: 5 min) and the oxidising ability of the reaction mixture dropped to 19%. At 0° however, the reaction was very slow and after fifteen hours the oxidising ability had only decreased to 81%. The monocathylate of 2,6-dimethylhydroquinone was treated with benzeneseleninic anhydride and hexamethyldisilazane and after two hours the oxidising ability had decreased to 54%. This is a higher value than for normal selenoimine formation because the phenol is already in a higher oxidation level. The products were a mixture of selenoimine and quinone.

Ortho-quinone formation appears to be slower than either hydroxylation or selenoimine formation. Thus the reaction of 2,4-di-t-butylphenol with benzeneseleninic anhydride in refluxing tetrahydrofuran gave t1 = 6 min -f and the oxidising ability fell to 31%. At room temperature, however,

r. 92.

the oxidising ability only decreased to 69% after two hours, although the reaction appeared to have stopped. Only a trace of quinone was found and this seems good evidence for the formation of intermediate of type

(18) (or its equivalent) as previously discussed.

OH OH OSePh

(18)

When the diphenyldiselenide was recovered from reactions where either quinones or selenoimine was formed the yield was complementary to the oxidising ability of the solution. Thus, for example, in run (6) when the oxidising ability had decreased to 19% the yield of diphenyldiselenide was 72%. However, in the hydroxylation case this result could not be obtained using an acidic work-up procedure, and the yield of diselenide was low. When the reaction mixture was quenched with potassium dihydrogenphosphate buffer solution however, the expected amount of diselenide was recovered.

It seems likely that in the first two cases the diphenyldiselenide comes from disproportionation of benzeneselenenic acid, which is formed during the reactions.

3PhSe0H (PhSe)2 + PhSe02H + H2O

In the hydroxylation reaction, it is possible that the selenenic acid is not formed and that some acid-stable, base-sensitive compound is formed. This does not then give the diselenide on acidic work-up. Inter- mediate (15) could be such a compound. 93.

0 PhSeOSePh (15)

However, when the pale yellow solution, prepared by treatment of benzeneselenenyl chloride with the lithium salt of benzeneseleninic acid in tetrahydrofuran, which is thought to contain (15) was treated with either acid or buffer solution the diselenide was recovered quantitatively.

7. Oxidation of Benzylic Alcohols with Benzeneseleninic Anhydride

In view of the interesting results obtained from the reaction of benzeneseleninic anhydride with phenols, a study of the reactions of aliphatic alcohols was undertaken.

Several benzylic alcohols were smoothly converted into ketones in high yield. The results are tabulated below.

Alcohol Equivalents of Product Yield anhydride OH

Ph I Ph 1 Ph2 C=0 85% 0 OH Ph H I Ph 1 PhCOCOPh 92% OH OH le Ph 1 1 Ph 2 770

However, the reaction between benzilic acid and the anhydride gave only 5% of the ketone, even after heating in toluene for twenty four hours.

Previously23 it had been reported that this reaction gave benzophenone in 65% yield at room temperature.

94.

HO CO2H Ph Se 0 Ph Ph 2 2 3 Ph Ph 5%

The mechanism of the oxidation of benzylic alcohols is probably as follows:

0 Ph Se (i-0 Se(0)Ph 01 iii O'Se Ph O H ,,L, ______, Ph, Ph Ph ' Ph Ph H

In contrast, cinnamyl alcohol did not react with the anhydride after stirring for twenty four hours in tetrahydrofuran, although cinnamaldehyde 6 is formed at higher temperatures

Ph Se 0 PhA/\ 0 H 2 2 3 > Ph o RT 95.

EXPERIMENTAL

Melting points were determined on a Kofler hot stage and are uncorrected. Infra-red spectra were recorded on a Unicam SP 200 or

Perkin Elmer 257 spectrophotometer. Ultra-violet spectra were recorded in ethanol, unless otherwise stated, on a Unicam SP 800 spectrophotometer.

N,m,r, spectra were recorded in acid-free deuterochloroform with tetra- methylsilane as an internal reference on a Varian EM 360 instrument. Mass spectra were recorded on an A.E.I.M.S. 9 spectrometer. Microanalyses were carried out within the Department of Imperial College.

Thin-layer chromatography, both preparative and analytical, was carried out using GF254 silica plates.

19 Solvents were purified and dried according to standard techniques.

Petrol refers to the fraction with b.p. 40-60°. Removal of solvents under reduced pressure was carried out below 40°.

The following abbreviations are used:

THE : Tetrahydrofuran

mCPBA meta-Chloroperbenzoic acid

P.l.c.: Preparative layer chromatography.

The following abbreviations apply to n.m.r. data:

singlet

d doublet

t triplet

quartet

bs broad singlet

m multiplet 96.

Benzeneseleninic Anhydride

A stirred suspension of diphenyldiselenide (10g) in water (10 ml)

at 60° was treated cautiously with concentrated nitric acid (ca. 10 ml)

in 1 ml aliquots until evolution of the oxides of nitrogen had ceased.

After cooling at 4° overnight, the white crystals of the nitric acid complex

of benzeneseleninic acid m.p. 112° were isolated by filtration, washed

with water and dried in air.

The complex was heated in vacuo at 120° for 72 h to give the anhydride (ca 90%) as a white powder m.p. 164° (lit.,9 165°).

Benzeneselenenyl Chloride

A stirred solution of diphenyldiselenide (3.14 g, 10 mmol) in hexane

(25 ml) at 100 was treated with a solution of sulphuryl chloride (1.35 g,

10 mmol) in hexane (5 ml). After 30 min, the solvent was evaporated and the orange solid was recrystallised from benzene to give benzeneselenenyl chloride (306 mg, 80%) as large orange crystals, m.p. 62-63° (lit.16 m.p.

62,-,64°).

Benzeneseleninyl Chloride

A solution of benzeneselenenyl chloride (190 mg, 1 mmol) in dry dichloromethane (3 ml) was treated with ozone, passed through a calcium sulphate drying tube at 0° until the colour had faded to a pale yellow.

Dry oxygen (15 min) followed by nitrogen (15 min) was passed through the solution to remove excess ozone. The benzeneseleninyl chloride solution 16 was used without further purification . 97.

Oxidation of Sodium 2,4-Xylenolatc with Benzeneseleninic Anhydride

A stirred solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry THF

(4 ml) was treated with sodium hydride (80% suspension in oil, 22 mg,

1.5 equiv.) and to the resulting solution was added benzeneseleninic anhydride (180 mg, 0.5 mmol). After 2 h the reaction was quenched with aqueous potassium dihydrogenphosphate buffer solution (10%, 10 ml) and extracted with chloroform (3 x 10 ml). The organic phase was dried

(anhydrous sodium sulphate) and concentrated and p.l.c. (on silica, using ether/petrol, 1:1 as eluent) gave the p-hydroxydienone (1), (20 mg, 31%) as an oil, T: 2,7-3.5 (2H, m), 3.95 (1H, d), 7.8 (1H, bs), 8.2 (3H, d), and 8,7 (3H, s), m/e 138 (Mt).

2,4-Xylenol (21 mg, 34%) was also recovered.

Oxidation of 2,4-Xylenol with Benzeneseleninic Anhydride

The previous experiment was repeated without prior formation of the xylenol sodium salt. The EThydroxydienone (1), (19 mg, 30%) was again the only identifiable product.

Hydroxydienone Dimer (2)

Prepared by the sodium periodate oxidation of 2,4-xylenol according to the method of Adler et al.3 in 19% yield (lit.3 20% yield) m.p. 236°

(lit.3 m.p. 237-238°).

Oxidation of Sodium 2,6-Xylenolate with Benzeneseleninic Anhydride

A stirred solution of 2,6-xylenol (61 mg, 0.5 mmol) in dry THF (4 ml) was treated with sodium hydride (80% suspension in oil, 23 mg, 1.5 equiv.) and to the resulting solution was added benzeneseleninic anhydride (180 mg, 98.

0,5 mmol). After 2 h the reaction was quenched with aqueous potassium

dihydrogenphosphate buffer solution (10%, 10 ml) and extracted with

chloroform (3 x 10 ml). The organic phase was dried (anhydrous sodium

sulphate) and concentrated. P.l.c. (on silica using ether/petrol, 1:1

as eluent) gave the o-hydroxydienone dimer (3) as an oil (9 mg, 15%),

T: 8.2 (3H, s), 8.7 (6H, bs), and 8.8 (3H, s), m/e 276 (M+), 2,6-dimethyl-

henzoquinone,(3mg, 5%), m,p. 71° (lit.5 m.p. 71-72°) and 3,3,5,5-tetra-

methylbiphenoquinone (5 mg, 8%), m.p. 210-213° (lit.27 m.p. 212-215°).

2,6-Xylenol (30 mg, 50%) was also recovered.

Oxidation of Sodium Mesitolate with Benzeneseleninic Anhydride

A stirred solution of mesitol (68 mg, 0.5 mmol) in dry THE (4 ml)

was treated with sodium hydride (80% suspension in oil, 20 mg, 1.25 equiv.).

To the resulting solution was added benzeneseleninic anhydride (180 mg,

0,5 mmol). After 2.5 h, the reaction was quenched with aqueous potassium

dihydrogenphosphate buffer solution (10%, 10 ml) and extracted with

chloroform (3 x 10 ml). The organic phase was dried (anhydrous sodium

sulphate) and concentrated. P.l.c. (on silica, using ether/petrol, 1:1

as eluent) gave the p-hydroxydienone (5), (36 mg, 48%) m.p. 121-123°

(lit.2° m.p. 123-4°), T: 3.35 (2H, s), 7.70-8.10 (1H, bs), 8.10 (6H, s),

and 8.55 (3H, s), m/e 152 (Mt).

A further product was obtained, believed to be 3,5-dimethy1-4-

hydroxybenzaldehyde (26 mg, 17%) m.p. 111-112° (lit.5 m.p. 113.5-114°),

v max, (Nujol): 3600 (br) and 1702 cm.-1, T: 0.2 (1H, s), 2.5 (2H, s), and 7.7 (6H, s), m/e 150 (e). 99.

Oxidation of the Sodium Salt of Tetracycline Ring-A Model Ester (7) with

Benzeneseleninic Anhydride

A stirred solution of the ester (196 mg, 1 mmol) in THF (5 ml)

has treated with sodium hydride (80% suspension in oil, 30 mg, 1 equiv.)

to form the monoanion. After 10 min benzeneseleninic anhydride (360 mg, 7 1 mmol) was added and stirring was continued for 45 min. Literature

work-up gave a mixture of three products which was chromatographed on

silica plates using ether/ethyl acetate mixtures as eluent to give

hydroxydienone (8), (100 mg, 47%) m.p. 109-110° (lit.7 m.p. 111°), quinone

(9), (44 mg, 21%), m.p. 66-67° (lit.7 m.p. 68°•) and benzeneseleninic acid

(17 mg, 9%) m,p. 122-3° (lit.22 m.p. 122-4°).

Repeating the experiment using only 0.33 equivalents (120 mg) of

the anhydride gave the hydroxydienone (8), (47 mg, 22%) in reduced yield.

Competitive Oxidation of Mesitol and 2,6-Di-t-Butyl-4-Methylphenol with

Benzeneseleninic Anhydride

A stirred solution of mesitol (68 mg, 0.5 mmol) and 2,6-di-t-buty1-

4r,methylphenol (110 mg, 0.5 mmol) in dry THF (7 ml) was treated with

benzeneseleninic anhydride (180 mg, 0.5 mmol). After 20 min, the reaction

mixture was filtered and p.l.c. (on silica, using petrol followed by ether/

petrol mixtures as eluent gave unreacted mesitol (34 mg, 50%) and 2,6-di- t-buty1-4,methylphenol (104 mg, 95%).

Competitive Benzoylation of Mesitol and 2,6-Di-t-Butyl-4-Methylphenol

A stirred solution of mesitol (68 mg, 0.5 mmol) and 2,6-di-t-butyl-

4-methylphenol (110 mg, 0.5 mmol) in benzene (5 ml) was treated with benzoyl chloride (70 mg, 0.5 mmol) and pyridine (2 ml). After 2 h the reaction mixture was diluted with chloroform (20 ml), washed with dilute aqueous 100.

hydrochloric acid (3 x 10 ml) and water (20 ml) and the organic pha,;e

was dried (anhydrous sodium sulphate). Concentration and p.l.c. on silica,

using petrol followed by petrol/ether mixtures as eluent gave unreacted

mesitol (37 mg, 55%) and 2,6-di-t-butyl-4-methylphenol (106 mg, 97%).

Oxidation of 2,6-Di-t-Butyl-4-Methylphenol with Benzeneseleninic Anhydride

A stirred solution of 2,6-di-t-butyl-4-methylphenol (110 mg, 0.5

mmol) in dry THF (5 ml) was treated with benzeneseleninic anhydride

(180 mg, 0.5 mmol). After 2 h the reaction mixture was filtered and

concentrated. P.l.c. (on silica, using ether/petrol, 1:1 as eluent) gave

a red oil (12 mg, 11%) T: 3,40 (1H, bs ), 3.85 (1H, bs), 7.86 (3H, s),

and 8,74 (9H, s), m/e 178. The oil decomposed rapidly and further puri-

fication could not be effected.

Oxidation of Thymol with Benzeneseleninic Anhydride

A stirred solution of thymol (75 mg, 0.5 mmol) in THF (5 ml) was

treated with benzeneseleninic anhydride (180 mg, 0.5 mmol). After 2 h

the reaction mixture was filtered and concentrated. No identifiable

products could be isolated by chromatography. Thymol (30 mg, 40%) was

recovered.

Oxidation of Carvacrol with Benzeneseleninic Anhydride

The previous experiment was repeated using carvacrol instead of thymol. A mixture of unidentified products was again obtained and carvacrol

(35 mg, 47%) was recovered.

Oxidation of 2-Naphthol with Benzeneseleninic Anhydride

A stirred solution of 2-naphthol (72 mg, 0.5 mmol) in dry THF (5 ml) 101.

was treated with benzeneseleninic anhydride (540 mg, 1.5 mmol) at room temperature. After 3 h the reaction mixture was filtered and concentrated.

Chromatography (silica gel column, using chloroform/petrol mixtures as eluents)gave (i) 1-phenylseleno-2-naphthol (14) as white crystals (42 mg,

28%), m.p, 76-78° (lit.5 m,p. 77-78°) and (ii) 1,2-naphthoquinone (28 mg,

35%), m,p. 144-146° (lit.5 m.p. 145-6°).

Oxidation of 1-Phenylseleno-2-Naphthol with Benzeneseleninic Anhydride

A solution of 1-phenylseleno-2-naphthol (150 mg, 0.5 mmol) in dry

THF (5 ml) was added to a stirred suspension of benzeneseleninic anhydride

(180 mg, 0.5 mmol) in THF (5 ml), maintained at 50°. An orange colour was rapidly produced. After 30 min the reaction mixture was diluted with chloroform (20 ml), washed with aqueous sodium bicarbonate solution (10%,

2 x 20 ml) and water (20 ml), dried (anhydrous sodium sulphate) and evaporated to dryness in vacuo. Chromatography (silica gel column, using ether/ petrol 20% as eluent) gave 1,2-naphthoquinone as orange crystals (72 mg,

89%) m.p. 143-145° (lit.5 m.p. 145-6°).

Lithium Phenylseleninate

A solution of benzeneseleninic acid (190 mg, 1 mmol) in dry THF

(5 ml) was treated with butyl lithium (64 mg, 1 mmol) at room temperature.

After 10 min, the solvent was removed under reduced pressure and the residue was washed with ether (3 x 5 ml) and dried in vacuo to give lithium phenylseleninate (182 mg, 92%) as a white powder.

Diphenylseleninylselenenate (15)

A solution of benzeneselenenyl chloride (95 mg, 0.5 mmol) in dry THF

(5 ml) was added to a stirred suspension of lithium phenylseleninate (107 mg, 102.

0.5 mmol) in THF (3 ml) with careful exclusion of moisture. The initial orange colour disappeared rapidly to give a pale yellow solution. After filtration, the mixture was chromatographed (silica gel column, using petrol/ chloroform mixtures as eluents) to give diphenyldiselenide (94 mg, 60%) and benzeneseleninic acid (19 mg, 20%) as the only identifiable products.

Attempts to crystallise the seleninylselenenate (15) from the pale yellow solution were unsuccessful. Subsequent experiments with the reagent (15) were therefore carried out using the yellow solution without further purification.

Reaction of 2-Naphthol with Diphenylseleneninylselenenate (15)

A solution of 2-naphthol (72 mg, 0.5 mmol) in THF was added to a solution of the seleninylselenenate reagent (15) (0.5 mmol) in THF (8 ml)

After 2 h chromatography (silica gel column, using ether/petrol, 5% as eluent) gave 1-phenylseleno-2-naphthol (93 mg, 62%) m.p. 75-77° (lit.7 m.p. 770).

Oxidation of Diphenyldiselenide with m-Chloroperbenzoic Acid

A solution of diphenyldiselenide (157 mg, 0.5 mmol) in THF (10 ml) was treated with m-chloroperbenzoic acid. (180 mg, 2 equivs.) to give a pale yellow solution. Chromatography gave diphenyldiselenide as the only identifiable product.

A solution of 2-naphthol (72 mg, 0.5 mmol) in THF (3 ml) was added to the pale yellow solution and after 2 h, p.l.c. (on silica gel, using ether /petrol, 5% as eluent) yielded 1-phenylseleno-2-naphthol (48 mg,

32%) m.p, 75-77° (lit.7 m.p. 77°), 103.

Preparation of Quinones from Phenols (General Method)

A solution of the phenol (0.5 mmol) in dry THF (5 ml) was added

dropwise over 15 min to a stirred suspension of benzeneseleninic anhydride

(180 mg, 0.5 mmol) in THF (10 ml) at 50°. The disappearance of starting

material was monitored by analytical t.l.c, Further oxidant was added

(ca, 0,1 equiv.) until no phenol remained. The reaction mixture was

dissolved in chloroform (25 ml) washed with aqueous sodium bicarbonate

solution (10%, 2 x 20 ml) and water (20 ml) and dried (anhydrous sodium

sulphate). Evaporation under reduced pressure followed by chromatography

(silica gel column, using ether/petrol, 20%, followed by ether as eluent)

gave the quinone as a pure crystalline solid.

Conversion of 2-Naphthol to 1,2-Naphthoquinone

Using the above method 2-naphthol (72 mg, 0.5 mmol) was converted

to 1,2-naphthoquinone (51 mg, 63%) m.p. 144-6; (lit.5 m.p. 145-6°).

Conversion of 1-Naphthol to 1,2-Naphthoquinone

Using the general method 1-naphthol (72 mg, 0.5 mmol) was converted

to 1,2-naphthoquinone (50 mg, 62%) m.p. 146-7° (lit.5 m,p. 145-6°).

Conversion of Thymol to 3-Methy1-6-Isopropy1-1,2-BenZoquinone (1,2-Thymo-

quinone).

Using the general method thymol (75 mg, 0.5 mmol) was converted

to 1,2-thymoquinone (49 mg, 59%) m.p. 60-61° (Nujol): 1680 cm-1, ,v max. T (CDC13): 3.0-3.6 (2H, m), 6.6-7,2 (1H, m), 7.8 (3H, s), 8.7 (3H, s),

and 8.8 (3H, s), Amax. (Et0H): 273 (e 2375) and 415 ( 1770) nm, + m/e: 166 (M ), (Found: C, 73,26; H, 7.50; requires C, 73.20; _ C10H1202 H, 7,32%). 104.

Conversion of Carvacrol to 1,2-Thymoquinone

Using the general method,. carvacrol (75 mg, 0.5 mmol) was converted

to 1,2-thymoquinone (50 mg, 60%) m.p. 60-61°.

Conversion of 2,4-Di-I:-Butylphenol to 3,5-Di-t-Butylbenzoquinone

Using the general method, 2,4-di-t-butylphenol (103 mg, 0.5 mmol)

was converted to 3,5-di-t-butylbenzoquinone (74 mg, 68%) m.p. 108-112°

(lit.11 m.p. 114°).

Reaction of 2,4-Di-t-Butylphenol with Benzeneseleninyl Chloride

A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in dry THF 0 (5 ml) at -78 was treated with a solution of benzeneseleninyl chloride

(105 mg, 1 equiv) in THF (5 ml) and the mixture was allowed to warm to room temperature. P.l.c. (on silica gel, using ether/petrol, 20% as eluent)

gave 3,5-di-t-butylbenzoquinone (24 mg, 22%) and unreacted starting

material (56 mg, 54%) as the only identifiable materials.

Attempted Trapping of Intermediate (18)

(i) A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in dry THF

(5 ml) was treated with sodium hydride (80% suspension in oil, 23 mg, 1.5 equiv.) to give the anion. A solution of benzeneseleninyl chloride (105 mg,

1 equiv.) in THF (5 ml) was added at -78° and the reaction mixture was allowed to warm to room temperature.

Treatment of the resulting solution with benzenethiol (500 mg) gave no catechol-type products, as monitored by t.l.c. Addition of lithium cyanide (150 mg) gave no catechol products after stirring for 12 h.

(ii) A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF 105.

(5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol)

and the mixture was stirred for 3 h. Filtration and chromatography gave

diphenyldiselenide (82 mg, 52%) as the only identifiable product.

Treatment of the reaction mixture with either benzenethiol (500 mg)

or lithium cyanide (150 mg) gave no catechol-type products.

(iii)A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF o (5 ml) at 50 was treated with lithium cyanide (150 mg) and benzeneseleninic

anhydride (180 mg, 0.5 mmol). T.l.c. analysis showed that 3,5-di-t-butyl-

benzoquinone was the major product, and no catechols could be detected.

Attempted Preparation of Intermediate (18)

(i)A stirred solution of 3,5-di-t-butylcatechol (111 mg, 0.5 mmol)

in THF (5 ml) was treated with sodium hydride (80% suspension in oil,

20 mg, 1.3 equiv.) to form the monoanion. A solution of benzeneselenenyl

chloride (95 mg, 0.5 mmol) was added and stirring was continued for 2 h.

Chromatography (silica gel column, using ether/petrol, 10% as eluent)

gave 3,5-di-t-butylbenzoquinone (42 mg, 38%) as the only identifiable

product,

(ii)A solution of 3,5-di-t-butylcatechol (111 mg, 0.5 mmol) in THF

(5 ml) was treated with pyridine (1 ml) and benzeneselenenyl chloride

(95 mg, 0.5 mmol). Filtration and chromatography (silica gel column,

using ether/petrol, 10% as eluent gave 3,5-di-t-butylbenzoquinone (86 mg,

78%) as the only identifiable product.

Phenylselenation using Intermediate (18)

A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF (5 ml)

was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) and the reaction mixture was stirred for 2 h. 2-Naphthol (72 mg, 0,5 mmol) was 106.

added and after 15 min, p.1,c. (on silica gel, using ether/petrol, 10% as eluent) yielded 1-phenylseleno-2-naphthol (27 mg, 18%).

Attempted Trapping of Intermediate (18) as the Catechol Diacetate

A solution of 2,4-di-t-butylphenol (103 mg, 0.5 mmol) in THF (5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) and the reaction mixture was stirred for 2 h. Zinc (200 mg), acetic acid (3 drops), acetic anhydride (3 ml) and pyridine (1 drop) were added and t.l.c. analysis showed no catechol diacetate to be present.

Other Attempted Conversions of Phenols to o-Quinones

Using the general method, 2,4-xylenol (61 mg, 0.5 mmol), 3,4-xylenol

(61 mg, 0,5 mmol), o-cresol (56 mg, 0.5 mmol), o-nitrophenoi (70 mg,

0,5 mmol), resorcinol (55 mg, 0.5 mmol) and phloroglucinol (63 mg, 0.5 mmol) all gave intractable mixtures of products from which no o-quinones could be isolated.

Oxidation of 4-t-Butylphenol with Benzeneseleninic Anhydride

A solution of 4-t-butylphenol (75 mg, 0.5 mmol) in THF (5 ml) was treated with benzeneseleninic anhydride at 50° in the usual way. A mixture of products was observed. P.l.c. (on silica gel, using ether/petrol, 10% as eluent) gave 4-t-buty1-6-phenylseleno-1,2-benzoquinone (6 mg, 4%) m.p.

11920° (lit.7 m.p. 120°).

4-Phenylseleno-1,2-Naphthoquinone (28)

A solution of 2-naphthol (72 mg, 0.5 mmol) in THF (5 ml) at 50° was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) and the mixture was stirred for 24 h. Filtration and p.l.c. (on silica gel using 107.

ether/petrol, 10% as eluent) gave 4-phenylseleno-1,2-naphthoquinone (3 mg,

2%) m.p. 169-171° (lit.7 m.p. 172° (dec)).

Attempted Phenylselenation of 1,2-Naphthoquinone

(i)Using diphenyldiselenide: A solution of 1,2-naphthoquinone

(13 mg, 0.1 mmol) in THF (8 ml) was treated with diphenyldiselenide

(157 mg, 5 equiv.) at room temperature. After 24 h no phenylselenated

quinone could be detected by t.l.c.

(ii)Using diphenylseleninylselenenate (15): A solution of 1,2-

naphthoquinone (13 mg, 0.1 mmol) in THF (5 ml) was added to a solution

of reagent (15), (5 equiv.) and the mixture was stirred for 24 h. P.l.c.

(on silica gel, using ether/petrol, 10% as eluent) gave the phenyl-

selenonaphthoquinone (1.2 mg, 4%) m.p. 169-170° m.p. 172°).

(iii)Using diphenyldiselenide and mCPBA: The pale yellow solution

formed by reaction of diphenyldiselenide (157 mg, 0.5 mmol) with mCPBA

(180 mg, 1.0 mmol) in THF (8 ml) was treated with a solution of 1,2-

naphthoquinone (13 mg, 0.1 mmol) in THF (3 ml) and the mixture was stirred

for 24 h. No phenylselenoquinone could be detected by t.l.c.

(iv)Using benzeneseleninic anhydride: A solution of 1,2-naphtho-

quinone (13 mg, 0.1 mmol) in THF (5 ml) was treated with benzeneseleninic

anhydride (180 mg, 0.5 mmol) and the mixture was stirred for 24 h.

Filtration and p.l.c. (on silica gel, using ether/petrol, 10% as eluent)

gave the phenylselenoquinone (0.9 mg, 30) m.p. 169-170° (lit.7 m.p.

172°)

Oxidation of 3,5-Di-t-Butylcatechol with Benzeneseleninic Anhydride

A solution of 3,5-di-t-butylcatechol (111 mg, 0.5 mmol) in THF 108.

•(5 ml) was treated at room temperature with benzeneseleninic anhydride (180 mg, 0.5 mmol). After 15 min the reaction mixture was filtered and

chromatographed (silica gel column, using petrol/chloroform mixtures as

eluents) to give 3,5-di-t-butylbenzoquinone (96 mg, 88%) m.p. 109-112° 11 o (lit. m.p. 114 ).

Oxidation of catechol with Benzeneseleninic Anhydride

A solution of catechol (55 mg, 0.5 mmol) in THF (5 ml) was treated

at room temperature with benzeneseleninic anhydride (180 mg, 0.5 mmol).

An immediate reaction occurred but no identifiable products could be

isolated by chromatography.

Oxidation of 2,6-Dimethylhydroouinone with Benzeneseleninic Anhydride

A solution of 2,6-dimethylhydroquinone (69 mg, 0.5 mmol) in THF

(5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) at

room temperature. Further oxidant (ca. 0.2 mmol) was added until t.l.c.

showed complete disappearance of quinol. The reaction mixture was filtered

and, after p.l.c. (on silica gel using ether/petrol, 10% as eluent) gave 2,6-

diMethylbenzoquinone (60 mg, 88%) m.p. 71-73° (lit.5 m.p. 72-73°).

Oxidation of Hydroquinone using Benzeneseleninic Anhydride

A solution of hydroquinone (55 mg, 0.5 mmol) in THF (5 ml) was

treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) at room tempera-

ture, Filtration and p.l.c. (on silica gel using ether/petrol, 10% as

eluent) gave benzoquinone (45 mg, 84%) m.p. 114-116° (lit.5 m.p. 115-117°).

Oxidation of 1,4-Dihydroxynaphthalene with Benzeneseleninic Anhydride

A solution of 1,4-dihydroxynaphthalene (80 mg, 0.5 mmol) in THF 109.

(5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol) at room temperature. Work-up in the usual way gave naphthoquinone (73 mg, 5 92%) m.p. 123-124° (lit. m.p. 125°).

Formation of Selenoimine (34) using Sodium Hexamethyldisilazide

A solution of 2,4-xylenol (25 mg, 0.2 mmol) in dry toluene (2 ml) was treated with sodium hexamethyldisilazide (60 mg, 0.3 mmol, 1.5 equiv.) and benzeneseleninic anhydride (75 mg, 0.2 mmol) under nitrogen with stirring. A deep red colour developed. After 45 min the mixture was poured into water (5 ml) and extracted with chloroform (2 x 5 ml). Chro- matography (silica gel column, using ether/petrol, 20% as eluent) yielded the selenoimine (34), (22 mg, 38%) m.p. 120-1° (lit.7 m.p. 120-10).

Formation of Selenoimine (34) using Hexamethyldisilazane

A solution of 2,4-xylenol (25 mg, 0.2 mmol) in dry benzene (2 ml) was treated with hexamethyldisilazane (35 mg, 1.1 equiv) and benzeneseleninic anhydride (75 mg, 0.2 mmol). Chromatography (silica gel column, using ether/petrol, 20% as eluent) gave selenoimine (34), (35 mg, 61%).

Optimisation of Selenoimine Formation

Formation of selenoimine (34) was repeated, varying the reaction conditions:

(i) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane

(35 mg, 1.1 equiv) and benzeneseleninic anhydride (25 mg, 0.33 equiv.) to give selenoimine (34), (13 mg, 23%).

(ii)2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane 110.

(35 mg, 1.1 equiv.) and benzeneseleninic anhydride (150 mg, 2 equiv.) to give selenoimine (34), (37 mg, 6496);

(iii) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane

(70 mg, 2.2 equiv.) and benzeneseleninic anhydride (75 mg, 1 equiv.) to

give selenoimine (34), (37 mg, 64%);

(iv) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane

(70 mg, 2.2 equiv.) and benzeneseleninic anhydride (150 mg, 2 equivs.) to

give selenoimine (34), (41 mg, 70%);

(v) 2,4-xylenol (25 mg, 0.2 mmol) was treated with hexamethyldisilazane

(35 mg, 1.1 equivs.) and benzeneseleninic anhydride (75 mg, 1 equiv.) with

strict exclusion of laboratory light. Selenoimine (34) was again isolated

(35 mg, 61%) after 45 min.

With oxygen bubbled through the reaction mixture the same yield of selenoimine was obtained.

General Method of Formation of Selenoimines

A solution of the phenol (0.5 mmol) in dry benzene (3 ml) was treated

with hexamethyldisilazane (88 mg, 1.1 equiv.) and benzeneseleninic an-

hydride (180 mg, 0.5 mmol) at room temperature, with stirring. After 30

mins the reaction mixture was diluted with chloroform (10 ml) and filtered.

P.1,c. (on silica gel, using ether/petrol mixtures as eluents) gave the selenoimine as a crystalline solid.

Conversion of Phenol to Selenoimine (35)

Using the general method, phenol (47 mg, 0.5 mmol) was converted to selenoimine (35), (59 mg, 45%), m.p. 75-76°, (Nujol): 1630, vmax. -1 1580, 1520, and 760 cm , T: 3.0-3.3 (2H, m) and 2.0-2.9 (7H, m), Xmax.: 460 (e 3000 ) and 260 ( 2100 ) nm, m/e: 261 (M+), (Found:

N, 5.25. C H NOSe requires C, 55.0; H, 3.3; N, 5.3%). C, 55.06; H, 3.46; 12 9

Selenoimine (41) was also isolated as an unstable orange oil, and tPis was immediately treated with zinc (50 mg), acetic acid (2 drops) acetic anhydride (1 ml) and pyridine (1 drop) to give 4-aminophenol-

N,0-diacetate (9 mg, 10%), m.p. 148-150° (lit5 m.p. 150-157°).

Conversion of Carvacrol to Selenoimine (36)

Using the general method, carvacrol (75 mg, 0.5 mmol) was converted 1 to selenoimine (36), (92 mg, 58%), m.p. 59-60°, 1610 cm , T: vmax. 2.0-3.8 (7H, m), 6.3-6.9 (1H, m), 8.0 (3H, s), 8.7 (3H, s), and 8.8 (3H, s).X 264 (e 3300), 435 ( 11000), and 473 (9200)nm, m/e 319 (Mt) max. (Found: C, 60.66; H, 5.27; N, 4.36. C e NOSe requires C, 60.4; H, 5.3; 1 17 N, 4.4%).

Conversion of Thymol to Selenoimine (37)

Using the general method, thymol (75 mg, 0.5 mmol) was converted to selenoimine (37), (89 mg, 56%), m.p. 39-40°, 1610 cm-1, T: 2.0- vmax. 3.7 (7H, m), 6.6-7.0 (1H, m), 7.6 (3H, s), 8.8 (3H, s), and 8.9 (3H,

0,A 272 (e 3250), 433 (9600), and 468 (10150) nm, m/e: 319 (M max, l.), (Found: C, 60.25; H, 5.30; N, 4.12. C H NOSe requires C, 60.4; H, 5.3; 16 17 N, 4.4%).

Reductive Acetylation of Selenoimines (36) and (37)

(i) Selenoimine (36): The selenoimine (32 mg, 0,1 mmol) was dissolved in acetic anhydride (2 ml), Zinc dust, (60 mg), acetic acid (3 drops) and pyridine (1 drop) were then added. A vigorous reaction set in which was moderated by ice cooling, The reaction mixture was diluted with 112.

chloroform (20 ml), filte-r.ed, washed with aqueous sodium bicarbonate solution (2 x 20 ml) and water (20 ml), dried (anhydrous sodium sulphate) and evaporated under reduced pressure. Trituration of the residual oil, first with petrol then with ether gave the N,0-diacetate (18 mg, 81%)

m.p. 224-226°.

An authentic sample was prepared by nitrating thymol at -10° with

a four fold excess of nitric acid in acetic acid (20% solution). Steam

distillation gave the o-nitrophenol which was reductively acetylated with zinc, acetic anhydride, acetic acid and pyridine to give the N,0-diacetate

(74%) m.p. 228-30°, The melting point was undepressed on admixture with the material prepared by reductive acetylation of the selenoimine.

(ii) Selenoimine (37): The N,0-diacetate was prepared in the usual way and compared (m.p. and mixed melting-point) with an authentic sample

prepared via the nitrophenol, as above.

N,O,diacetate from selenoimine (37) m.p. 164-166°

N,0-diacetate from nitrophenol m.p. 160-163°

Reduction of Selenoimine (34) to 6-Amino-2,4-Xylenol

(i)A solution of selenoimine (34), (15 mg, 0,05 mmol) in dry benzene

(2 ml) was treated with benzenethiol (0.3 ml). After 4 h, the mixture became colourless and p.l,c. (on silica gel, using petrol/chloroform, 50% as eluent) yielded the crude aminoxylenol (6 mg, 85%) as an oil, v max. -1 3300 and 3400 cm , m/e: 137 (Mt).

(ii)A solution of selenoimine (34), (15 mg, 0.05 mmol) in dry benzene (2 ml) was treated with thioglycollic acid (0.5 ml). After 12 h the mixture became colourless and p.l.c. (on silica gel, using petrol/ chloroform, 50% as eluent) yielded the crude aminoxylenol (2.8 mg, 40%), 113.

as an oil.

(iii) A solution of selenoimine (34), (3 mg) in dry benzene (1 ml)

remained unchanged after 12 h passage of hydrogen sulphide gas.

Conversion of 2,6-Xylenol to Selenoimine (42)

(i) A solution of 2,6-xylenol (25 mg, 0.2 mmol) in dry benzene (2m1)

was treated with hexamethyldisilazane (35 mg, 1.1 equiv.) and benzene-

seleninic anhydride (75 mg, 0.2 mmol). A deep orange colour was produced.

P.l.c. (on silica gel, using ether/petrol, 20% as eluent)gave selenoimine

(42) as orange needles (27 mg, 48%), m.p. 140-141°, (lit.7, m.p. 140-141°).

Conversion of Monocathylate (43) to Selenoimine (42)

A solution of monocathylate (42 mg, 0.2 mmol) in dry benzene (3 ml)

was treated with sodium hexamethyldisilazide (60 mg, 1.5 equiv.) and benz-

eneseleninic anhydride (75 mg, 0.2 mmol). The reaction mixture was diluted

with chloroform (10 ml) and washed with water (10 ml). The organic phase

was dried (anhydrous sodium sulphate) and after p.l.c. (on silica gel,

using ether/petrol, 20% as eluent) gave selenoimine (42), (25 mg, 28%).

Conversion of Monocathylate (44) to Selenoimine (45)

A solution of hydroquinone monocathylate (44), (91 mg, 0.5 mmol) was

treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzenesele-

ninic anhydride (180 mg, 0.5 mmol). Filtration followed by p.l.c. (on

silica gel, using ether/petrol, 20% as eluent) gave the selenoimine (45),

(47 mg, 45%), m.p. 66-68°, vmax.(Nujol): 1740 and 1615 cm-1, T: 2.0-

2.6 (6H, m), 2.7-3.4 (2H, ABq, J = 9Hz), 5.5-5.9 (2H, q), and 8.6 (3H, t),

X max. 260 (e 5500), 410 (4000), and 464 (11000) nm, m/e: 210 (M) 114.

(Found: C, 51,53; H, 3.94; N, 3.98, C15H13N04Se requires C, 51.5;

H, 3.7; N, 4.0%).

Attempted Conversion of 1,2-Thymoquinone to Selenoimine (36)

A solution of 1,2-thymoquinone (82 mg, 0.5 mmol) in dry benzene

(3 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and

benzeneseleninic anhydride (180 mg, 0.5 mmol). After 3 h, t.l.c. showed

that no selenoimine (36) was present in the reaction mixture. Chromatogra-

phy yielded a mixture of unidentifiable products.

Conversion of 1-Naphthol to Selenoimines (47) and (48)

A solution of 1-naphthol (72 mg, 0.5 mmol) in dry benzene (3 ml) was

treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzeneseleni-

nic anhydride (180 mg, 0.5 mmol). After 30 min the reaction mixture was

filtered and p.l.c. (on silica gel, eluting three times with ether/petrol

5%) gave (i) selenoimine (47), (77 mg, 49%), m.p. 164-166° (lit.7, m.p.

164°, and (ii) selenoimine (48), (26 mg, 17%), m.p. 124-126° (lit.7

m.p, 126-7°).

Conversion of 2-Naphthol to Selenoimines (47) and (48)

A solution of 2-naphthol (72 mg, 0.5 mmol) in dry benzene (3 ml)

was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzene-

seleninic anhydride (180 mg, 0.5 mmol). After 30 min the reaction mixture

was filtered and p.l.c. (on silica gel, eluting three times with ether/

petrol, 5%) gave (i) selenoimine (47), (38 mg, 24%), m.p. 164-1660 and

(ii) selenoimine (48), (57 mg, 37%), m.p. 124-126°. 115.

Conversion of 1,2-1aphthoquinone to Selenoimines (47) and (48)

A solution of 1,2-naphthoquinone (79 mg, 0.5 mmol) in dry benzene

(3 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and

benzeneseleninic anhydride (180 mg, 0.5 mmol). After 30 min the reaction

mixture was filtered and p.l.c. (on silica gel, eluting three times with

ether/petrol, 5%) gave (i) selenoimine (47), (54 mg, 35%), m.p. 164-

166o and (2) selenoimine (48), (16 mg, 10%), m.p. 124-126°.

Formation of Selenoimine (34) using Benzeneselenenyl Chloride

A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)

was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and ben-

zeneselenenyl chloride (95 mg, 0.5 mmol) at room temperature with stirring.

After 35 min, the reaction mixture was filtered and p.l.c. (on silica

gel, using ether/petrol, 20% as eluent) afforded selenoimine (34), (58mg, o 40%), m.p. 120-121 , (lit.7 m.p. 120-1°).

Formation of Selenoimine (34) using Benzeneseleninic Acid

A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)

was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzene-

seleninic acid (95 mg, 0.5 mmol) at room temperature with stirring. After

45 min the reaction mixture was filtered and p.l.c. (on silica-gel, using

ether/petrol, 20% as eluent) afforded selenoimine (34), (36 mg, 25%),

m,p, 120r,121° (lit.7 m.p. 120-121°).

Formation of Selenoimine (34) using Ammonia

A solution of 2,4-'xylenol (61 mg, 0.5 mmol) in dry THE (3 ml) was treated with liquid ammonia (3 ml) with careful exclusion of moisture. 116.

Benzeneseleninic anhydride (180 mg, 0.5 mmol) was added and the mixture was stirred at room temperature until all the excess ammonia had evaporated. Filtration and p.l.c. (on silica-gel, using ether/petrol,

20% as eluent) afforded selenoimine (34), (1.5 mg, 1%) and unreacted

2,4-,,xylenol (48 mg, 79%) as the only identifiable products.

Attempted Formation of Selenoimine (34) using t-Butylamine

A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml) was treated with t-butylamine (40 mg, 1.1 equiv.) and benzeneseleninic anhydride (180 mg, 0.5 mmol). After 12 h, t.l.c. indicated that no selenoimine (34) had been formed.

Preparation of. Tris-(trimethylsily1)-amine (49)

A solution of sodium hexamethyldisilazide (1.85 g, 10 mmol) in dry toluene (5 ml) was treated with trimethylsilylchloride (1.1 g, 10 mmol) and the mixture was heated to reflux for 18 h. Fractional vacuum distillation of the resulting solution gave the tris-reagent (49), (1.4 g, 23 60%) as a white waxy solid, m.p. 69-70° (lit. m.p. 69-71°).

Formation of Selenoimine (42) using Tris-(trimethylsily1)-amine

A solution of 2,6-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml) was treated with tris-(trimethylsily1)-amine (125 mg, 1.1 equiv.) and benzeneseleninic anhydride (180 mg, 0.5 mmol). After 1 h the reaction mixture was filtered and p.l.c. (on silica-gel, using ether/petrol, 20% as eluent) gave selenoimine (42), (27 mg, 19%), m.p. 140-141° (lit.7, m,p. 140-141°). 117.

•Attempted Formation of Selenoimine (34) using Tris-(trimethylsily1)-amine

and Benzeneselenenyl Chloride

A solution of 2,4-xylenol (61 mg, 0.5 mmol) in dry benzene (3 ml)

was treated with tris-(trimethylsilyl)-amine (125 mg, 1.1 equiv.) and

benzeneselenenyl chloride (95 mg, 0.5 mmol) with stirring at room

temperature. After 45 min the reaction mixture was filtered and p.l.c.

(on silica gel, using ether/petrol, 20% as eluent) gave a mixture of

unidentifiable products. No selenoimine (34) could be detected.

Reaction of Hexamethyldisilazane with Benzeneseleninic Anhydride

A solution of hexamethyldisilazane (163 mg, 1 mmol) in dry THF

(5 ml) was treated with benzeneseleninic anhydride (360 mg, 1.0 mmol) at

room temperature with stirring, A faint yellow colour was produced after

1 h, shown by t.l.c. to be due to formation of a trace of diphenyl-

diselenide. After 12 h, the reaction mixture was filtered to remove O unreacted benzeneseleninic anhydride (342 mg, 95%) m.p. 164-5°, (lit.9

mt p, 164°) and distillation of the filtrate gave unreacted hexamethyl-

disilazane (150 mg, 92%).

The reagents (same quantities) were mixed with toluene (1 ml) in

a sealed tube and heated at 100° for 18 h. Benzeneseleninic anhydride

(346 mg, 96%) and hexamethyldisilazane (155 mg, 95%) were recovered

unchanged. Diphenyldiselenide (6 mg, 2%) was isolated from the reaction

mixture by chromatography (silica-gel column, eluting with petrol).

Reaction of Benzeneseleninic Anhydride with Tris-(trimethylsily1)-amine

A solution of tris-(trimethylsily1)-amine (125 mg, 0.53 mmol) in

dry THF (5 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5

mmol) at room temperature with stirring. After 12 h, t.l.c. showed 118.

that no reaction had occurred and filtration gave unreacted benzeneseleninic anhydride (167 mg, 93%). The silazane was recovered (119 mg,

95%) by chromatography (silica-gel column, eluting with chloroform).

Reaction of Hexamethyldisilazane with Benzeneselenenyl Chloride

A solution of hexamethyldisilazane (1.63 g, 10 mmol) in dry THF

(5 ml) was treated with a solution of benzeneselenenyl chloride (1.90 g,

10 mmol) in THF (3 ml) at room temperature. An immediate reaction occurred to give a mixture of unidentifiable products. Diphenyldiselenide

(0,86 g, 5596) was isolated by chromatography (silica-gel column, eluting

With petrol),

The reaction was repeated at 0° but no difference was noted.

Reaction of Sodium Hexamethyldisilazide with Benzeneselenyl Chloride

A solution of benzeneselenenyl chloride (95 mg, 0.5 mmol) in dry

THF (5 ml) was treated with sodium hexamethyldisilazide (93 mg, 0.5 mmol) at room temperature, with stirring. A rapid reaction took place to give a mixture of unidentifiable products. Diphenyldiselenide (43 mg, 55%) was isolated by chromatography (silica-gel column, using petrol as eluent).

The reaction was repeated at -10° and 0° but the same mixture of products was obtained.

Benzeneselenium Trichloride

A solution of diphenyldiselenide (314 mg, 1 mmol) in hexane (3 ml) was treated with sulphurylchloride (500 mg, 3.7 mmol), dropwise with stirring, A white precipitate of benzeneselenium trichloride was formed.

Filtration followed by air drying (vacuum drying causes decomposition) 119.

gave the trichloride (430 mg, 80%) as a white powder, m.p. 130-132° (lit 4 m.p. 133-134°) which was stored in a desiccator over P205.

Reaction of Benzeneselenium Trichloride with Tris-(trimethylsilyl)-amine

A solution of tris-(trimethylsilyl)-amine (125 mg, 0.53 mmol) in dry THF (5 ml) was treated at room temperature with benzeneselenium trichloride (131 mg, 0.5 mmol) with stirring. After 12 h, t.l.c. showed that no reaction had occurred. The reaction mixture was warmed o at 50 for 3 h, but again no reaction was observed. The solvent was distilled off and the solid residue was triturated with hexane (2 x 5 ml).

Filtration gave the unreacted benzeneselenium trichloride (112 mg, 86%), and evaporation of the filtrate gave crude tris-(trimethylsilyl)-amine

(115 mg, 92%). Diphenyldiselenide was shown by t.l.c. to be present in trace amounts.

Reaction of Benzeneseleninic Anhydride with Hexamethyldisilazane in the

Presence of Boron Trifluoride

A suspension of benzeneseleninic anhydride (180 mg, 0,5 mmol) in dry THF (5 ml) was treated with boron trifluoride etherate (70 mg, 1 equiv.)

The anhydride immediately dissolved. Hexamethyldisilazane (81 mg, 0.5 mmol) was added and the mixture was stirred for 1 h. T.l.c. indicated that no reaction had occurred. The solution was evaporated under reduced pressure to give an oily solid. Trituration with petrol followed by filtration yielded unreacted benzeneseleninic anhydride (170 mg, 94%).

Formation of Selenoimine (34) using Benzeneseleninyl Chloride

A solution of 2,4-xylenol (61 mg, 0,5 mmol) in dry THF (3 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and a solution of 120.

benzeneseleninyl chloride (103 mg, 0.5 mmol) in dichloromethane (5 ml) was added dropwise, with stirring. After 40 min, the mixture was concentrated under reduced pressure and p.l.c. (on silica-gel, using ether/petrol, 15% as eluent) afforded selenoimine (34), (26 mg, 18%)

In e p t 120121°, (lit.7 m.p. 120-121°).

Reaction of Lithium Hexamethyldisilazide with Benzeneseleninyl Chloride

A solution of benzeneseleninyl chloride (103 mg, 0.5 mmol) in dry dichloromethane (10 ml) was treated with lithium hexamethyldisilazide

(85 mg, 1 equiv.) with stirring, at room temperature. After 10 min, a white precipitate of lithium chloride appeared. Filtration gave a colourless solution, which rapidly decomposed on concentration under reduced pressure, Chromatography (silica-gel column, using petrol as eluent) gave diphenyldiselenide (61 mg, 78%) as the only identifiable product.

The same reaction was performed in the presence of 2,6-di-t-butyl-___ phenol (103 mg, 0,5 mmol). Diphenyldiselenide (40 mg, 51%.\ was again obtained as the major product. 3,3,5,5-Tetra-t-butylbiphenoquinone (52)

(22 mg, 24%) was also isolated as yellow crystals, m.p. 227-228° (lit.25 m,p, 240241°), Amax.: 420 (c 35 000), 269 (3 000), 259 (3 500) and 249 (3680) nm, (lit.25 Amax.: 427 (66 000), 271 (4240), 262 (4800), and

253 (4320) nm, m/e 411 (Mt)).

Reaction of 2,6-Di-t-Butylphenol with Hexamethyldisilazane and Benzenesele- ninic Anhydride

A solution of 2,6-di-t-butylphenol (103 mg, 0.5 mmol) in dry THE

(5 ml) was treated with hexamethyldisilazane (100 mg, 1.25 equiv.) and benzeneseleninic anhydride (180 mg, 0.5 mmol) at room temperature, with stirring. After 45 min, the reaction mixture was filtered and p.l.c. 121.

(on silica gel using petrol as eluent) gave (i) diphenyldiselenide (97 mg,

62%) and (ii) 3,3,5,5-tetra-t-butylbiphenoquinone (40 mg, 39%), m.p. 25 o 226n2280 (lit. m.p. 240-241 ). No selenoimines could be detected.

Reaction of Benzeneseleninyl Chloride with Ammonia

A solution of benzeneseleninyl chloride (103 mg, 0.5 mmol) in dry dichloromethane (10 ml) was treated with liquid ammonia (redistilled,

2 ml) and the reaction mixture was allowed to warm to room temperature.

After 20 min a white precipitate of ammonium chloride was observed.

When no ammonia remained in the solution, the reaction mixture was filtered under nitrogen to give a pale yellow solution. Concentration under reduced pressure caused the yellow solution to decompose to a red/black oil, Storage of the yellow solution at 4° for 1 week did not cause any product to crystallise. Addition of petrol was similarly unsuccessful.

Formation of Selenoimine (34) using Benzeneseleninyl Chloride and Ammonia

Using the method described above, benzeneseleninyl chloride (103 mg, 0.5 mmol) was treated with liquid ammonia (2 ml) to give after filtration, a clear pale yellow solution. A solution of 2,4-xylenol (61 mg,

0,5 mmol) in dichloromethane (3 ml) was added and the reaction mixture was stirred at room temperature for 2 h. A pale red colour developed.

Concentration under reduced pressure followed by p.l.c. (on silica gel, using ether/petrol, 20% as eluent) gave selenoimine (34), (6 mg, 4%), ma), 120n121°, (lit.7 m.p. 120-1210).

Formation of Selenoimine (48) using Benzeneseleninyl Chloride and

Ammonia

To the pale yellow solution resulting from treatment of benzenese- 122.

leninyl chloride (103 mg, 0.5 mmol) with liquid ammonia (2 ml), (see above), was added a solution of 2-naphthol (72 mg, 0.5 mmol) in dichloromethane

(3 ml). The mixture was stirred for 1 h, during which time a pale orange colour developed. Concentration under reduced pressure, followed by p.1,c. (on silica gel, eluting three times with ether/petrol, 5%) gave selenoimine (48), (7.8 mg, 5%) m.p. 124-126° (lit.7 m.p. 126-127°). No trace of selenoimine (47) could be detected.

Conversion of Benzhydrol to Benzophenone using Benzeneseleninic Anhydride

A solution of benzhydrol (92 mg, 0.5 mmol) in dry THF (15 ml) was treated with benzeneseleninic anhydride (180 mg, 0.5 mmol). The mixture was heated under reflux for 3 h, by which time t.l.c. showed complete absence of benzhydrol. The solution was cooled to room temperature, concentrated under reduced pressure and p.l.c. (on silica-gel using ether/petrol, 5% as eluent) afforded benzophenone (77 mg, 85%) as white o 5 o crystals m.p. 47-49 (lit. m,p. 49 ).

Conversion of Hydrobenzoin to Benzil using Benzeneseleninic Anhydride

A solution of hydrobenzoin (107 mg, 0.5 mmol) in dry THF (5 ml) was treated with benzeneseleninic anhydride (360 mg, 1 mmol). The mixture was heated under reflux for 3 h, by which time, t.l.c. showed complete absence of hydrobenzoin. Benzoin was formed during the reaction but this was subsequently oxidised further. the solution was cooled to room temperature, concentrated under reduced pressure and p.l.c. (on silica gel using ether/petrol, 5% as eluent) afforded benzil (81 mg, 77%) as pale yellow crystals, m.p. 93-95°, (lit.5 m.p. 950). 123.

Conversion of Benzoin to Benzil using Benzenescloninic Anhydride

A solution of benzoin (106 mg, 0.5 mmol) in d22/ THE (15 ml ) was

treated with benzeneseleninic anhydride (180 mg, 0.5 mmol). The mixture

was heated under reflux for 3 h, by which time t.l.c. showed complete

absence of benzoin. The solution was cooled to room temperature, con-

centrated under reduced pressure and p.l.c. (on silica-gel, using ether/

petroleum, 5% as eluent) afforded benzil (96 mg, 92%) as pale yellow

crystals, m.p. 93-95°, (lit.5 m.p. 95°).

Conversion of Benzilic Acid to Benzophenone using Benzeneseleninic

Anhydride

A solution of benzilic acid (228 mg, 1 mmol) in dry toluene (10 ml)

was treated with benzeneseleninic anhydride (360 mg, 1 mmol). The

mixture was heated at 100° for 24 h. T.l.c. showed that most of the start-

ing material was still present. Addition of more oxidant had no notice-

able effect. The solution was cooled to room temperature, filtered and

concentrated under reduced pressure. P.l.c. (on silica-gel, using ether/

petrol, 5% as eluent)gave benzophenone (9 mg, 5% as a white crystalline o 5 solid, m,p. 48-49 (lit. m.p. 490).

Iodimetric Titration Procedure for Studying Phenol Oxidations with

Benzeneseleninic Anhydride

In a typical run, a solution of the phenol (0.25 mmol) in dry THE

(4 ml) was treated with benzeneseleninic anhydride (90 mg, 0.25 mmol)

with stirring at room temperature. To measure the oxidising ability of the reaction mixture at a given time, the solution was quenched with dilute

sulphuric acid (2N, 10 ml) and extracted with diethylether (2 x 10 ml).

The aqueous phase was added to an acidic solution of potassium iodide

(0,5 g in 10 ml 2NH2SO4) and ethanol (10 ml) was added. The liberated

iodine was titrated with aqueous sodium thiosulphate solution (0.1 N) 124.

using starch indicator.

The diphenyldiselenide was recovered by column chromatography

(silica gel, using petrol as eluent).

The general procedure was also applicable where further reagents,

e,g, hexamethyldisilazane were present in the reaction mixture.

In order to recover the expected amount of diphenyldiselenide

from the hydroxylation reactions, it was found necessary to quench the reaction mixture with an aqueous solution of potassium dihydrogen-

phosphate buffer solution (10%) instead of sulphuric acid.

The experimental results are tabulated in the Discussion section. 125.

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