Bull. SOC. Chim. Belg. vol. 82/n" 3-4/ 1973

SYNTHESIS OF a,B-UNSATURATED ORTHO-HYDROXY AROMATIC KETONES BY FRIES

REARRANGEMENT OF a,B-UNSATURATED PARA-CRESYLESTERS.

C. Van de Sandex and M. Vandewalle Department of Organic Chemistry, State University of Ghent,

Krijgslaan, 271, S.4, 8-9000 Gent, Belgium. Received 5.02.73 - Accepted 14.02.73

ABSTRACT : The Fries rearrangement of a,E-unsaturated para-cresyl esters is reinvesti- gated. Spectroscopic data are included.

INTRODUCTION.

In the Fries rearrangement phenolic esters are converted into the corres-

ponding ortho- and para-hydroxy ketones by the action of anhydrous aluminium

chloride. The reaction is of general application to phenolic esters of satu-

rated aliphatic acids. Little work however has been carried out with unsatu-

rated phenolic esters, and only few spectroscopic data have been presented.

Colonge and Chambard'l) studied the behaviour of acrylic, methacrylic, dime-

thylacrylic, crotonic and cinnamic esters when subjected to the action of a

suspension of aluminium chloride in carbon disulphide. Very poor yields of

hydroxy ketones were observed. Sven and coworker^(^-^) found that the pre- dicted ortho-hydroxy ketones were obtained in fairly good yields if no solvent

was used, i.e. if the ester was heated with finely powdered anhydrous aluminium

chloride. The ortho hydroxy ketones I could not be obtained completely pure

and presented themselves as oils; they were isolated as the 2,4-dinitrophenyl-

hydrazones and the yields then were 31 to 86 %.

5' 0 0

I II: m Ia : R = Me

Ib : R = Et

Ic : R = n.Pr

Id : R = i.Pr

Ie : R = n.Bu

If : R = i.Bu

Bursary of the National Foundation for Scientific Pesearch.

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I n connection with mass s p e c t r a l s t u d i e s ( 9 ) , w e were i n t e r e s t e d i n t h e

ortho-hydroxy ketones I , of which Ia, Ic and Id were repor ted by Sven and a 1 ( 2 f 5 ) '

Therefore t h e r e a c t i o n of para-cresy les te rs I1 with anhydrous aluminium chlo-

r i d e was re inves t iga ted .

DISCUSSION.

Following r e s u l t s were obtained :

1) The hydro lys is of t h e r e a c t i o n mixture by a d d i t i o n of ice and d i l u t e hydro-

gen c h l o r i d e r e s u l t e d i n t h e ortho-hydroxy ketones I contaminated by some

5-10 0 of t h e isomeric chroman-4-ones 111. Probably t h i s c y c l i s a t i o n i s

caused by the s t r o n g l y exothermal hydro lys is as g e n t l e hea t ing of 2-hydroxy-

crotonophenone i n a c i d i c medium indeed y i e l d s 2-methyl-chroman-4-one . The formation of chroman-4-ones I11 can be reduced to 1-2 % i f t h e cooled

r e a c t i o n mixture is f i r s t f i n e l y crushed and then slowly added t o ice and

d i l u t e hydrogen c h l o r i d e under vigorous s t i r r i n g .

2 ) Separat ion of t h e products cannot be achieved by d i s t i l l a t i o n i n vacuum.

Canpounds I,, Ib and 1, separa ted by adsorp t ion chromatography are c r y s t a l -

l i n e s o l i d s , i n c o n t r a s t with t h e observat ion of Sven t h a t 1, and Ic were

o i l s .

por ted by Amakasu'l') who prepared t h i s compound by another route .

The melt ing poin t of 1, (54-55') i s i n agreement with t h e va lue re-

TLC and combined s p e c t r a l a n a l y s i s were used t o check p u r i t y of a l l t h e com-

pounds i s o l a t e d . The s p e c t r a l d a t a are c o n s i s t e n t wi th t h e proposed s t r u c t u r e s :

- UV-spectra a r e charac te r i sed by absorp t ion a t Amax % 355 nm ( E %44500) and

272 nm ( E 17000).

- In t h e IR-spectra t h e OH-stretching band i s broad and f a i r l y weak, due t o

hydrogen bonding.

t u r a t e d ketone) and a t r a n s double bond wagging band near 900 cm-' confirm

t h e presence of t h e enone moiety.

A carbonyl s t r e t c h i n g band near 1650 c m - l (a, B,a', B'-unsa-

- Mass s p e c t r a l fragmentation mainly occurs through loss of t h e R-group ( m / e - 1 6 1 ) and f i s s i o n of t h e C1-C2 bonds ( m / e = 135) . All molecular i o n s a r e pre-

s e n t with moderate abundance (10 - 2 0 % of base peak) . The elemental compo-

s i t i o n s were confirmed by high r e s o l u t i o n mass s p e c t r m e t r y .

- Complete a n a l y s i s of t h e 6 0 MHz 'H-NMR s p e c t r a i s impossible because of over-

l a p of t h e s i g n a l s f o r aromatic (3'H; 4 ' H ; 6'H) and o l e f i n i c protons ( 2 H ; 3H).

The p u r i t y of t h e samples is however evidenced by t h e absence of any s i g n a l

a t 6 - 5.9 (2H i n compounds 11) and a t 6 % 4.3-4.4 ( 2 H i n compounds 111).

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- The a romat i c s u b s t i t u t i o n as w e l l as t h e t r a n s c o n f i g u r a t i o n o f t h e enone

carbon-carbon doub le bond are confirmed by 300 MHz 'H-NMR s t u d i e s : 6 5 6.8

(3 'H); 7 .2(4 'H); 7 .5(6 'H) and J 5 8 . 5 ( 3 ' - 4 ' ) ; 2 . 0 ( 4 ' - 6 ' ) ; 15.0(2-3) ; 1.1

(2-4 ) ; 6.8 (3 -4 ) .

EXPERIMENTAL SECTION.

The esters I1 were p repa red acco rd ing t o methods d e s c r i b e d i n l i tera-

t u r e ( 2 ) . UV- and IR-spectra were recorded on a Cary 15 and a Pye-Unicam SP

1000 spec t romete r r e s p e c t i v e l y . Mass s p e c t r a were o b t a i n e d on an AEI-MS902

mass spec t romete r . High r e s o l u t i o n neasurements were c a r r i e d o u t a t a reso-

l u t i o n of 15000. NMR-spectra were reco rded on a Varian A-60 and a Var i an

HR-300.

General procedure f o r p r e p a r a t i o n of compounds I.

The ester I1 (0.03 mole) i s w e l l s t i r r e d and cooled. F i n e l y powdered

anhydrous aluminium c h l o r i d e (0.045 mole) i s added i n small p o r t i o n s over a

p e r i o d of 15 minutes . The r e a c t i o n mix tu re is t hen g r a d u a l l y hea ted (30 min.)

t o 140-145OC and l e f t a t t h i s t empera tu re f o r 3 hours . The coo led r e a c t i o n

mix tu re is ground i n a mortar and s lowly added t o ice and d i l u t e hydrogen

c h l o r i d e under v igo rous s t i r r i n g . The oily or gummy p r e c i p i t a t e is e x t r a c t e d

wi th benzene. The combined e x t r a c t s are washed w i t h a 1 % aqueous b i c a r b o n a t e

s o l u t i o n , water and then d r i e d ove r MgS04.

d i s t i l l e d and chromatographed on a s i l i c a column (30 g s i l i c a / l g mix tu re )

u s i n g i s o o c t a n e - e t h e r ( 2 0 : l ) ; t h e f r a c t i o n s e l u t e d are checked by TLC on si-

l i ca .

A f t e r e v a p o r a t i o n t h e r e s i d u e is

I f t h e s t a r t i n g material is s o l i d , t h e ester I1 is w e l l n i x e d w i t h a lu -

minium c h l o r i d e and t h e r e s u l t i n g mass s lowly hea ted u n t i l r e a c t i o n o c c u r s .

Heat ing is i n t e r r u p t e d when t h e c o n t e n t s of t h e f l a s k are comple t e ly l i q u e f i e d .

The r e a c t i o n mix tu re i s then f u r t h e r t r e a t e d as mentioned above.

l-(2'-hydroxy-5'-methyl-phenyl)-but-2-en-l-one ( I ) .

Yield : 61 %; mpt. 54-55'C; Rfcbenzene, sa t . ) : 0.52.

UV : Amax (methanol) = 355 run ( E = 4700); 272 nm ( E = 17000) .

I R : 3200 cm-'(w) i 1660 cm-'(s); 1590 cm-l(s) ; 1497 c r n - l ( m ) i 1448 cm-'(m) ;

1380 c m - l ( w ) ; 1370 c m - l ( w ) i 1348 c m - l (m) ; 1310 c m - l ( m ) ; 1270 cm-'(m) :

1245 c m - ' ( w ) i 1218 cm- ' (m) ; 1190 cm-'(s); 1035 cm-'(m); 970 cm-l(m).

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MS : m/e : 176(21.5); 175(13); 162(16.2); 161(100): 135(26.5): 134(3.1); 107

(8.2) ; 106 (2.5) ; 105 (3.8) ; 91 (5.5) ; 79 (2.6) ; 78 (3.4) ; 77 (10.5) ; 69 (8.6) ;

53(3.8); 52(2.2); Sl(4.8).

'H-NMR (300 MHz) : CC14

6 = 2.04(4H); 2.31(5'H); 6.80(3'H); 6.99(2H); 7.18(4'H); 7.12(3H); 7.47 (6'H);

12.03(OH).

J = 8.5(3'-4'); 1.9(4'-6'); 14.9(2-3); 1.2(2-4); 6.9(3-4).

1-(2'-hydroxy-5'-methyl-phenyl)-pent-2-en-l-one (I,).

Yield : 42 %; bpt. 124'/0.9 mm; Rf(benzene, sat.) : 0.61; mpt. < 40°C.

UV : Amax (methanol) = 355 nm ( c = 4700); 272 nm ( E = 17000).

IR : 3200 cm-'(w); 1660 cm-'(e.); 1590 cm-l(s); 1492 cm-'(s); 1351 crn-'(m);

1310 cm-l(w) ; 1297 cm'l (w) ; 1272 cm-'(w) ; 1246 c m - l ( r n ) ; 1218 cm-'(m) i

1190 cm-l(s); 1135 cm- ' (m) ; 999 cm-l(rn): 979 cm-'(m).

MS : lgO(11.5); 189(2.5); 162(16.5); 161(100): 135(18); 134(2.0); 107(6.0);

106(2.0); 105(3.5); gl(5.5); 83(2.5); 79(3.0); 78(4.5); 77(14); 53(7.0);

52(3.0); 51(6.0) ;

'H-NMl? (300 MHz) : CC14.

6 = 1.20(5H); 2.31(5'H); 2.42(4H); 6.80(3'H); 6.95(2H); 7.15(3H); 7.22(4'H);

7.47(6'H); 12.33(08).

J = 8.5(3'-4'); 1.9(4'-6'); 15.0(2-3); 1.4(2-4); 6.5(3-4); 7.3(4-5).

1-(2'-hydroxy-5'-methyl-phenyl-n-hex-2-en-l-one (Ir).

Yield : 42 %; mpt. < 40'C; Rf(benzene, sat.) : 0.63.

UV : Amax (methanol) = 355 nm ( E = 4700); 272 nm ( E = 17000).

IR : 3200 cm-'(w); 1655 cm-l(s): 1588 cm-l(s); 1492 cm-'(e); 1370 cm-l(w);

cm-l(s) i 1030 cm-l (w) ; 1345 cm-'(w) ; 1310 cm-l(m) ; 1280 cm-'(m) ; 1187

980 cm-'(m).

MS : m/e : 204(11.0); 203(2.2); 162(17.0); 161(100)

107 (4.8) ; 106 ( 1 . 4 ) ; 105 (2.2) ; 91 (4.0) ; 7 9 (2.1)

52(1.6); 51(3.0).

'H-NMR (300 MHz) : CC14

135 (16.0) ; 134 (1.7) ;

78 (2.8) ; 77 (8.5) ; 53 (3.8) ;

6 = 1.02(6H); 1.60(5H); 2.31(5'H); 2.32(48); 6.80(3'H); 6.96(2H); 7.10(3H);

7.19(4'H); 7.47(6'H); 12.30(OH).

J = 8.5(3'-4'); 2.0(4'-6'); 15.1(2-3); 1.0(2-4); 6.8(3-4); 7.3(4-5); 7.3(5-6).

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l-(2'-hydroxy-5'-methyl-phenyl)-i.hex-2-en-l-one (Id).

Yield : 53 8; bpt. 110°/0.2 nun; Rf(benzene, Sat.) : 0.64.

UV : Amax(methanol) = 355 nm ( E = 4700); 272 nm ( E = 17000).

IR : 3200 cm-'(w) ; 1655 cm-'(s) ; 1594 cm-'(S) ; 1492 cm-l (s) ; 1370 Cm-'(W) i

983 cm-l(m) ; 1349 cm-l(w) ; 1298 cm-'(m) ; 1194 cm-'(m) ; 1D28 cm-l (m) ;

MS : m/e : 204(10.0); 203(0.6); 162(15.0); 161(100); 135(22.0); 134(1.0);

107(3.8); 106(1.0); 105(1.6); 97(2.0); gl(3.0); 79(1.8); 78(3.6); 77t6.8);

53(3.4); 52(1.6); 51(2.8).

'H-NMR (300 M H ~ ) : cci4.

6 = 1.62(5H); 2.30(5'H); 2.58(48); 6.79(3'H); 6.90(2H); 7.06(3H); 7.18(4'H);

7.46(6'H) ; 12.03 (OH).

J = 8.5(3'-4'); 2.0(4'-6'); 15.0(2-3); 1.1(2-4); 6.7(3-4); 6.7(4-5).

1-(2'hydroxy-5'-methyl-phenyl)-n-hept-2-en-l-one (Ip).

Yield : 47 $; bpt. 110°/0.3 mm; Rf(benzene, sat.) : 0.66.

uv : Xmax (methanol) = 354 run ( c = 4800); 272 nm (E =17000).

IR : 3200 cm-'(w) ; 1655 cm-l(s) ; 1594 cm-l(s); 1495 cI'n-l(m) ; 1370 cm-'(W) ;

1350 cm-'(w) ; 1300 cm-'(m) ; 1188 cm-'(m) ; 983 cm-l (w) . MS : m/e : 218(10.0); 217(1.6); 162(14.0); 161(100); 135(23.0); 134(2.2);

lll(9.4); 107(6.4); 106(1.4); 105(2.4); gl(4.7); 79(3.0); 78(2.6);

77(8.2); 53(2.7); 52(1.0); 51(1.8).

'H-NMR (300 M H ~ ) : cci4.

6 = 0.96(78); 1.41(6H); 1.54(5H); 2.30(5'H); 2.33(48); 6.80 (3'H); 6.95(2H);

7.10(3H); 7.19(4'H); 7.47(6'H).

J = 8.6(3'-4'); 2.0(4'-6'); 15.0(2-3); 1.1(2-4); 7.1(3-4); 7.3(4-5); 7.3(5-6);

7.2(6-7).

1-(2'-hydroxy-5'-methyl-phenyl)-i.henyl)-i.hept-2-en-l-one (If).

Yield : 44 8; bpt. 128'/0.9 nun; Rf(benzene, sat.) : 0.67.

UV : Amax(methanol) = 355 nm (E = 4800); 272 nm ( E = 17000).

IR : 3200 cm-'(w) ; 1655 cm-'(s) ; 1593 cm-'(s) ; 1492 cm-l(m) ; 1370 cm-'(w) ;

1310 cm-'(w) ; 1290 cm-'(m) ; 1188 cm-'(m); 983 cm-l(w).

MS : m/e : 218 (17.0) ; 217 (2.0) ; 162 (13.8) ; 161(100) i 135 (39.0) ; 134 (4.0) ;

lll(27.0) ; 107 (10.5) ; 106 (1.5) ; 105 (3.0) ; gl(5.0) ; 79 (4.5) i 78 (4.0) ;

77(12.0); 53(5.0); 52(2.5); 51(4.5).

- 3 0 3 -

~H-NMR (300 M H ~ ) : cci4.

6 = 0.98(6H); 1.85(58); 2.22(4H); 2.30(5'H); 6.79(3'H); 6.94(2H); 7.08(3H);

7.18 (4'H) ; 7.47 (6'H).

J = 8.5(3'-4'); 2.0(4'-6'); 15.0(2-3); 1.1(2-4); 6.8(3-4); 7 . 0 ( 4 - 5 ) ; 6.8(5-6).

ACKNOWLEDGEMENTS.

We thank the "Nationaal Fonds voor Wetenschappelijk Onderzoek" for financial

support to the laboratory and for a grant to one of us (C.V., Aspirant NFWO).

REFERENCES.

1) J. Colonge, R . Chambard; Bull. SOC. Chim. France 573 (1953).

2) A.B. Sven, V.S. Misrai J. Indian Chem. SOC., 25, 393 (1948). 3) A.B. Sven, V.S. Misra; ibid. 26, 149 (1949). 4 ) A.B. Sven, V.S. Misra; ibid. 2, 337 (1949). 5) A.B. Sven, V.S. Misra; ibid. 3, 339 (1949). 6) A.B. Sven, S.S. Parmar ibid., 2, 661 (1951). 7) A.B. Sven, S.S. Parmar ibid., 30, 720 (1953).

8 ) G.W.K. Cavill, F.M. Dean, A. MC Gookin, B.M. Marshall, A. Robertsonj

9) C. Van de Sande, J. Serum, M. Vandewalle; Org. Mass Spectrometry, 5(12),

J. Chem. SOC. 4573 (1954).

1333 (1972).

10) T. Amakasu, K. Sato; J. Org. Chem., 2(5), 1433 (1966).

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