Indian Journal of Chemistry Vol. 41B, July 2002, pp. 1460-1466

Interesting product formation during O-alkylation and subsequent rearrangement of two building blocks of dibromotyrosine based natural products

Uppuluri V Mallavadhani*, Anita Mahapatra, K Narasimhan & L D Sahoo

Forest and Marine Products Division, Regional Research Laboratory (CSIR), Bhubaneswar 751 01 3, India

Received 26 June 2001; accepted (revised) 8 January 2002

The a-alkylation (allylationipropargylation) of 3,5-dibromo-4-hydroxybenzaldehyde 1 and the corresponding acetophenone 2 results in the formation of aryl-aryl coupled product by loss of formyl groups, aryl-aryl ether and aryloxy acetone in addi tion to the expected 0-allyl! propargyl ethers. While the thermal Claisen rearrangement of allyl ethers 1 and 2 furnishes the C-allyl products by loss of bromine, the propargyl ether 7 surprisingly resisted rearrangement and underwent oxidation to yield the corresponding carboxyl ic acid.

Sponges of the order Verongeda are known to elabo­rate a variety of pharmacologically active dibromotyro­sine based natural products. Most of the metabolites are found with either oxazolidone rings or spiroxazoline systems or both. I

Synthesis of such metabolites is chaJlenging and of current interest. 3,5-Dibromo-4-hydroxybenzaldehyde 1 and the corresponding acetophenone 2 are found to be the key synthons for a number of dibromotyrosine based natural products.2

.3 In fact compound 1 was iso­lated from the chlorofonn extract of the marine annelid Thelepus setosus by Higa et at. 4.5

4:° 4:CH3 h Ih

Sr Sr Sr Sr

OH OH

2

In connection with our development work on Ve­rongeda metabol ites, we require large quantities of allyl ethers of 1 and 2. During the course of 0-allylation/propargylation reactions and subsequent rear­rangement studies, we observed very interesting prod­uct formation (Scheme I).

Generally, O-all y lationJpropargy lation reactions have been reponedly carried out in acetone solvent. Since, compound 1 is an aldehyde and there is a possi­bility of its condensation with solvent acetone, the ini­tial O-allylation reactions were studied in the absence of acetone under a variety of experimental conditions including PTe. However, the required O-allyl com­pound was obtained in very poor yields. Hence, the reaction was studied under conventional O-allylation

conditions (allyl bromide - K2C03 - acetone). Al­though, the required allyl ether 3 (m.p.78°C) was ob­tained in 60% yield, the two expected side Claisen­Schmidt products 4 and 5 were also formed in 6% and 25% respectively. As the vruiation in experimental conditions could not prevent the side product forma­tion, compound 1 was subjected to O-propargylation under identical experimental conditions to see the ef­fect of allylating agent on the side product formation. Significantly this reaction furnished the expected propargyl ether 7 (20%), two Claisen-Schmidt conden­sation products 8 (8%), 9 (21.5%) and an additional and most interesting compound 6 (3.60%, m.p. 135 -36°C). Compound 6 was characterised by physical, chemical and spectroscopic data (IH NMR, IR and Mass) as 1,1'-dipropargyloxy-2,2',6,6'-tertabromo­biphenyl, which is a dimer of 2,6-dibromopropargyloxy aryl ether coupled at 4-position. The fonnation of 6 by the loss of formyl group followed by aryl-aryl coupling is very unusual under the conditions studied. Generally, the defonnylation was reported with the use of metals at elevated temperatures or under photochemical condi­tions.6

.g

To the best of our knowledge this is the first report of loss of formyl group followed by aryl-aryl coupling during mild allylation conditions.

As there is no change on the side product fonnation even by changing the allylating agent, we have ex­tended our studies to the corresponding 3,5-dibromo-4-hydroxyacetophenone 2. Although, no condensation products were obtained in this case, the reaction gave still interesting results. Compound 2 under identical allylation conditions furnished the required allyl ether 10 (45 %, m.p. 54-55°C) alongwith an aryl-aryl ether 11 (6.5%, m.p. 204°C) and an aryloxy acetone 12 (8.5%,

MALLAVADHANI et al. : O-ALKYLATION OF 3,5-DIBROMO-4-HYDROXYBENZALDEHYDEIACETOPHENONE 1461

(ii)

CHO/ ~ CHO

+ + S Sr Sr Sr Sr

y 3 5 13 4 CHO

~ / (iv)

Sr Sr

H

~ ~ CHO

Sr

+ + + Sr Sr Sr

Sr 7 8 9

~ COOH 6

COCH3

Sr Sr

Sr Sr 14 ~

H ~ COCH3 COCH3 COCH3 2

~ ?(COCH3 + I +

Sr Sr Sr ~ ~ Sr Sr

7 COCH3 ~ r

10 11 12

Sr '-':::

H

15

Reagents and conditions: (i) Allyl bromide-acetone-K2C03, reflux, 6 hr; (ii) Acetone-K2C03,stirring, Room Temp. ,1 hr;

(iii) Propargyl bromide-acetone-K2C03,rerflux, 6 hr; (iv) crXylene, reflux, 10 hr; (v) Liquid paraffin, /). , (225 DC) , 5 hr

Scheme I

1462 INDIAN J. CHEM., SEC B, JULY 2002

m.p. 82-83°C). Based on physical, chemical and spec­troscopic data, compound 12 was characterized as 1-(4'-acety 1-3' ,5'-dibromoarylox y )acetone.

Compound 12 can be formed either via ally l ether 10 or by direct alky lation of compound 2 with bro­moacetone. The latter process can be ruled out, as bromoacetone formation is difficult in the absence of free bromjne. It is noteworthy to mention here that

. there is no effect of K2C03, whether it is freshly cal­cined or uncalcined, on the formation of 12. Literature search revealed that allyl group can be converted to the corresponding ketone in two different ways such as i) palladium catalysed oxidation with or without an iron complex9" o and ii) bromination followed by hy­drolysis and oxidation of the resulting secondary al­cohol with oxidants like oxyhalides ll and halates l2

•

Method (ii) may be reasonable here but formation of such oxidants in the conditions used is rather unusual. Under these circumstances, it is presumed that com­pound 12 might be formed from 10 by Markownikoff's addition of the liberated HBr to the allyl ether to produce secondary bromo compound lOA followed by hydrolysis to secondary alcohol l OB with acetone / K2C03 and subsequent oxidation to the ketone l3 (Scheme II).

Compounds 3, 7 and 10 with all the arrha and para positions blocked, form as useful models for Claisen

d· 14- 16 Cl rearrangement stu res . ean rearrangement was observed for compounds 3 and 10 in a-xylene and

10 HBr

•

10A

B

gave compounds 13 (46%, m.p. 75-76°C) and 15 (33%, m.p. 126-27°C) respectively. The formation of compounds 13 and 15 can be rationalised in terms of symmetry allowed [3,3] allyl shift fo llowed by loss of bromonium ion during aromatisation step (Schem e III).

However, the propargyl ether surprisingly resisted rearrangement in most of the solvents tried, but found to undergo oxidation to the corresponding carboxylic acid 14 (15%, m. p. 184-86°C) when heated in liquid paraffin at 225°C.

Experimen tal Section Melting points were determined on Bucchi appara­

tus in open capillaries and are uncorrected. IR spectra were recorded on a lASCO-5300 Fr-IR Spectropho­tometer as KBr pellets or neat and band positions were reported in wave numbers (cm· I

) ; 'H NMR spec­tra on a Bruker ACF-200 (GEMINI-200) Spectropho­tometer in CDCl3 with TMS as intemal standard; and mass spectra on a VG micro mass 70-70 H instrument or on lEOL lMS-DX 303 GC-MS in trument. Acme grade silica gel-G for TLC and silica gel 100-200 mesh for column chromatography were used through­out the work.

3,5-Dibromo-4-hydroxybenzaldehyd e 1. To a stirred mixture of 4-hydroxybenzaldehyde (8.5g, 69.5 mmoles) in acetic acid (100 mL), bromine (7.5 mL) in acetic acid (40 mL) was added dropwise over a period

[0 )

Br

OH 108 12

Scheme II - Probable pathway for the formation of 12

R R R

* [3,3) ~ • •

Br h- Br Br Br h- "

~ OH

3. R = CHO 13.R=CHO

7. R = COCH3 15. R = COCH3

Scheme III

MALLAVADHANI el al. : O-ALKYLATION OF 3,5-DIBROMO-4-HYDROXYBENZALDEHYDEIACETOPHENONE 1463

of 15 min. The reaction mixture was stirred at room temperature for a further period of 15 min. The resulting orange red coloured solution was poured onto ice cold water (2.5 litre) with stirring to give a pale yellow curdy precipitate. The precipitate was filtered under suction and washed with excess sodium metabisulphite solution . The resulting solid on recrystallisation from methanol gave compound 1 as colourless sh ining needles (17.24 g, 88%), m.p. 186-87°C (lit. 17, m.p.181 0C) .

3,5-Dibromo-4-hydroxyacetophenone 2. Bromine (4.7 mL) in acetic acid (80 mL) was added dropwise through a separating funnel to 4-hydroxyace­tophenone (6 g, 44 mmoles) in a mixture of acetic acid (10 mL) and water (28 mL) over a period of 15 min. with stirring. After addition of bromine the reac­tion mixture was further stirred for 15 min. The re­sulting orange red coloured solution was poured onto ice cold water (1 Itr) with stirring to give a pale curdy precipitate. The precipitate was filtered under suction and washed with excess saturated sodium metabisul­phite solution. The residue on recrystallisation from methanol gave compound 2 as colourless hard shining needles (9.67 g, 75 %), m.p. 186-87°C (1it. IS , m.p. 187°C).

Allylation of compound 1. A mixture of compound 1 (5 g, 17.83 mmoles), allyl bromide (2.3 mL, 26.66 mmoles) and freshly ignited K2C03 (4.68g, 26.66 mmoles) was refluxed in dry acetone (100 mL) for 6 hr, by which time no starting material was found on TLC. After cooling to room temperature the reaction mixture was filtered to remove K2C03. The filtrate on evaporation under reduced pressure gave a pale yellow oil (8.33 g), which showed three major spots on TLC (Rr 0.83,0.37 and 0.13; benzene). The above reaction mixture was chromatographed over a column of silica gel eluted with solvents of increasing polarity. Compound 3 (3.42 g) was obtained from n­hexane elution, whereas compound 4 (0.33 g) and compound 5 (1.6 g) were obtained from n-hexane -ethyl acetate (95:5) and n-hexane - ethyl acetate (90: 10) mixtures, respectively.

4-Allyloxy-3,5-dibromobenzaldehyde 3. Obtained as colourless shinning needles (3.42 g, 60%), m.p. 78°C; Rr: 0.83 (benzene); Ferric colour test: -ve; IR (KBr) : 1691 (-C=O), 1579, 1543, 1452, 1417, 1361, 1182, 978, 952, 871, 746, 733 and 671; IH NMR : 8 4.61 (d, 2H, J=5.86 Hz, -OCH2), 5.38 (m, 2H, =CH2), 6.15 (m, 1 H, -CH=), 8.0 (s, 2H,Ar-H) and 9.83 (s, 1 H,-CHO); Mass (mlz, %) : 322 (M+ +4, 6.5), 320 (M++2, 19.5), 318 (M+, 7.8), 281 (3.9), 279(16.7),

277(5.2), 242(6.5), 240 (6.5), 132(20.8), 75 (10), 41(100). Anal. Calcd for CIOHsBr202 : C,37.50 ; H, 2.50. Found: C, 37.63; H, 2.42%.

l-Acetyl-2-(4-allyloxy-3,5-dibromophenyl) ethy­lene 4. Obtained as pale yellow oil (330 mg, 5%); Rr 0.37 (benzene); Ferric colour test: -ve; IR (neat) : 1707 (-C=O), 1664, 1639, 1608, 1537, 1467, 1419, 1359, 1263, 976, 923 and 742; 'H NMR : 82.40 (s, 3H, -COCH3), 4.62 (dd, 2H, J = 5.86Hz , -OCH2) ' 5.42 (m, 2H, -CH2), 6.18 (m, 1 H, -CH=), 6.66 (d, IH, J = 16.28 Hz, -CH=CH-), 7.36 (d, IH, J =16.2 Hz, -CH=CH-) 7.72 (s, 2H, Ar-H); Mass (mlz, %) : 358 (M+, 8.2), 320 (1.5), 318(8.2), 316 (1.5), 292(1.5), 290(5.9), 288(1.5), 280(11.2), 278(11.2), 103(9.7), 43(55.9), 41(100). Anal. Calcd for CI3HI2Br20 2 : C,43.33 ; H, 3.33. Found: C, 43.47; H, 3.07%.

l-Acetyl-2-( 4'-allyloxy-3' ,5'-dibromophenyl) etha­nol5. Obtained as colourless oil (1.6 g, 25%); Rr O.13 (benzene); Ferric colour test: -ve; IR (neat) : 3460 (-OH), 1712 (-C=O), 1672, 1645, 1610, 1537, 1466, 1359, 1259, 1082, 978, 738; IHNMR : 8 2.22(s,3H, -COCH3) , 2.82(d, 2H, J =5.29 Hz, -CH2 -),3.6 (br.s, IH, -OH),4.53 (d, 2H, J = 5.86Hz, -OCH2), 5.07 (t, IH, -CHOH), 5.39 (m, 2H, =CH2), 6.2 (m, IH, -CH=), 7.5 (s, 2H, 2 x Ar-H); Mass (mlz, %) : 380 (M++4, 1.49), 378 (M++2, 2.22), 376 (M+, 1.49), 321 (7.4), 241 (3 .7) , 239 (4.4), 85 (20.8), 69 (13.4), 41 (100). Anal. Calcd for C13HI4Br203 : C,41.26 ; H, 3.70. Found: C, 41.12; H, 3.80%.

Propargylation of compound 1. A mixture of compound 1 (1.9 g, 6.7 mmoles), propargyl bromide (0.9 mL, 10 mmoles), K2C03 (1.4 g, 10 mmoles) was refluxed in acetone (50 mL) for 6 hr. The reaction mixture after usual work up followed by column chromatography over si lica gel eluted with solvents of increasing polarity. Compound 6 (150 mg) was obtained from n-hexane elution whereas compounds 7(430 mg), 8(200 mg), and 9 (550 mg) were obtained from n-hexane-ethyl acetate (98:2), n-hexane-ethyl acetate (95:5), n-hexane-ethyl acetate (85: 15) mixtures respectively.

1,l'-Dipropargyloxy-2,2' ,6,6'-tetrabromo biphenyl 6. Obtained as colourless shining needles (150 mg, 3.60%), m.p. 135-36°C; Rr 0.64 (n-hexane-benzene, 90:10); Ferric colour test: -ve; 2,4-DNP : -ve; IR (KBr) : 3285, 3067, 2361, 1558, 1539, 1439, 1419, 1365, 1244, 1064,993,954,854,738,680; IH NMR : 82.59 (t, IH, =CH), 4.79 (d, 2H, J=2.44 Hz, -OCH2)' 7.7 (s, 2H, 2 x Ar-H); Mass (mlz, %); 371 (5.9), 369 (28.3), 367 (29.8), 365 (7.4), 340 (l0.4), 338 (11.9),

1464 INDIAN J. CHEM., SEC B, JULY 2002

332 (17.9), 331 (64.1), 329 (67.1), 326 (20.8), 303 (33.5), 301 (34.3), 291 (47.7), 289 (100), 287 (C9HsOBr2, 49.2), 250 (7.4), 222 (4.4), 182 (8.9), 180 (11.9), 143 (35.0), 141 (38.8), 101 (16.4), 74 (13.4), 62 (79.1), 39 (83.5). Anal. Calcd for C,gH IOBr402 : C,37.37 ; H, 1.73. Found: C, 37.30; H, 1.80%.

3,5-Dibromo-4-propargyloxybenzaldehyde 7. Obtained as shining plates (430 mg, 20%), m.p. 135°C; Rr : 0.66 (n-hexane-ethyl acetate, 95 :5); Ferric colour test: -ve ; IR (KBr) : 3254, 2125, 1693, 1577, 1547, 1440,1361,1257, 1188,1066, 981, 922, 875, 746; 'H NMR: 8 2.57(t,lH, =CH), 4.77 (d, 2H, 1 =2.69 Hz, -OCH2), 8.05 (s, 2H, 2 x Ar-H), 9.88 (s, IH, -CHO); Mass (mlz, %) : 320 (M++4, 7.2), 318 (M++2, 14.5),3 16 (M+, 7.2), 291 (5.4),289 (9.0),287 (5.4), 281 (1.8), 279 (3.6), 277 (1.8), 253 (5.4), 251 (9.0), 249 (5.4), 239 (90), 237 (94.5), 225 (20.0), 223 (41.8),221 (21.8), 172 (12.7), 170 (12.7), 143 (18.0), 141 (18.0), 102 (32.7), 75 (20.0),74 (20.0), 63 (61.8), 62 (64.5), 61 (30.9), 39 (100), 28 (43.6). Anal. Calcd for C,oH6Br202 : C,37.73 ; H, 1.88. Found: C, 37.78; H,I.84%.

l-Acetyl-2-(4'-propargyloxy-3' ,5'-dibromophenyl) ethylene 8. Obtained as colourless needles (200 mg, 8%) m.p. 98 - 102°C; Rr 0.38 (n-hexane-ethyl acetate, 95:5); Ferric colour test: -ve; IR (KBr) : 3296, 3225, 2129, 1684, 1668, 1614, 1537, 1464, 1444, 1365, 126 1,999,979, 744,636; 'H NMR : 82.38 (s, 3H, -COCH3), 2.58 (t, IH, =CH), 4.8 (d, 2H, 1=2.28 Hz, -OCH2), 6.65 (d, IH, -CH), 7.33 (d, IH, 1=16.2 Hz, =CH), 7.7 (s, 2H, 2 x Ar-H); Mass (mlz, %) : 360 (M++4, 31.3), 358 (M++2, 77.6), 356 (M+, 37.3), 321 (46.2), 319 (97), 317 (49.2), 293 (23.8), 291 (53.7), 289 (26 .8), 279 (70.1), 277 (71.6), 240 (10.4), 210 (29.8), 197 (8.9), 195 (8.9), 184 (11.9), 182 (11.9), 169 (26.1), 167 (25.3), 131 (25.3), 116 (29.8), 103 (70.1), 102 (31.3), 88 (34.3), 62 (32.8),43 (100), 39 (88). Anal. Calcd for C13H IOBr20 2 : C,43.57 ; H, 2.79. Found: C, 43.98; H, 2.63%.

l-Acetyl-2-( 4'-propargyloxy-3' ,5' -dibromophenyl) ethanol 9. Obtained as pale yellow oil (550 mg, 21.5%): Rr 0.17(n-hexane-ethyl acetate,90: 10); Ferric colour test: -ve; IR (neat): 3437,3296,2127, 1711, 1547, 1460, 1365, 1255, 1066, 987, 877, 740; 'H NMR : 8 2.27 (s,3H,-COCH3), 2.59 (t,IH, =CH), 2.84(d,2H, 1=6.7Hz, -CHOH-CH2 -COCH3), 3.61 (br. s, IH, -OH), 4.76 (d, 2H, 1=2.24 Hz, -OCH2), 5.09 Ct, 1 H, -CH-OH), 7.54 (s, 2H, 2 x Ar-H); Mass (mlz) : 378 (M++4), 376 (M++2), 374 (M+), 321, 319, 317, 239,237,216,214, 131, 102,85,63,58,43 (100%).

Anal. Calcd for C13H'2Br203 : C,41.48 ; H, 3.19. Found: C, 41.52; H, 3.15%.

Allylation of compound 2. Compound 2 (1.97 g, 6.6 mmoles) was refluxed with a mixture of allyl bromide (1.15 mL, 13.2 mmoles) and K2C03 (1.82 g, 13.2 mmoles) in acetone (50 mL) for 6 hr. After usual work up the reaction mixture showed 3 major spots on TLC (Rr : 0.73, 0.54, 0.40, n-hexane-ethyl acetate, 90: 10). The reaction mixture (2 .5 g) was subjected to column chromatography over silica gel (100 g) and eluted with solvents of increasing polarity. Compound 10(1.0 g), 11(235 mg) and 12(200 mg) were obtained from n-hexane-ethyl acetate (98:2) , n-hexane-ethyl acetate(95:5) and n-hexane-ethyl acetate(85: 15) mixtures, respectively.

4-Allyloxy-3,5-dibromoacetophenone 10. Obtained as colourless shining needles (1.0 g, 45%); m.p. 54-55°; Rr 0.73 (n-hexane-ethyl acetate, 90: 10); Ferric colour test: -ve; IR (KBr) : 3443, 3074, 2862, 1682, 1583, 1543, 1464, 1371, 1265, 1095,976,922, 887, 736, 607; 'H NMR : 8 2.55 (s, 3H, -COCH3), 4.58 (dd, 2H, -OCH2), 5.4 (m, 2H, =CH2) , 6.15 (m, 1 H, -CH=), 8.1 (s, 2H, 2 x Ar-H) ; Mass (m/z, %) : 336 (M++4, 15),334 (M++2, 30), 332 (M+, 15),32 1 (8.3), 319 (20), 317 (8.3), 281 (6.6), 279 (3 1.6), 277 (6.6), 267 (11.6), 265 (23.5), 263 (12.5), 255 (21.6), 253 (25), 199(10), 197 (11.6), 158 (58), 156 (61), 143 (58 .3), 141 (61.6), 103 (20), 102 (15), 90 (35), 77 (65), 74 (68.3), 41 (100). Anal. Calcd for CIIH IOBr20 2: C,39.52 ; H, 2.99. Found: C, 39.72; H, 2.90%.

6-Allyloxy-3,4'-diacetyl-5,Z' ,6' -tribromodiphenyl ether 11. Obtained as colourless amorphous powder (235 mg, 6.5%); m.p. 204°C; Rr : 0.54 (n-hexane­ethyl acetate, 90: 10); Ferric colour test: -ve; IR (KEr) : 1678, 1597, 1400, 1371 , 1269, 1165, 1066, 935; 'H NMR: 8 2.77 (s,3H,-COCH3), 2.95 (s,3H,­COCH3), 4.82 (d,2H. 1=4.8 Hz, -OCH2), 5.5 (m, 2H, =CH2), 6.25 (m, IH, -CH=), 7.25 (s, IH, Ar-H), 8.2 (s, 2H, 2 x Ar-H), 8.65 (s, IH, Ar-H); Mass (mlz, %): 550 (M++6), 548 (M++4, 2%), 546 (M++2, 15.6),544 (M+, 15.6), 542 (6.0), 321 (25), 319 (58), 317 (25), 278 (11), 277 (22), 275 (CgHsOBr2 ,12), 271 (4),269 (C II HIO0 3Br, 4). Anal. Calcd fo r C'9H'SBr304 : C,41.68 ; H, 2.74%. Found: C, 41.55 ; H, 2.84%.

1-(4'-Acetyl-3',5'-dibromoaryloxy) acetone 12. Obtained as colourless shining needles (200 mg, 8.5%); m.p. 82-83°C; Rr. 0.4 (n-hexane-ethyl acetate, 90: 10); Ferric colour test: -ve; IR (KBr) : 1734, 1682, 1579, 1541, 1460, 1385, 1284, 1261, 1033,962,883,

MALLAVADHANI et al. : O-ALKYLATION OF 3,5-DIBROMO-4-HYDROXYBENZALDEHYDEIACETOPHENONE 1465

736, 607; 'H NMR: 8 2A(s,3H,-COCH), 2.6(s,3H, -COCH), 4.55 (s, 2H,-OCH2), 8.1 (s, 2H, Ar-H); Mass (m/z, %): 352 (M+ +4,1.6), 350(M+ +2,4.16), 348(M+,1.6), 31 O( 1.6), 308 (5), 306 (1.6), 279 (11.6), 271 (20), 269 (20.8), 229 (16.6), 227 (16.6), 198 (6.6), 155 (10.8), 153 (6.6), 143 (10.8), 141 (10), 74 (38.3), 62 (35), 43 (100). Anal. Calcd for CllH IOBr20 ): C,37.71 ; H, 2.85. Found: C, 37.68; H, 2.88%.

Thermal reaction of compound 3. Compound 3 (1 g, 3.1 mmoles) was refluxed in a-xylene (10 mL) for 10 hr. The reaction mixture was worked up by passing through a small column of silica gel set in /1-

hexane. The initial column fractions gave a-xylene (-10 mL). The column was further eluted with n­hexane-ethyl acetate (98:2) to yield a residue which on recrystallisation from n-hexane-chlorofom gave compound 13 as colourless shining needles (0.2 g, 46%) based on starting material recovery); m.p. 75-76°C; Rr 0.59 (n-hexane-ethyl acetate, 90: 10); Ferric colourless ; +ve; 2,4-DNP : +ve; IR (KBr) : 3229 (-OH), 1670 (-C=O), 1591 , 1566, 1473, 1331, 1286, 1234, 1163, 1082,976, 893, 680; 'H NMR: 83 .5 (m, 2H, -CH2 -),5 .15-5.2 (m, 2H, =CH2), 6.0 (m, lH, -CH=), 6.2 (s, IH, -OH), 7.65 (brs, IH, Ar-H), 7.92 (brs, IH, Ar-H); Mass (m/z, %) : 242 (M++2, 90.2), 240 (M+, 94.2), 239 (55 .7), 2 13 (9.8), 2 11 (6.5), 133 (31.1), 132 (100), 131 (1404),118 (2 1.3), 115 (15.5), 105 (24 .5), 104 (15.5), 103 (24.5), 102 (9.8), 77 (5204), 63 (2004), 51 (45.9). Anal. Calcd for CIOH9Br02 : C,49.79 ; H, 3.73. Found: C, 49.94; H, 3.66%.

Thermal reaction of compound 7 . Compound 7 (50 mg, 0.15 mmole) in liquid paraffin (0.5 mL) was heated on a metal-bath at 225°C. The reaction was monitored by TLC and fou nd complete after 5 hr. The reaction mixture was disso lved in n-hexane and passed th rough a small colu mn of si lica gel. After removing paraffin by n-hexane elution the column was eluted with n-hexane-ethyl acetate (85 : 15). Fractions with Rr 004 (Il-hexane-ethyl acetate, 80:20) were combined and concentrated under vacuum to give a pale brown residue which on crystallisation from n-hexane-chloroform gave compound 14 as colourless amorphous powder (20 mg, 3804%); m.p. 184-86°C; lR (KBr): 3470, 3294, 2363, 1699, 1587, 1548, 1417, 1363, 1282, 1242, 1138,997,898, 767, 736, 671; 'H NMR : 8 2.56 (t, 1 H, == CH), 2.79 (br. s, IH , -OH), 4.89 (d, IH , 1 = 3.1Hz, -OCH2), 8.18 (s, IH, Ar-H), 8.24 (s, IH , Ar-H); Mass (m/z, %) : 336

(M++4, 9), 334 (M++2, 18),332 (M+, 9), 298 (12),296 (31),294 (12), 281 (15),279 (31), 277 (16),255 (97), 253 (100), 241 (9), 239 (18), 237 (10), 174 (6), 157 (1.5), 129 (3). Anal. Calcd for CIOH6Br20): C,35 .92 ; H, 1.79. Found: C, 35.66; H, 1.84%.

Thermal reaction of compound 10. Compound 10 (250 mg, 0.7 mmole) was refluxed in a-xylene (2 mL) for 10 hr. The reaction mixture was diluted with n-hexane and passed through a column of silica gel (10 g) set in n-hexane. The initial column fractions on evaporation gave solvent a-xylene (- 2 mL). The column was further eluted with n-hexane-ethyl acetate (95:5) and fractions with similar Rr (0.61, n-hexane­ethyl acetate, 90: 10) were mixed and concentrated to give a residue which on recrystallisation from 12-

hexane - chloroform gave compound 15 as colourless shining needles (62 mg, 33%); m.p. 126-27°C; Ferric colour test: +ve; IR (KBr) : 3148, 1647, 1601 , 1548, 1475, 1421 , 1361, 1304, 1246, 1184,997, 902, 827, 675, 607; 'H NMR : 82.55 (s, 3H, -COCH), 3.5 (d, 1=6.7 Hz, 2H, -OCH2), 5. 15 (m, 2H, =CH2), 6.0 (m, 2H,-CH= & -OH), 7.7 (s, 1H, Ar-H), 8.0 (s, IH , Ar­H); Mass (m/z, %) : 256(M++2, 23.3), 254(M+, 23.3), 241 (80),239 (85), 213 (3.3),2 11 (5), 132 (46 .6),131 (35), 104 (21.6), 103 (36.6), 102 (16.6), 77 (56.6), 63 (28 .3), 51 (41.6), 43 (100). Anal. Calcd for C ll H ll Br02: C,51.76 ; H, 4.31. Found: C, 51.70; H, 4.39%.

Acknowledgement Authors are highly thankful to Prof. Y N Misra,

Director and Dr Y R Rao, Head, Forest and Marine Products Divi sion, Regional Research Laboratory, Bhubaneswar for their encouragement.

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