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Chalcone dihalides—II
Tmhdion.
Vol. 28. pp. 5360.
Pnpamon PEW 1972.
Pnoted 10 Grcdt
CHALCONE
BriUin
DIHALIDES-IIt
THE SIMILARITY OF THE EFFECTS 4-METHOXYPHENYL SUBSTITUENTS D. J. DONNELLY. J. A.
DONNELLY*.
OF 2-THIENYL AND IN THE SIDE CHAIN and E. M.
PHILBIN
Dep;~r~ment of Chemistry. IJnlLcrsity College. Dublin 4. Ireland (Received in the UK 26 May 1971; Acceptedfor publication 20 September 1971) Abstract -- 2.3-Dibromo-2’-hydroxy-3-(2-thienyl)propiophenones. with base. gave mixtures of the corresponding chromone and coumaranone and were readily converted into their 3-alkoxyl derivatives. Chromones were obtained by pyrolysing the dibromides and coumaranones by treatment of the 3-alkoxyl derivatives with aqueous ethanolic alkali.
THE effects of the five-membered heterocyclic systems, 2-thienyl and 2-furyl. on side-chain reactivity have been shown by Braude and Fawcett’ to be intermediate between those of phenyl and Cmethoxy-phenyl It seemed possible, therefore, that 2,3-dibromo-2’-hydroxy-3-(2-furyl)and 3-(2-thienyl) propiophenones (II and III) would react like their 3-(4-methoxyphenyl) analogues (e.g. I) and be convertible into heterocyclic-substi.tuted chromones and coumaranones required’ in another study. 2,3-Dibromo-2’-hydroxy-3-phenylpropiophenones (i.e. 2’-hydroxychalcone dibromides) with ortho or paru alkoxyl substituents in the benzyl group (e.g. I) are converted into flavones and,,‘or aurones by aqueous ethanolic alkali.3 The product is determined4 by the reaction conditions: flavone predominates if the reaction is carried out in an ethanolic suspension at room temperature but aurone if it is carried out in a warm ethanolic solution. The 3-j2-thienyl) analogues (III, a-e) synthesized are listed in Table 1 with the products of their reactions with aqueous ethanolic KOH at room
n
I
~:R=R’=R”=R’*‘=H b: R = R’ = R”’ = H: R” = C] c: R = R’ = (,Mez R” = R”’ = ” d:R = R’= R”‘= H:R”= O& e: R = R”’ = H: R’ = OMe: R” = Br
111
l
Part 1. D. J. Donnelly. J. A. Donnelly. J. J. Murphy. E. M. Philbin and T. S. Wheeler. Chum. Comm.
351 (1966). 53
2,3-Dibromo-2’-hydroxy-5’-methoxy-3(2-thienyl)propiophenone (IIId) 2,3,5’-Tribromo-2’-hydroxy-4’-methoxy3_(2-thienyl)propiophenone (IIIe)
Chalcone dibromide -. .-______ 2,3-Dibromo-2’-hydroxy-3-(2-thienyl)propiophenone (Illa) 2,3-Dibromo-5’-chloro-2’-hydroxy-3-(2-thienyl)propiophenone (Illb) 2,3-Dibromo-2’-hydroxy-3’,4’-dimethoxy3-(2-thienyI)propiophenone (IIIc)
Aqueous alcoholic alkali reaction products Alkoxyl derivatives -__. __ ._ __. -. .___ Z-(2-thienyl)chromone IVa) 2-bromo-2’-hydroxy-3-methoxy-3~2-thienyI)propiophenone (Via) 2-(2-thenyIidene)coumaranone (Va) 6-chloro-2-(2-thienyl)chromone (IVb) 2-bromo-S’-chloro-2’-hydroxy-3-methoxy-3~2-thienyl)propiophenone 5-.zhloro-2-(2-thenylidene)coumaranone (Vb) (VIb) 2-bromo-2’-hydroxy-3,3’,4’-lrimethoxy-3~2-thienyl)propiophenone 7,8-dimethoxy-2-(24hienyI)chromone (IVc) 6,7-dimethoxy-2-(2-thenylidene)(VW coumaranone (Vc) 2-bromo-2’-hydroxy-3,5’dimethoxy-3~2-thienyl)propiophenone (VId) 6methoxy-242~thienyI)chromone (IVd) .. 5-methoxy-2-(2-thenylidenejcoumaranone (Va) &brom-7-methoxy-2-(2-thienyl)chromone 2,5’-dibromo-2’-hydroxy-3,4’-dimethoxy-3~2-thienyl)propiophenone (IVe) (VW 5-bromo-6-methoxy-2-(2-thenylidene)coumaranone (Ve)
TABLE I
55
Chalcone dihalides-II
temperature. These products are analogous to those obtained* from 2’-hydroxy4 methoxychalcone dibromides. 2,3-Dibromo-2’-hydroxy-3-(2-thienyl)propiophenone (Ma), at room temperature gave 2-(2-thienyl)chromone (IVa) and 2-(2-thenylidene) coumaranone (Va) in the ratio 18:l while, from a warm solution, this ratio was 2:7. Attempts to synthesize a 3-(2-furyl)dibromopropiophenone have, so far, failed.
V
IV
The synthesis of flavones by the pyrolysis of chalcone dibromides’ has been extended to the preparation of 2-(2-thienyl)chromones from 2,3-dibromo-2’-hydroxy-3(2-thienyl)propiophenones (III, ae) and provided alternative syntheses of the chromanes (IV, a-e). TABLE 2. UV AND VISIBLESPECTRAOF CHIKMONIS AND COUMARANONES
Compound IVa
L
logs
-.--
-.-
--
--
Compound
*GUI
log c --
IVb
222w 260 323 227(s) 270 284(s) 327 233(s) 251(s) 259 321 223 274 32%) 342 409 218(s) 283 348(s) 391
4.11 415 4.38 406 4.16 4.10 4.39 4.30 4.26 4.34 4.42 4.08 4.06 4.09 4.15 4.22 4.23 3.78 4.24 4.39
Ve
23~~) 258 334 401
4.10 4.03 4.3 1 4.09
VlIIb
248 330 401
4.18 4.23 4.47
226(s) 257 318 221(s) 261 327
3.93 4.13 4.35 4.27 4.29 4.33
IVe
240 257 327
4.21 4.16 444
IXa
IXb
258(s) 261 30%) 334
428 4.35 4.30 4.34
Va
Vb
229 264 337(s) 350 416 228 259s) 270 357 40-l 249 344 392
4.16 4.06 4.14 4.20 4.18 4.07 3.89 404 4.27 4.12 4.09 4.30 4.43
vc
IVC
Vd
Villa
IVd
2-Bromo-2’-hydroxy-3,3’,4’-trimethoxy-3-(2-thienyl)_ proptophcnonc 6,7-Dimethoxy-3-(2-thenylidene) coumaranone 7,8.Dimethoxy-2~2-thienyl~hromone
E
F G
2,3-Dibromo-2’-hvdroxy-3’,4’dimethoxy-3-(2-thienyl)propiophenone 7,8-Dimethoxy-2~2-thienyi~hromone
2-Bromo-5’-cbloro-2’.hydroxy-3-methoxy-3(2-thieny))propiophenone S-Chloro-2-(2-thenylidene)coumaranone 6-Chlor~2-(2-thieny1~hromone 2’-Hydroxy-3’,4’-dimethoxy-3-(2-thienyl)acrylophenone
B
F G A
E
c
F G B
E
2-(2.~jenyi~hromone 2-(2-Thenyiidene)coumaranone 2-Bromb2’-hydroxy-3-methoxy-3-(2-thienyl)propiophenone 2-(2-Thenylidene)coumaranone 2~2-Thienyi~hromone 2,3-Dibromo-S-chloro-2’-hydroxy-3~2-thienyl)propiophenone 6-Chloro-2_12-thienyl)chromone 5-Chloro-2-(2-thenylidene)courmaranone
D
-.-
136. 137 138-140
--...
EtOH-H,O EtOH-H 2O
MeOH
EtOH-Hz0
134-136
@48
3.10
0.05
0.49
EtOH-H,O
140-141
1.34
0.26
2.20
042 0.06
3.07
C,6H,,Br%S
C,,HIIO.S
C,,H,2O*S
C,sH,,BrlO,S
C,,H,,O$
61.8 62.05 401 4OQ 62.0 62.5 62.1 62-5 47.6 47.9
592) 59-1 44.7 44.8
37.1 36.8
49.7 49-3
68.1 68.4
40.3 40.0
C
(%) (“A) H
4.8 4.9 3.1 3.1 4.2 4.2 44 4.2 4.2 4.3
2.9 2.7 3.6 3.2
2.2 2.1
4.1 3.8
3.5 3.5
2.2 2.6
-
---- ..-..
Found Required
-.-.-
C,,H,,BrCIO,S
2 C,,H,CIO$
C,,H,Br,ClO,S
C,,G,,BQS
0.08 0.28 1.95 0.14
10 WWV
C,$+,,Br,O,S
0.36 0.02
190
3.91
156-157
Formula or reference
..._. -__- . ..- .__---.
C6Ht.
EtOH
MeOH MeOH
MeOH
MeOH MeOH
MeOH ligroin C,H,
MeOH MeOH MeOH
-..-
Yield
130-131
f80-181 165-167 109-110
111-112
167-169 180-181
126-127 101-102 133-134
101-102 126-127 102 -103
101-102 126-127
2-(2-Thienyl)chromone 2-(2.Thenylidene~ou~r~onc
C
MeQH MeOH
Cd%
124-125
2,3-Dibramo-2’-hydroxy~3-(2-thienyl)propiophenone
B
-.-...-. ..__--_-..
---
Solvent of crystalli7ation
..-. -- .-..-_
-.-.-.. .-.--_-
_ ..___
M.p.
--
Products
Reaction ‘YPe
TABLE 3.
.._.
20.2 19.9
35.1 35.5
13.4 13.5 30.3 30.7
45.7 46-O
40.7 41.0
--..--
IN.
S
_
23.3 23-2
9.2 9.1
107 11.0 6-8 7.1 11.2 11.1 109 11.1 7.3 81)
12.4 12‘2
7.1 7.55
9.9 9.4
13.8 140
8.4 8.2
.____-..-.
OMe
219-220 19551%
5-Bromo-6-methoxy-2-(2-thenylidene)coumaranone
243-245
7-Bromo-4,4’,6-trimethoxyaurone
2,3’-Dibromo-2’-hydroxy-3.4’,6’-trimethoxy-3(4-methoxyphenyl)propiophenone 7-Bromo-4,4’,6-trimethoxyaurone 8-Bromo-5-hydroxy4’,7dimethoxyflavone
3’-Bromo-2’-hydroxy+‘$‘-trimethoxychalcone
F G
A
E
189-190 240-242
4’,7,8-Trimethoxyflavone 8-Bromo-4’,5,7-trimethoxyflavone
G C
185-186
242-244 249-250
161-162
195-196 219-220 157-158
F G D
144-145
144-145
137-138 127-128 178-179
2-Bromo-2’-hydroxy-3.5’dimethoxy-3-(2-thienyl)propiophenone 5-Methoxy-2_(2-thenylidene)coumaranone 6-Methoxy-2-(2-thienyl)chromone S’-Bromo-2’-hydroxy-4’-methoxy-3-(2-thienyl)acrylophenone 2,3,5’-Tribromo-2’-hydroxy-4’-methoxy-3(2-thienyl)propiophenone 6-Bromo-7-methoxy-2_2-thlenyi)chromone 91-92
137-138
5-Methoxy-2-(2-thenylidenejcoumaranone
112-113 127-128
--,.F-_.,‘Yy....”
.., _ \_ _..._
2,3-Dibromo-2’-hydroxy-5’-methoxy-3(2-thienyl)propiophenone 6-Methoxy-2-(2-thienyl)chromone
_
2,5’-Dibromo-2’-hydroxy-3.4’dimethoxy-3(2-thienyl)propiophenone S-Bromobmethoxy-2-(2-thenylidene)coumaranone 6-Bromo-7-methoxy-2-(2-thimyl)chromone 4’,6,7-trimethoxyaurone
E
C
B
F G A
E
C
B
.
EtOH-Me&O
Me,CO Me&O
MeOH
Me&O
MeOH EtOH-Me,CO
MeOH EtOH AcOH-H,O
MeOH
MeOH
EtOH
C,H,
MeOH-H,O MeOH-H,O EtOH-Me,CO
MeOH
MeOH-H,O
MeOH-H,O
GH,
2.52
0.50
3.32
@29
@46
3.10
0.55
2.32
004
0.56
2.72
.1.28
0.42
164
0.15
0.33
246
1.W
C,BH,~B~O~
C,,H,aBrO,
CldboBr206
C,JJ,Wh
8 C,BH,,B~OJ
C&&,
C,sH,,Br,04S
C,.H,BrO,S
C ,AB%S
C,,H,,Br,O,S
c~H,IBfl,s
C,sH,sB*.S
C,hH,,O,S
C,,H,oO,S
C,IH,,BrlOJS
C,d,AW
54.7 54.1 55-O 55.0
55.1 55.3 55.4 55.3 45.2 45.3
69.2
690
49.2 49.5 33.5 33.7 49.8 49.9 5U2 494 394 40.0
64.8 64.6 40-15 40.05 65.6 65.1 65.3 65.1 48.2 48.5
3.6 3.5 4.7 4.4
3.9 3.9 3.9 3.9 3.9 4.0
5.3 5.2
3.2 3.3 2.0 2.2 2.85 2.7 3.0 2.7 3.3 3.1
4.6 4.6 2.9 2.9 3.6 39 4.0 3.9 4.1 4.1
20.9 21.2 21.0 2@3
206 20-4 20.1 20.4 31.6 31.7
23.8 23.6 48.0 48.05 23.8 23.7 23.8 237 35.4 35.5
22.3 21.5
37.9 38.05
16.2 16.5 23.5 23.7
23.9 23.8 23.7 23.8 24.7 24.6
29.5 29.8
96 9.45 6.6 6.4 9.8 9.5 9.6 9.5 7.2 7.1
12.5 12.3 7.5 7.6 12.5 12.4 12.5 12.4 9.0 8.6
Y
2 g 2 P g
D.J.
58
DONNELLY. J. A. DONNELLY
and E.M.
PHILBIN
A characteristic of chalcone dibromides with orrho or para alkoxyl substituents in the benzyl group is the ease with which the B-bromine atom is solvolised6 in refluxing alcohol. It has now been found that the 2,3-dibromo-3-(2+hienyl)propiophenones (III, a-e) behave similarly and are readily converted into their 2-bromo-3-methoxyl derivatives (VI a-e) (Table 1). Thus, 2,3dibromo-2’-hydroxy-3-(2_thienyl)propiophenone (IIIa), on heating in MeOH, formed 2-bromo-2’-hydroxy-3-methoxy-3-(2thienyl)propiophenone (Via). These OMe derivatives (VI, a-e), with aqueous KOH in warm alcoholic solution, cyclized’ to the corresponding 2-(Zthenylidene)coumaranones (V, a-e). Two 2,3-dibrom*3-(4-methoxyphenyl)propiophenones were examined : 2’-acetoxy-3’,4,4’-trimethoxychalcone dibromide (VIIa) and 3’-bromo-2’-hydroxy-4,4’,6’trimethoxychalcone dibromide (VIIb). The former (VIIa), when treated with aqueous KOH in hq ethanolic solution, gave 4’,6,7trimethoxyaurone (VIIIa): its pyrolysis gave 4’,7,8-trimethoxyflavone (IXa) (Badhwar, Kang, and Venkataraman8 have R
OH COCHBrCH(OMe) R”
a:
R =
R”
=
R”’
=
b:
R = R’ = R”’
R’
=
=
H;
R”
c:
R = R’ = OMe;
H =
Cl
R” = R;’ = H
d:R=R’=R;=H;R”=OMc H; R’ = OMe; R” = Br
e:R=R’,‘=
VI OMe
Meo~:~B,HBrcJo R”
a: R = Ok: R’ = OMc: p = H b: R = H: R’ = Br: R” = DMe R”
0
OMe
HO
0
60
D. J. DONNELLY.J. A. DONNELLYand E. M. PHKLBIN
tcmp for 12 hr before being poured into dilute HCI. The precipitate, 3-bromo-4’,6’-dimethxy-2’-(4-methoxybetuoyloxy)ucetophene, crystallized from acetone as platelets (14 g), m.p. 187-188”. (Found: C 52.8: H,4.3: Br, 19.7: OMe., 229. C,,H,,Br06 requires: C, 52.8: H.4.2: Br. 19.5: OMe, 22.8%). A solution ofthe diketone (1 R)in AcOH (20 ml) and HCl(@5 ml) was heated on a steambath for 5 min and poured into water. The product, 8-bromo-$‘,S,7-trimethoxyflavone, crystallized from ethanolic acetone in needles (05 g), m.p. 240-242”. AU chromones gave a light yellow solution in H,SO, which showed a bright blut fluorescence in UV light: the aurones gave dark red non-fluorescing solutions &Brom~5-hydroxy-4’,7-Dimethoxflavone (XI) gave a deep brown colour with ethanolic FeCl,.
REFERENCES 1 ’ 3 ’ s 6 ’ s ’ lo
E. A. Braude and J. S. Fawcett, J. Chem. Sot. 4158 (1952) D. Donnelly, R Geogbegan, C O’Brien, E. Philbin, and T. S. Wheeler, .I. Med. Chem 8, 872 (1965) J. E. Gowan and T. S. Wheeler, Name Index @Organic Reactions, p. 149, Longmans, London (1960) K. v. Auwers and L. Anschutz, Ber. Dtsch. Chem Ges. S4,1543 (1921) S. M. Nadkami, A. M. Warriar, and T. S. Wheeler, J. Chem Sot. 17% (1937) F. J. Pond and A. S. Schoffstall J. Am Chem. Sot 22, 658 (1900) G. V. Bhide, K. R. Chandorkar, H. K. Pendse, and S. D. Limaye, Rasaymatn 2,135 (1956) 1. C. Badhwar, K. S. Kang, and K Venkataraman, J. Chem Sot. 1107 (1932) W. A. Hutchins and T. S. Wheeler, Ibid. 91 (1939) A. Corvaisier and J. Tirouflet, Compt. Rend. 2!!4, 1276 (1960) ’ ’ A. Felix and P. Friedlander, Monutsch. 31, 55 (1910) ” J. A. Donnelly, Tetrahedron Letters 19, 1 (1959)
Vol. 28. pp. 5360.
Pnpamon PEW 1972.
Pnoted 10 Grcdt
CHALCONE
BriUin
DIHALIDES-IIt
THE SIMILARITY OF THE EFFECTS 4-METHOXYPHENYL SUBSTITUENTS D. J. DONNELLY. J. A.
DONNELLY*.
OF 2-THIENYL AND IN THE SIDE CHAIN and E. M.
PHILBIN
Dep;~r~ment of Chemistry. IJnlLcrsity College. Dublin 4. Ireland (Received in the UK 26 May 1971; Acceptedfor publication 20 September 1971) Abstract -- 2.3-Dibromo-2’-hydroxy-3-(2-thienyl)propiophenones. with base. gave mixtures of the corresponding chromone and coumaranone and were readily converted into their 3-alkoxyl derivatives. Chromones were obtained by pyrolysing the dibromides and coumaranones by treatment of the 3-alkoxyl derivatives with aqueous ethanolic alkali.
THE effects of the five-membered heterocyclic systems, 2-thienyl and 2-furyl. on side-chain reactivity have been shown by Braude and Fawcett’ to be intermediate between those of phenyl and Cmethoxy-phenyl It seemed possible, therefore, that 2,3-dibromo-2’-hydroxy-3-(2-furyl)and 3-(2-thienyl) propiophenones (II and III) would react like their 3-(4-methoxyphenyl) analogues (e.g. I) and be convertible into heterocyclic-substi.tuted chromones and coumaranones required’ in another study. 2,3-Dibromo-2’-hydroxy-3-phenylpropiophenones (i.e. 2’-hydroxychalcone dibromides) with ortho or paru alkoxyl substituents in the benzyl group (e.g. I) are converted into flavones and,,‘or aurones by aqueous ethanolic alkali.3 The product is determined4 by the reaction conditions: flavone predominates if the reaction is carried out in an ethanolic suspension at room temperature but aurone if it is carried out in a warm ethanolic solution. The 3-j2-thienyl) analogues (III, a-e) synthesized are listed in Table 1 with the products of their reactions with aqueous ethanolic KOH at room
n
I
~:R=R’=R”=R’*‘=H b: R = R’ = R”’ = H: R” = C] c: R = R’ = (,Mez R” = R”’ = ” d:R = R’= R”‘= H:R”= O& e: R = R”’ = H: R’ = OMe: R” = Br
111
l
Part 1. D. J. Donnelly. J. A. Donnelly. J. J. Murphy. E. M. Philbin and T. S. Wheeler. Chum. Comm.
351 (1966). 53
2,3-Dibromo-2’-hydroxy-5’-methoxy-3(2-thienyl)propiophenone (IIId) 2,3,5’-Tribromo-2’-hydroxy-4’-methoxy3_(2-thienyl)propiophenone (IIIe)
Chalcone dibromide -. .-______ 2,3-Dibromo-2’-hydroxy-3-(2-thienyl)propiophenone (Illa) 2,3-Dibromo-5’-chloro-2’-hydroxy-3-(2-thienyl)propiophenone (Illb) 2,3-Dibromo-2’-hydroxy-3’,4’-dimethoxy3-(2-thienyI)propiophenone (IIIc)
Aqueous alcoholic alkali reaction products Alkoxyl derivatives -__. __ ._ __. -. .___ Z-(2-thienyl)chromone IVa) 2-bromo-2’-hydroxy-3-methoxy-3~2-thienyI)propiophenone (Via) 2-(2-thenyIidene)coumaranone (Va) 6-chloro-2-(2-thienyl)chromone (IVb) 2-bromo-S’-chloro-2’-hydroxy-3-methoxy-3~2-thienyl)propiophenone 5-.zhloro-2-(2-thenylidene)coumaranone (Vb) (VIb) 2-bromo-2’-hydroxy-3,3’,4’-lrimethoxy-3~2-thienyl)propiophenone 7,8-dimethoxy-2-(24hienyI)chromone (IVc) 6,7-dimethoxy-2-(2-thenylidene)(VW coumaranone (Vc) 2-bromo-2’-hydroxy-3,5’dimethoxy-3~2-thienyl)propiophenone (VId) 6methoxy-242~thienyI)chromone (IVd) .. 5-methoxy-2-(2-thenylidenejcoumaranone (Va) &brom-7-methoxy-2-(2-thienyl)chromone 2,5’-dibromo-2’-hydroxy-3,4’-dimethoxy-3~2-thienyl)propiophenone (IVe) (VW 5-bromo-6-methoxy-2-(2-thenylidene)coumaranone (Ve)
TABLE I
55
Chalcone dihalides-II
temperature. These products are analogous to those obtained* from 2’-hydroxy4 methoxychalcone dibromides. 2,3-Dibromo-2’-hydroxy-3-(2-thienyl)propiophenone (Ma), at room temperature gave 2-(2-thienyl)chromone (IVa) and 2-(2-thenylidene) coumaranone (Va) in the ratio 18:l while, from a warm solution, this ratio was 2:7. Attempts to synthesize a 3-(2-furyl)dibromopropiophenone have, so far, failed.
V
IV
The synthesis of flavones by the pyrolysis of chalcone dibromides’ has been extended to the preparation of 2-(2-thienyl)chromones from 2,3-dibromo-2’-hydroxy-3(2-thienyl)propiophenones (III, ae) and provided alternative syntheses of the chromanes (IV, a-e). TABLE 2. UV AND VISIBLESPECTRAOF CHIKMONIS AND COUMARANONES
Compound IVa
L
logs
-.--
-.-
--
--
Compound
*GUI
log c --
IVb
222w 260 323 227(s) 270 284(s) 327 233(s) 251(s) 259 321 223 274 32%) 342 409 218(s) 283 348(s) 391
4.11 415 4.38 406 4.16 4.10 4.39 4.30 4.26 4.34 4.42 4.08 4.06 4.09 4.15 4.22 4.23 3.78 4.24 4.39
Ve
23~~) 258 334 401
4.10 4.03 4.3 1 4.09
VlIIb
248 330 401
4.18 4.23 4.47
226(s) 257 318 221(s) 261 327
3.93 4.13 4.35 4.27 4.29 4.33
IVe
240 257 327
4.21 4.16 444
IXa
IXb
258(s) 261 30%) 334
428 4.35 4.30 4.34
Va
Vb
229 264 337(s) 350 416 228 259s) 270 357 40-l 249 344 392
4.16 4.06 4.14 4.20 4.18 4.07 3.89 404 4.27 4.12 4.09 4.30 4.43
vc
IVC
Vd
Villa
IVd
2-Bromo-2’-hydroxy-3,3’,4’-trimethoxy-3-(2-thienyl)_ proptophcnonc 6,7-Dimethoxy-3-(2-thenylidene) coumaranone 7,8.Dimethoxy-2~2-thienyl~hromone
E
F G
2,3-Dibromo-2’-hvdroxy-3’,4’dimethoxy-3-(2-thienyl)propiophenone 7,8-Dimethoxy-2~2-thienyi~hromone
2-Bromo-5’-cbloro-2’.hydroxy-3-methoxy-3(2-thieny))propiophenone S-Chloro-2-(2-thenylidene)coumaranone 6-Chlor~2-(2-thieny1~hromone 2’-Hydroxy-3’,4’-dimethoxy-3-(2-thienyl)acrylophenone
B
F G A
E
c
F G B
E
2-(2.~jenyi~hromone 2-(2-Thenyiidene)coumaranone 2-Bromb2’-hydroxy-3-methoxy-3-(2-thienyl)propiophenone 2-(2-Thenylidene)coumaranone 2~2-Thienyi~hromone 2,3-Dibromo-S-chloro-2’-hydroxy-3~2-thienyl)propiophenone 6-Chloro-2_12-thienyl)chromone 5-Chloro-2-(2-thenylidene)courmaranone
D
-.-
136. 137 138-140
--...
EtOH-H,O EtOH-H 2O
MeOH
EtOH-Hz0
134-136
@48
3.10
0.05
0.49
EtOH-H,O
140-141
1.34
0.26
2.20
042 0.06
3.07
C,6H,,Br%S
C,,HIIO.S
C,,H,2O*S
C,sH,,BrlO,S
C,,H,,O$
61.8 62.05 401 4OQ 62.0 62.5 62.1 62-5 47.6 47.9
592) 59-1 44.7 44.8
37.1 36.8
49.7 49-3
68.1 68.4
40.3 40.0
C
(%) (“A) H
4.8 4.9 3.1 3.1 4.2 4.2 44 4.2 4.2 4.3
2.9 2.7 3.6 3.2
2.2 2.1
4.1 3.8
3.5 3.5
2.2 2.6
-
---- ..-..
Found Required
-.-.-
C,,H,,BrCIO,S
2 C,,H,CIO$
C,,H,Br,ClO,S
C,,G,,BQS
0.08 0.28 1.95 0.14
10 WWV
C,$+,,Br,O,S
0.36 0.02
190
3.91
156-157
Formula or reference
..._. -__- . ..- .__---.
C6Ht.
EtOH
MeOH MeOH
MeOH
MeOH MeOH
MeOH ligroin C,H,
MeOH MeOH MeOH
-..-
Yield
130-131
f80-181 165-167 109-110
111-112
167-169 180-181
126-127 101-102 133-134
101-102 126-127 102 -103
101-102 126-127
2-(2-Thienyl)chromone 2-(2.Thenylidene~ou~r~onc
C
MeQH MeOH
Cd%
124-125
2,3-Dibramo-2’-hydroxy~3-(2-thienyl)propiophenone
B
-.-...-. ..__--_-..
---
Solvent of crystalli7ation
..-. -- .-..-_
-.-.-.. .-.--_-
_ ..___
M.p.
--
Products
Reaction ‘YPe
TABLE 3.
.._.
20.2 19.9
35.1 35.5
13.4 13.5 30.3 30.7
45.7 46-O
40.7 41.0
--..--
IN.
S
_
23.3 23-2
9.2 9.1
107 11.0 6-8 7.1 11.2 11.1 109 11.1 7.3 81)
12.4 12‘2
7.1 7.55
9.9 9.4
13.8 140
8.4 8.2
.____-..-.
OMe
219-220 19551%
5-Bromo-6-methoxy-2-(2-thenylidene)coumaranone
243-245
7-Bromo-4,4’,6-trimethoxyaurone
2,3’-Dibromo-2’-hydroxy-3.4’,6’-trimethoxy-3(4-methoxyphenyl)propiophenone 7-Bromo-4,4’,6-trimethoxyaurone 8-Bromo-5-hydroxy4’,7dimethoxyflavone
3’-Bromo-2’-hydroxy+‘$‘-trimethoxychalcone
F G
A
E
189-190 240-242
4’,7,8-Trimethoxyflavone 8-Bromo-4’,5,7-trimethoxyflavone
G C
185-186
242-244 249-250
161-162
195-196 219-220 157-158
F G D
144-145
144-145
137-138 127-128 178-179
2-Bromo-2’-hydroxy-3.5’dimethoxy-3-(2-thienyl)propiophenone 5-Methoxy-2_(2-thenylidene)coumaranone 6-Methoxy-2-(2-thienyl)chromone S’-Bromo-2’-hydroxy-4’-methoxy-3-(2-thienyl)acrylophenone 2,3,5’-Tribromo-2’-hydroxy-4’-methoxy-3(2-thienyl)propiophenone 6-Bromo-7-methoxy-2_2-thlenyi)chromone 91-92
137-138
5-Methoxy-2-(2-thenylidenejcoumaranone
112-113 127-128
--,.F-_.,‘Yy....”
.., _ \_ _..._
2,3-Dibromo-2’-hydroxy-5’-methoxy-3(2-thienyl)propiophenone 6-Methoxy-2-(2-thienyl)chromone
_
2,5’-Dibromo-2’-hydroxy-3.4’dimethoxy-3(2-thienyl)propiophenone S-Bromobmethoxy-2-(2-thenylidene)coumaranone 6-Bromo-7-methoxy-2-(2-thimyl)chromone 4’,6,7-trimethoxyaurone
E
C
B
F G A
E
C
B
.
EtOH-Me&O
Me,CO Me&O
MeOH
Me&O
MeOH EtOH-Me,CO
MeOH EtOH AcOH-H,O
MeOH
MeOH
EtOH
C,H,
MeOH-H,O MeOH-H,O EtOH-Me,CO
MeOH
MeOH-H,O
MeOH-H,O
GH,
2.52
0.50
3.32
@29
@46
3.10
0.55
2.32
004
0.56
2.72
.1.28
0.42
164
0.15
0.33
246
1.W
C,BH,~B~O~
C,,H,aBrO,
CldboBr206
C,JJ,Wh
8 C,BH,,B~OJ
C&&,
C,sH,,Br,04S
C,.H,BrO,S
C ,AB%S
C,,H,,Br,O,S
c~H,IBfl,s
C,sH,sB*.S
C,hH,,O,S
C,,H,oO,S
C,IH,,BrlOJS
C,d,AW
54.7 54.1 55-O 55.0
55.1 55.3 55.4 55.3 45.2 45.3
69.2
690
49.2 49.5 33.5 33.7 49.8 49.9 5U2 494 394 40.0
64.8 64.6 40-15 40.05 65.6 65.1 65.3 65.1 48.2 48.5
3.6 3.5 4.7 4.4
3.9 3.9 3.9 3.9 3.9 4.0
5.3 5.2
3.2 3.3 2.0 2.2 2.85 2.7 3.0 2.7 3.3 3.1
4.6 4.6 2.9 2.9 3.6 39 4.0 3.9 4.1 4.1
20.9 21.2 21.0 2@3
206 20-4 20.1 20.4 31.6 31.7
23.8 23.6 48.0 48.05 23.8 23.7 23.8 237 35.4 35.5
22.3 21.5
37.9 38.05
16.2 16.5 23.5 23.7
23.9 23.8 23.7 23.8 24.7 24.6
29.5 29.8
96 9.45 6.6 6.4 9.8 9.5 9.6 9.5 7.2 7.1
12.5 12.3 7.5 7.6 12.5 12.4 12.5 12.4 9.0 8.6
Y
2 g 2 P g
D.J.
58
DONNELLY. J. A. DONNELLY
and E.M.
PHILBIN
A characteristic of chalcone dibromides with orrho or para alkoxyl substituents in the benzyl group is the ease with which the B-bromine atom is solvolised6 in refluxing alcohol. It has now been found that the 2,3-dibromo-3-(2+hienyl)propiophenones (III, a-e) behave similarly and are readily converted into their 2-bromo-3-methoxyl derivatives (VI a-e) (Table 1). Thus, 2,3dibromo-2’-hydroxy-3-(2_thienyl)propiophenone (IIIa), on heating in MeOH, formed 2-bromo-2’-hydroxy-3-methoxy-3-(2thienyl)propiophenone (Via). These OMe derivatives (VI, a-e), with aqueous KOH in warm alcoholic solution, cyclized’ to the corresponding 2-(Zthenylidene)coumaranones (V, a-e). Two 2,3-dibrom*3-(4-methoxyphenyl)propiophenones were examined : 2’-acetoxy-3’,4,4’-trimethoxychalcone dibromide (VIIa) and 3’-bromo-2’-hydroxy-4,4’,6’trimethoxychalcone dibromide (VIIb). The former (VIIa), when treated with aqueous KOH in hq ethanolic solution, gave 4’,6,7trimethoxyaurone (VIIIa): its pyrolysis gave 4’,7,8-trimethoxyflavone (IXa) (Badhwar, Kang, and Venkataraman8 have R
OH COCHBrCH(OMe) R”
a:
R =
R”
=
R”’
=
b:
R = R’ = R”’
R’
=
=
H;
R”
c:
R = R’ = OMe;
H =
Cl
R” = R;’ = H
d:R=R’=R;=H;R”=OMc H; R’ = OMe; R” = Br
e:R=R’,‘=
VI OMe
Meo~:~B,HBrcJo R”
a: R = Ok: R’ = OMc: p = H b: R = H: R’ = Br: R” = DMe R”
0
OMe
HO
0
60
D. J. DONNELLY.J. A. DONNELLYand E. M. PHKLBIN
tcmp for 12 hr before being poured into dilute HCI. The precipitate, 3-bromo-4’,6’-dimethxy-2’-(4-methoxybetuoyloxy)ucetophene, crystallized from acetone as platelets (14 g), m.p. 187-188”. (Found: C 52.8: H,4.3: Br, 19.7: OMe., 229. C,,H,,Br06 requires: C, 52.8: H.4.2: Br. 19.5: OMe, 22.8%). A solution ofthe diketone (1 R)in AcOH (20 ml) and HCl(@5 ml) was heated on a steambath for 5 min and poured into water. The product, 8-bromo-$‘,S,7-trimethoxyflavone, crystallized from ethanolic acetone in needles (05 g), m.p. 240-242”. AU chromones gave a light yellow solution in H,SO, which showed a bright blut fluorescence in UV light: the aurones gave dark red non-fluorescing solutions &Brom~5-hydroxy-4’,7-Dimethoxflavone (XI) gave a deep brown colour with ethanolic FeCl,.
REFERENCES 1 ’ 3 ’ s 6 ’ s ’ lo
E. A. Braude and J. S. Fawcett, J. Chem. Sot. 4158 (1952) D. Donnelly, R Geogbegan, C O’Brien, E. Philbin, and T. S. Wheeler, .I. Med. Chem 8, 872 (1965) J. E. Gowan and T. S. Wheeler, Name Index @Organic Reactions, p. 149, Longmans, London (1960) K. v. Auwers and L. Anschutz, Ber. Dtsch. Chem Ges. S4,1543 (1921) S. M. Nadkami, A. M. Warriar, and T. S. Wheeler, J. Chem Sot. 17% (1937) F. J. Pond and A. S. Schoffstall J. Am Chem. Sot 22, 658 (1900) G. V. Bhide, K. R. Chandorkar, H. K. Pendse, and S. D. Limaye, Rasaymatn 2,135 (1956) 1. C. Badhwar, K. S. Kang, and K Venkataraman, J. Chem Sot. 1107 (1932) W. A. Hutchins and T. S. Wheeler, Ibid. 91 (1939) A. Corvaisier and J. Tirouflet, Compt. Rend. 2!!4, 1276 (1960) ’ ’ A. Felix and P. Friedlander, Monutsch. 31, 55 (1910) ” J. A. Donnelly, Tetrahedron Letters 19, 1 (1959)