Preparation of new 2,3-diphenylpropenoic acid esters - Good yields even for the more hindered Z isomers

Article abstract of DOI:10.3390/90400256

The potassium salt of E- and Z-2,3-diphenylpropenoic acids prepaxed in situ could be esterified efficiently in DMSO with the appropriate alkyl halides at room temperature. In this way 10 previously undescribed esters of these acids were synthesised and characterised. Excellent yields were observed for most of the E isomers and the more hindered Z esters were also obtained in good yields, far better than those obtained applying the classical acid-catalysed esterification reaction.

Full text of DOI:10.3390/90400256

Molecules 2004, 9, 256-263
molecules
ISSN 1420-3049
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Preparation of New 2,3-Diphenylpropenoic Acid Esters – Good
Yields Even for the More Hindered Z Isomers
László Boros, Károly Felföldi and István Pálinkó*
Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720 Hungary, Tel.
(+36) 62 544 288, Fax (+36) 62 544 200.
*Author to whom correspondence should be addressed; e-mail: palinko@chem.u-szeged.hu
Received: 8 March 2004 / Accepted: 18 March 2004 / Published: 31 March 2004
Abstract: The potassium salt of E- and Z-2,3-diphenylpropenoic acids prepared in situ
could be esterified efficiently in DMSO with the appropriate alkyl halides at room
temperature. In this way 10 previously undescribed esters of these acids were synthesised
and characterised. Excellent yields were observed for most of the E isomers and the more
hindered Z esters were also obtained in good yields, far better than those obtained
applying the classical acid-catalysed esterification reaction.
Keywords: Esterification of E- and Z-2,3-diphenylpropenoic acids; DMSO/KOH/alkyl
halide reactant
Introduction
According to published accounts, the acid-catalysed esterification reaction can be conveniently
used for preparing various esters of E-2,3-diphenylpropenoic acid (E-1), while it is not applicable for
the Z isomer (Z-1), due to steric congestion in the transition state [1, 2]. For illustration purposes the
reactivities of the two isomers were studied under the acid-catalysed esterification conditions and
compared to that of the saturated analogue, 2,3-diphenylpropionic acid (Table 1).

Molecules 2004, 9
257
Table 1. Esterification by the CH3OH/H2SO4/reflux method a
Reaction
Acid
Yield %a
time h
0.5
4
2,3-Diphenylpropionic acid
E-2,3-Diphenylpropenoic acid
Z-2,3-Diphenylpropenoic acid
94
77
17
15
aSee Experimental part
It can be seen that the reactivities of the unsaturated acids were lower than those of the saturated
one and for the Z isomer the ester yield was very low, in spite of the prolonged reaction time.
Accordingly, the synthesis of the methyl or the ethyl esters of E-2,3-diphenylpropenoic acid by the
ROH/H+/reflux method is suggested [3, 4], while the methyl ester of the Z isomer can be obtained in
another way, through the reaction with diazomethane [5].
Another important method for producing esters is the reaction of the carboxylate anion with
alkylating reagents. Variations in the method are possible: the counter ion (cation), the solvent and the
alkylating agent may all be altered [6-12]. Not long ago we described the preparation of the methyl
esters of o-methoxy-substituted Z-2,3-diphenylpropenoic acids from the corresponding 3-phenyl-
coumarin using the DMSO/KOH/CH3I system [13]:
O
O
OCH3
COOCH3
1. DMSO, 2eqv. KOH, 1 h, 40oC
2. 2 eqv. CH3I, 30 min, room temp.
H
R
R
R = H or OCH3
Since it is highly probable that the first step in the reaction is the formation of the bis-potassium
salt of the phenolic carboxylic acid, which further reacts with methyl iodide, it seemed to be plausible
to find out whether the DMSO/KOH/alkyl halide system can be used for the esterification of E- (E-1)
and Z-2,3-diphenylpropenoic (Z-1) acids with special emphasis on the latter.
Results and discussion
In our procedure 1.4 equivalents of powdered KOH were added to the carboxylic acid dissolved in
DMSO. The mixture was stirred for 30 min then it was reacted with 1.5 equivalents of various alkyl
halides at room temperature for a preset reaction time and the ester was isolated by pouring it into
water. Through application of this method 10 as yet undescribed esters of the two carboxylic acids
were prepared, besides the already known E-2 [2], Z-2 [2], E-3 [4], Z-3 [4] and E-4 [14] esters:

Molecules 2004, 9
258
1. DMSO, 1.4 eqv. KOH
30 min, room temperature
2. 1.5 eqv. alkyl halide
0.5-2 h, room temperature
H
COOR
H
COOH
E-2: R = Me
E-3: R = Et
E-4: R = iPr
E-5: R = Bu
E-6: R = iBu
E- 7: R = allyl
E-1
E- 8: R = benzyl
E- 9: R = 3-chlorobenzyl
E-10: R = 3-phthalimido-
propyl
1. DMSO, 1.4 eqv. KOH
30 min, room temperature
COOR
COOH
2. 1.5 eqv. alkyl halide
0.5-2 h, room temperature
H
H
Z-1
Z-2: R = Me
Z-3: R = Et
Z-4: R = iPr
Z-6: R = iBu
Z-8: R = benzyl
The results obtained are summarised in Tables 2 and 3. The yields depended on the relative
reactivities of the corresponding alkyl halides.
Table 2. Preparation of various esters of E- (E-1) and Z-2,3-diphenylpropenoic acid (Z-1)a
Reaction
time (h)
Ester
Formula
E-2
Yielda
(%)
Entry Acid
Alkyl halide
MeI
1
2
3
4
5
6
E-1
Z-1
E-1
E-1
Z-1
E-1
0.5
0.5
0.5
1
95
91
80
75
78
36
C16H14O2
Z-2
MeI
C16H14O2
E-3
EtI
C17H16O2
E-3
EtBr
C17H16O2
Z-3
EtI
0.5
2
C17H16O2
E-4
iPrBr
C18H18O2

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259
Z-4
C18H18O2
E-5
7
Z-1
E-1
E-1
E-1
E-1
Z-1
E-1
E-1
E-1
Z-1
E-1
E-1
E-1
iPrBr
2
1
1
1
1
1
1
1
1
1
1
1
1
38
91
55
2-3
31
38
79
82
75
78
79
83
92
8
BuI
C19H20O2
E-5
9
BuBr
C19H20O2
E-5
10
11
12
13
14
15
16
17
18
19
BuCl
C19H20O2
E-6
iBuI
C19H20O2
Z-6
iBuI
Allyl bromide
BnBr
C19H20O2
E-7
C18H16O2
E-8
C22H18O2
E-8
BnCl
C22H18O2
Z-8
BnBr
C22H18O2
E-9
1-Bromo-3-chloropropane
C18H17ClO2
E-10
2-Bromoethyl phenyl
ether
C23H19O3
E-11
N-(3-Bromopropyl)-
phthalimide
C26H21NO4
aSee Experimental part
Conclusions
Ten new propenoic acid esters were synthesized (and characterised) along with some known
derivatives, starting from the corresponding acids applying the DMSO/KOH/alkyl halide method. The
reactions were simple, the reaction times were shorter and the yields were much higher with regards to
the Z isomer than in any of the other known methods.
Acknowledgements
This work was supported by the National Science Fund of Hungary through grant OTKA T034184.
The financial help is highly appreciated.

Molecules 2004, 9
260
Experimental
General
The E- and Z-2,3-diphenylpropenoic acids were prepared according to a known procedure [1]. The
alkyl halides were Fluka or Aldrich products. The DMSO was dried over a molecular sieve and
distilled before use. The purities of the products were checked by thin-layer chromatography (Fluka
1
13
60778 Silica gel TLC card, 5% EtOH in benzene). The H- (500 MHz) and C-NMR (125 MHz)
spectra were recorded with a Bruker DRX 500 instrument in CDCl3 solutions. The GC-MS
measurements were performed on a HP Model 5890 GC/HP 5970 MS (EI, 70 eV) instrument.
Chromatography was done on a 30-m HP-1 capillary column, the heating program was: 100°C for 3
min, then 10°C/min to 250°C. Analytical samples were obtained either by crystallisation from aqueous
ethanol or acetone or, for oily products, after column chromatography (silica gel, 1:1 hexane-CH2Cl2).
Isolated yields are tabulated in Tables 1 and 2.
General Procedures
Acid-catalysed esterification
The carboxylic acid (2.5 mmol) was dissolved in methanol (30 mL), then conc. H2SO4 (0.5 mL)
was added and the mixture was refluxed. The reaction was followed by thin-layer chromatography.
The excess alcohol was evaporated, the residue was dissolved in diethyl ether (30 mL), the ethereal
solution was washed free of acid, then dried and the ether was evaporated.
Esterification with the DMSO/KOH/alkyl halide system
The carboxylic acid (10 mmol) was dissolved in DMSO (15 mL), then powdered KOH (0.75 g, 14
mmol) was added and the mixture was stirred for 30 min. Then the alkyl halide (15 mmol) was added
under continuous stirring. Stirring was continued for the preset time given in Table 2, then the mixture
was poured into cold water (70 mL) and the precipitated product was extracted with diethyl ether. The
ethereal solution was washed free of acid, dried and the ether was evaporated. Besides the already
described compounds the new molecules prepared by this method were as follows: isopropyl Z-2,3-
diphenylpropenoate (Z-4), butyl E-2,3-diphenylpropenoate (E-5), isobutyl E-2,3-diphenylpropenoate
(E-6); isobutyl Z-2,3-diphenylpropenoate (Z-6); allyl E-2,3-diphenylpropenoate (E-7); benzyl E-2,3-
diphenylpropenoate (E-8); 3-chloropropyl E-2,3-diphenylpropenoate (E-9); 2-phenoxyethyl E-2,3-
diphenylpropenoate (E-10); 3-phtalimidopropyl E-2,3-diphenylpropenoate (E-11).

Molecules 2004, 9
261
Table 3. Physical and spectroscopic data of various esters of E- (E-1) and Z-2,3-diphenylpropenoic
acid (Z-1)
M.p. °
C
GC-MS
Rt (min) and m/z
(rel.int. %)
1H-NMR
13C-NMR
20
Ester
nD
Rf
δ, ppm, CDCl3
δ, ppm, CDCl3
(Lit.)
29.8; 238 (M+, 72),
205 (15), 179 (93),
178 (100), 152 (23),
121 (84)
31.4; 238 (M+, 66),
205(14), 179 (90), 178
(100), 152 (26), 121
(86)
75-76
(75-76
[2])
E-2
–
0.81
excellent agreement with literature data [15]
excellent agreement with literature data [15]
Z-2
E-3
Z-3
E-4
Z-4
oil
oil
oil
1.6198
1.5960
1.6073
–
0.83
0,83
0.86
0.89
0.91
14.2, 61.1, 127.6, 128.1,
1.26-1.29 (t, 3H), 4.23-
31.2; 252 (M+, 67),
128.4, 128.8, 129.7, 130.4, 179 (90), 178 (100),
4.27 (q, 2H), 7.02-7.35
(m, 10H), 7.83 (s, 1H)
132.7, 134.6, 135.8, 140.0,
167.7
152 (23), 135 (50),
107 (36)
32.9; 252 (M+, 65),
179 (94), 178 (100),
152 (25), 135 (51),
107 (37)
1.16-1.19 (t, 3H), 4.23-
4.27 (q, 2H), 7.02 (s,
13.8, 61.2, 126.4, 128.1,
128.2, 128.3, 128.6, 131.1,
1H), 7,30-7,47 (m, 10H) 135.3, 135.8, 136.9, 169.5
1.26-1.27 (d, 6H), 5.12- 21.8, 68.5, 127.6, 128.1,
31.4; 266 (M+, 48),
68-70
(70-71
[14])
5.14 (m, 1H), 7.02-7.35 128.4, 128.7, 129.8, 130.4, 179 (100), 178 (93),
(m, 10H),
7.84 (s, 1H)
133.2, 134.7, 135.9, 139.6,
167.2
152 (20), 118 (20),
107 (27)
1.17-1.19 (d, 6H), 5.17-
5.20 (m, 1H), 7.01 (s,
1H),
21.4, 68.9, 126.3, 128.1,
128.2, 128.3, 128.35,
128.6, 130.6, 135.7, 135.8,
137.0, 169.1
33.7; 266 (M+, 48),
179 (100), 178 (92),
152 (21), 118 (20),
107 (27)
49-51
–
7.28-7.47 (m, 10H)
0.89-0.92 (t, 3H), 1.32-
1.42 (m, 2H), 1.60-1.65
(m, 2H), 4.18-4.21 (t,
2H), 7.03-7.34 (m, 10H),
7.82 (s, 1H)
13.6, 19.1, 30.6, 64.9,
39; 80 (M+, 49), 224
127.6, 128.1, 128.4, 128.8, (25), 179 (100), 178
E-5
E-6
oil
1.5788
1.5765
0.93
0.88
129.7, 130.5, 134.3, 132.7,
136.0, 139.9, 167.8
(90), 152 (19), 107
(43)
0.87-0.88 (d, 6H), 1.91-
19.1, 27.8, 71.2, 127.7,
37; 280 (M+, 38), 224
(24), 207 (14), 179
1.94 (m, 1H), 3.97-3.98 128.1, 128.5, 128.9, 129.7,
oil
(d, 2H), 7.04-7.34 (m,
10H) 7.84 (s, 1H)
129.9, 130.6 132.9, 134.7, (100), 178 (80), 152
136.1, 140.0, 167.8 (16), 107 (28)

Molecules 2004, 9
262
Table 3. Cont.
0.76-0.77 (d, 6H), 1.83-
19.0, 27.4, 71.6, 126.4,
37.9; 280 (M+, 33),
224 (21), 207 (15),
1.85 (m, 1H), 3.95-3.96 128.2, 128.3, 128.5, 128.7,
Z-6
oil
oil
1.5860
0.92
0.85
(d, 2H), 7.03 (s, 1H),
7.26-7.47 (m, 10H)
132.1, 135.5, 135.9, 136.9, 179 (100), 178 (84),
169.8
152 (16), 107 (23)
4.68-4.70 (m, 2H), 5.17- 65.5, 117.6, 127.7, 128.1,
5.26 (m, 2H), 5.89-5.95 128.5, 128.9, 129.7, 130.5,
(m, 1H), 7.03-7.34 (m, 132.1, 132.5, 134.6, 135.8,
34.4; 264 (M+, 56),
179 (82), 178 (100),
152 (25), 105 (26)
E-7
E-8
1.6013
10H), 7.86 (s, 1H)
140.4, 167.3
66.6, 127.71, 127.74,
127.9, 128.1, 128.4, 128.5,
129.0, 129.7, 130.5, 132.4,
134.5, 135.7, 136.1, 140.5,
167.4
5.24 (s, 2H), 7.02-7.34
(m, 15H), 7.86 (s, 1H)
59-61
–
0.88
–
–
67.2, 126.5, 128.3, 128.4,
128.5, 128.7, 128.8, 131.7,
5.20 (s, 2H), 7.01 (s,
Z-8
E-9
69-71
oil
–
0.93
0.92
1H), 7.15-7.43 (m, 15H) 135.0, 135.1, 135.7, 136.9,
169.4
2.04-2.10 (m, 2H),
31.5, 41.1, 61.7, 127.7,
48.2; 300 (M+, 37),
179 (100), 178 (99),
152 (21), 107 (39)
3.473.50 (t, 2H), 4.31- 128.1, 128.5, 129.0, 129.6,
4.33 (t, 2H), 7.03-7.34 130.5, 132.4, 134.5, 135.8,
1.5983
(m, 10H), 7.83 (s, 1H)
140.4, 167.4,
63.7, 66.1, 115.0, 121.3,
4.18-4.19 (t, 2H), 4.52- 128.0, 128.3, 128.7, 129.2,
4.54 (t, 2H), 6.88-7.32 129.7, 129.8, 130.0, 130.8,
(m, 15H), 7.84 (s, 1H) 132.5,, 134.7, 135.8, 140.9,
158.8, 167.8
E-10
E-11
78-80
–
–
0.51
0.75
–
–
27.6, 35.0, 62.4, 123.1,
2.04-2.09 (m, 2H), 3.74- 127.7, 128.0, 128.5, 128.9,
3.77 (t, 2H), 4.24-4.27 (t, 129.7, 130.6, 132.0, 132.4,
2H), 7,0-7.81 (m, 14H), 133.8, 143.5, 135.7, 140.3,
77-77.5
7.78 (s, 1H)
167.5, 168.2
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