Reaction of 3-arylidenepropenoic acid derivatives with triethylamine and other amines; Unexpected reductions and vinylogations

Article abstract of DOI:10.1016/j.tet.2016.03.097

Exposure of ethyl 2-cyano-3-(2-methoxy-5-nitrophenyl)acrylate 1f to triethylamine in hot ethanol resulted in the formation of the dihydro derivative 2f and vinylogue 3f in high yields. Single crystal X-ray data are provided for 3f. Similar reactions were observed for various analogues. The reaction was studied changing aryl substituent, amines and solvents. Pyridyl, thienyl analogues were also examined. The study was extended to cyclic molecules incorporating such systems like thiazolidinedione 8, 3-cyanocoumarin 9 and 4-arylidene-isoquinoline-2,4-diones 11. The last group gave vinylogated products, 4-cinnamylidene-isoquinolinediones and 4-hydroxylated species. A few examples of arylidene derivatives from malononitrile, ethyl acetoacetate, acetyl acetone and ethyl methylsufonylacetate were investigated. Ethyl cinnamate and β-nitrostyrene were unaffected. The reaction is considered to be possibly radical mediated, since addition of free radical quencher suppressed the reaction. Contrary to the effects of thermal conditions, irradiation of 1f in ethanol at 254 and 365 nm gave complex mixtures. A few other interesting observations in this study are noted: vinylogation of 1f with acetaldehyde to 3f; formation of 3f from 1f by the treatment with triethylamine, palladium carbon and reduction of 1f to 2f by triethylammonium formate in DMF.

Full text of DOI:10.1016/j.tet.2016.03.097

Accepted Manuscript
Reaction of 3-Arylidenepropenoic acid derivatives with triethylamine and other
amines; unexpected reductions and vinylogations
Attimogae Shivamurthy Harisha, Suresh Parameshwar Nayak, Kuppuswamy
Nagarajan, Tayur Narasingarow Guru Row, Amar A. Hosamani
PII:
S0040-4020(16)30240-X
10.1016/j.tet.2016.03.097
TET 27637
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 January 2016
Revised Date: 15 March 2016
Accepted Date: 31 March 2016
Please cite this article as: Harisha AS, Nayak SP, Nagarajan K, Guru Row TN, Hosamani AA, Reaction
of 3-Arylidenepropenoic acid derivatives with triethylamine and other amines; unexpected reductions
and vinylogations, Tetrahedron (2016), doi: 10.1016/j.tet.2016.03.097.
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ACCEPTED MANUSCRIPT
Graphical Abstract

ACCEPTED MANUSCRIPT
Reaction of 3-Arylidenepropenoic acid derivatives with
triethylamine and other amines; unexpected reductions and
vinylogations
Attimogae Shivamurthy Harishaa,b, Suresh Parameshwar Nayakb, Kuppuswamy Nagarajan*,a,
Tayur Narasingarow Guru Row c , Amar A. Hosamanic
a Alkem Laboratories Ltd., R & D Centre, Industrial Estate, 4th Phase, Bangalore-560 058, India.
bDepartment of Chemistry, Mangalore University, Mangalagangothri, Mangalore-574 199, India.
cSolid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore -560 012,
India.
ABSTRACT
Exposure of ethyl 2-cyano-3-(2-methoxy-5-nitrophenyl)acrylate 1f to triethylamine in hot
ethanol resulted in the formation of the dihydro derivative 2f and vinylogue 3f in high yields.
Single crystal X-ray data are provided for 3f. Similar reactions were observed for various
analogues. The reaction was studied changing aryl substituent, amines and solvents. Pyridyl,
thienyl analogues were also examined. The study was extended to cyclic molecules incorporating
such systems like thiazolidinedione 8, 3-cyanocoumarin 9 and 4-arylidene-isoquinoline-2,4-
diones 11. The last group gave vinylogated products, 4-cinnamylidene-isoquinolinediones and 4-
hydroxylated species. A few examples of arylidene derivatives from malononitrile, ethyl
acetoacetate, acetyl acetone and ethyl methylsufonylacetate were investigated. Ethyl cinnamate
and β-nitrostyrene were unaffected. The reaction is considered to be possibly radical mediated,
since addition of free radical quencher suppressed the reaction. Contrary to the effects of thermal
conditions, irradiation of 1f in ethanol at 254 and 365 nm gave complex mixtures. A few other
interesting observations in this study are noted: vinylogation of 1f with acetaldehyde to 3f;
formation of 3f from 1f by the treatment with triethylamine, palladium carbon and reduction of
1f to 2f by triethylammmonium formate in DMF.
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Keywords:
3-Aryl-2-cyanoprop-2-enoates
Triethylamine
Reduction
Vinylogation
*
Corresponding author. Tel.:+ 91 9886713958
E-mail address: dknb69@yahoo.com (K. Nagarajan).
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1. Introduction
In the course of our successful endeavors to achieve a new synthesis of entacapone1a,1b from the
precursor
2-cyano-N,N-diethyl-3-(3-hydroxy-4-methoxy-5-nitrophenyl)acrylamide
by
demethylation with triethylamine under mild conditions, we encountered an interesting and
unexpected reaction with compound 1f having a methoxyl group para to the nitro in the 3-aryl-2-
cyanopropenoic ester system. The reaction led to the dihydro derivative 2f and 3f, a vinylogue of
1f.1a We report in this paper single crystal X-ray data of 3f (supplementary section) and also
experimental details of the reaction involving reduction and vinylogation as well as unpublished
work encampassing extension of the scope of the novel reaction. The preliminary
communication summarized our important findings and gave a speculative mechanism.
2. Results and discussion
Reaction of 1f with triethylamine led to dihydro derivative 2f and butadiene 3f. Their structures
were confirmed by extensive NMR and mass spectral data and comparison with authentic
compounds. In the case of 3f single crystal X-ray studies (Fig. 1) corroborated the structure and
defined its geometry. Crystal data are given in (Table 1, supplementary section).
As an extension of the novel reaction we prepared various substituted of 3-aryl-2-propenoic acid
derivatives (Table 2, supplementary section) and subjected them to reaction with triethylamine in
ethanol, with the results recorded in (Table 3). The composition of the reaction mixture was
analyzed using proton NMR spectra. The following diagnostic peaks were used among other
features. Dihydro compounds 2; two multiplets for 1H each between δ 3 and 4 ppm; butadienes 3
proton multiplet around 7.5 ppm; unreacted starting material, singlet at about 8.6 ppm and
hydrolysed aldehyde, singlet at around δ 10.5 ppm. Dihydro derivatives 2 were generally
synthesized for reference purposes by treatment of 1 with sodium borohydride in ethanol.
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Butadiene derivatives 3a and 3b were made for reference purposes by reaction of
cinnamaldehyde and 2-methoxycinnamaldehyde with ethyl cyanoacetate.
Table 3: Analysis of reaction products of 1(a-t) in triethylamine - data of dihydro
derivatives, butadienes, starting materials 1(a-t) and hydrolyzed aldehydes (see table 2 for
structural details)
Compounds
% ratio (By NMR)
Aldehyde % starting material %
3(a-t) Butadiene%
2(a-t) Dihydro %
1a
15
0
0
85
b
c
d
e
f
24
16
6.5
15
16
--
7
0
56
76
93.5
74
0
0
5
03
0
48.5
48.5
03
g
h
Major i
38
0
0
11
0
38
13
0
i
5
0
95
j
iii
k
50
Major ii
0
0
46
0
traces
0
l
m
50
53
0
25
46
25
n
o
p
q
--
traces
No reaction
Decarboxyethoxylated product
The major product corresponds to the products obtained by attempted reduction with
04
NaBH4 in ethanol
iii
r
s
08
08
08
74
t
No reaction
1
i Diagnostic peaks were seen over a curvy base line in the H-NMR spectrum. Hence presence of starting material
and butadiene could not be estimated.
ii rest unanalyzable humps
iii complex mixture
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Butadiene 3f which was the first novel compound observed in our triethylamine reactions was
synthesized by heating 1f with acetaldehyde solution in toluene at 60-65°C for 14 h in presence
of pyridine. We consider it unlikely that 1f would split under these conditions ejecting ethyl
cyanoacetate and that the resultant aldehyde would react with acetaldehyde to give the
cinnamaldehyde which could then condense with ethyl cyanoacetate to form 3f.
It is tempting to speculate that the reaction may proceed as follows.
Scheme 1. Synthesis of 3f
A scifinder search revolved that such a reaction is not known and hence further extension would
be warranted. Cross over experiments may throw light on this reaction.
We have already mentioned in the earlier communication that the reduction–vinylogation
reaction was probably radical mediated. In this connection we studied the 1H-NMR of 1f in
DMSO-d6 solution in the presence of triethylamine from 25 to 50°C but observed no line
broadening which can be expected to happen if radicals had been created.
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Towards gleaning more insight we conducted the reaction of 1f with triethylamine in ethanol at
70 to 75°C under a few different conditions;
a) In the presence of free radical scavenger
b) Under irradiation.
c) In the presence of furan to trap the diethyl-vinylamine.
The reaction of 1f with triethylamine in ethanol at 70-75°C was suppressed by addition of 10%
2, 6-ditertiarybutyl phenol and almost complete suppression was observed by the addition of
10% of TEMPO. The reaction was complex in the presence of dibenzoylperoxide and also when
the reaction solution was irradiated at 254 nm and 365 nm. In an attempt to capture the
postulated intermediate N, N-diethylvinylamine with the diene, furan triethylamine reaction of 1f
was conducted in the presence of furan. Surprisingly there was no reaction at all! It is possible
that the furan we used contained some peroxides (Sigma Aldrich data). An electron deficient
diene would have been more appropriate but we could not access one readily. We have
speculated in the earlier communication that the reduction –vinylogation reaction of
triethylamine may be dependent on the reduction potential of 3-aryl-2-cyanopropenoic acid
derivatives. Our observation that the thermal nonreactivity of phenazine towards triethylamine in
ethanol in contract to its behavior on irradiation 2 may be attributed to this factor.
While this work was in progress we came across reports of reduction of acrylic and cinnamic
esters by Pd/C and triethylamine (no hydrogen) in toluene at 140°C.3 When we subjected 1f to
these reagents at 70-75°C for 12 h, to our surprise we obtained the butadiene 3f with no evidence
for the formation of the dihydro derivative 2f! Entry 1 in (Table 4) shows that in the absence of
Pd/C, the reaction leads to about 84% recovery of 1f and formation of about equal amounts (7%,
8%) of 2f and 3f. Similar reactions were observed with 1a and the o-methoxy derivative 1b,
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where at the end of the reaction period of 12 h, NMR analysis of the product mixture showed it
to be containing almost 50% each of starting material and butadiene with no evidence for the
formation of 2a and 2b. We propose to study the generality of the reaction and report results in
due course. The fate of two hydrogen atoms released concomitant with the formation of
butadienes is an intriguing issue to be solved. Reaction of 1f with triethylammonium formate in
4
DMF formed the dihydro derivative 2f to the extent of 80% (NMR), the rest being accounted
for by un reacted starting material.
In our preliminary communication we had mentioned extension of the study to analogues of 1f
wherein the aryl substituents have been varied: 1a, 1e, 1g and 1h and also to hetero aryl
analogues 2-thienyl 1i, 2-pyridyl 1j, 3-pyridyl 1k and 4-pyridyl 1l for which experimental details
are provided; NaBH4 reduction of 1j has been reported to give the interesting ethyl 3-
aminoindolizine-2-carboxylate 4 as shown in (Scheme 2). The triethylamine reaction of 1j,
however gave a complex mixture in which we could not locate 4.
Scheme 2. Formation of ethyl 3-aminoindolizine-2-carboxylate
We next explored the behavior of arylidenemalononitriles 1m and 1n wherein the ester group in
1b and 1f had been replaced by a CN group. Both underwent reduction to the extent of 50%, the
rest being accounted for by unchanged starting material 25% and aldehyde 25%. The
7

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diethylamide 1o corresponding to 1f was mostly unreacted. Obviously, the diethyl carbamoyl
group is less electron withdrawing than ester or nitrile.
1p representing 1f with the nitrile group being replaced by a COCH3 group was reduced to the
extent of 2%, the major product being the decarboxyethoxylated product 5. The structure was
1
deduced from mass (220.0) and H NMR spectrum. The latter showed the presence of a trans-
ethylene system (6.85, d, J 16.5Hz, 7.80, d, J 16.5Hz) and the absence of the ester group. It
appears that the adjacent CH3CO group to carboethoxy group in 1p has made the latter
vulnerable to ethanol which possibly leaves as diethyl carbonate.
It was of interest to study an analogue of 1f in which a CN group has been replaced by a CH3SO2
moiety. Condensation of benzaldehyde with ethyl methylsulfonyl acetate gave the benzylidene
1
compound 1q HNMR (400MHz, CDCl3) 1.25 (3H, t, J 7.0Hz), 3.24(3H, s, OMe), 4.4 (2H, q, J
7.0Hz), 7.39-7.46(5H, m), 7.83(1H, s, vinyl). Reaction of 1q with triethylamine in ethanol at 70-
75°C for 12 h led largely to the diasteroisomeric ethanol addition products 6 and 7
(stereochemistry unspecified) in the ratio of 3:1. These also resulted in an attempted reduction of
1q with NaBH4 in ethanol.
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The product was gummy and no attempt was made to separate the pure components and assign
appropriate structures.
Condensation product of 2-methoxy-5-nitrobenzaldehyde with diacetyl in presence of
piperidine catalyst gave the aldol. Dehydration with acetic anhydride gave the required product
1r. Upon reaction of 1r with triethylamine under standard conditions; a complex mixture of
products was obtained NMR analysis of which indicated significant formation of the dihydro
derivative and starting aldehyde. The study was extended to l carrying only one EWG at the
nonaryl terminal of the ethylenic system. Ethyl cinnamate did not react with triethylamine to
any detectable extent. The 2-methoxy analogue 1s was obtained by a literature procedure
involving condensation of 2-methoxybenzaldehyde with the half ester of malonic acid with
concomitant decarboxylation.5 1s upon reaction with triethylamine was affected to about 25%,
most of the rest being starting material. The product mixture analyzed by 1H NMR showed it to
consist of the dihydro derivative (8%), butadiene (8%) and starting aldehyde (8%) besides 1s.
β-Nitro styrene 1t did not undergo any reaction with triethylamine under the standard
conditions. Our observations so far have not helped us to define the structural requirement for
reduction – vinylogation in systems represented by 1.
The reaction of 1f with various amines, solvents and at different temperatures have been
studied; results are presented in the table 4. It is to be noted that di-isopropylethylamine (DIPE)
in ethanol gave mostly the dihydro derivative 2f with some minor impurities (NMR). Pure 2f
9

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was isolated in 70% yield. It seems to be possible to use DIPE for reduction of such electron
deficient systems in lieu of NaBH4 or catalytic reduction.
Table 4: Reaction of 1f with various amines and solvents at different temperatures
Solvent
Base
Temperat SM Aldehyde Dihydro Butadiene
ure in °C
Toluene
Dioxane
Triethylamine
Triethylamine
70-75
70-75
70-75
70-75
40-45
60-65
70-75
50-55
50-55
50-55
50-55
70-75
60-65
84
46
15
85
01
03
06
0
08
07
23
21
06
28
Acetonitrile Triethylamine
58
Xylene
Ethanol
Ethanol
Ethanol
Ethanol
Toluene
Ethanol
Ethanol
Ethanol
Triethylamine
Triethylamine
Triethylamine
Triethylamine
Diethylamine
Diethylamine
Ethylamine
07
No reaction
Reaction initiated (about 8% dihydro)
06
91
90
0
49
5
45
4
Traces
01
05
04
Complex
Complex
100
Piperidine
Diisopropylethylamine
0
0
0
Acetonitrile Diisopropylethylamine
0
0
85(15% unknown)
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Acetonitrile
N,N-dimethylisopropylamine 70-75
85
94
0
14
05
-
Dimethylcyclohexamine
1-vinyl-2-pyrrolidone
N-benzyldimethylamine
N, N-diethylaniline
Ethyl vinyl ether
---
70-75
70-75
70-75
70-75
70-75
70-75
70-75
01
trace
No reaction
96
18
63
04
01
0
0
0
43
19
0
36
No reaction
No reaction
---
10

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We extended the scope of our study to reactions of molecules containing conjugated systems in
a cyclic framework.
5-(2-Methoxy-5-nitrobenzylidene)thiazolidine-2,4-dione 8 obtained by reaction of 2-methoxy-
5-nitrobenzaldehyde with thiazolidine-2, 4-dione, was unaffected by triethylamine.
6
The cyanocoumarin 9 was prepared by condensing salicylaldehyde with ethyl cyanoacetate
and subjected to reaction with triethylamine under standard conditions. The crude product was
an intractable mixture. In the complex NMR spectrum, an aldehyde CH was seen at δ 10.85
ppm and the signals for the CH2 and CH3 of triethylamine at δ 3.18 and 1.3 ppm. In the mass
spectrum a peak at 102 was from triethylamine. In the negative mode, a strong peak at m/z 186
could not be assigned to any reasonable structure.
Interesting results were observed with the 4-arylidene-isoquinoline-2, 4-diones 11(a-d) obtained
by condensation of isoquinoline-1, 3-dione 10 with benzaldehydes (Scheme 3). The products
were complex but chromatographic purification afforded the cinnamylidene- isoquinolinediones
12(a, b, c) (Scheme 4) as mentioned in our preliminary communications. The reaction mixture
from 12a was investigated in detail by LC-MS NMR studies. The chromatogram was compared
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with those of 11a, 12a and 13, the dihydro derivatives of 11a made for reference purpose by
catalytic reduction.7a LC-MS of the mixture from 12a showed peaks with RT 2.80 (32%), 3.08
(13%), 3.19(10%) and 3.5(30.5%). The peak at RT 3.5 with mass of 274 (MH-) was identified
as being due to butadiene 12a with a characteristic dd in the NMR spectrum at δ 8.7 ppm due to
the β proton. Pure 12a was isolated in 27% yield by chromatography and was identified with the
product from 10 and cinnamaldehyde.
The other major peak at RT 2.80 had a mass of 266 (MH-) is considered to be hydroxylated
species 15a arising from the radical 14. 15a has been reported in literature7b from the
photochemical addition of toluene to phthalonimide. The NMR spectrum of 15a has an AB
quartet δ 3.14 (1H, d, J 12.8Hz) and 3.23 (1H, d, J 12.8Hz) due to the benzylic CH2 and dd at δ
6.70 ppm with J 7.1Hz due to the ortho protons of the phenyl group as characteristic features.
The NMR spectrum of the crude triethylamine reaction product of 11a did exhibit such peaks
predominantly at δ 3.14 (1H, d, J 13Hz), 3.26(1H, d, J 12.9Hz), 6.7(2H, d, J 7.1Hz). It is to be
noted that the major difference in the NMR spectra of 15a and 13 is that benzylic CH2 in the
latter is coupled to C (4)H, while in the former C4 is attached to the OH. 15a is obviously
formed from 14 by reaction with hydroxyl radical arising from the solvent ethanol. We had
postulated that radical 14 could dimerise but there was no evidence for such a dimeric product
in a careful scrutiny of the LC-MS.
The minor products with RT 3.08 (13%) and 3.19 (10%) with respective masses of 408 and 311
have not yet been securely identified. The dihydro derivative 13 was present if at all to a
negligible extent.
The complex NMR spectrum of the crude product form 11b showed that it was largely
unchanged (ene proton at δ 8.35 ppm). Diagnostic signals for the butadiene 12b were seen as dd
12

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at δ 8.7 ppm. The presence of the hydroxylated species 15b was indicated by the AB quartet at δ
3.2(J 13Hz) and 3.3(J 13Hz). The LCMS showed three significant peaks at RT 2.84(13.7%),
3.25(69%), and 3.54(10.4%). The peak at RT 3.5 was due to unchanged 11b, m/z 278 (MH-)
and the peak at 3.54 was due to the butadiene 12b with m/z 306(MH+). The most polar peak at
R.T 2. 84 min with m/z 296 (MH-) was considered to be the hydroxylated species 15b in
analogy to 15a. Butadiene 12b was isolated from the mixture by chromatography in 8% yield.
The complex NMR spectrum of the crude product from 11c showed about equal amounts of
unreacted 11c (ene proton signal at δ 8.2 ppm), butadiene 12c (quartet at δ 8.16 ppm) and the
hydroxylated species 14c AB quartet (δ 3.11 and 3.18 ppm). Pure 12c was isolated in 19% yield
by chromatography.
The NMR spectrum of the crude product from 11d revealed the presence of four Ar OMe
signals in near equal quantities. Significant quantity of unreacted 11d was identified by the
signal at δ 8.22 ppm. Butadiene 12d, quartet (δ 8.6ppm) and 4-hydroxy derivative 14d (AB
quartet at δ 3.15 and 3.22 ppm) were present. Our earlier speculation of formation of dimeric
products is seen now to be erroneous. In all cases, characteristic singlets for the proton of the
aldehyde used for preparing 11 were seen between δ 9.9 and 10.5 ppm.
Scheme 3. Synthesis of arylidene isoquinoline-1, 3-dione
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Scheme 4. Formation of 4-cinnamylidene-isoquinolinediones
Ar
Ph
Ar
H2C
H2C
H2C
OH
NH
O
O
O
4
NH
NH
O
O
O
15(a, b, c, d)
14
13
a) Ar= C6H5
b) Ar= 2ꢀOCH3ꢀC6H4
c) Ar= 4ꢀOCH3ꢀC6H4
d) Ar= 3ꢀOCH3ꢀC6H4
3. Conclusions
Our study demonstrates that reaction of highly unsaturated systems like 1f can undergo
reduction and vinylogation with triethylamine in hot ethanol. The two reactions occur to varying
degrees depending upon nuclear substituents, solvents and amines. In one case at least 1f,
diisopropylethylamine (DIPE) gave the dihydro derivative 2f as the single observed product.
Homologation was also observed in an unsaturated cyclic system, 4-arylideneisoquinoline-1, 3-
dione 11. In these cases, additionally hydroxylated products at C-4 were obtained rather than the
dihydro species. Observations reported in this study need to be followed up by further
mechanistic studies and structure- reactivity correlations.
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4.0. Experimental
4.1. General
All chemicals used for synthesis were from commercial sources and used without further
purification, unless otherwise indicated. The products were isolated by column chromatography
over silica gel 230-400 mesh. IR spectra were recorded by using Perkin Elmer-Spectrum BX
FT-IR spectrometer.1H NMR and 13C NMR were recorded at 300MHz or 400MHz and 13C
spectra at 75MHz with TMS as an internal standard. Mass spectra were obtained in Agilent
1200 Series LC/MSD VL system. Photo reactions were carried out in Heber immersion type
photo reactor (125 and 400 watts). Melting points were determined by using Buchi melting
point-545 instrument and are uncorrected. Analytical thin-layer chromatography (TLC) was
carried out on Merck silica gel 60G-254 plates (25mm) and developed with solvents mentioned.
The purity of compounds was analyzed by using HPLC Agilent 1200 instrument.
4.2. General experimental procedure for triethylamine reactions- formation of butadienes
and dihydro derivatives
To a solution of 3-aryl-2-cyanoprop-2-enoic acid derivatives (0.01mol) in ethanol (20 mL), was
added a solution of triethylamine (0.03mol) in ethanol (20 mL) and the mixture heated at 70-
75°C for 12 h. After completion of the reaction, ethanol was completely distilled off under
vacuum. The residue was dissolved in dichloromethane, washed with water and the organic
layer distilled off completely under vacuum to afford crude product mixture from which the
butadiene and dihydro derivatives were obtained by column chromatography (20% ethyl acetate
/ hexane).
4.3. General conditions for borohydride reduction of 3-aryl-2-cyanoprop-2-enoic acid
derivatives
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Sodium borohydride powder (0.01mol) was added to a stirred solution of 3-aryl-2-cyanoprop-2-
enoic acid derivatives (0.01mol) in ethanol (10mL). The resulting suspension was stirred at 20-
25°C until the TLC test shows disappearance of starting material. Ethanol was distilled off
under reduced vacuum to afford crude products and the dihydro derivatives were obtained by
column chromatography (30% ethyl acetate / hexane).
4.3.1. Ethyl 2-cyano-3-phenylacrylate (1a)
nmax (liquid film) 3000, 2979, 2223, 1726, 1607 cm-1; dH (400MHz CDCl3) 1.4(3H, t, J
7.15Hz, OCH2CH3), 4.4(2H, q, J 7.14Hz, OCH2CH3), 7.5(3ArH, m), 8.0(2ArH, d, J 7.14Hz),
8.2(1H, s, vinyl); m/z 200.2 (MH-). Data were consistent with reported values in the literature.8
Action of triethylamine on (la) in hot ethanol
NMR spectrum showed about 15% of dihydro derivative 2a, the rest was unreacted starting
material, butadiene was not formed.
Authentic dihydro 2a9and butadiene 3a10 were prepared as per literature.
The dihydro compound 2a was identical with the authentic sample (TLC and NMR). (1.5g,
75%) as colourless oil; nmax (liquid film) 3000, 2979, 2244, 1726 cm-1; dH (400MHz, CDCl3)
1.3 (3H, t, J 7.1Hz, OCH2CH3), 3.2(1H, dd, J 13.8, 8.4Hz, CH2-CH), 3.3(1H, dd, J 13.8, 5.8Hz,
CH2-CH), 3.8(1H, dd, J 8.4, 5.8Hz, CH2-CH), 4.2(2H, q, J 7.15Hz, OCH2CH3), 7.23-
7.38(5ArH, m); m/z 202.1(MH-)
The butadiene compound 3a was prepared from cinnamaldehyde and ethyl cyanoacetate. (2.0g,
88%) as yellow coloured powder; nmax (liquid film) 2988, 2947, 2205, 1747, 1602 cm-1;
dH(400MHz, CDCl3) 1.4 (3H, t, J 7.1Hz, OCH2CH3), 4.3(2H, q, J 7.1Hz, OCH2CH3), 7.30 (2H,
m, -CH=CH-CH=), 7.42(3ArH, m), 7.58(2ArH, m), 8.02(1H, dd, J 7.7, 3.1Hz, -CH=CH-
CH=); m/z 227.2 (MH-).
16

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4.3.2 Ethyl 2-cyano-3-(2-methoxyphenyl)acrylate (1b)
nmax (liquid film) 3073, 2942, 2223, 1596cm-1; dH (400MHz, CDCl3) 1.4(3H, t, J 7.1Hz,
OCH2CH3), 3.9(3H, s, OMe), 4.4(2H, q, J 7.1Hz, OCH2CH3), 6.9(1ArH, d, J 8.3Hz), 7.0(1ArH,
t, J 7.5Hz), 7.5(1ArH, t, J 7.2Hz), 8.28(1ArH, d, J 7.7Hz), 8.75(1H, s, vinyl); HRMS (CI, NH3):
MNa+, found m/z 254.0795. C13H13NO3Na requires m/z 254.0788. Data are consistent with the
reported literature.11
Action of triethylamine on (1b) in hot ethanol
The crude product was characterized by NMR spectrum which showed approximately unreacted
starting material about 56%, butadiene 16% and dihydro compound24%. The crude mixture was
separated by column chromatography.
Dihydro compound (2b):
Rf (30% EtOAc/hexanes) 0.65; (1.5g, 65%), as a white solid; mp 111-112°C (EtOAc-hexane);
dH (400MHz, CDCl3) 1.27 (3H, t, J =7.15Hz, OCH2CH3), 3.11(1H, dd, J 13.4, 3.3Hz,),
3.36(dd, J =13.4, 6.6Hz, 2H), 3.85(3H, s, OMe), 3.92(1H, dd, J 3.3, 6.6Hz, CH2-CH), 4.24(2H,
q, J 7.15Hz, OCH2CH3), 6.93(2ArH, m), 7.2(1ArH, dd, J 7.4, 1.4Hz), 7.29(1ArH, dd, J
9.3,1.6Hz,); HRMS (CI, NH3): MNa+, found m/z 256.0951. C13H15NO3Na requires m/z
256.0944. This was identical with an authentic sample obtained by reducing 1b with sodium
borohydride in ethanol (mix mp 112-113°C).
Butadiene compound (3b):
Rf (30% EtOAc/hexanes) 0.75; mp 104-105°C (EtOAc-hexane); dH (400MHz, CDCl3) 1.4 (3H,
t, J 7.1Hz, OCH2CH3), 3.9(3H, s, OMe), 4.3(2H, q, J 7.1Hz, OCH2CH3), 6.9(1H, d, J 8.2Hz, -
CH=CH-CH=), 7.0(1H, t, J 7.4Hz, -CH=CH-CH=), 7.40(2ArH, m), 7.61(m, 2ArH), 8.0(1H, d,
J 11.7Hz, -CH=CH-CH=); dC (100.6 MHz, CDCl3) 162.43, 158.47, 156.39, 144.18, 132.48,
128.69, 123.61, 123.45, 120.88, 114.68, 111.22, 103.32, 62.03, 55.51, 14.08; HRMS (CI, NH3):
17

ACCEPTED MANUSCRIPT
MNa+, found m/z 280.0945. C15H15NO3Na requires m/z 280.0944. The butadiene was identical
with the authentic sample (mix mp 103-104°C).8, 12
Reaction in toluene leads to 5% butadiene and 10% dihydro derivatives the rest being starting
material. There was no reaction in acetonitrile. The reaction with diisopropylethylamine, in
ethanol or in acetonitrile showed complete disappearance of starting material, no hydrolyzed
aldehyde and major formation of dihydro derivative.
4.3.3 Ethyl 2-cyano-3-(3-methoxyphenyl)acrylate (1c) 13
nmax (liquid film) 3078, 2940, 2230, 1730, 1598cm-1; dH (400MHz, CDCl3) 1.4 (3H, t, J
7.1Hz, , OCH2CH3), 3.9 (3H, s, OMe), 4.4(2H, q, J 7.1Hz, OCH2CH3), 7.1(1ArH, dd, J 6.4,
1.8Hz), 7.4(1ArH, t, J 8.0Hz), 7.5(1ArH, d, J 7.7Hz), 7.49(1ArH, d, J 7.7Hz,), 8.2(1H, s,
vinyl); m/z 231.1(MH+).
Action of triethylamine on (1c) in hot ethanol
NMR analysis of crude product indicated the formation of dihydro derivative 2c for about 16%,
hydrolyzed aldehyde about 7%. Approximately 76% of starting material did not undergo
reaction.
Authentic 2c was made from 1c by reduction with sodium borohydride in ethanol.
Rf (30% EtOAc/hexanes) 0.60; (1.5g, 65%) as a orange oil; nmax (liquid film) 3070, 2982,
2251, 1744cm-1; dH (400MHz, CDCl3) 1.27(3H, t, J 7.1Hz, OCH2CH3), 3.1(1H, dd, J 13.8,
8.5Hz, CH2-CH), 3.25(1H, dd, J 13.8, 5.8Hz, CH2-CH), 3.7(1H, dd, J 8.5, 5.8Hz, CH2-CH),
3.8(3H, s, OMe), 4.24(2H, q, J 7.1Hz, OCH2CH3), 6.8(3ArH, m), 7.3(1ArH, q, J 7.1, 2.3Hz);
m/z 232.1(MH-).
18

ACCEPTED MANUSCRIPT
4.3.4 Ethyl 2-cyano-3-(4-methoxyphenyl)acrylate (1d)
nmax (liquid film) 3093, 2982, 2233, 1596cm-1; dH (300MHz, CDCl3) 1.3 (3H, t, J 7.2Hz,
OCH2CH3), 3.89(3H, s, OMe), 4.4(2H, q, J 7.2Hz, OCH2CH3), 7.0(2ArH, d, J 9.0Hz),
8.0(2ArH, d, J 9.0Hz), 8.2(1H, s, vinyl); m/z 231.1(MH+). Data are consistent with the values
reported in literature.14
Action of triethylamine on (1d) in hot ethanol
NMR spectrum of the crude product showed almost completely unchanged starting material, the
rest was approximately 6.5% of dihydro derivatives 2d (δ 3.1-3.3 ppm).
4.3.5 Ethyl 3-(4-chlorophenyl)-2-cyanoacrylate (1e)
nmax (liquid film) 3073, 2962, 2213, 1743, 1662, 807cm-1; dH (400MHz, CDCl3) 1.4 (3H, t, J
7.1Hz, OCH2CH3), 4.4(2H, q, J 7.1Hz, OCH2CH3), 7.48(2ArH, m), 7.93(2ArH, m), 8.2(1H, s,
vinyl); m/z =234.2(MH-). Data are consistent with reported literature values.8
Action of triethylamine on (1e) in hot ethanol.
The NMR spectrum of crude product indicated that the dihydro derivative 2e was formed to
about 17% the rest was almost completely starting material.
Authentic 2e was prepared by reduction of 1e with sodium borohydride.
(1.3g, 50%), as a colourless oil, nmax (liquid film) 3089, 2983, 2251, 1596, 807cm-1; dH
(300MHz, CDCl3) 1.27 (3H, t, J 7.16Hz, OCH2CH3), 3.10 (1H, dd), 3.18(1H, dd) 3.6 (1H, dd),
4.2(2H, q, J= 7.14Hz, OCH2CH3), 7.15(2ArH, m), 7.3(2ArH, m).
4.3.6 Ethyl 2-cyano-3-(2-methoxy-5-nitrophenyl)acrylate (1f) 1a
Ethyl cyanoacetate (11.3g, 0.1mol) was taken in ethanol (100 mL) to which added 2-3 drops of
piperidine were added and the mixture stirred for 10-15 min. 2-Methoxy-5-nitrobenzaldehyde 4
(18.1g, 0.1mol) was added slowly to the mixture which was then stirred at 25-30°C until a TLC
19

ACCEPTED MANUSCRIPT
test showed the reaction was complete. The precipitate was filtered off, washed with ethanol
and then recrystallized from the ethanol to afford 1f. Rf (50% EtOAc/hexanes) 0.67; mp 186-
1a
188°C(lit., 186-187°C); nmax (liquid film) 3074, 2954, 2226, 1721, 1603, 1518, 1354 cm-1;
dH (400MHz, CDCl3) 1.4 (3H, t, J 7.1Hz, OCH2CH3), 4.4(2H, q, J 7.1Hz, OCH2CH3), 4.0(3H,
s, OMe), 7.0(1ArH, d, J 9.2Hz), 8.39(1ArH, dd, J 9.2, 2.8Hz), 8.4(1H, s, vinyl), 9.0(1ArH, d, J
2.6Hz); HRMS (CI, NH3): MH+, found m/z 277.0816. C13H13N2O5 requires m/z 277.0819.
Action of triethylamine on (1f) in hot ethanol
The NMR spectrum showed the mixture to have approximately 3% starting material, 48.5%
butadiene and 48.5% dihydro compound. The HPLC analysis gave the composition as starting
material 8%, 23% butadiene 3f and dihydro compound 2f 65%. The mismatch is obviously due
to the fact that the HPLC area% has not been corrected for the response factor. The crude
mixture was separated by column chromatography (20% EtOAC / hexanes) to get 3f in the
earlier fraction and 2f in the later fraction.
Authentic dihydro 2f1a and butadiene 3f1a were prepared.
Dihydro compound (2f)
1a
Rf (50% EtOAc/hexanes) 0.65; (1.5g, 53%) as a off white solid, mp 110-111°C (lit., 112-
113°C); nmax (liquid film) 3074, 2919, 2253, 1739, 1509, 1346 cm-1; Purity: 97.25 % (HPLC);
dH (400MHz, CDCl3) 1.32 (3H, t, J 7.1Hz, OCH2CH3), 3.22 (1H, dd, J 8.5, 13.7Hz, CH2-CH),
3.40(1H, dd, J=6.8,13.7Hz, CH2-CH), 3.92(1H, dd, J=8.5, 6.5Hz, CH2-CH), 4.0(3H, s, OMe),
4.3(q, J 7.1Hz, 2H, OCH2CH3), 7.0(1ArH, d, J 9.0Hz), 8.13(1ArH, d, J 2.6Hz), 8.25(1ArH, dd,
J 9.0, 2.7Hz); HRMS (CI, NH3): MH+ found m/z 279.0970, C13H15N2O5 requires m/z 279.0975.
Butadiene compound (3f)
20

ACCEPTED MANUSCRIPT
1a
Rf (50% EtOAc/hexanes) 0.90; (1.2g, 40%) as a light green solid, mp 186-188°C(lit., 187-
188°C); nmax (liquid film): 2988, 2947, 2223, 1715, 1605, 1522, 1346 cm-1; Purity: 95.92 %
(HPLC); dH (400MHz, CDCl3) 1.39 (3H, t, J 7.1Hz, OCH2CH3), 4.00(3H, s, OMe), 4.33 (2H,
q, J 7.1Hz, OCH2CH3), 7.11 (1ArH, d, J 9.1Hz), 7.47(1H, dd, J 10.6, 15.2Hz, -CH=CH-CH=),
7.53 (1H, d, J 15.2Hz, -CH=CH-CH=), 8.01 (1H, d, J 10.6Hz, -CH=CH-CH=), 8.28 (1ArH, dd,
J 9.0, 2.5Hz,), 8.43 (1ArH, d, J 2.5Hz); dC (75 MHz, CDCl3) 162.53, 162.03, 155.09, 141.65,
141.12, 127.28, 126.07, 124.36, 114.21, 111.25, 106.00, 105.98, 62.48, 56.61, 14.12; m/z 301.8
(MH-); HRMS (CI, NH3): MH+ found m/z 303.0974. C15H15N2O5 requires m/z 303.0975.
Acetaldehyde (0.88g, 0.02mol) was added to toluene (20mL) containing 1f (2.77g, 0.01mol)
and catalytic amount of pyridine and the solution heated to 60 to 65°C for 14 h. After
completion of the reaction, toluene was completely distilled off under vacuum. The residue was
dissolved in dichloromethane, washed with water and the organic layer distilled off completely
under vacuum to afford crude product mixture from which the butadiene 3f was obtained by
column chromatography (20% EtoAc/ hexanes); (1.5g, 49%) as a light green colored solid.
4.3.7 Ethyl 2-cyano-3-(4-nitrophenyl)acrylate (1g)
nmax (liquid film) 3073, 2942, 2220, 1733, 1521, 1338cm-1; dH (400MHz, CDCl3) 1.4 (3H, t, J
7.15Hz, OCH2CH3), 4.4(2H, q, J 7.12Hz, OCH2CH3), 8.1(2ArH, d, J 5.1Hz,), 8.3(1H, s, vinyl),
8.4(2ArH, d, J 4.9Hz,); m/z 246.1(MH-). Data are consistent with reported literature values.15
Action of triethylamine on (1g) in hot ethanol
NMR spectrum of the crude product showed only diagnostic peaks for the dihydro derivative 2g
seen over a curvy base line. Hence presence of starting material and butadiene could not be
estimated.
21

ACCEPTED MANUSCRIPT
Attempted reduction of 1g with sodium borohydride in ethanol led to a mixture of the dihydro
derivative 2g and alcohol formed by reduction of the ester.
4.3.8 Methyl 2-cyano-3-(2-methoxy-5-nitrophenyl)acrylate (1h)
This was prepared by the conditions used for 1f, (2.75g, 76%) as a white solid; mp 152-153°C
(MeOH); nmax (liquid film) 3074, 2954, 2223, 1735, 1600, 1542, 1371cm-1; dH (300MHz,
CDCl3) 4.0(3H, s, OCH3), 4.1(3H, s, OMe), 7.1(1ArH, d, J 9.2Hz), 8.44(1ArH, dd, J 9.2,
2.7Hz), 8.5(1H, s, vinyl), 9.13(1ArH, d, J= 2.6Hz); HRMS (CI, NH3): MNa+, found m/z
285.0493, C12H10N2NaO5 requires m/z 285.0482.
Action of triethylamine on (1h) in hot methanol
The NMR spectrum of the crude product showed a mixture of approximately unreacted starting
material about 38%, 13% butadiene, 38% dihydro and 11% of starting aldehyde (diagnostic
peak for butadiene δ 7.51 ppm, dihydro δ 3.3 -3.4 ppm as in 2f).
4.3.9 Ethyl 2-cyano-3-(thiophen-2-yl)acrylate (1i)
nmax (liquid film) 3073, 2942, 2230, 1723, 1610 cm-1; dH (400MHz, CDCl3) 1.38 (3H, t, J
7.1Hz, OCH2CH3), 4.37(2H, q, J 7.1Hz, OCH2CH3), 7.22(1ArH, dd, J 3.8, 1.1Hz), 7.7(1ArH, d,
J 1.1Hz,), 7.8(1ArH, d, J 3.7Hz), 8.3(1H, s, vinyl); HRMS (CI, NH3): MNa+ found m/z
230.0252. C10H9NO2S Na requires m/z 230.0252. Above data are in agreement with the reported
values.16
Action of triethylamine on (1i) in hot ethanol
The NMR spectrum indicated formation of about 5% dihydro (δ 3.45, 3.75 ppm). The rest was
starting material.
22

ACCEPTED MANUSCRIPT
4.3.10 Ethyl 2-cyano-3-(pyridin-2-yl)acrylate (1j)
nmax (liquid film) 3080, 2870, 2226, 1714, 1626 cm-1; dH (400MHz, CDCl3) 1.4 (3H, t, J =
7.1Hz, OCH2CH3), 4.3(2H, q, J= 7.1Hz, OCH2CH3), 7.4(1ArH, m), 7.82(1ArH, m), 7.9(1ArH,
d, J 7.8Hz,), 8.28(1H, s, vinyl), 8.8(1ArH, d, J 4.6Hz,); m/z 203.1(MH+); Data agree with the
reported values.17
Action of triethylamine on (1j) in hot ethanol
NMR spectrum of crude product was very complex but showed no starting material.
Sodium borohydride reduction of (1j) is reported in the literature to give ethyl 3-
aminoindolizine-2-carboxylate.16b nmax (liquid film) 3056, 2939, 2251, 1743 cm-1; dH
(300MHz, DMSO) 1.28 (3H, t, J 6.9Hz), 4.24(2H, q, J 6.9Hz), 6.12(NH2, br s), 6.40(3ArH, m),
7.16(1ArH, q, J 2.7Hz), 7.77(1ArH, d, J 5.7Hz).
It was not possible to ascertain whether (ethyl 3-aminoindolizine-2-carboxylate) was present in
the crude triethylamine reaction product.
Methyl 2-cyano-3-(pyridin-2-yl)acrylate was also reduced by NaBH4 to give respective methyl
3-aminoindolizine-2-carboxylate (1.2g, 60%), as a white solid; mp 105-106°C; nmax (liquid
film) 3422, 2925, 2221, 1681, 1609 cm-1; dH (300MHz, CDCl3) 3.88 (3H, s, CH3), 4.8(br s,
NH2), 6.44(2ArH, t, J 6.6Hz), 6.55(1ArH, s), 7.20(1ArH, d, J 9.9Hz), 7.40(1H, s); m/z 189.0
(MH-).
4.3.11 Ethyl 2-cyano-3-(pyridin-3-yl)acrylate (1k)
nmax (liquid film) 3090, 2906, 2221, 1715, 1613 cm-1; dH (400MHz, CDCl3) 1.3 (3H, t, J
7.1Hz, OCH2CH3), 3.4(2H, q, J 7.1Hz, OCH2CH3), 7.5(1ArH, dd, J 8.1, 4.8 Hz), 7.8(1ArH, dd,
23

ACCEPTED MANUSCRIPT
J 4.8, 1.4Hz), 7.9(1ArH, d, J 2Hz), 8.2(1H, s, vinyl), 8.6(1ArH, d, J 8.2Hz); m/z 203.1(MH+).
Data confirm to the reported literature.16
Action of triethylamine on (1k) in hot ethanol
The NMR spectrum of the crude product was complex but it could be roughly estimated that
almost 53% of dihydro and aldehyde were present.
4.3.12 Ethyl 2-cyano-3-(pyridin-4-yl)acrylate (1l)
nmax (liquid film) 3060, 2981, 2253, 1754, 1632 cm-1; dH (400MHz, CDCl3) 1.4(3H, t, J
7.1Hz, OCH2CH3), 4.4(2H, q, J 7.1Hz, OCH2CH3), 7.8(2ArH, br s), 8.18(1H, s, vinyl), 8.9
(2ArH, br s); HRMS (CI, NH3): MH+ found m/z 203.0819. C11H10N2O2 requires m/z 203.0821.
Data are consistent with those reported in literature.18
Action of triethylamine on (1l) in hot ethanol
(1.2g, 59%), as a colourless oil; Rf (50% EtOAc/hexanes) 0.55; nmax (liquid film) 3060, 2981,
2253, 1720cm-1; dH (400MHz, CDCl3) 1.27 (3H, t, J 7.1Hz, OCH2CH3), 3.20 (1H, dd, J 14.0,
8.1, CH2-CH), 3.22(1H, dd, J 14.0, 5.9Hz, CH2-CH), 3.77(1H, dd, J 8.1, 5.9Hz, CH2-CH),
4.26(2H, q, J 7.1Hz, OCH2CH3) 7.24(d with fine structure, 2ArH), 8.60(d with fine structure,
2ArH); HRMS (CI, NH3): MNa+ found m/z 227.0797. C11H12N2O2Na requires m/z 227.0796.
NMR spectrum of crude product showed almost complete consumption of starting material and
formation of dihydro compound 2l as the major product, residual triethylamine and unidentified
products.
Authentic 2l was made for 1l by reduction with sodium borohydride in ethanol. Obtained as a
colourless oil; (1.7g, 85%) as colourless oil; nmax (liquid film) 3035, 2910, 2223, 1716 cm-1.
dH (400MHz, CDCl3) 1.27 (3H, t, J 7.1Hz, OCH2CH3), 3.20 (1H, dd, J 14.0, 8.1,CH2-CH),
24

ACCEPTED MANUSCRIPT
3.22 (1H, dd, J 14.0, 5.9Hz, CH2-CH), 3.77(1H, dd, J 8.1, 5.9Hz, CH2-CH), 4.26(q, J 7.1Hz,
2H, OCH2CH3) 7.24(2ArH, d, J 4.5Hz), 8.60(2ArH, d, J 4.6Hz); m/z 203.1(MH-).
4.3.13 (2-Methoxybenzylidene) propanedinitrile (1m)
nmax (liquid film) 3080, 2954, 2223, 1618, 1335 cm-1; dH (400MHz, CDCl3) 3.92 (3H, s,
OMe), 6.98(1ArH, d, J 8.3Hz,), 7.08(1ArH, t, J 7.6Hz), 7.58(1ArH, t with fine structure),
8.18(1ArH, dd, J 8.0, 1.52Hz), 8.3(1H, s, vinyl); Data match values with the one reported in
literature.19
Action of triethylamine on (1m) in hot ethanol
The NMR of the crude product showed clearly the presence of dihydro derivatives to about 50%
and unreacted starting material 25%, hydrolyzed product 2-methoxybenzaldehyde about 25%.
There was no obvious presence of butadiene.
Reduction of (1m) using NaBH4
(1.1g, 59%), as a colorless oil, Rf (50% EtOAc/hexanes) 0.50; nmax (neat) 3080, 2954, 2223,
1335 cm-1; dH (400 MHz, CDCl3) 3.3 (2H, d, J 7.7Hz, CH2-CH), 3.8(3H, s, OMe), 4.16(1H, t, J
7.7Hz, CH2-CH), 6.91(1ArH, d, J 8.2Hz), 6.96(1ArH, t, J 7.4Hz), 7.2(1ArH, d, J 7.0),
7.35(1ArH, m); m/z 187.1(MH+).
4.3.14 (2-Methoxy-5-nitrobenzylidene)propanedinitrile (1n)
Malononitrile (6.6g, 0.1mol) was taken in ethanol (100mL) to which were added 2-3 drops of
piperidine and the mixture stirred for 10 min. 2-Methoxy-5-nitrobenzaldehyde (18.1g, 0.1mol)
was added slowly to the mixture which was then stirred at 25-30°C until a TLC test showed the
reaction was complete. The precipitate was filtered off, washed with ethanol and recrystallized
from ethanol to afford 1n; nmax (liquid film) 3080, 2948, 2232, 1606, 1338 cm-1; dH (400MHz,
CDCl3) 4.07 (3H, s, OMe), 7.12(d, J 9.2Hz, 1H), 8.2(1H, s, vinyl), 8.46(1ArH, dd, J 9.2,
25

ACCEPTED MANUSCRIPT
2.6Hz,), 9.0(1ArH, d, J 2.6Hz); HRMS (CI, NH3): MNa+, found m/z 252.0376. C11H7N3O3Na
requires m/z 252.0380.
Action of triethylamine on (1n) in hot ethanol
NMR spectrum of the crude product showed about 46% aldehyde, traces starting material and
about 53% dihydro compound 3.26 (2H, d, J 7.7Hz), 4.06(1H, t, J 7.7Hz). Authenticate dihydro
compound for reference purposes could not be made by the usual NaBH4 reduction of 1n since
one CN group also got reduced in the process.
4.3.15 2-Cyano-N, N-diethyl-3-(2-methoxy-5-nitrophenyl)acrylamide (1o)
To a solution of N, N-diethylcyanoacetamide (14.1g, 0.1mol) in toluene (100mL) was added
IRA 96 resin (0.2g) and 2-methoxy-5-nitrobenzaldehyde (18.1g, 0.1mol). Then the mixture was
heated to reflux, released water being collected azeotropically, until TLC test showed the
absence of starting materials. The reaction mixture was filtered hot. The filtrate was evaporated
completely and the residue was purified with ethanol to afford 1o. (2.2g, 73%) as a white solid;
mp 134-135°C (EtOH); nmax (liquid film) 3074, 2934, 2212, 1633, 1518, 1342 cm-1; dH
(400MHz, CDCl3) 1.2 (6H, br s (CH3)3), 3.5(4H, br s,(CH2)2), 4.0(3H, s, OMe), 7.0(1ArH, d, J
9.2Hz), 7.94(1H, s, vinyl), 8.3(1ArH, dd, J 9.2, 2.3Hz), 9.0(1ArH, d, J 2.4Hz,); m/z 303.2
(MH+).
(1o) was unaffected by triethylamine in hot ethanol under the usual conditions.
4.3.16 Ethyl 2-(2-methoxy-5-nitrobenzylidene)-3-oxobutanoate (1p).
Ethyl acetoacetate (1.30g, 0.01mol) was added to a solution of 2-methoxy-5-nitrobenzaldehyde
(1.81g, 0.01mol) in ethanol (20mL). The reaction mass cooled to 0-5°C, and saturated with HCl
gas. The precipitate product was filtered off to afford 1p. (1.93g, 65%) as a white solid; mp
113-114°C (EtOH); Rf (50% EtOAc/hexanes) 0.68; nmax (liquid film) 3078, 2944, 1730, 1656,
1342 cm-1; dH (400MHz, CDCl3) 1.3 (3H, t, J 7.18Hz, OCH2CH3), 2.44(3H, s, CH3), 4.0(3H, s,
26

ACCEPTED MANUSCRIPT
OMe), 4.4(2H, q, J 7.1Hz, OCH2CH3), 7.0(1ArH, d, J 9.1Hz), 7.8(1H, s, vinyl), 8.28(1ArH, dd,
J 9.1, 2.8Hz), 8.3(1ArH, d, J 2.8Hz); m/z 293.1(M+).
Action of triethylamine on (1p) in hot ethanol
The reaction of 1p with triethylamine was carried out in ethanol at 70-75°C for 12 h. After
completion of the reaction, ethanol was completely distilled off. The NMR of the crude product
clearly showed absence of starting material, trace of hydrolyzed aldehyde (about 4%). Besides
small amounts unidentified materials the major product was the decarboethoxylated, i.e 2-
methoxy-5-nitrobenzylideneacetone; dH(400MHz, CDCl3) 2.40 (3H, s, CH3), 4.02 (3H, s,
OMe), 6.85 (1H, d, J 16.4 Hz), 7.0 (1ArH, d, J 9Hz,), 7.80(1H, d, J 16.4Hz), 8.26 (1ArH, dd, J
9.3, 2.7 Hz), 8.4(1ArH, d, J 2.7 Hz); m/z 220(MH-).
4.3.17 Ethyl 2-(methylsulfonyl)-3-phenylacrylate (1q)
nmax (liquid film) 2985, 2932, 1731, 1622, 1140 cm-1; dH (400MHz, CDCl3) 1.25 (3H, t, J
7.0Hz), 3.24(3H, s, CH3), 4.4 (2H, q, J 7.0Hz), 7.39-7.46(5H, m), 7.83(1H, s, vinyl); HRMS
(CI, NH3): MNa+ found m/z 277.0514. C12H14O4SNa requires m/z 277.0511. Data match values
in reported literature. 20
Action of triethylamine on (1q) in hot ethanol
The NMR spectrum of the product had traces of the hydrolyzed product. The major products (6,
7) corresponded to the ones obtained by reaction of 1q with NaBH4 in ethanol.
Attempted reduction of (1q) using NaBH4
NMR and mass spectra clearly showed that reduction had not taken place and ethanol had added
to the double bond. This addition can lead to diastereoisomeric products. These were present in
the NMR spectrum in the ratio of 3:1. Reaction as usual gave a colourless oil product. dH
(400MHz, CDCl3) 1.0 (3H, t, J 7.1Hz), 1.12(3H, t, J 7.1Hz), 4.99 (PhCH, d, J 10Hz), 5.07
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ACCEPTED MANUSCRIPT
(PhCH, d, J 6H); HRMS (CI, NH3): MNa+ found m/z 323.0931. C14H20O5SNa requires m/z
323.0929.
4.3.18 3-(2-Methoxy-5-nitrobenzylidene)pentane-2, 4-dione (1r).
2, 4-Pentadione (1.0g, 0.01mol) was added to a solution of 2-methoxy-5-nitrobenzaldehyde
(1.8g, 0.01mol) in methanol (20mL). The reaction mass was cooled to 0-5°C, then HCl gas was
passed until saturation. Reaction mass was filtered to give the aldol.
The product was taken in acetic anhydride and heated to 60-65°C for 30 min to effect
dehydration of the aldol. The reaction mass was cooled to 20-25°C and dropped into ice cold
water. Ethyl acetate was added and the mass stirred. The ethyl acetate layer was separated and
distilled off completely under vacuum. The solid obtained was characterized as 1r. (1.8g, 68%)
as a off white solid; mp 176-177°C (EtOH); nmax (liquid film) 3082, 2947, 1708, 1548, 1353
cm-1; dH (400MHz, CDCl3) 2.32 (3H, s, CH3), 2.46(3H, s, CH3), 4.0(3H, s, OMe), 7.0(1ArH, d,
J 9.1Hz), 7.6(1H, s), 8.26(1ArH, d, J 2.8), 8.28(1ArH, dd, J 9.1, 2.8Hz); HRMS (CI, NH3):
MH+ found m/z 264.0868. C13H14NO5 requires m/z 264.0869.
Action of triethylamine on (1r) in hot ethanol.
NMR of the crude product could not be analyzed.
4.2.19 Ethyl 3-(2-methoxyphenyl)acrylate (1s) 151
nmax (liquid film) 3080, 2979, 1618, 1710, 1631 cm-1; dH (400MHz, CDCl3) 1.32 (3H, t, J
7.1Hz, OCH2CH3), 3.9(3H, s, OMe), 4.25(2H, q, J 7.1Hz, OCH2CH3), 6.5(1H, d, J 16.1Hz),
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