An effective new access to ethyl 2-[(alkylamino)(cyano)methyl] acrylates: first synthesis of ethyl 3-cyano-2-(hydroxymethyl) acrylate

Article abstract of DOI:10.1016/j.tet.2009.04.028

A regioselective coupling of ethyl 2-(bromomethyl)-3-cyanoacrylate and primary amines is described to give ethyl 2-[(alkylamino)(cyano)methyl] acrylates in good yields. Whereas the conversion of allyl bromide in the presence of TEAF leads to the first syn

Full text of DOI:10.1016/j.tet.2009.04.028

Tetrahedron 65 (2009) 4904–4907
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An effective new access to ethyl 2-[(alkylamino)(cyano)methyl] acrylates:
first synthesis of ethyl 3-cyano-2-(hydroxymethyl) acrylate
*
Aı¨cha Arfaoui, Hassen Amri
Laboratoire de Chimie Organique et Organome´tallique, Universite´ de Tunis El Manar, Faculte´ des Sciences, Campus Universitaire, 2092 Tunis, Tunisia
a r t i c l e i n f o
a b s t r a c t
Article history:
A regioselective coupling of ethyl 2-(bromomethyl)-3-cyanoacrylate and primary amines is described to
give ethyl 2-[(alkylamino)(cyano)methyl] acrylates in good yields. Whereas the conversion of allyl bro-
mide in the presence of TEAF leads to the first synthesis of ethyl 3-cyano-2-(hydroxymethyl) acrylate.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 21 January 2009
Received in revised form 13 March 2009
Accepted 2 April 2009
Available online 17 April 2009
Keywords:
Ethyl 2-(bromomethyl)-3-cyanoacrylate
Regioselectivity
Functionalized allylamines
Ethyl 3-cyano-2-(hydroxymethyl) acrylate
Triethylammonium formate (TEAF)
1. Introduction
or ketonitriles),15–17 nitroesters,18 succinonitrile19 and
a-alkyli-
dene-1,5-(diesters,20 ketoesters,21 cyanoesters22), we have de-
veloped convenient methodology for the synthesis of a new family
of 2-methylene-1,3-cyanoesters 3. The reaction proceeds via sub-
stitution of a bromine atom by a tertiary amine such us 1,4-dia-
zabicyclo[2.2.2]octane23,24 providing a quaternary ammonium salt,
which can be readily replaced through a direct substitution by cy-
anide anion25,26 leading to the methylenic compounds 327 in good
yield (78%) in the presence of the unknown isomerization product 4
(22%). Repeated efforts to avoid the simultaneous formation of
Acrylic compounds are good Michael acceptors due to their
great reactivity as electrophiles towards various nucleophiles. In-
deed, bromomethylation at the
a position of these acrylic sub-
strates reveals a range of useful products for organic synthesis,
particularly in the preparation of natural1–4 and biologically active
compounds.5–8 Bromomethylated esters of type
homologous difunctionalized products of type
1
and their
are useful
2
synthons in several synthetic applications. The allylic bromide
1a9,10 constitutes a basic intermediate to react as an electrophilic
compound in a range of reactions11–13 (Scheme 1).
methylene derivatives 3 and b-cyanoester 4 failed. However, the
mixture of regioisomers 3 and 4 can be easily separated by column
chromatography (Scheme 2).
R
Br
A
Br
2a : A = CO2R
2b : A = P(O)OEt2
1a : R = H
1b: R = alkyl
Br
A = CO2Et, CN, COR
A
CO2R
1
2
Br
N
N
CN
NC
DABCO
KCN
+
Scheme 1.
THF : H2O
CO2Et
CO2Et
CO2Et
CO2Et
4-E (22%)
1a
3 (78%)
Scheme 2.
2. Results and discussion
In previous work, we described a simple and convenient
synthesis of -functionalized -(bromomethyl) acrylic acid ester
As part of our ongoing work on the synthesis of
a
-alkylidene-
1,3-(cyano or ester) phosphonates,14
a
-alkylidene-1,4-(ketoesters
b
a
1a and demonstrated that it can be utilized to prepare some a-
(gem-difunctional methyl) acrylic acid esters.28,29 It seemed
plausible to elaborate a new electrophilic difunctional allylic
bromide such as 5, readily obtained using the known tandem
* Corresponding author.
E-mail address: hassen.amri@fst.rnu.tn (H. Amri).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.028

A. Arfaoui, H. Amri / Tetrahedron 65 (2009) 4904–4907
4905
bromination–dehydrobromination of ethyl 2-(cyanomethyl) ac-
rylate 3 in the presence of triethylamine according to the method
published previously30 (Scheme 3).
drop of hydrochloric acid in methanol led to ethyl 3-cyano-2-
(hydroxymethyl) acrylate 9 (1:1 mixture of E/Z isomers) as yellow
liquid (Scheme 6).
NC
NC
NC
5-Z,E
OCHO
Br
OH
TEAF, MeCN
SN2
HCl cc
MeOH
CN
NC
Br
Br
CN
Br2
CCl4, reflux
Et3N
25 °C
CO2Et
CO2Et
CO2Et
9-Z,E (65%)
8-Z,E (85%)
CO2Et
Br
CO2Et
CO2Et
3
R
OH
5-Z,E (78%)
7a : EWG = CO2R
7b : EWG = CN
Scheme 3.
EWG
It is important to indicate that the regioisomer 4 could also be
effectively converted into allyl bromide 5 through a simple trans-
formation of the conjugated cyanoester 4 in the presence of N-
bromosuccinimide (NBS)31 using catalytic benzoyl peroxide under
reflux of carbon tetrachloride in good yield (Scheme 4).
Scheme 6.
3. Conclusion
Starting from Baylis–Hillman-derived bromide 1a, we de-
veloped a simple method for the synthesis of allyl bromide 5,
a useful compound for the access to difunctionalized allylamines 6
and allylic alcohol 9.
NC
NC
Br
NBS
PhCO3H cat.
CCl4, reflux
CO2Et
CO2Et
4
5-Z (70%)
Scheme 4.
4. Experimental
4.1. General
Table 1
Synthesis of ethyl 2-[(alkylamino)(cyano)methyl] acrylates 6a–h
All reactions were monitored by TLC on silica gel plates (Fluka
Kieselgel 60 F254). For column chromatography, Fluka Kieselgel
70–230 mesh was used. 1H and 13C NMR spectra (fully decoupled)
were recorded on Bruker AMX 300 in CDCl3 as solvent and TMS as
the internal standard. IR spectra were recorded with a Perkin–
Elmer paragon 1000 FT-IR spectrophotometer. Mass spectrometry
was performed on an Autospec 200, Micromass (Waters)
instrument.
6a–h
R
Time (h)
Yield (%)
6a
6b
6c
6d
6e
6f
PhCH2
3
3
1
1
1
1
62
60
58
56
76
70
Ph(CH3)CH
p-FC6H4CH2
p-MeOC6H4CH2
p-ClC6H4CH2
cC6H11
CH2
N
6g
6h
1
1
70
55
O
CH2
4.2. Synthesis of ethyl 2-(cyanomethyl) acrylate 3 and ethyl 3-
cyano-2-methylacrylate 4
Allylamines are interesting synthetic targets because of their
key function as intermediates in several synthetic fields, as well as
their physiological properties,32 biological activities33,34 and their
presence in several natural products.35,36 Two main pathways can
be considered for the reaction of allyl bromide 5 with primary
amines in methanol. The reactivity of these amines is governed
essentially by their steric factor. The regioselective and abnormal
(SN20) substitution of bromide can be explained by the increased
4.2.1. Typical procedure
Into a 250 mL flask was introduced 5 g (25.90 mmol) of ethyl 2-
(bromomethyl) acrylate 1a in aqueous THF (104 mL, THF/H2O¼3:1).
DABCO 3.20 g (28.49 mmol) was added and the mixture was stirred
at room temperature for 2 h until the allyl bromide salt was formed.
To the obtained salt was added under stirring at 0 ꢀC for 2 h,
31.08 mmol (2 g) of potassium cyanide (KCN). The mixture was
then hydrolyzed by addition of a saturated solution of NH4Cl. After
extraction with diethyl ether (3ꢁ75 mL), the organic layer was
dried over anhydrous magnesium sulfate. The solvent was evapo-
rated under reduced pressure and the crude mixture was separated
by chromatography on silica gel (AcOEt/Hexane, 1:10) to give the
ethyl 2-(cyanomethyl) acrylate 3 (2.81 g, 78%) and ethyl 3-cyano-2-
methylacrylate 4 (0.79 g, 22%).
electrophilicity of the b-carbon 5 leading to a new family of ethyl 2-
[(alkylamino)(cyano)methyl] acrylates 630,37,38 that contain a ter-
minal methylene group (Table 1, Scheme 5).
NC
NC
NHR
NC
5-Z,E
Br
RNH2
MeOH, 0 °C
4.2.2. Ethyl 2-(cyanomethyl) acrylate 3
CO2Et
CO2Et
CO2Et
6
Yield: (2.81 g, 78%) as a colourless oil; nmax (liquid film) 2305,
1717, 1641 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 6.46 (s, 1H, H2C]),
Scheme 5.
6.09 (1s, 1H, H2C]), 4.25 (q, 2H, J¼7.1, CH2CH3), 3.4 (s, 2H,CH2CN),
The easy conversion of the 2-functional allyl bromide into the
corresponding allylic alcohols 7a,b39,40 considered as important
raw materials for the foods industry led us to investigate the first
1.33 (t, 3H, J¼7.1, CH2CH3). 13C NMR (CDCl3,
d ppm): 164.6, 130.6,
128.3, 116.8, 61.7, 61.7, 14.1. HRMS calcd for C7H9NO2: 139.0633;
found: 139.0688.
synthesis of a,b-difunctional allylic alcohol 9 via the use of a tan-
dem reaction: formylation–hydrolysis41 starting from cyanoester 5-
Z,E. Indeed, due to the reduced size of the formate anion compared
with amines, the reaction of 5-Z,E with an excess (2.5 equiv) of
triethylammonium formate (TEAF) in acetonitrile at 0 ꢀC afforded
the corresponding allyl formate 842–44 via a direct allylic sub-
stitution (SN2) and subsequent hydrolysis in the presence of one
4.2.3. Ethyl 3-cyano-2-methylacrylate 4
Yield: (0.79 g, 22%) as a colourless oil; nmax (liquid film) 2226,
1714, 1626 cmꢂ1
;
1H NMR (CDCl3,
d
ppm, J Hz): 6.32 (s, 1H, HC]),
4.30 (q, 2H, J¼7.0, CH2CH3), 1.28 (s, 3H, CH3), 1.36 (t, 3H, J¼7.0,
CH2CH3). 13C NMR (CDCl3,
ppm): 164.7, 150.2, 115.5, 107.5, 62.2,
16.9, 13.9. HRMS calcd for C7H9NO2: 139.0633; found: 139.0626.
d

4906
A. Arfaoui, H. Amri / Tetrahedron 65 (2009) 4904–4907
4.3. Synthesis of ethyl 2-(bromomethyl)-3-cyanoacrylate 5:
general procedure
4.4.3. Ethyl 2-(cyano(1-phenylethylamino)methyl) acrylate 6b
Yield: 0.71 g, 60%, as a yellow oil; nmax (liquid film) 3420 (br),
2305, 1715, 1636 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 7.31 (m, 5H,
4.3.1. Allyl bromide 5 from 3
C6H5), 6.39 (s, 1H, H2C]), 6.00 (s, 1H, H2C]), 4.51 (s, 1H, CHCN),
4.26 (q, 2H, J¼7.0, CH2CH3), 1.98 (br s, 1H, –NH–), 1.40 (d, 3H, J¼7.0,
To a mixture of 5 g (35.93 mmol) of ethyl 2-(cyanomethyl)
acrylate 3 diluted in 35 mL of anhydrous carbon tetrachloride
was added dropwise under magnetic stirring 1.90 mL (37.37 mol)
of bromine in 25 mL of CCl4 at such a rate that the bromine
colour gradually disappeared. The end of the reaction was in-
dicated by the persistence of the brownish colour. After the
completion of the reaction indicated by TLC analysis, 7.51 mL
(53.89 mmol) of anhydrous triethylamine was added at 0 ꢀC.
After stirring overnight, filtration under reduced pressure of the
formed ammonium salt, then evaporation of the solvent, gave
the oily residue that was purified by chromatography on silica
gel (AcOEt/Hexane, 1:10) leading to a mixture of (Z/E: 41/59)
allyl bromides 5 (6.11 g, 78%).
CH3) 4.26 (t, 3H, J¼7.0, CH2CH3). 13C NMR (CDCl3,
d ppm): 164.3,
142.6, 135.7, 128.7, 128.6, 128.4, 118.1, 61.6, 56.9, 38.1, 24.6, 14.1.
HRMS calcd for C15H18N2O2: 258.1368; found: 258.1381.
4.4.4. Ethyl 2-(cyano(4-fluorobenzylamino)methyl) acrylate 6c
Yield: 0.70 g, 58%, as a yellow oil; nmax (liquid film) 3386 (br),
2305, 1730, 1604 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 7.32, 7.02
(2 m, 4H, C6H4), 6.44 (s, 1H, H2C]), 6.08 (1s, 1H, H2C]), 4.53 (s, 1H,
CHCN), 4.27 (q, 2H, J¼7.0, CH2CH3), 3.92 (q, 2H, JAB¼14.2, CH2Ph),
2.16 (br s, 1H, –NH–), 1.32 (t, 3H, J¼7.0, CH2CH3). 13C NMR (CDCl3,
d
ppm): 164.3, 160.7, 135.2, 133.5, 130.1, 128.6, 117.6, 115.2, 61.7, 50.5,
31.0, 13.9. HRMS calcd for C14H15FN2O2: 262.1118; found: 262.1098.
4.3.2. Allyl bromide 5 from 4
4.4.5. Ethyl 2-(cyano(4-methoxybenzylamino)methyl) acrylate 6d
Yield: 0.70 g, 56%, as a yellow oil; nmax (liquid film) 3367 (br),
A mixture of 7.69 g (50.26 mmol) of ethyl 3-cyano-2-methyl-
acrylate 4-E diluted in 153 mL of anhydrous carbon tetrachloride,
10.74 g (60.30 mmol) of NBS and 0.10 g of benzoyl peroxide was
added to a 250 mL flask fitted with a condenser protected by cal-
cium drying tube. The mixture was stirred at reflux for 80 h and
then filtered under reduced pressure. After evaporation of the
solvent, the crude oil was purified by chromatography on silica gel
(AcOEt/Hexane, 1:10) providing the pure allyl bromide 5-Z (7.67 g,
70%).
2253, 1724, 1612 cmꢂ1; 1H NMR (CDCl3,
d ppm, J Hz): 7.28, 6.88 (4H,
C6H4), 6.44 (s, 1H, H2C]), 6.06 (1s, 1H, H2C]), 4.52 (s, 1H, CHCN),
4.27 (q, 2H, J¼7.0, CH2CH3), 3.87 (q, 2H, JAB¼14.2, CH2Ph), 3.80 (s,
3H, OCH3),1.60 (br s,1H, –NH–),1.29 (t, 3H, J¼7.0, CH2CH3). 13C NMR
(CDCl3,
d ppm): 164.4, 159.2, 135.3, 130.6, 129.7, 128.6, 117.8, 114.0,
61.7, 55.3, 50.8, 50.3, 14.1. HRMS calcd for C15H18N2O3: 274.1317;
found: 274.1303.
4.4.6. Ethyl 2-((4-chlorobenzylamino)(cyano)methyl) acrylate 6e
Yield: 0.97 g, 76%, as a yellow oil; nmax (liquid film) 3337 (br),
4.3.3. Ethyl 2-(bromomethyl)-3-cyanoacrylate 5-Z
Yield: 6.11 g, 78%, as a viscous yellow oil; nmax (liquid film) 2305,
2305, 1727, 1669 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 7.30 (s, 4H,
1730, 1624, 693 cmꢂ1
;
1H NMR (CDCl3,
d
ppm, J Hz): 6.07 (s, 1H,
C6H4), 6.44 (s, 1H, H2C]), 6.08 (s, 1H, H2C]), 4.52 (s, 1H, CHCN),
4.27 (q, 2H, J¼7.0, CH2CH3), 3.92 (q, 2H, JAB¼14.2, CH2Ph), 2.01 (br s,
HC]), 4.37 (q, 2H, J¼7.0, CH2CH3), 4.22 (s, 2H, CH2Br), 1.38 (t, 3H,
J¼7.0, CH2CH3). 13C NMR (CDCl3,
d
ppm): 161.8, 147.9, 114.4, 108.4,
1H, –NH–), 1.32 (t, 3H, J¼7.0, CH2CH3). 13C NMR (CDCl3,
d ppm):
62.9, 28.2, 13.8. HRMS calcd for C7H8BrNO2: 216.9738; found:
216.9754.
164.3, 136.3, 135.1, 133.4, 128.7, 128.7, 117.8, 61.7, 50.5, 50.4, 15.3.
HRMS calcd for C14H15ClN2O2: 278.0822; found: 278.0836.
4.3.4. Ethyl 2-(bromomethyl)-3-cyanoacrylate 5-E
4.4.7. Ethyl 2-(cyano(cyclohexylamino)methyl) acrylate 6f
Yield: 7.67 g, 70%, as a viscous yellow oil; nmax (liquid film) 2305,
Yield: 0.76 g, 70%, as a yellow oil; nmax (liquid film) 3421 (br),
1724, 1623, 693 cmꢂ1
.
1H NMR (CDCl3,
d
ppm, J Hz): 6.40 (s, 1H,
2305, 1715, 1669 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 6.41 (s, 1H,
HC]), 4.33 (s, 2H, CH2Br), 4.31 (q, 2H, J¼7.0, CH2CH3), 1.33 (t, 3H,
H2C]), 6.08 (s, 1H, H2C]), 4.65 (s, 1H, CHCN), 4.28 (q, 2H, J¼7.0,
CH2CH3), 2.74 (qt, 1H, J¼7.0, C6H11), 1.94 (br s, 1H, –NH–), 1.77 (m,
6H, C6H11), 1.30 (m, 4H, C6H11), 1.32 (m, 3H, CH2CH3). 13C NMR
J¼7.0, CH2CH3). 13C NMR (CDCl3,
d ppm): 162.4, 148.8, 114.1, 109.6,
62.8, 23.8, 14.0. HRMS calcd for C7H8BrNO2: 216.9738; found:
216.9754.
(CDCl3, d ppm): 164.4, 136.0, 127.9, 118.6, 61.8, 54.8, 48.3, 33.8, 25.8,
24.6, 14.0. HRMS calcd for C13H20N2O2: 236.1525; found: 236.1603.
4.4. Synthesis of ethyl 2-[(alkylamino)(cyano)methyl]
acrylates 6a–h
4.4.8. Ethyl 2-(cyano(pyridin-2-ylmethylamino)methyl) acrylate 6g
Yield: 0.79 g, 70%, as a brown oil; nmax (liquid film) 3421 (br),
2305, 1726, 1607 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 8.55 (m, 1H,
4.4.1. General procedure
C6H4N), 7.67 (m, 1H, C6H4N), 7.28 (m, 1H, C6H4N), 7.21 (m, 1H,
C6H4N), 6.48 (s, 1H, H2C]), 6.15 (s, 1H, H2C]), 4.74 (s, 1H, CHCN),
4.29 (q, 2H, J¼7.0, CH2CH3), 4.06 (q, 2H, JAB¼14.2, CH2C6H4N), 2.07
(br s, 1H, –NH–), 1.32 (t, 3H, J¼7.0, CH2CH3). 13C NMR (CDCl3,
To a solution of ethyl 2-(bromomethyl)-3-cyanoacrylate 5 (1 g,
4.59 mmol) in 15 mL of absolute methanol was added dropwise
primary amine (4.59 mmol). The mixture was stirred at room
temperature at 0 ꢀC for 1–3 h. The mixture was concentrated and
the organic residue obtained was purified by chromatography on
silica gel (AcOEt/Hexane, 1:10).
d
ppm): 167.7, 164.3, 157.6, 149.5, 135.1, 122.9, 128.8, 122.4, 117.7,
61.7, 52.2, 50.6, 14.1. HRMS calcd for C13H15N3O2: 245.1164; found:
245.1160.
4.4.2. Ethyl 2-((benzylamino)(cyano)methyl) acrylate 6a
4.4.9. Ethyl 2-(cyano(furan-2-ylmethylamino)methyl) acrylate 6h
Yield: 0.59 g, 55%, as a brown oil; nmax (liquid film) 3417 (br),
Yield: 0.69 g, 62%, as a yellow oil; nmax (liquid film) 3393 (br),
2305, 1730, 1605 cmꢂ1
;
1H NMR (CDCl3,
d
ppm, J Hz): 7.30 (m, 5H,
2305, 1725, 1640 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 7.39 (s, 1H,
C6H5), 6.44 (s, 1H, H2C]), 6.07 (s, 1H, H2C]), 4.54 (s, 1H, CHCN),
4.27 (q, 2H, J¼7.0, CH2CH3), 3.95 (q, 2H, JAB¼14.2, CH2–Ph), 2.01
(br s, 1H, –NH–), 1.31 (t, 3H, J¼6.5, CH2CH3). 13C NMR (CDCl3,
C5H6O), 6.45 (s, 1H, H2C]), 6.33 (s, 1H, C5H6O), 6.29 (s, 1H, C5H6O),
6.09 (s, 1H, H2C]), 4.57 (s, 1H, CHCN), 4.27 (q, 2H, J¼8.0, CH2CH3),
3.95 (q, 2H, JAB¼14.2, CH2C5H6O), 2.06 (br s, 1H, –NH–), 1.31 (t, 3H,
d
ppm): 164.5, 138.0, 135.5, 129.0, 128.8, 128.7, 128.0, 117.9, 61.8,
J¼7.8, CH2CH3). 13C NMR (CDCl3,
d ppm): 164.3, 151.4, 142.7, 134.9,
51.5, 51.4, 14.1. HRMS calcd for C14H16N2O2: 244.1212; found:
244.1224.
128.9, 117.6, 110.3, 108.4, 61.7, 50.7, 43.9, 14.1. HRMS calcd for
C12H14N2O3: 234.1004; found: 234.1016.

A. Arfaoui, H. Amri / Tetrahedron 65 (2009) 4904–4907
4907
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fitted with a condenser protected by calcium drying tube were
added 20.53 mmol of triethylammonium formate (TEAF). After
hydrolysis, the organic layer was extracted by ether and then dried
over MgSO4. After evaporation of the solvent, the formate 8-Z,E
(44:56) (1.28 g, 85%) was purified by chromatography on silica gel
(AcOEt/Hexane, 1:10). Two drops of concentrated hydrochloric acid
were added to 8 diluted in 10 mL of absolute methanol with stirring
for 1 h at 25 ꢀC. The allylic alcohol 9-Z,E (44:56) (0.83 g, 65%)
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4.5.1. Ethyl 3-cyano-2-(formyloxymethyl) acrylate 8-Z,E
Yield: 1.28 g, 85%, as a yellow oil; nmax (liquid film) 2830, 2306,
1734, 1696, 1636 cmꢂ1 1H NMR (CDCl3,
; d ppm, J Hz): 8.22 (s, 1H,
26. Hong, W. P.; Lim, H. N.; Park, H. W.; Lee, K. J. Bull. Korean Chem. Soc. 2005, 26,
655–657.
27. Japanese Patent, Kokai Tokkyo Koho, Fujitsu Ltd, Japan 1985, 3 pp. Application:
JP 83-224330 19831130.
CHO), 6.66 (s, 1H-E, HC]), 6.11 (s, 1H-Z, HC]), 5.18 (s, 2H-E, CH2),
5.07 (s, 2H-Z, CH2), 4.32 (q, 2H, J¼7.0, CH2CH3), 4.32 (t, 3H, J¼7.0,
CH2CH3). 13C NMR (CDCl3,
d ppm): 162.8, 159.8, 146.1, 113.9, 111.2,
`ras, J.; Amri, H. Synth. Commun. 1996, 26,
62.8, 59.4, 14.0. HRMS calcd for C8H9NO4: 183.0532; found:
183.0522.
28. Ben Gharbia, S.; Besbes, R.; Villie
1685–1692.
29. Be´ji, F.; Lebreton, J.; Villie`ras, J.; Amri, H. Synth. Commun. 2002, 32, 3273–3278.
´
30. Besbes, R.; Villieras, M.; Amri, H. Indian J. Chem. 1997, 36B, 5–8.
4.5.2. Ethyl 3-cyano-2-(hydroxymethyl) acrylate 9-Z,E
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Yield: 0.83 g, 65%, as a yellow oil; nmax (liquid film) 3378 (br),
2305, 1725, 1623 cmꢂ1; 1H NMR (CDCl3,
d ppm, J Hz): 6.84 (s, 1H-Z,
HC]), 6.14 (s, 1H-E, HC]), 4.85 (s, 2H-Z, CH2), 4.48 (s, 2H-E, CH2),
4.35 (q, 2H, J¼7.0, CH2CH3), 2.70 (br s, 1H, OH), 1.38 (t, 3H, J¼7.0,
CH2CH3). 13C NMR (CDCl3,
d ppm): 162.7, 151.7, 115.26, 104.2, 62.4,
61.3, 13.9. HRMS calcd for C7H9NO3: 155.0582; found: 155.0590.
38. Belta¨ıef, I.; Besbes, R.; Ben Amor, F.; Amri, H.; Villie´ras, M.; Villie´ras, J. Tetra-
hedron 1999, 55, 3949–3958.
References and notes
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1998, 1765–1768.
41. Beltaı¨ef, I.; Besbes, R.; Amri, H.; Villie´ras, J. Tetrahedron Lett. 1997, 38, 813–814.
42. Alexander, J.; Renyer, M. L.; Veerapanane, H. Synth. Commun. 1995, 25,
3875–3881.
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