Synthesis of 2-cyanoacryloyl chloride and its interaction with O- and S-nucleophiles

Article abstract of DOI:10.1016/j.mencom.2013.11.019

Reaction of 2-cyanoacrylic acid with oxalyl chloride gives quantitatively 2-cyanoacryloyl chloride capable of esterifying thiols and fluorinated alcohols.

Full text of DOI:10.1016/j.mencom.2013.11.019

Mendeleev
Communications
Mendeleev Commun., 2013, 23, 356–357
Synthesis of 2-cyanoacryloyl chloride
and its interaction with O- and S-nucleophiles
Valerie A. Dyatlov,*a Iskander R. Rustamov,a Tatiana A. Grebeneva,a
Viktor I. Maleev,b Yuri G. Gololobovb and Vyacheslav V. Kireeva
a D. I. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russian Federation.
Fax: +7 499 978 9153; e-mail: dyatlov.va@mail.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation
DOI: 10.1016/j.mencom.2013.11.019
Reaction of 2-cyanoacrylic acid with oxalyl chloride gives quantitatively 2-cyanoacryloyl chloride capable of esterifying thiols and
fluorinated alcohols.
Alkyl-2-cyanoacrylates are among the most reactive monomers.1
Although, they can undergo polymerization through both free
radical and anionic mechanisms, the latter has attracted more
interest owing to the ease of initiation. Even traces of weak
nucleophiles such as water, amines, alcohols or phosphines cause
instantaneous hardening of a liquid monomer, which would cause
problems during synthesis and handling of 2-cyanoacrylates.
The most common synthetic route for their preparation is base-
catalyzed Knoevenagel condensation of cyanoacetates and form-
aldehyde with following acid-catalyzed thermolysis of intermediate
polymer.2 This method is suitable for the synthesis of volatile
monomers with relatively low molecular weight. However, it
becomes much more complicated for products containing bulky
ester moieties. To the best of our knowledge such monomers as
2-cyanoacrylate aliphatic (³C8) esters or bis-2-cyanoacrylates
could not be accessed by this method. Another popular synthetic
approach is based on temporary protection of C=C bond via in situ
formation of the Diels–Alder anthracene adducts. This method
is suitable for preparation of monofunctional monomers only,3,4
whereas obtaining multifunctional or aryl 2-cyanocrylates by this
technique is not reported.
mers can be effectively used as immaculate hydrophobic additives
improving biodegradation stability of cyanoacrylate based medical
adhesives, drug delivery systems and materials for tissue engi-
neering. We have also studied the key methods for preparation
of 2-cyanoacryloyl chloride as the important intermediate for
applied synthetic chemistry.†
Chlorination agents commonly used for preparation of acid
chlorides turned out inconsistent with 2-cyanoacrylic acid. Thionyl
and benzoyl chlorides did not afford the target product and the
reactions were probably stopped at a stage of mixed anhydride.
Interaction of 2-cyanoacrylic acid with phosphorus pentachloride
proceeded through a formation of 2-cyanoacryloyl chloride at
room temperature that was next subjected to chlorination yielding
2,3-dichloro-2-cyanopropanoyl chloride (Scheme 1). This impurity
stayed as a contaminant of the main product that could not be
removed by a conventional purification and caused a lot of
complications at the esterification stage. Further chlorination of
2-cyanoacryloyl chloride resulted fully in 2,3-dichloro-2-cyano-
propanoyl chloride that was synthesized for the first time and
seems promising for some organic syntheses.
A novel synthetic pathway of preparation of 2-cyanoacrylates
is proposed as a result of successful synthesis of 2-cyanoacrylic
acid by high temperature vacuum pyrolysis of ethyl 2-cyano-
acrylate5 with ethylene being a secondary product. Note that
2-cyanoacrylic acid molecule contains two electrophilic sites (C=C
and C=O) which can interact with nucleophiles like alcohols,
phenols and thiols. Therefore, its esterification requires a protec-
tion of double bond or an activation of carbonyl group. Direct
esterification with alcohols leads to polymerization of substantial
part of corresponding ester. It follows a reversible addition of
alcohol to C=C bond initiating anionic polymerization.6 Thiols
though can react irreversibly with no polymerization providing
adducts in almost quantitative yield. Both reactions can be re-
directed toward carbonyl group by obtaining intermediate acid
halides. 2-Cyanoacryloyl chloride was first described as the product
of chlorination of 2-cyanoacrylic acid with PCl5.7 Later it was
studied as an intermediate for preparation of bis-2-cyanoacrylates8,9
and surface active esters containing bulky residues in ester moiety.6
However, methods for the synthesis of cyanoacryloyl chloride
and its reactions with weak nucleophiles require further studies.
Herein, we have synthesized and fully characterized the new
ester of 2-cyanoacrylic acid containing perfluorinated aromatic
moiety as well as perfluorinated bis-2-cyanoacrylate. These mono-
Cl
Cl
H2C
NC
O
H2C
NC
O
O
PCl5
PCl5
C6H6, 25 °C
OH
Cl
NC
Cl
Scheme 1
Chlorination with dichloro(methoxy)methane (Scheme 2) can
also generate 2-cyanoacryloyl chloride, however, the conversion
did not exceed 70% at 40°C. Increase in the reaction temperature
caused polymerization rather than improvement of the yield.
O
Cl
H2C
NC
O
H2C
NC
O
Cl2CHOMe
C6H6, 40 °C
– HC(O)OMe
80 °C
OH
Cl
CN
n
Scheme 2
The most convenient reagent was oxalyl dichloride (Scheme 3)
that gave pure 2-cyanoacryloyl chloride in quantitative yield.
†
For synthetic procedures and characteristics of products obtained, see
Online Supplementary Materials.
© 2013 Mendeleev Communications. All rights reserved.
– 356 –

Mendeleev Commun., 2013, 23, 356–357
H2C
O
H2C
NC
O
H2C
NC
O
(COCl)2
+
Me(CH2)9SH
+ CO2 + CO + HCl
C6H6, 25 °C
C6H6,
40 °C, 1 h
NC
Cl
O
OH
Cl
H2C
H2C
+
S
Scheme 3
NC
S(CH2)9Me
NC
S(CH2)9Me
Only a few representatives of fluorine containing 2-cyanoacrylic
acid esters are known. We have synthesized the first representatives
of aromatic perfluorinated esters and bis-2-cyanoacrylate by inter-
action of 2-cyanoacryloyl chloride with perfluorinated phenol and
diol, respectively (Scheme 4).
Scheme 5
PCl5 as Lewis acid simplifying elimination Cl– from chloro-
anhydride two molecules of thiol can interact with carbonyl group.
Further elimination of respective alcohol results in dithioester.
CF3
F3C
HO
OH
CF3
O
O
CH2
CN
1
The product has a standard set of signals in H NMR spectrum
H2C
NC
O
F3C
O
CF3
F3C
typical of thioester, however, 13C NMR spectrum reveals two
sets of signals related to carbonyl groups of thioester and dithio-
ester. Eventually the final stage of nucleophilic attack caused
an activation of C=C bond with formation of corresponding
adduct.
C6H6, 25 °C,
1 h
CF3
F3C
H2C
NC
O
F
F
In summary, 2-cyanoacrylic acid chloride was quantitatively
prepared by treatment of 2-cyanoacrylic acid with oxalyl chloride
making it readily available and promising for the preparation of
novel useful polymeric materials.
Cl
HO
F
H2C
NC
O
O
F
F
F
F
F
F
C6H6, 40 °C,
1 h
F
This work was supported by the Russian Foundation for Basic
Research (grant no. 13-03-00850).
Scheme 4
Online Supplementary Materials
Pentafluorophenyl 2-cyanoprop-2-enoate was obtained in
quantitative yield. It is a solid (mp 75–77°C); for comparison,
1,1,1,4,4,4-hexafluoro-2,3-bis(trifluoromethyl)butane-2,3-diyl
bis(2-cynoprop-2-enoate) is a high-boiling liquid. Both substances
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2013.11.019.
References
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were fully characterized by H, 13C and 19F NMR spectra and
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nucleophiles embraced several stages. At first, nucleophile reacts
with an activated carbonyl group resulting in ester or thioester.
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Received: 30th May 2013; Com. 13/4130
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