US 20070213553A1

(19) United States

(12) Patent Application Publication (10) Pub. No.: US 2007/0213553 A1
Liu et al. (43) Pub. Date: Sep. 13, 2007
(54) METHOD FOR PRODUCING A Publication Classification
CYANOACRYLATE MONOMER
(51) Int. Cl.
C07C 253/30 (2006.01)
(76) Inventors: Hongbo Liu, Hillsborough, NJ (US); (52) U.S. Cl. .............................................................. 558/.441
Sandra Gonzalez, Hillsborough, NJ (57) ABSTRACT
(US) A method for producing a cyanoacrylate monomer, com
prising the steps of (a) reacting cyanoacetate and formalde
Correspondence Address: hyde or paraformaldehyde in the presence of a base or amine
PHILIP S. JOHNSON base catalyst to form an O-cyanoacrylate prepolymer or
JOHNSON & JOHNSON oligomer mixture; (b) Subjecting the C-cyanoacrylate pre
ONE JOHNSON & JOHNSON PLAZA polymer or oligomer mixture to a Substrate having free acid,
NEW BRUNSWICK, NJ 08933-7003 (US) acid derivative, or free aldehyde or ketone groups to remove
the catalyst and to obtain a purified C-cyanoacrylate pre
(21) Appl. No.: 11/372,959 polymer or oligomer, and (c) Subjecting the purified C-cy
anoacrylate prepolymer or oligomer to depolymerization to
(22) Filed: Mar. 10, 2006 obtain an O-cyanoacrylate monomer.
US 2007/0213553 A1 Sep. 13, 2007

METHOD FOR PRODUCING A CYANOACRYLATE to prevent premature initiation and/or polymerization of the
MONOMER monomers. In particular, gaseous acidic inhibitors such as
sulfur dioxide, nitric oxide, hydrogen fluoride, and the like,
FIELD OF THE INVENTION are combined with the monomers as they are formed during
the depolymerization process. More specifically, the gaseous
0001. A method for producing cyanoacrylate monomers, acidic inhibitors mix with the monomeric vapors as they are
which may be polymerized to form an adhesive, is described produced during the depolymerization process and dissolve
herein.
in the monomeric liquid when the monomeric vapors are
BACKGROUND collected and condensed into a liquid. The presence of the
acidic inhibitors in the monomeric vapors and condensed
0002 Monomer and polymer adhesives are used in both liquid prevent the monomers from prematurely polymeriZ
industrial (including household) and medical applications. ing during the manufacturing process. However, the use of
Included among these adhesives are the cyanoacrylate the gaseous acidic inhibitors described in the prior art
monomers and polymers. Such as the C-cyanoacrylates. requires additional operations for feeding and maintaining a
Since the discovery of the adhesive properties of these steady stream of inhibitors, as well as for disposing these
monomers and polymers, they have found wide use due to harmful gases at the end of the process. Furthermore, there
the speed with which they cure, the strength of the resulting is a potential for an excess amount of inhibitors to be
bond formed, and their relative ease of use. These charac introduced into the monomers produced, which may
teristics have made the C-cyanoacrylate adhesives the pri adversely affect the initiation of the polymerization of the
mary choice for numerous applications such as bonding monomer and the cure rate of the adhesive.
plastics, rubbers, glass, metals, wood, and more recently,
biological tissues. 0007 V. Vijayalakshmi, et al. (Alkyl and Substituted
0003 Cyanoacrylate monomers are generally produced Alkyl 2-Cyanoacrylates. Part 1. Synthesis and Properties, V.
by forming C-cyanoacrylate prepolymer or oligomer and Vijayalakshmi, et al., J. Adhesion Sci. Technol., 4(9), 733
then cracking or depolymerizing the C-cyanoacrylate pre 750 (1990)), report the use of phosphoric acid to neutralize
polymer or oligomer to produce monomeric cyanoacrylate. the base catalysts used to prepare the cyanoacrylate prepoly
More particularly, C-cyanoacrylate prepolymer or oligomer mer or oligomer after the formation of the cyanoacrylate
is commonly produced by first reacting cyanoacetate with prepolymer or oligomer. The solid salts formed by the
formaldehyde, or a functional equivalent Such as the poly neutralization reaction are removed by decanting the aliquot.
meric form paraformaldehyde, in the presence of a base, The cyanoacrylate prepolymer or oligomer is then depoly
which acts as a catalyst for the reaction between the merized by heat in the presence of POs and hydroquinone.
cyanoacetate and paraformaldehyde to produce the C-cy The authors report the Successful synthesis of a range of
anoacrylate prepolymer or oligomer. Depolymerization is cyanoacrylate monomers. However, it is believed that rela
generally effected by heating the polymer under reduced tively non-volatile phosphoric acid remains in the prepoly
pressure while distilling off and condensing the monomeras mer or oligomer, which could potentially promote undesired
it is being generated. side reactions, i.e., such as hydrolysis, during the depoly
0004 Monomers of C.-cyanoacrylates are anionically merization process. For the preparation of cyanoacrylate
polymerizable or free radical polymerizable, or polymeriz monomers, such as alkoxycarboalkyl cyanoacrylates, that
able by Zwitterions or ion pairs to form adhesive polymers. are susceptible to hydrolytic decomposition reactions. Such
Once polymerization has been initiated, the cure rate can be potentially undesirable reactions may result in reduced
very rapid. It is also known that monomeric forms of yields and an increased amount and complexity of impurities
C-cyanoacrylates are extremely reactive, and that polymer in the final monomeric product.
ization can be initiated very easily in the presence of even 0008 Although various efforts have been reported in the
minute amounts of an initiator, such as moisture present in prior art to improve the depolymerization process, there is a
the air or on moist Surfaces such as animal (including need for a process that avoids the use of harmful gases Such
human) tissue. Although these are desirable properties of the as Sulfur dioxide, nitric oxide, hydrogen fluoride, or the use
cyanoacrylate monomers, it is desirable to strike a balance of neutralizing agents that have the potential to promote
between maintaining the cyanoacrylate monomers in its undesired side reactions, i.e., such as hydrolysis, during the
monomeric form, initiating polymerization at a time when depolymerization process.
polymerization is desirable to form an adhesive bond, with
out reducing the cure rate of the adhesive. SUMMARY OF THE INVENTION
0005. Due to the inherent high reactivity of the mono 0009. A method is described for producing a cyanoacry
meric C-cyanocrylates, in situ polymerization or re-poly late monomer, comprising the steps of (a) reacting cyanoac
merization often occurs during the depolymerization step of etate and formaldehyde or paraformaldehyde in the presence
the manufacturing process, preventing effective recovery of of a base or amine base catalyst to form an O-cyanoacrylate
the monomer. This in situ polymerization or re-polymeriza prepolymer or oligomer mixture; (b) Subjecting the C-cy
tion problem is particularly severe for highly reactive mono anoacrylate prepolymer or oligomer mixture to a substrate
mers such as short chain alkyl cyanoacrylates and having free acid, acid derivative, or free aldehyde or ketone
cyanoacrylate with side chain ester groups. groups to remove the catalyst and to obtain a purified
0006 U.S. Pat. No. 2,721,858 and U.S. Pat. No. 6,057, C-cyanoacrylate prepolymer or oligomer, and (c) Subjecting
472 report the use of acidic gaseous inhibitors to maintain the purified C-cyanoacrylate prepolymer or oligomer to
the cyanoacrylate monomers in their monomeric form, i.e., depolymerization to obtain an O-cyanoacrylate monomer.
US 2007/0213553 A1 Sep. 13, 2007

DETAILED DESCRIPTION OF THE 0016. The amount of resin required should be sufficient to
INVENTION substantially remove the catalyst. For example, the molar
ratio of the reactive functional groups on the resin to the
0010 Cyanoacrylate monomers are produced in the con catalyst may range from about 1:1 to about 100:1; preferably
ventional manner by first reacting or condensing cyanoac from about 2:1 to about 50:1; and more preferably from
etate with formaldehyde, or a functional equivalent such as about 5:1 to about 20:1.
the polymeric form paraformaldehyde, in the presence of a
base or amine base, which acts as a catalyst for the reaction 0017 Depolymerization is then effected in the conven
between the cyanoacetate and paraformaldehyde to produce tional manner by heating the polymer under reduced pres
the C-cyanoacrylate prepolymer or oligomer. Sure while distilling off and collecting the monomeras it is
being generated.
0011. The C-cyanoacrylate prepolymer or oligomer is 0018 Suitable cyanoacetates that may be utilized in the
then subjected to a Substrate having free acid, acid deriva process described herein may be represented by the follow
tive, or free aldehyde or ketone groups to remove the ing formula (I):
catalyst and to obtain a purified C-cyanoacrylate prepolymer
or oligomer according to the present invention. For example,
the prepolymer or oligomer, in the form of a solution in an (I)
appropriate organic solvent, such as methylene chloride, O
acetone, ethylacetate, etc., may be exposed to resin having
free acid, acid derivative, or free aldehyde or ketone groups CNCH-C-O-R
to remove the base or amine base catalyst.
0012. The catalyst used herein includes base catalyst and R may be an alkyl group, linear, branched or cyclic, having
amine base catalyst. Base catalysts that may be used to a combined number of carbon atoms from 1 to 20. Alterna
condense the cyanoacetate with formaldehyde, or the func tively, R may be a group having a formula R. O—R.
tional equivalent Such as the polymeric form paraformalde where R and R are each independently an alkyl group.
hyde, include but are not limited to alkali metal or alkaline linear, branched or cyclic, having a combined number of
earth hydroxide, Such as Sodium or potassium hydroxide, carbon atoms from 1 to 20; or R may be group having a
Sodium or potassium methoxide and Sodium or potassium formula R COO-Rs, where R and Rs are each indepen
t-butoxide; and carbonates or bicarbonates, such as sodium dently an alkyl group, linear, branched or cyclic, having a
or potassium carbonate and sodium or potassium bicarbon combined number of carbon atoms from 1 to 20. Examples
ate. of cyanoacetates that may be utilized in the process
0013 When the catalyst is a base catalyst, the resin may described herein include but are not limited to alkyl
be an acidic ion-exchange resin. Specifically, the prepolymer cyanoacetates, alkoxyalkyl cyanoacetates, alkoxycarboalkyl
or oligomer Solution may be introduced into a packed cyanoacetates and the combination thereof. Particular
column of the acidic ion-exchange resin or the prepolymer examples include but are not limited to the following
cyanoacetates:
or oligomer Solution may be put into a Suspension of acidic
ion-exchange resin particles. The acid groups present on the
resin that may be used for removing a base catalyst include
are but not limited to sulfonic acid and carboxylic acid.
Examples of commercially available acidic ion-exchange
resins include acidic DoweX(R) macroporous resins from The
Dow Chemical Company (Midland, Mich., U.S.A.),
r re
3-(2-Cyano-acetoxy)-butyric acid ethyl ester
(Et-B-HBT-CAc)
macroporous sulfonic acid resins such as Product No. 8022
2, from Agela Technologies, Inc. (Newark, Del. USA), and
Amberlite(R) resins from Rohm & Haas (Philadelphia, Pa.,
USA).
0014) Amine base catalysts that may be used include but
are not limited to primary, secondary, and tertiary amines.
Examples of amine base catalysts include but are not limited
to alkylamines such as methylamine, dialkylamine Such as
dimethylamine, trialkylamines such as triethylamine, cyclic
r
3-(2-Cyano-acetoxy)-hexanoic acid ethyl ester
(Et-B-CPL-CAc)

amines such as piperidine, aromatic amines Such as 0019 Cyanoacrylates that may be prepared according to
pyridines, and hydroxylamines. the methods described herein can be represented by the
0.015 When the catalyst is an amine base catalyst, the following formula (II):
acidic ion-exchange resins described above may be used, as
well as resins bearing other amine reacting functional groups (II)
other than acid groups. Such amine reacting functional CN
groups include but are not limited to acid derivatives such as
anhydrides and acid halides, aldehydes, ketones, and isocy
anates. Examples of commercially available resins bearing
amine reacting functional groups are StratoSphereTM PL
FMP resin and HypoGel(R) aldehyde resins (Sigma-Aldrich
Corp., St. Louis, Mo., USA).
US 2007/0213553 A1 Sep. 13, 2007

R may be an alkyl group, linear, branched or cyclic, having 0022. The slightly brown colored reaction mixture was
a combined number of carbon atoms from 1 to 20. Alterna evaporated using a rotary evaporator to remove the Solvent,
tively, R may be a group having a formula R. O—R. yielding a brown colored viscous residue which turned into
where R and R are each independently an alkyl group. a solid gel after cooling to room temperature. This solid gel
linear, branched or cyclic, having a combined number of was oligomer of 3-(2-Cyano-acryloyloxy)-hexanoic acid
carbon atoms from 1 to 20; or R may be group having a ethyl ester.
formula R COO-Rs, where R and Rs are each indepen 0023 The oligomer, 0.40 g of hydroquinone (HQ) and
dently an alkyl group, linear, branched or cyclic, having a 2.0 g of POs were combined in a 250 ml round bottom flask.
combined number of carbon atoms from 1 to 20. Examples A simple vacuum distillation was set up where all glassware
of cyanoacrylates include but are not limited to alkyl pieces were previously treated with 5N HSO solution and
cyanoacrylates, alkoxyalkyl cyanoacrylates, alkoxycar
boalkyl cyanoacrylates and combination thereof. Particular dried in a vacuum oven after rinsing with deionized water
examples include but are not limited to the following (DI water). The above mixture of oligomer, hydroquinone
cyanoacrylates: and POs was heated to up to 140°C. to remove low boiling
impurities and then to above 160° C. in an oil bath under
vacuum to carry out the depolymerization. The monomeric
CN Et-f-CPL-CA was generated from the reaction but rapidly
polymerized along the distillation path. No free flowing
H O O monomeric Et-f-CPL-CA was collected in the receiving
end. Instead, 6.7 g of polymerized mass was recovered as a
H O O colorless and transparent Solid.
3-(2-Cyano-acryloyloxy)-butyric acid ethyl ester EXAMPLE 1B
(Et-B-HBT-CA)
CN
Synthesis of 3-(2-Cyano-acryloyloxy)-hexanoic acid
". H O O
9N-1 0024
ethyl ester (Et-B-CPL-CA)

CN

3-(2-Cyano-acryloyloxy)-hexanoic acid ethyl ester

(Et-B-CPL-CA) ". H O O
N-1
While the following examples demonstrate certain embodi
ments of the invention, they are not to be interpreted as
limiting the scope of the invention, but rather as contributing 3-(2-Cyano-acryloyloxy)-hexanoic acid ethyl ester
to a complete description of the invention (Et-B-CPL-CA)

COMPARATIVE EXAMPLE 1A
0025. A mixture of 45.45 g of 3-(2-Cyano-acetoxy)-
Synthesis of 3-(2-Cyano-acryloyloxy)-hexanoic acid hexanoic acid ethyl ester (Et-B-CPL-CAc), 7.2 g of
ethyl ester (Et-B-CPL-CA) paraformaldehyde, 0.06 ml of piperidine and 150 ml toluene
was stirred in a 250 ml round bottom flask equipped with a
0020 magnetic stir bar. A Dean-Stark trap and a condenser were
attached to the reaction flask. The reaction flask was
immersed in an oil bath. The reaction mixture was heated to
CN
reflux and the reaction was allowed to proceed overnight.
0026. The slightly brown colored reaction mixture was
". H O O
On 1 evaporated using a rotary evaporator to remove the Solvent,
yielding a brown colored viscous residue which turned into
a solid gel after cooling to room temperature. This solid gel
was oligomer of 3-(2-Cyano-acryloyloxy)-hexanoic acid
3-(2-Cyano-acryloyloxy)-hexanoic acid ethyl ester ethyl ester.
(Et-B-CPL-CA) 0027. A macroporous sulfonic acid ion-exchange resin
(MP-SOH resin, Product No. 8022-2, Agela Technologies,
0021. A mixture of 45.45 g of 3-(2-Cyano-acetoxy)- Inc., Newark, Del., USA) in the amount of 18 g was
hexanoic acid ethyl ester (Et-B-CPL-CAc), 7.2 g of conditioned in 150 ml CHCl, for one hour. The conditioned
paraformaldehyde, 0.06 ml of piperidine and 150 ml toluene resin was poured into a glass column (with sintering filter at
were stirred in a 250 ml round bottom flask equipped with the bottom) with 1.25" O.D to form a tightly packed column
a magnetic stir bar. A Dean-Stark trap and a condenser were with a height of about 3.7". On top of this packed column a
attached to the reaction flask. The reaction flask was layer of sand was deposited.
immersed in an oil bath. The reaction mixture was heated to 0028. The oligomer of 3-(2-Cyano-acryloyloxy)-hex
reflux and the reaction was allowed to proceed overnight. anoic acid ethyl ester was dissolved in 150 ml CHCl to
US 2007/0213553 A1 Sep. 13, 2007

form a brownish solution. This solution was eluted through 2-octylcyanoacrylate. Final yield was 48% and the purity
the above packed column by gravity. Slightly yellow colored was 98% (by GC-MS). No polymerization along the distil
oligomer Solution was collected and evaporated to obtain a lation path was observed.
slightly yellow colored solid gel. This solid gel was depo 0036) "H NMR (CDC1, appm): 7.02 (s, 1H), 6.60 (s,
lymerized as described in Example 1A. Two separate mono 1H), 5.30 (m. 1H), 1.70 (m, 1H), 1.58 (m, 1H), 1.30 (m. 1H),
meric 3-(2-Cyano-acryloyloxy)-hexanoic acid ethyl ester 0.88 (t, 3H).
fractions were collected from the depolymerization reaction, 0037 Boiling point: -80° C./0.60 mmHg.
an early fraction of 21 g (88% by GC) and a later fraction
of 7 g (99% by GC). Both fractions were free flowing What is claimed:
colorless liquids. No polymerization along the distillation 1. A method for producing a cyanoacrylate monomer,
path was observed as in Example 1A. The less pure early comprising the steps of:
fraction was Subjected to a second distillation under vacuum (a) reacting cyanoacetate and formaldehyde or paraform
yielding 13 g of monomeric 3-(2-Cyano-acryloyloxy)-hex aldehyde in the presence of a base or amine base
anoic acid ethyl ester with improved purity (97% by GC). A catalyst to form an O-cyanoacrylate prepolymer or
combined 20% yield of the monomeric 3-(2-Cyano-acry oligomer mixture;
loyloxy)-hexanoic acid ethyl ester was obtained as a result. (b) Subjecting the C-cyanoacrylate prepolymer or oligo
0029. A very small amount of this monomer product was mer mixture to a substrate having free acid, acid
placed in between two moist fingertips and bonded the derivative, or free aldehyde or ketone groups to remove
fingertips strongly within one minute. the catalyst and to obtain a purified C-cyanoacrylate
prepolymer or oligomer,
0030 "H NMR (CDC1, 8ppm): 7.03 (s, 1H), 6.60 (s, (c) subjecting the purified C-cyanoacrylate prepolymer or
1H), 5.40 (m, 1H), 4.15 (q, 2H), 2.65 (m, 2H), 1.70 (m, 2H), oligomer to depolymerization to obtain a C-cyanoacry
1.38 (m, 2H), 1.22 (t, 3H), 0.95 (t, 3H). late monomer.
0031) Boiling point: 107-114° C./-0.40 mmHg. 2. The method of claim 1, where the C-cyanoacrylate is
selected from the group consisting of alkyl cyanoacrylates,
EXAMPLE 2 alkoxyalkyl cyanoacrylates, alkoxycarboalkyl cyanoacry
lates and combination thereof.
Synthesis of 3-(2-Cyano-acryloyloxy)-butyric acid 3. The method of claim 1, where the base catalyst is an
ethyl ester (Et-B-HBT-CA) alkali metal or alkaline earth hydroxide or a carbonate or
0032 3-(2-Cyano-acryloyloxy)-butyric acid ethyl ester bicarbonate
(Et-B-HBT-CA) was synthesized using the procedure 4. The method of claim 3, where the base catalyst is
described in Example 1B starting with 79.68 g (0.4 mole) selected from the group consisting of sodium or potassium
(2-Cyano-acetoxy)-butyric acid ethyl ester (Et-f-HBT hydroxide, Sodium or potassium methoxide, sodium or
CAc), 13.2 g (0.44 mole) paraformaldehyde and 0.12 ml potassium ethoxide, Sodium or potassium t-butoxide,
piperidine. Following the catalyst removal using 16 g of Sodium or potassium carbonate and Sodium or potassium
MP-SOH resin in a packed column, the oligomer was bicarbonate.
depolymerized. Crude product was re-distilled to afford 20 5. The method of claim 1, where the amine base catalyst
g of colorless monomeric 3-(2-Cyano-acryloyloxy)-butyric is a primary, secondary and/or tertiary amines.
acid ethyl ester. Final yield was 24% and the purity was 95% 6. The method of claim 5, where the amine base catalyst
(by GC-MS). No polymerization along the distillation path is selected from the group consisting of alkylamine, dialky
was observed. lamine, trialkylamine, cyclic amines, piperidine, aromatic
amines and hydroxylamines.
0033 H NMR (CDC1, 8ppm): 7.03 (s, 1H), 6.60 (s, 7. The method of claim 3, where the substrate having free
1H), 5.40 (m, 1H), 4.15 (q, 2H), 2.65 (m, 2H), 1.40 (d. 3H), acid groups is a cationic ion exchange resin selected from
1.24 (t, 3H). the group consisting of resins having Sulfonic acid or
0034) Boiling point: 90-98° C./0.46 mmHg. carboxylic acid groups.
8. The method of claim 4, where the substrate having free
EXAMPLE 3 acid groups is a cationic ion exchange resin selected from
the group consisting of resins having Sulfonic acid or
Synthesis of 2-octylcyanoacrylate carboxylic acid groups.
0035 2-Octylcyanoacrylate was synthesized using the 9. The method of claim 5, where the substrate having free
procedure described in Example 1B starting with 98.64 g amine reacting functional group consisting of free acid, acid
(0.5 mole) of 2-octylcyanoacetate, 16.5 g (0.55 mole) of derivative, aldehyde, ketone, and isocyanate groups.
paraformaldehyde and 0.15 ml of piperidine. Following the 10. The method of claim 6, where the substrate having
catalyst removal using 42 g of MP-SOH resin in a packed free amine reacting functional group consisting of free acid,
column, the oligomer was depolymerized. Crude product acid derivative, aldehyde, ketone, and isocyanate groups.
was re-distilled to afford 50 g of colorless monomeric k k k k k