Wound Adhesive from Cyanoacrylate: Synthesis and

Characterization

Rajangam Vinodh1, Cadiam Mohan Babu

1, Aziz Abidov

1,

Rramaswamy Ravikumar1, Muthiahpillai Palanichamy

1, Eun Young Choi

2

and Hyun Tae Jang1*

1 Department of Chemical Engineering, Hanseo University, Seosan 360-706, South Korea

2Department of Cosmetology, Hanseo University, Seosan 360-706, South Korea

htjang@hanseo.ac.kr

Abstract. 1-octyl cyanoacryalte is a main component of medical cyanoacrylate

glues. As it rapidly polymerizes with water as an initiator, there are practical

difficulties in designing simple synthetic routes. Any synthetic routes that

evolve free nucleophilic products cannot, therefore be successful. Its synthesis

too has not been reported in the open literature so far. Synthetic methods, which

involve esterification of cyanoacetic acid with a chosen alcohol, polymerization

by knoevenagel condensation and subsequent depolymerization, are applied to

the synthesis of lower membered alkyl cyanoacryaltes in which the alkyl groups

carry less than 8 carbons. We have synthesized 1-octyl cyanoacetate by a usual

method involving p-toluene sulphonic acid as the catalyst. Its conversion to

poly (1-octyl cyanoacrylate) is effected with 1, 3, 5-trioxane in a solvent free

route, although paraformaldehyde has been suggested in few patents. Its FTIR

spectrum confirmed its functional groups: Its –OH stretching yielded a broad

band around 3400 cm-1. Its depolymerization to high yield of 1-octyl cyano

acrylate is under progress: during depolymerization p-toluene sulphonic acid,

hydroquinone and phosphorous pentoxide are tried. We have avoided high

temperature pyrolysis, as it is verified to degrade long alkyl chain.

Keywords: 1-octyl cyanoacrylate; Wound adhesive; Medical glue; p-toluene

sulphonic acid

1 Introduction

Presently, wound closure techniques have evolved from the earliest development of suturing

materials to resources that include synthetic absorbable sutures, staples, tapes, and adhesive

compounds. The creation of natural glues, surgical staples and tapes to substitute sutures has

supplemented the armamentarium of wound closure techniques. The use of tissue adhesives

has long appealed to surgeons and they have been extensively studied for nearly four decades

for diverse applications including tissue adhesion, wound closure, hemostasis, and closure of

cerebrospinal fluid (CSF) leaks, vascular embolization and application of skin grafts [1].

The ideal method of laceration and incision closure should be simple, safe, rapid,

inexpensive, painless, bactericidal, and result in optimal cosmetic appearance of the scar. The

cyanoacrylate tissue adhesives offer many of these characteristics. Developed in 1949, the

cyanoacrylate adhesives are applied topically to the outermost skin layer. The cyanoacryaltes

Advanced Science and Technology Letters Vol.121 (AST 2016), pp.434-439

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ISSN: 2287-1233 ASTL Copyright © 2016 SERSC

are supplied as monomers in a liquid form. On contact with tissue anions, they polymerize

forming a strong bond that holds the apposed wound edges together. The cyanoacrylate

adhesives usually slough off with wound re-epithelialization within 5–10 days and do not

require removal.

The use of cyanoacrylates has increased significantly in recent years owing to their unique

combination of chemical and physical properties, namely: (1) they cure rapidly at room

temperature; (2) they form strong bonds with a wide variety of different materials without the

addition of a catalyst; (3) they can be easily and safely applied either manually or by automatic

equipment; and (4) they are ready to use without mixing or using a primer [2]. These unique

materials were discovered in 1951 in the course of applied research directed towards the

characterization of stronger, tougher and more heat-resistant acrylate polymers for jet plane

canopies [3].

Sutures have conventionally been the method of approximating wound edges due to their

high tensile strength and favorable cosmetic outcomes. Sutures do, however, have some

downfalls in that they require increased time and a skilled individual to accomplish good

cosmetic outcomes. Over the past four decades, advances have seen other forms of wound

closure methods emerge that address some of the disadvantages of sutures [4-10].

2 Experimental

2.1 Materials

1-octyl cyanoacrylate, cyano acetic acid and P-toluene sulphonic acid were purchased from

Sigma Aldrich, USA. All the other chemicals and solvents bought from Daejung Chemical,

South Korea.

2.2 Preparation of 1-octyl cyanoacrylate

It involves three stages, (i) Preparation of 1-octyl cyano acetate; (ii) Preparation of poly (1-octyl

cyano acrylate) and (iii) Preparation of 1-octyl cyano acrylate.

2.3 Synthesis of 1-octyl cyano acetate

8 g cyano acetic acid, 13 g 1-octanol, 1.0 g p-toluene sulphonic acid and 50 mL toluene were

taken in a 100mL RB flask. It is attached to a Dean-stark trap which in turn attached to a water

condenser. The contents of the flask were heated to 130 C under stirring for 12 h. Water

formed in this esterification was removed by forming azeotrope with toluene in order to

complete esterification. The total amount of water collected in the trap was equal to 3 g. The

round bottom flask was cooled and toluene in it vacuum evaporated. The light red liquid in

the flask was transferred to a 250 mL separating funnel. The trace of residual cyano acetic acid

and p-toluene sulphonic acid were removed by extraction with 20 mL portions of saturated

sodium bicarbonate solution two times. The liquid was then finally washed with 20 mL portions

of water two times, and the liquid transferred to a clean 100 mL beaker. 2 g of anhydrous

magnesium sulphate was added to it, shaken well and allowed to stand for 5h. Then the clear

liquid was transferred to a 100 mL round bottom flask and vacuum evaporated.

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2.4 Synthesis of poly (1-octyl cyano acrylate)

4 g of 1-octyl cyano acrylate was taken in a 100 mL round bottom flask. 1.4 g of para

formaldehyde, 1.0 g of magnesium acetate and 3 mL acetic acid were added to it. The flask was

attached to a reflux condenser and the contents were vigorously stirred at 90 C for 24 h. On

cooling the flask a thick gel of poly (1-octyl cyano acryalte) was obtained. 20 mL ethyl acetate

was added to the flask to dissolve poly (1-octyl cyano acryalte). The solution was transferred to

a 250 mL separating funnel. Its acetic acid is removed by extraction with 20 mL portions of

saturated sodium bicarbonate solution. Then the ester layer was washed 2 times with 20 mL

portion of water. The ester layer was transferred to a 100 mL beaker, and 4g of anhydrous

magnesium sulphate added to it, shaken well and allowed to stand for 5 h. The clear liquid was

then transferred to a clean, dry RB flask and vacuum evaporated. The viscous liquid that

remained in the flask was transferred to a bottle and FTIR analyzed. The schematic

representation of wound healing illustrated in figure 1.

Adhesive

Cyanoacrylate glue container

Fig. 1. Schematic illustration of synthesized adhesive to cure skin wound healing

3 Results and Discussion

3.1 Fourier Transform Infra Red Spectroscopy

Figure 2 shows the FTIR spectrum of 1-octyl cyanoacetate obtained by the reaction of 1-

octanol and cyanoacetic acid. The alkyl –CH2- stretching vibrations yielded intense peaks at

2929 and 2857 cm-1. The –CN stretching occurred at 2265 cm-1. The intense sharp peak at 1749

cm-1 is due to C=O stretch. The –CH2- bending vibrations showed peaks at 1395 and 1467 cm-

1.The group of peaks at 1335, 1266 and 1187 cm-1 are due to ester –COO- vibrations. The peak

at 1007 cm-1 is due to –O-C vibration. The –CH2- wagging occurred at 724 cm-1.

Advanced Science and Technology Letters Vol.121 (AST 2016)

436 Copyright © 2016 SERSC

53

6.7

15

82

.65

72

4.4

0

93

4.2

0

10

07

.85

11

88

.11

12

66

.74

13

36

.02

13

95

.59

14

67

.28

17

50

.81

22

65

.50

28

57

.80

29

29

.54

34

84

.53

-0

10

20

30

40

50

60

70

80

90

100%

T

500 1000 1500 2000 2500 3000 3500 4000

Wavenumbers (cm-1)

Wave number (cm-1)

% T

ran

smit

tan

ce

Fig. 2. FTIR spectrum of 1-octyl cyanoacetate

3.2 Thermogravimetric Analysis

Fig. 3. TGA of 1-octyl cyanoacrylate

Advanced Science and Technology Letters Vol.121 (AST 2016)

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The results of TGA of poly (1-octyl cyanoacrylate) are illustrated in Fig. 3. The thermogram

showed absence of weight loss below 150 C illustrating absence of any entrapped solvent. The

weight loss between 150 and 225 C is assigned to residual 1-octyl cyanoacetate. The steady

weight loss between 225 and 300 C is due to degradation of the polymer into monomer. As the

decomposition occurred in one stage without leaving any residue, the decomposition evidently

rejects random degradation. The polymer is proved to be formed by addition rather than

condensation. The present thermogram depicts the same features as that obtained by piperidine.

Hence, both the polymers are verified to be formed by addition, though their molecular weights

are different. Piperidine is miscible with 1-octyl cyanoacetate; formation of 1-octyl

cyanoacrylate might be more rapid than its polymerization. It accounts for formation of high

molecular weight polymer with piperidine. In contrast potassium carbonate is immiscible with

1-octyl cyanoacetate, so the rate of formation of polymer sight be lower than the rate of

formation of 1-octyl cyanoacrylate.

4 Conclusions

1-Octanol and 2-cyanoacetic acid were esterified in the presence of p-toluene sulphonic acid to

form 1-octyl-2-cyanoacetate. The ester was subjected to the Knoevenagel condensation with

formaldehyde to form poly(1-octyl-2-cyanoacetate) using potassium carbonate or piperidine as

initiators. The polymer was depolymerized using poly phosphoric acid catalyst under vacuum

to obtain the monomer. A simple method of obtaining monomer was also attempted by the

reaction of 1-octyl- 2-cyano acetate and diiodomethane in the presence of potassium carbonate.

This process directly yields the monomer. The second method looks better than the others, and

it can be applied to any type of alcohols.

Acknowledgments. This research was supported by the Korea Association of University

Research Institute and Industry program funded by the Small and medium Business

Administration (C0330026, 2015).

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