Biomedical Engineering Reference
In-Depth Information
2
General Features and Synthesis of Alkyl Cyanoacrylate
Monomers
Alkyl cyanoacrylates represent a class of very reactive monomers widely
employed for biomedical purposes as surgical glues for the closure of skin
wounds (Skeist and Miron 1977 ; Coover et al. 1990 ; King and Kinney 1999 ;
Oowaki et al. 2000 ; Hollock 2001 ; Marcovich et al. 2001 ; Reece et al. 2001 ),
embolitic material for endovascular surgery (Oowaki et al. 2000 ; Pollak and
White 2001 ; Reece et al. 2001 ) and for nerves regenerating purposes (Merolli
et al. 2010 ). Indeed, alkyl cyanoacrylate monomers exhibit a remarkable reactiv-
ity toward nucleophiles and have excellent adhesive properties resulting from the
bonds of high strength they are able to form with most polar substrates, including
living tissues and skin.
The synthesis of alkyl cyanoacrylates has been first described in the patent
literature (Ardis 1949 ; Jeremias 1956 ; Joyner and Shearer 1956 ; Joyner and
Hawkins 1955 ). The main strategy to achieve a-cyanoacrylates is based on a two-
step procedure (Fig. 1 ). The corresponding alkyl cyanoacetate is reacted with form-
aldehyde in the presence of a basic catalyst, to form PACA oligomers by
Knoevenagel condensation reaction, followed by their thermal depolymerization
reaction which lead to the alkyl cyanoacrylate monomer. To prevent repolymeriza-
tion events, protonic or Lewis acids with small amounts of a free-radical inhibitors
are usually employed.
Slight improvements of this synthetic procedure were achieved, essentially by
playing with the nature of the solvent mixture (Tseng et al. 1990 ; Sahadev et al.
2003 ), by applying a transesterification approach for making cyanoacrylates bearing
longer alkyl ester chains (Malofsky and Badejo 2001 ), or by using pyrrolidine as a
more efficient catalyst for the condensation step (Yadav et al. 2004 ).
Recently, a novel approach has been reported for the synthesis of cyanoacrylate
derivatives (Kryger et al. 2010 ). Sonication of polymers containing a dicyanocy-
clobutane mechanophore moiety led to the selective cleavage of the mechanophore,
thus releasing the corresponding cyanoacrylate monomers.
CN
CN
CN
H 2 O
n
n
+ nCH 2 O
O
COOR
n
O
R
O
O
R
Fig. 1 Synthesis of alkyl cyanoacrylate monomer via Knoevenagel condensation reaction and
subsequent thermal depolymerization
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