Macromolecular polyyne-containing benzoxazines for cross-linked polymerization

Article abstract of DOI:10.1016/j.tetlet.2012.07.141

A Mannich condensation of 2,4-di-tert-butylphenol, p-bromophenethylamine, and formaldehyde followed by a Sonogashira coupling of the resulting 3-(4-bromophenethyl)-6,8-di-tert-butyl-3,4-dihydro-2H-benz[1,3]oxazine (1-Br) with TMSCCH gave acetylenic benzoxazine 1-C₂TMS which was a precursor for polyynic derivatives. Firstly, it was deprotected with K₂CO ₃ in iPrOH/MeOH to give the terminal acetylene 1-C₂H, which was subsequently dimerized to the symmetrical diyne 1-C₄-1. Next, 1-C₂H was transformed to 1-C₄TMS via a Cadiot-Chodkiewicz coupling, and then 1-C₄TMS was homocoupled with in situ deprotection to give octatetrayne 1-C₈-1. X-ray diffraction studies of 1-C₈-1 showed distinctive chain bending and a packing analysis revealed the potential for 1,n-topochemical polymerization that implies a cross-linking opportunity. 2012 Elsevier Ltd. All rights reserved.

Full text of DOI:10.1016/j.tetlet.2012.07.141

Tetrahedron Letters 53 (2012) 5471–5474
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Macromolecular polyyne-containing benzoxazines for cross-linked
polymerization
⇑
Nurbey Gulia, Jolanta Ejfler, Sławomir Szafert
Department of Chemistry, University of Wrocław, 14 F. Joliot-Curie, 50-383 Wrocław, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A Mannich condensation of 2,4-di-tert-butylphenol, p-bromophenethylamine, and formaldehyde fol-
lowed by a Sonogashira coupling of the resulting 3-(4-bromophenethyl)-6,8-di-tert-butyl-3,4-dihydro-
2H-benz[1,3]oxazine (1-Br) with TMSC„CH gave acetylenic benzoxazine 1-C2TMS which was a precursor
for polyynic derivatives. Firstly, it was deprotected with K2CO3 in iPrOH/MeOH to give the terminal acet-
ylene 1-C2H, which was subsequently dimerized to the symmetrical diyne 1-C4-1. Next, 1-C2H was trans-
formed to 1-C4TMS via a Cadiot–Chodkiewicz coupling, and then 1-C4TMS was homocoupled with in situ
deprotection to give octatetrayne 1-C8-1. X-ray diffraction studies of 1-C8-1 showed distinctive chain
bending and a packing analysis revealed the potential for 1,n-topochemical polymerization that implies
a cross-linking opportunity.
Received 5 May 2012
Revised 27 June 2012
Accepted 19 July 2012
Available online 10 August 2012
Keywords:
Polyynes
Topochemical polymerization
Benzoxazines
Macromolecules
Polymerization
Ó 2012 Elsevier Ltd. All rights reserved.
1,3-Benzoxazines constitute a fast developing and sought-after
class of heterocyclic monomers that upon thermal or catalytic cur-
ing produce thermosetting phenolic resins which possess many
useful properties1 including biological activity.2 Among the most
important properties of polybenzoxazines are near-zero shrinkage,
high thermal stability, low water absorption, high UV retardance,
and good mechanical performance.1,3 Another factor, which makes
benzoxazines an attractive target is their preparation accessibility.
The majority of monomers are available via simple Mannich con-
densation from inexpensive and commercially available phenols,
primary amines, and formaldehyde1 although other synthetic ap-
proaches are also extensively utilized.4–10
In order to improve mechanical and other properties of poly-
benzoxazine resins further various monomer modifications have
been developed. The introduction of a reactive functional group
for further processing seems a natural strategy. Among many that
have been tested, acetylenic benzoxazines have been targeted by
several groups.3a,11 Such functionalization has an additional
advantage since the resulting acetylenic precursors can initially
be polymerized at the C„C bond in solution or in solid state (e.g.
via 1,n-topochemical pathway) before polymerization at the
benzoxazine moiety. The benzoxazine polymer can also be cross-
linked through the acetylenic substituent. The resulting hyper-
branched materials with improved mechanical and/or conductive
Compounds with unsaturated carbon chains (conjugated poly-
mers) usually have unique properties, such as nonlinear optical re-
sponses (NLOs) or large molecular first- and second-order
hyperpolarizabilities, b and c
, respectively.12
With this in mind, we initiated a project that started with the
preparation and characterization of a series of novel acetylenic
benzoxazine monomers that would constitute a group of precur-
sors for highly-branched conductive polymers.
3-(4-Bromophenethyl)-6,8-di-tert-butyl-3,4-dihydro-2H-benz
[1,3]oxazine (1-Br) was prepared by a routine Mannich condensa-
tion using a methanolic solution of 2,4-di-tert-butylphenol, p-
bromophenethylamine, and formaldehyde, as shown in Scheme
1. The mixture was refluxed for 90 h and the final white crystalline
product was obtained in a 64% yield as described in the experimen-
tal section in the Supplementary data.
Next, the acetylenic fragment was introduced to 1-Br by a Sono-
gashira coupling using TMSC„CH and the Pd(PPh3)2Cl2/Cu(OAc)2/
NEt3 catalytic system. Work-up gave analytically pure 1-C2TMS in
a 68% yield as a beige solid. Deprotection of 1-C2TMS with K2CO3 in
a iPrOH/MeOH mixture (v/v, 3/1) at room temperature gave after
24 h, the terminal acetylenic 1-C2H in a 95% yield that was dimer-
ized to 1-C4-1 and chain-extended to 1-C4TMS. Dimerization to the
diyne was performed via oxidative coupling with Cu(OAc)2 in pyr-
idine yielding 97% of the target dimer. The chain extension was at-
tained through the Cadiot–Chodkiewicz protocol with the use of
IC„CTMS, Pd(PPh3)2Cl2, and CuI in the presence of iPr2NH. 1-
C4TMS was isolated in a 33% yield as a yellow solid and was subse-
quently dimerized to 1-C8-1 with in situ deprotection by K2CO3 but
without isolation of the terminal diacetylene 1-C4H as shown in
properties possess extensive
p
delocalization and highly polariz-
able
p-electron systems which introduce new characteristics.
⇑
Corresponding author. Tel.: +48 71 375 7122; fax: +48 71 238 2348.
E-mail address: slawomir.szafert@chem.uni.wroc.pl (S. Szafert).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.141

5472
N. Gulia et al. / Tetrahedron Letters 53 (2012) 5471–5474
Br
Si
NH2
OH
HC2TMS
O
N
formaldehyde
O
N
Pd(PPh3)2Cl2
Cu(OAc)2, NEt3
50-60 °C, 48 h
+
MeOH, reflux
90 h
78% (1-C2TMS)
Br
(1-Br)
64%
K2CO3
i PrOH/MeOH
3/1, rt , 24 h
O
N
O
N
Cu(OAc)2
N
pyridine, 55 °C
3 h
O
97% (1-C4-1)
95% (1-C2H)
IC2TMS
Pd(PPh3)2Cl2, CuI
HNiPr2, THF, rt, 2 h
Si
1) K2CO3
MeOH/i PrOH
1/3, rt, 24 h
O
O
N
N
N
2) Cu(OAc)2
pyridine, 50 °C,
3 h
O
33% (1-C4TMS)
41% (1-C8-1)
Scheme 1. Synthesis of 1-C4-1 and 1-C8-1.
Scheme 1. Workup on a silica gel column gave the tetrayne 1-C8-1
in a 41% yield as a yellow solid.
As can be noticed in Figure 1 the chain conformation is an
unsymmetric bow with a C(11)–C(41) distance of 11.732 Å. The
sum of all bonds within the carbon chain adds to 11.780 Å which
accounts for a 0.41% contraction.15 Similar deformations were ob-
served in organic tetraynes TMS-C8-TMS16 (0.48%) and tBu-C8-
tBu17 (0.34%) although they were much more pronounced in other
organometallic compounds.15 Also the average chain bond angle of
177.5° (the smallest for all organic tetraynes)15 supports a distinc-
tive deformation.
Searching for an alkyne polymerization potential, the packing
analysis was next performed. The compound crystallizes in the
P-1 space group, so the molecules form one set of parallel chains.
The closest chain–chain distance in 1-C8-1 is 3.880 Å that seems
surprisingly short for such a bulky end-group. The / angle, which
is a measure of the chain–chain translation15 equals 50.2°, which
accounts for the offset value of 3.162 Å and the fractional offset
of 0.27.15 It is noteworthy, that the ideal values of the / angle
and the chain–chain separation to ensure the highest possibility
of topochemical polymerization are 45° and ca. 3.5 Å (for the 1,4-
polymerization).
All compounds gave correct microanalyses and/or HRMS peaks
and their structures followed from their NMR (1H and 13C) proper-
ties and X-ray analysis. For instance, in the proton spectrum of 1-
Br, the diagnostic signals of the methylene protons of the two –
CH2– groups from the newly formed heterocycle gave singlets at
d 4.86 and 4.02 ppm. The proton spectrum of 1-C2TMS revealed
an additional singlet at d 0.24 ppm assigned to the protons of the
trimethylsilyl group. Also the 13C NMR spectrum of 1-C2TMS
showed two additional signals at d 105.4 and 93.8 ppm assigned
to the carbons from the acetylenic fragment and a signal at d
0.2 ppm from the carbon atoms of the TMS fragment. Next, both
the 1H and 13C NMR spectra of 1-C2H confirmed the successful re-
moval of the TMS group showing the absence of the corresponding
signals in both spectra. Instead, the singlet of the terminal proton
appeared at d 2.74 ppm. Both, the symmetric and unsymmetric
C4 compounds, 1-C4-1 and 1-C4TMS, showed signals of chain car-
bons at d 82.8 and 75.2 ppm for 1-C4-1, and at d 90.6, 88.1, 77.1,
and 74.0 ppm for 1-C4TMS. The terminal TMS group signals of
the latter compound emerged at d 0.23 ppm and at À0.18 ppm in
1H and 13C NMR spectra, respectively. Also the 13C NMR spectrum
of 1-C8-1 showed all the carbon chain signals between d 78.1 and
63.9 ppm.
Yellow plates of 1-C8-1 were grown by slow evaporation of a
CHCl3 solution. The crystal structure was determined as described
in the Supplementary data. As depicted in Figure 1, the molecule of
1-C8-1 is non-centrosymmetric. Both phenyl rings are twisted by
8.1°. The triple bond distances within the carbon chain are
1.216(6), 1.216(6), 1.213(6), and 1.198(6) Å and are similar to
those found for C„C in ethyne13 (1.2033 Å) and butadiyne
(1.217–1.20964 Å).14 The single bond distances are 1.355(6),
1.351(6), and 1.377(6) Å and are similar to those found for other
tetraynes.15a,b
The oxazine rings in the benzoxazine end-caps crystallize in a
preferred (also for further polymerization) distorted half-chair
conformation with
h and u parameters of 127.3(5)° and
272.1(6)°, respectively, for the O(1), C(22), N(1), C(21), C(31),
C(36) ring and 50.6(6)° and 98.0(6)° for the ring defined by the
O(2), C(52), N(2), C(51), C(61), and C(66) atoms.18 The correspond-
ing within-the-oxazine-ring torsion angles at both ends of 1-C8-1
are: 13.5(5)° for C(31)–C(36)-O(1)-C(22) and À12.5(5)° for C(61)–
C(66)-O(2)-C(52), 49.3(4)° for C(36)-O(1)-C(22)-N(1) and
À46.2(5)° for C(66)-O(2)-C(52)-N(2), 65.8(4)° for O(1)-C(22)-
N(1)-C(21) and À64.4(4)° for O(2)-C(52)-N(2)-C(51), 46.3(4)° for
C(22)-N(1)-C(21)-C(31) and À48.9(5)° for C(52)-N(2)-C(51)-C(61),
À14.7(5)° for N(1)-C(21)-C(31)-C(36) and 19.3(6)° for N(2)-C(51)-
C(61)-C(66), and À2.8(6)° for C(21)-C(31)-C(36)-O(1) and

N. Gulia et al. / Tetrahedron Letters 53 (2012) 5471–5474
5473
Figure 1. The molecular structure of 1-C8-1 with atom-labeling.
À0.1(6)° for C(51)-C(61)-C(66)-O(2) and they do not differ signifi-
cantly. Consequently, the positions of the methylene carbon C(22)
and nitrogen N(1) as well as the carbon C(52) and N(2) in relation
to the planes defined by C(31) to C(36) and C(61) to C(66) atoms,
respectively, are also similar. The position of both atoms on the
opposite sides of the plane of the phenyl ring is believed to be an
important factor that promotes polymerization. In 1-C8-1, the
C(22) atom deviates from the phenyl plane by À0.3402 Å while
the nitrogen N(1) is 0.4525 Å above it. These values for the other
end of 1-C8-1 are À0.2859 and 0.4543 Å.
the phenolic moiety that resulted in two kinds of polymers.20 Late-
ly, also Schönfeld, Marquet, and Sebastián presented elegant mech-
anistic studies on the subject.21
In order to establish the potential of the new benzoxazines in
the ROP process their thermal analysis was performed. TGA-DSC
was employed to monitor the thermal behavior of the compounds
and measurements were performed in N2 and in an oxidative
atmosphere at a speed of 20 °C/min from 50° C to 500–700 °C. Fig-
ure 2 shows the resulting curves (in N2) and the melting points are
summarized in Table 1.
One of the most important reactions of benzoxazines is their
thermal ring opening polymerization (ROP).19 In 2000, Wang and
Ishida discussed two different mechanisms for such a process
depending on the position of substituents in the aromatic ring of
Each compound exhibits a main thermal transition of the endo-
thermal type that was assigned to the melting process. Only in case
of the dimer 1-C4-1, does the process begin at a much higher tem-
perature that exceeds 238 °C. There are basically no differences
Figure 2. DSC for benzoxazines: 1-Br (top, left), 1-C2TMS (top, right), 1-C2H (bottom, left), and 1-C4-1 (bottom, right).

5474
N. Gulia et al. / Tetrahedron Letters 53 (2012) 5471–5474
Table 1
References and notes
Melting point of benzoxazines and the temperatures of initiation of mass loss process
1. (a) Ghosh, N. N.; Kiskan, B.; Yagci, Y. Prog. Polym. Sci. 2007, 32, 1344–1391; (b)
Yagci, Y.; Kiskan, B.; Ghosh, N. N. J. Polym. Sci., Part A: Polym. Chem. 2009, 47,
5565–5576.
Compound
mp (°C)
Temp. of mass loss (°C)
1-Br (N2)
1-Br (air)
117
116
106
106
103
103
238
—
197
199
215
200
195
199
257
217
2. (a) Moloney, G. P.; Craik, D. J.; Iskander, M. N. J. Pharm. Sci. 1992, 81, 692–697;
´
(b) Gammill, R. B. J. Org. Chem. 1981, 46, 3340–3342; (c) Chylinska, J. B.;
1-C2TMS (N2)
1-C2TMS (air)
1-C2H (N2)
1-C2H (air)
1-C4-1 (N2)
1-C4-1 (air)
Janowiec, M.; Urban´ ski, T. Br. J. Pharmacol. 1971, 43, 649–657; (d) Matzanke, N.;
Lowe, W.; Perachon, S.; Sokoloff, P.; Schwartz, J.-C.; Stark, H. Eur. J. Med. Chem.
1999, 34, 791–798; (e) Largeron, M.; Lockhart, B.; Pfeiffer, B.; Fleury, M. J. Med.
Chem. 1999, 42, 5043–5052; (f) Buon, C.; Chacum-Lefevre, L.; Rabot, R.;
Bouyssou, P.; Coudert, G. Tetrahedron 2000, 56, 605–614; (g) Kajino, M.;
Shibouta, Y.; Nishikawa, K.; Meguro, K. Chem. Pharm. Bull. 1991, 39, 2896–2905;
(h) Largeron, M.; Mesples, B.; Gressens, P.; Cecchelli, R.; Spidding, M.; Le Ridant,
A.; Fleury, M.-B. Eur. J. Pharmacol. 2001, 424, 189–194.
3. (a) Mihrace, E.; Baris, K.; Burcin, G.; Yagci, Y. Macromolecules 2007, 40, 4724–
4727; (b) Agag, T.; Takeichi, T. Macromolecules 2003, 36, 6010–6017; (c) Kumar,
K. S. S.; Nair, C. P. R.; Sadzana, R.; Ninan, K. N. Eur. Polym. J. 2007, 43, 5084–
5096.
4. (a) Palmieri, G. Eur. J. Org. Chem. 1999, 4, 805–811; (b) Alvarez, M.; Granados,
R.; Mauleon, D.; Rosell, G.; Salas, M.; Salles, J.; Valls, N. J. Med. Chem. 1987, 30,
1186–1193; (c) Rivera, A.; Gallo, G. I.; Gayon, M. E. Synth. Commun. 1994, 24,
2081–2089.
5. Campi, E. M.; Jackson, W. R.; McCubbin, Q. J.; Trnacek, A. E. J. Chem. Soc., Chem.
Commun. 1994, 2763.
6. Vilkas, M.; Makani, S.; Mafroud, A. E. K. Acad. Sci. Ser. 2 1851, 1988, 307. Chem.
Abstr. 1989, 111, 7311w.
depending on the atmosphere in which the process is conducted
(N2 vs air).
In each case, another endothermal process occurs around
250 °C, but it is associated with the initiation of mass loss as visu-
alized by the TGA curves. Hence, based on these results, and the 1H
NMR spectra of the resulting material, we conclude that instead of
polymerization a decomposition process starts to occur at this
point.
In summary, we have demonstrated an effective synthetic strat-
egy to approach benzoxazine end-capped polyynes with different
lengths of the carbon chain. The compounds were characterized
by spectroscopic methods and by X-ray crystallography which
showed the C8 chain with a substantially bent conformation. The
packing analysis of 1-C8-1 showed one set of parallel chains that
were separated by 3.880 Å. This and the value of the / angle of
50.2° revealed a significant potential of the compound for topo-
chemical polymerization. 1-Br, both C2 compounds and the but-
adiynic dimer 1-C4-1 were subject to thermal analysis showing
an endothermal process (above the melting point) that was associ-
ated with mass loss. This most probably excludes the thermal poly-
merization of the benzoxazine, although a catalytic polymerization
cannot be disqualified.
7. Colin, J. L.; Loubinoux, B. Tetrahedron Lett. 1982, 23, 4245–4246.
8. Aversa, M. C.; Giannetto, P.; Caristi, C.; Ferlazzo, A. J. Chem. Soc., Chem. Commun.
1982, 469–470.
9. Snieckus, V. Chem. Rev. 1990, 90, 879–933.
10. Katritzky, A. R.; Xu, Y.-J.; Jain, R. J. Org. Chem. 2002, 67, 8234–8236.
11. (a) Chernykh, A.; Agag, T.; Ishida, H. Macromolecules 2009, 42, 5121–5127; (b)
Demir, K. D.; Kiskan, B.; Yagci, Y. Macromolecules 2011, 44, 1801–1807.
12. (a) Bosshard, C.; Sutter, K.; Pretre, P.; Hulliger, J.; Florsheimer, M.; Kaatz, P.;
Gunter, P. Organic Nonlinear Optical Materials; Gordon and Breach: Amsterdam,
The Netherlands, 1995; (b) Klokkenburg, M.; Lutz, M.; Spek, A. L.; van der Maas,
J. H.; van Walree, C. A. Chem. Eur. J. 2003, 9, 3544–3554; (c) Prasad, P. N.;
Williams, D. J. Introduction to Nonlinear Optical Effects in Molecules and
Polymers; Wiley: New York, 1991; (d) van Walree, C. A.; Kaats-Richters, V. E.
M.; Veen, S. J.; Wieczorek, B.; van der Wiel, J. H.; van der Wiel, B. C. Eur. J. Org.
Chem. 2004, 3046–3056; (e) Zhao, Y.; Slepkov, A. D.; Akoto, C. O.; McDonald, R.;
Hegmann, F. A.; Tykwinski, R. R. Chem. Eur. J. 2005, 11, 321–329.
13. (a) Fast, H.; Welsh, H. L. J. Mol. Spectrosc. 1972, 41, 203–221; (b) McMullan, R.
K.; Kvick, Å.; Popelier, P. Acta Crystallogr. 1992, B48, 726–731.
14. (a) Tanimoto, M.; Kuchitsu, K.; Morino, Y. Bull. Chem. Soc. Jpn. 1971, 44, 386–
391; (b) Tay, R.; Metha, G. F.; Shanks, F.; McNaughton, D. Struct. Chem. 1995, 6,
47–55.
Acknowledgement
15. (a) Szafert, S.; Gladysz, J. A. Chem. Rev. 2003, 103, 4175–4205; (b) Szafert, S.;
Gladysz, J. A. Chem. Rev. 2006, 106, PR1–PR33.
16. Coles, B. F.; Hitchcock, P. B.; Walton, D. R. M. J. Chem. Soc. Dalton Trans. 1975,
442–445.
The authors would like to thank the National Science Center in
Poland (Grant N204 136339) for support of this research.
17. Lagow, R. J.; Kampa, J. J.; Wei, H.-C.; Battle, S. L.; Genge, J. W.; Laude, D. A.;
Harper, C. J.; Bau, R.; Stevens, R. C.; Haw, J. F.; Munson, E. Science 1995, 267,
362–367.
Supplementary data
18. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1974, 97, 1354–1358.
19. Russell, V. M.; Koening, J. L.; Low, H. Y.; Ishida, H. J. Appl. Polym. Sci. 1998, 70,
1413–1425.
20. Wang, Y.-X.; Ishida, H. Macromolecules 2000, 33, 2839–2847.
21. Liu, C.; Shen, D.; Sebastián, R. M.; Marquet, J.; Schönfeld, R. Macromolecules
2011, 44, 4616–4622.
Supplementary data (synthetic procedures, materials and meth-
ods, 1H and 13C NMR spectra, and X-ray data for 1-C8-1 (CCDC-
872155)) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2012.07.141.