Direct synthesis of poly(arylmethyl sulfone) monodendrons

Article abstract of DOI:10.1055/s-2006-926296

Synthetic efforts toward poly(arylmethyl sulfone) dendrimers are described. A molecule designed to function as a protected AB₂ monomer, phenyl 3,5-bis(chloromethyl)benzenesulfonate was synthesized in four steps from dimethyl 5-sulfoisophthalate

Full text of DOI:10.1055/s-2006-926296

SHORT PAPER
397
Direct Synthesis of Poly(arylmethyl Sulfone) Monodendrons
A
rylmethyl Sulfon
i
e
Mono
u
dendrons xia Zhao, James E. Hanson*
Department of Chemistry and Biochemistry, Seton Hall University, South Orange, NJ 07079-2694, USA
Fax +1(973)7619772; E-mail: hansonja@shu.edu
Received 24 July 2005
Dedicated to Professor Peter B. Dervan, a 1,1-diazene pioneer, on the occasion of his 60th birthday.
CH2Prot
SO2Prot
Abstract: Synthetic efforts toward poly(arylmethyl sulfone) den-
drimers are described. A molecule designed to function as a protect-
ed AB2 monomer, phenyl 3,5-bis(chloromethyl)benzenesulfonate
was synthesized in four steps from dimethyl 5-sulfoisophthalate in
59% overall yield. This monomer was coupled to sodium benzene-
sulfinate to give the generation 1 monodendron, phenyl 3,5-bis-
(phenylsulfonylmethyl)benzenesulfonate. However, deprotection
of the generation 1 monodendron by literature methods of reduction
and hydrolysis were not successful.
NaO2S
SO2Na
Cl
Cl
protected halide
‘Frechet’ monomer
protected sulfinate
‘Hanson’ monomer
Figure 1 Potential monomers for poly(arylmethyl)sulfone synthe-
sis
Key words: sulfones, polymers, dendrimers
shown in Figure 1. We chose to develop a route employ-
ing the latter monomer.
Dendritic polymers have been the focus of considerable
study for the past twenty years.1 Many different function-
alities have been employed in the construction of den-
drimers, including amines, ethers, esters, and arenes. One
functionality that has not received much attention is the
sulfone moiety. Linear sulfone polymers are important en-
gineering plastics, primarily as the aromatic sulfone
ethers.2 There have been a few scattered reports of some
sulfone-containing dendrimers and hyperbranched poly-
mers,3 including a recent report of related arylmethyl sul-
fone dendrimers prepared by oxidation of the
corresponding arylmethyl sulfide dendrimers.4 In this pa-
per, we describe our efforts toward the direct synthesis of
poly(arylmethyl sulfone) dendrimers analogous to the
commonly used poly(arylmethyl ether) (‘Frechet’) struc-
tures.5
Accordingly, what appeared to be a suitable monomer
was prepared in 4 steps from the commercially available
dimethyl 5-sulfoisophthalate (1), as shown in Scheme 1.
The overall yield for this synthesis was 59%. The sul-
fonate group of 1 was transformed into the sulfonyl chlo-
ride of 2 through the use of thionyl chloride with a
catalytic amount of DMF.8 The DMF catalyst was re-
quired for a reasonable yield (79% with DMF, <10%
without). At 79%, this was the lowest-yielding step of the
synthesis. The resulting sulfonyl chloride was then con-
verted into a phenyl sulfonate with phenol and triethyl-
amine, generating compound 3.7,8 Triethylamine was
found to be a better base for this transformation than pyri-
dine (87% yield vs. 80%). Phenyl sulfonates are masked
sulfinates, since they are reported to be converted to the
sulfinate salts by reaction with base and hydrazine.9 The
isophthalate esters were then reduced to benzyl alcohols
by lithium borohydride in diethyl ether with a catalytic
amount of methanol to give 4.7 Again, the presence of the
methanol catalyst greatly enhanced the yield (89% with
catalyst, <10% without). Finally, the benzyl alcohols were
activated by conversion with thionyl chloride to the ben-
zyl chlorides of monomer 5.7
There are two obvious routes to poly(aryl sulfone) or
poly(arylmethyl sulfone) dendrimers and related hyper-
branched polymers. One is through the initial preparation
of polysulfide polymers followed by subsequent oxida-
tion to the sulfones. This method has been used in our own
work3c and by others.4 A second route is through direct
preparation of the sulfones by condensation of sulfinate
nucleophiles.6 In this communication, we describe our ef-
forts in this second direction. Condensation of sulfinate
ions (particularly arylsulfinates) with alkyl halides is a
common method for the preparation of simple sulfones.6
By analogy to the Frechet5 and Hanson7 monomers for
poly(arylmethyl ether) dendrimer synthesis, an A2B
monomer for poly(arylmethyl sulfone) dendrimer synthe-
sis would then require either two sulfinates and a protect-
ed halide, or two alkyl halides and a protected sulfinate as
Dendrimer synthesis employing monomer 5 was started
by coupling of 5 with two equivalents of sodium benzene-
sulfinate, as shown in Scheme 2. This produced protected
generation 1 monodendron 6 (G1 SO2Ph) in 77% yield.
The relatively low yield is somewhat troubling for the
production of higher generation poly(aryl sulfone) den-
drimers. More troubling was the failure of literature meth-
ods for conversion of the phenyl sulfonate to the sodium
sulfinate. Well established precedent made us expect that
basic hydrazinolysis of the phenyl sulfonate would give
the sodium sulfinate.9 This passes through an intermediate
sulfonylhydrazide, which deprotonates at N and frag-
ments into the sulfinate anion and an aminonitrene or 1,1-
SYNTHESIS 2006, No. 3, pp 0397–0399
x
x
.
x
x
.2
0
0
5
Advanced online publication: 13.01.2006
DOI: 10.1055/s-2006-926296; Art ID: M04905SS
© Georg Thieme Verlag Stuttgart · New York

398
Q. Zhao, J. E. Hanson
SHORT PAPER
SO3Na
SO2Cl
SOCl2
DMF
PhOH
Et3N
80 °C
MeO2C
CO2Me
MeO2C
CO2Me
1
2
79%
SO3Ph
SO3Ph
SO3Ph
LiBH4
MeOH
SOCl2
reflux
Et2O
reflux
MeO2C
CO2Me
Cl
Cl
OH
OH
5
96%
4
89%
3
87%
Scheme 1 Synthesis of monomer 5
diazene (H2N2).10 However, application of literature
methods to G1-sulfonate 6 did not result in decomposition
of the phenyl sulfonate. Other reductive methods (e.g.,
with LiAlH4) either failed or were unselective and re-
duced the benzyl sulfones as well.
was 200–400 mesh, 60 Å. Melting points were determined on a
Mel-Temp apparatus and are uncorrected. IR spectra were recorded
on the neat solids using a Perkin-Elmer Spectrum One FT-IR spec-
trophotometer at 4 cm–1 resolution. Nuclear magnetic resonance
spectra were obtained on a Varian 300 MHz FT-NMR spectrome-
ter. Elemental analyses were performed by Schwarzkopf Microan-
alytical Laboratory, Woodside, NY. Mass spectra were obtained on
an Agilent 1100 Series LC/MSD.
When these direct reductive methods failed, we also at-
tempted reduction following hydrolysis. This is a less de-
sirable multi-step approach, requiring hydrolysis of the
sulfonate to the sulfonic acid, chlorination to the sulfonyl
chloride, and reduction with sodium sulfite or zinc to give
Dimethyl 5-Chlorosulfonylisophthalate (2)
To a 250 mL round-bottomed flask equipped with a condenser and
a CaCl2 drying tube were added 5-sulfoisophthalic acid dimethyl es-
the sulfinate. The hydrolysis and chlorination appeared to ter sodium salt (1) (20.0 g, 67.6 mmol), SOCl2 (70 mL), and a few
drops of DMF. The flask was heated in an oil bath at 80 °C for 20
be successful, but reduction to the sulfinate failed. Failure
h, while the contents of the flask were stirred magnetically. After
of both reductive and hydrolytic–reductive deprotection
cooling to r.t. the reaction mixture was filtered to remove sodium
made us abandon this synthetic method as a route to larger
chloride formed during the reaction, and the excess of SOCl2 was
poly(arylmethyl sulfone) monodendrons and dendrimers.
removed by distillation under reduced pressure. The yellow residue
was filtered and then washed with hexane a few times. Recrystalli-
zation from EtOAc afforded 2 as white needles (15.7 g, 79%); mp
SO3Ph
SO2Na
SO3Ph
90 °C
DMF
110.5–111.0 °C.
+
2
IR (neat solid): 3075, 1728, 1433, 1377, 1259, 1174, 993, 876, 850,
749, 667 cm–1.
Cl
Cl
SO2
SO2
1H NMR (300 MHz, CDCl3): d = 4.05 (s, 6 H), 8.84 (s, 2 H), 9.20
(s, 1 H).
5
13C NMR (75 MHz, CDCl3): d = 53.5, 131.7, 132.9, 136.6, 145.3,
164.0.
G1 SO2Ph
6
77%
Dimethyl 5-Phenoxysulfonylisophthalate (3)
Scheme 2 Preparation of G1-monodendron 6
To a 100 mL three-necked flask equipped with a thermometer and
a nitrogen inlet were added PhOH (1.6 g, 17 mmol), CH2Cl2 (50
mL), and base [Et3N (1.73 g, 17.1 mmol), pyridine (1.35 g, 17.1
mmol), or NaOH (0.68 g, 17 mmol )]. The flask was surrounded by
an ice-water bath, sufficiently cold to lower the temperature of the
mixture to 10 °C. At this temperature, compound 2 (5.0 g, 17 mmol)
was added in portions over 30 min and the mixture was then stirred
for 5 h at a temperature below 20 °C. H2O (25 mL) and 1 N HCl soln
(25 mL) were added to quench the reaction, while cooling with ice–
In conclusion, we were able to prepare a first generation
poly(arylmethyl sulfone) monodendron from the protect-
ed AB2 monomer phenyl 3,5-bis(chloromethyl)benzene-
sulfonate (5). The monomer itself was prepared in four
steps and 59% yield. The first generation monodendron
was prepared from the monomer in 77% yield. Unfortu-
nately, the phenyl sulfonate protecting group did not con- water; the mixture was then extracted with CH2Cl2. The extract was
dried over Na2SO4 and concentrated under reduced pressure. Re-
crystallization from MeOH afforded 3 as a white crystalline solid
(4.84 g, 80%); mp 108–109 °C.
vert into the sulfinate salt under the conditions specified in
the literature (hydrazine and base), and other methods
were also unsuccessful in preparing the activated mono-
IR (neat solid): 3075, 1730, 1430, 1360, 1323, 1253, 1191, 1139,
dendron. We therefore abandoned attempts to create larg-
869, 752, 720, 693, 667 cm–1.
er dendrimers by this route.
1H NMR (300 MHz, CDCl3): d = 4.00 (s, 6 H), 7.01–7.32 (m, 5 H),
8.64 (s, 2 H), 8.97 (s, 1 H).
THF was purified by distillation from sodium/benzophenone imme-
diately before use as a reaction solvent. Except where noted, all oth-
er chemicals were purchased from commercial vendors and used
13C NMR (75 MHz, CDCl3): d = 53.2, 122.3, 128.0, 130.2, 132.4,
133.2, 136.0, 137.6, 149.8, 164.8.
without further purification. Silica gel for flash chromatography
Synthesis 2006, No. 3, 397–399 © Thieme Stuttgart · New York

SHORT PAPER
Arylmethyl Sulfone Monodendrons
MS (ESI): m/z = 565 [M + Na]+.
399
Phenyl 3,5-Bis(hydroxymethyl)benzenesulfonate (4)
To a suspension of LiBH4 (1.85 g, 84.9 mmol) in 100 mL of anhyd
Et2O were added compound 3 (5 g, 14 mmol) and anhyd MeOH
(2.69 g, 83.9 mmol). The resulting mixture was heated at reflux un-
der N2 for 24 h. The mixture was allowed to cool to r.t. and was then
diluted with CH2Cl2. NaOH soln (10%) was used to quench the re-
action and the reaction mixture was extracted with CH2Cl2. The ex-
tract was dried over Na2SO4 and concentrated under reduced
pressure. Purification by flash chromatography (hexane–EtOAc,
2:1) afforded 4 as white cubic crystals (3.7 g, 89%); mp 146–
147 °C.
Anal. Calcd for C26H22O7S3: C, 57.55; H, 4.09; S, 17.73. Found: C,
57.81; H, 3.77; S, 17.80.
References
(1) (a) For a series of reviews of dendrimers recently published,
see: Prog. Polym. Sci. 2005, 30, 217. (b) Jikei, M.;
Kakimoto, M.-A. Prog. Polym. Sci. 2001, 26, 1233.
(c) Tomalia, D. A.; Frechet, J. M. J. J. Polym. Sci., Part A:
Polym. Chem. 2002, 40, 2719. (d) Sheiko, S. S.; Moller, M.
Top. Curr. Chem. 2001, 212, 137. (e) Inoue, K. Prog.
Polym. Sci. 2000, 25, 453. (f) Hult, A.; Johansson, M.;
Malmstrom, E. Adv. Polym. Sci. 1999, 143, 1. (g) Bosman,
A. W.; Janssen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99,
1665.
(2) (a) Encyclopedia of Polymer Science and Engineering; John
Wiley: New York, 1988. (b) Polymeric Materials
Encyclopedia; CRC Press: Boca Raton, 1996. (c) Polymer
Handbook, 3rd ed.; Brandrup, J.; Immergut, E. H., Eds.;
Wiley-Interscience: New York, 1989.
(3) (a) Jikei, M.; Hu, Z.; Kakimoto, M.; Imai, Y.
Macromolecules 1996, 29, 1062. (b) Miller, T. M.; Neenan,
T. X.; Kwock, E. W.; Stein, S. M. J. Am. Chem. Soc. 1993,
115, 356. (c) Mellace, A.; Hanson, J. E.; Griepenburg, J.
Chem. Mater. 2005, 17, 1812. (d) Chang, Y.; Kwon, Y.;
Park, K.; Kim, C. Korea Polym. J. 2000, 8, 142.
IR (neat solid): 3289, 3076, 2878, 1587, 1486, 1363, 1316, 1188,
1144, 1022, 857, 778, 724, 690 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.63 (s, 4 H), 6.95–7.27 (m, 5 H),
7.58 (s, 1 H), 7.63 (s, 2 H).
13C NMR (75 MHz, CDCl3): d = 63.6, 122.1, 125.0, 127.1, 129.5,
130.3, 135.3, 142.7, 149.2.
Phenyl 3,5-Bis(chloromethyl)benzenesulfonate (5)
To a 100 mL three-necked flask equipped with a thermometer and
a condenser carrying a CaCl2 drying tube were added compound 4
(4.00 g, 13.6 mmol) and SOCl2 (40 mL). The flask was heated in an
oil bath at 75 °C for 24 h, while the contents of the flask were stirred
magnetically. After cooling to r.t., ice–water was added to quench
the reaction. The reaction mixture was extracted with CH2Cl2, then
the extract was dried over Na2SO4 and concentrated under reduced
pressure. Recrystallization with MeOH afforded monomer 5 as a
white solid (4.28 g, 96.2%); mp 154–155 °C.
(4) Chow, H. F.; Ng, M. K.; Leung, C. W.; Wang, G. X. J. Am.
Chem. Soc. 2004, 126, 12907.
(5) Hawker, C. J.; Frechet, J. M. J. J. Am. Chem. Soc. 1990, 112,
7638.
IR (neat solid): 3075, 1585, 1483, 1449, 1371, 1192, 1169, 1140,
1107, 912, 864, 776, 710, 688 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.60 (s, 4 H), 6.98–7.32 (m, 5 H),
7.74 (s, 1 H), 7.80 (s, 2 H).
13C NMR (75 MHz, CDCl3): d = 44.4, 122.2, 127.8, 128.2, 130.0,
134.2, 136.4, 140.0, 149.9.
(6) (a) Novembre, A. E.; Hanson, J. E.; Kometani, J. M.; Tai, W.
W.; Reichmanis, E.; Thompson, L. F.; West, R. J. Polym.
Eng. Sci. 1992, 32, 1476. (b) Hanson, J. E.; Jensen, K. H.;
Gargiulo, N.; Motta, D.; Pingor, D. A.; Novembre, A. E.;
Mixon, D. A.; Kometani, J. M.; Knurek, C. Microelectronics
Technology: Polymers for Advanced Imaging and
Packaging; Reichmanis, E.; Ober, C. K.; MacDonald, S. A.;
Iwayanagi, T.; Nishikubo, T., Eds.; ACS Symposium Series
614; American Chemical Society: Washington DC, 1995,
137–148. (c) Organic Functional Group Preparations, 2nd
ed.; Sandler, S. R.; Karo, W., Eds.; Academic Press: New
York, 1983, Part I.
(7) Tyler, T. L.; Hanson, J. E. Chem. Mater. 1999, 11, 3452.
(8) Hanson, J. E.; Reichmanis, E.; Houlihan, F. M.; Neenan, T.
X. Chem. Mater. 1992, 4, 837.
(9) (a) Freudenberg, K.; Hess, H. Justus Liebigs Ann. Chem.
1926, 448, 121. (b) Carter, P.; Stevens, T. S. J. Chem. Soc.
1961, 1743. (c) Lemal, D. M.; Rave, T. W.; McGregor, S. D.
J. Am. Chem. Soc. 1963, 85, 1944. (d) Lemal, D. M.; Rave,
T. W. J. Am. Chem. Soc. 1965, 87, 393.
Anal. Calcd for C14H12Cl2O3S: C, 50.77; H, 3.65; Cl, 21.41; S, 9.68.
Found: C, 50.86; H, 3.44; Cl, 21.17; S, 9.67.
Phenyl 3,5-Bis(phenylsulfonylmethyl)benzenesulfonate (G1
SO2Ph) (6)
To a 100 mL three-necked flask equipped with a thermometer, a
condenser, and a nitrogen inlet were added monomer 5 (5.00 g, 15.1
mmol), benzenesulfinic acid sodium salt (5.53 g, 33.7 mmol), and
DMF (50 mL). The flask was heated in an oil bath at 90 °C for 72
h, while the contents of the flask were stirred magnetically. After
cooling to r.t., ice-water was added to quench the reaction, followed
by filtration. Recrystallization with toluene afforded 6 as a yellow
solid (6.38 g, 77%).
IR (neat solid): 3075, 1590, 1488, 1448, 1369, 1325, 1191, 1165,
1136, 1084, 915, 858, 778, 749, 687 cm–1.
(10) (a) Sylwester, A. P.; Dervan, P. B. J. Am. Chem. Soc. 1984,
106, 4648. (b) Michaelis, A.; Luzembourg, K. Ber. Dtsch.
Chem. Ges. 1893, 26, 2174. (c) Lwowski, W. Reactive
Intermediates; Jones, M.; Moss, R. A., Eds.; Wiley: New
York, 1985, 325–327. (d) Lemal, D. M. Nitrenes; Lwowski,
W., Ed.; Wiley-Interscience: New York, 1970, 345–404.
1H NMR (300 MHz, DMSO-d6): d = 4.89 (s, 4 H), 6.89–7.40 (m, 5
H), 7.61–7.72 (m, 13 H).
13C NMR (75 MHz, DMSO-d6): d = 60.2, 122.4, 128.2, 130.0,
131.1, 132.2, 135.0, 135.8, 138.2, 140.0, 149.2.
Synthesis 2006, No. 3, 397–399 © Thieme Stuttgart · New York