Dendro-shaped blocks with arylsulfanyl fragments based on p-toluic acid

Article abstract of DOI:10.1016/j.mencom.2018.07.035

Chloromethylation of p-toluic acid affords 3,5-bis(chloro- methyl)-4-methylbenzoic acid whose subsequent treatment with arenethiols brings about spacer dendrimeric blocks containing polyfluoroarylsulfanyl fragments in a total yield of 60-75%.

Full text of DOI:10.1016/j.mencom.2018.07.035

Mendeleev
Communications
Mendeleev Commun., 2018, 28, 442–443
Dendro-shaped blocks with arylsulfanyl fragments
based on p-toluic acid
Victoria N. Berezhnaya,a,b Alexander M. Maksimov,*a
Vyacheslav E. Platonova and Vladimir V. Shelkovnikova,c
a N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian
Academy of Sciences, 630090 Novosibirsk, Russian Federation. E-mail: maksimov@nioch.nsc.ru
b Novosibirsk State University, 630090 Novosibirsk, Russian Federation
c Novosibirsk State Technical University, 630073 Novosibirsk, Russian Federation
DOI: 10.1016/j.mencom.2018.07.035
CO2H
Chloromethylation of p-toluic acid affords 3,5-bis(chloro-
methyl)-4-methylbenzoic acid whose subsequent treatment
with arenethiols brings about spacer dendrimeric blocks
containing polyfluoroarylsulfanyl fragments in a total yield
of 60–75%.
CO2H
Me
SH
R
F
F
F
F
F
F
F
F
F
S
F
S
F
F
MeONa
MeOH
+
Cl
Cl
Me
R
R
R = F, CF3, Cl
Spacer blocks of the dendron structure with aromatic rings, e.g.,
benzoyloxy and polyfluorobenzoyloxy fragments, serve as a
separator of chromophores and decrease their intermolecular
aggregation in the materials possessing nonlinear optical (NLO)
properties.1,2 Special attention is paid to dendrons containing
polyfluorinated aromatic rings, which are used in electro-optical
materials as functional blocks separating nonlinear optical chromo-
phores to increase the NLO coefficient.3–5 The oxygen-containing
polyfluorinated dendrons based on pentafluorobenzyloxy
fragments were described as electro-optical materials.6 Com-
pounds containing tetrafluorophenylene(bis)phenoxy fragments
were used for the synthesis of polymers with high thermal
stability and good optical characteristics.7 The positive factor for
NLO compounds is the enhanced polarizability of the molecule
asawhole.Atomicrefractionand, consequently, thepolarizability
of the sulfur atom or the C–S bond are greater than those for the
oxygen atom or the C–O bond.8 Therefore, one can expect that
the introduction of a sulfur atom instead of an oxygen one into
the dendro-shaped separating fragment of a NLO chromophore
will increase its polarizability. In this connection, the synthesis
of dendrons containing, for example, aryl- and polyfluoroaryl-
sulfanyl structural fragments is an actual task. Dendritic struc-
tures of palladium catalysts incorporating phenylsulfanyl fragments
are known.9,10 However, no description has been found for the
synthesis of the corresponding sulfur-containing polyfluoroaryl
dendrons.
thus obtained aryl benzyl sulfides, the CH2 group interrupts the
conjugation between their aromatic moieties. We used the chloro-
methylation reaction11 to synthesize the nucleus of the dendron.
The introduction of two chloromethyl groups into the benzene
ring requires relatively harsh reaction conditions, and the presence
of a donor substituent (e.g., methyl group) in the aromatic ring is
necessary to facilitate the process.
It is known12 that chloromethylation of p-toluic acid gives
3,5-bis(chloromethyl) derivative 1. In our hands, chloromethylation
of p-toluic acid with bis(chloromethyl) ether in commercially
available 93% H2SO4 at 5–10°C led to the mixture containing,
according to the NMR data, acid 1 and 3-(chloromethyl)-4-methyl-
benzoic acid13 2 in an equal ratio and small amount (~3%)
of chloromethyl ester 3 (Scheme 1, method A). Raising the
concentration of H2SO4 to 100% (12–15°C) increased the yield
of acid 1 and decreased the yield of the 3-monochloromethyl
derivative 2 (method B). When the reaction was carried out in
CO2H
CO2H
O(CH2Cl)2
Cl
Cl
Me
Me
1
CO2H
CO2CH2Cl
In this work, to create the nucleus of the dendrone, the following
functional moieties seemed necessary: group (e.g., carboxyl one)
that assures the attachment of the spacer block to the NLO
chromophore molecule, as well as groups suitable for obtaining
the branches of the dendrone and located in a meta-orientation
relative to each other and to the group joining the chromophore.
For the starting core of the spacer block, a toluic acid derivative
bearing two 3,5-positioned chloromethyl groups is generally
selected.
Since arenethioles are strong nucleophiles, it seems expedient
to introduce functional substituents into a dendrimer, which are
capable of reacting with nucleophiles. For this purpose, active
chloromethyl group of benzylic type was that of choice. In the
+
+
Cl
Cl
Cl
Me
Me
2
3
Method
NMR ratio 1:2:3
A
B
C
D
49:48:3
73:24:3
98:0:2
75:0:25
Scheme 1 Reagents and conditions: method A: 93% H2SO4, 12–15°C;
method B: 100% H2SO4, 12–15°C; methodC: 100% H2SO4, 30°C; method D:
30% oleum, 12–15°C.
© 2018 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2018, 28, 442–443
CO2H
30% oleum, a mixture of acid 1 and its chloromethyl ester 3 in
a ratio of ~3:1 was formed (method D). Chloromethylation of
p-toluic acid with 100% H2SO4 at ~30°C proceeded fully to afford
the target acid 1 with ~2% of chloromethyl ester 3 (method C).
The obtained product has a melting point of 170–180°C and
also contains 5–10% of by-products, probably formaldehyde
oligomers.11 For the further purification it was treated with water
at room temperature and sublimated, which provided pure
acid 1 in 87% yield. Ester 3 was hydrolyzed 93% H2SO4 to the
desired acid 1.
SH
R
X
X
X
X
i, 1, base
X
X
X
X
X
R
S
S
X
R
ii, H+
Me
X
X
4a–f
a X = R = H
d X = R = F
b X = H, R = But e X = F, R = CF3
c X = H, R = Cl
f X = F, R = Cl
Reactions of compound 1 with substituted arenethiols resulted
in 3,5-bis(arylsulfanylmethyl) derivatives being the target dendron
compounds 4a–f (Scheme 2). For this transformation, various
conditions were tested. Reaction in dioxane at room temperature
in the presence of K2CO3, took 7–9 days, while carrying out this
process at 85–90°C took 7–11 h. The processing in methanol in the
presence of sodium methoxide at room temperature requires 2 h,
followed by keeping the mass overnight, the yields of the target
products being 84–95%.†
Scheme 2
In summary, new spacer dendritic blocks for NLO dyes con-
taining arylsulfanyl structural fragments including polyfluorinated
ones, were obtained.
This work was supported by the Russian Science Foundation
(grant no. 16-13-10156). Authors acknowledge the Multi-Access
Chemical Service Center, Siberian Branch of the RussianAcademy
of Sciences for spectral and analytical measurements.
†
Reactions of 3,5-bis(chloromethyl)-4-methylbenzoic acid 1 with arene-
thiols.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2018.07.035.
Procedures A and B: A solution of the corresponding arenethiol
(4.2 mmol) in dioxane (5 ml) was immediately added to a suspension of
dichloro acid 1 (2 mmol) and anhydrous K2CO3 (8 mmol) in dioxane (5 ml)
with stirring. The mixture was stirred at room temperature for 7–9 days
(Procedure A) or at 85–90°C for 7–11 h (Procedure B) until the initial
acid disappeared (1H NMR monitoring). To isolate the product, the reaction
mass was poured into water (250 ml), acidified with 5% hydrochloric
acid and filtered. The precipitate formed was washed with water to pH 6
and dried at 50 °C. The yield of product 4 was close to quantitative.
Procedure C: A solution of MeONa in MeOH (1 equiv.) was added to
a solution of 3,5-bis(chloromethyl)-4-methylbenzoic acid 1 (1 equiv.) in
MeOH. Separately, solution of MeONa in MeOH (2 equiv.) was added to
a solution of arenethiol (2 equiv.) in methanol. The second solution was
added dropwise with stirring to the first solution of Na salt of acid 1 at
room temperature. Then the reaction mixture was stirred for more 2 h
and left overnight. An aliquot was sampled, acidified and analyzed by
GC-MS which indicated that the reaction mixture contained the target
dendron 4 in an amount of 96 to 98% and all the reactants were consumed.
The solvent was removed, the residue was treated with stirring with 5%
H2SO4 and hexane. The resulting slurry was filtered, the solid was washed
with water until neutral and dried at 110–120°C to constant weight.
Practically pure dendrons 4 were thus obtained.
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1
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For characteristics of compounds 4b–f, see Online Supplementary
Materials.
Received: 28th December 2017; Com. 17/5446
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