1202
V. Bertini et al.
LETTER
allowed to react until their complete disappearance (TLC two C(2) and two C=O signals in the 13C NMR spectra.
or GC, 24–120 hours), then the unreacted thiol functions The two signals show noticeably different intensities in
were capped with excess acetone to avoid cross-linking agreement with different stability and formation probabil-
through disulfide bond formation in subsequent handling. ity of the two stereoisomers.
The diketones 1 M in CHCl3 were mixed with the catalyst,
Preliminary reductive cleavages of the 1,3-dithiane rings
then slowly treated with the solution of P1 (10 hours,
in the polymers P2a–g (Scheme 1), carried out with vari-
0 °C) to favour reaction of only one carbonyl group, while
ous reducing agents, indicated reduction with Raney nick-
the addition of acetone was omitted. The reaction, moni-
el as quite unsatisfactory, while the reductions with
tored by the quantitative determinations of the diketone
sodium and liquid ammonia5,6 or with tributyltin hydride
through HPLC analysis using nitrobenzene as internal
(TBTH) and AIBN as radical initiator7–9 proved effica-
standard, always reached its end point when the amount
cious.
of diketone consumed corresponded to that of the 1,3-
The reduction with Na/NH3, which furnishes easily puri-
propanedithiol units incorporated. After dilution with
fiable products, was only applied to the copolymers
dichlorometane and washing with aqueous 20% sodium
P2a,b,d,e which do not possess an unmasked ketone or
acetate, the polymers P2 were precipitated as powders
ester group. The reaction was carried out satisfactorily by
from the following solvent/non-solvent systems: toluene/
adding a solution of P2 in anhydrous THF (0.05 M in 1,3-
dithiane units) to sodium in liquid ammonia (molar ratio
1,3-dithiane units/sodium 1:9, THF/NH3 1:2), with vigor-
ous stirring (30 min). The reaction mixture was treated
methanol for P2a, toluene/petroleum ether 40–60 °C for
P2b,d, THF/methanol for P2e and THF/petroleum ether
40–60 °C for P2c,f,g. Attempts to shorten the reaction
time by replacing boron trifluoride with titanium(IV)
with 1,2-dibromoethane in THF (protic solvents afford
chloride, successfully employed in reluctant thioacetal-
mixtures) to discharge the blue colour and the amide ion
was destroyed with pulverised ammonium chloride. After
evaporation of all the volatiles, the crude products were
isolated by flash chromatography on Merck 230–400
mesh silica gel using as eluent pentane/diethyl ether 100:5
for 2a and 2e, and 100:10 for 2b and 2d. Yields of com-
pounds 2 from 1 are listed in Table 1.
izations,4 resulted in contamination by colloidal titanium
dioxide and occasional cross-linking.
Table 1 lists 13C NMR and IR data of P2 copolymers re-
ferring to the dithiane C(2) and double bond C=O. The
C=O stretching frequencies and 13C chemical shifts con-
firm the presence of ester (P2c) and conjugated ketones
(P2f,g). The reaction of P1 with the unsymmetrical ke-
tones 1b,c,f,g produces two stereoisomeric 1,3-dithiane
units in the corresponding copolymers P2 as revealed by
The reduction with TBTH, which is compatible with var-
ious functional groups,7 even though it results in tin con-
taining by-products,10 was applied to all the copolymers
P2a–g. The process was carried out allowing a solution of
P2 in toluene (0.08 M in 1,3-dithiane units) to react with
TBTH and AIBN in the molar ratio 1:7:0.3 (1:7:0.2 for
P2f,g) at 105 °C under nitrogen for 2.5 hours (70 hours for
P2a and 4 hours for P2g). The mixture was added to twice
its volume of dichloromethane/diethyl ether 1:1, treated
with a 0.2 M iodine solution in diethyl ether until observa-
tion of a persistent faint brown colour to destroy the ex-
cess of reducing agent, then stirred for 24 hours with 50%
w/w aqueous KF to precipitate the insoluble tributyltin
fluoride.10 The products were isolated by flash chroma-
tography on Merck 230–400 mesh silica gel. For the crude
products from P2f,g initial elution with pentane for a total
removal of the toluene and recovery of 5g was necessary.
Eluents were used as follows: pentane/diethyl ether 100:2
for 2a–2e, 3d and 3e; pentane/diethyl ether 10:1 for 2f and
2g, followed by diethyl ether 100% for 4f, 4g. Yields from
1 are reported in Table 1.
Table 1 13C NMR and FTIR Data of 1,3-Dithiane Copolymers
P2a–g and Yields of the Reductive Demolition of P2 with Na/NH3 or
Tributyltin Hydride (TBTH) and AIBN as Initiator
P2
C(2)a
d ppm
C=Ob
d ppm
C=Ob
Productsc Na/NH3 TBTH
Yield% Yield%
n cm–1
P2a 54.4
2a
2b
83
75
11
90
P2b 59.3
58.7
P2c 52.7
170.8
170.6
1722
2c
82
51.8
P2d 62.7
P2e 52.6
2d
3d
70
61
69
23
2e
3e
79
9
P2f
64.0
63.3
192.6d
1677
1687
2f
4f
64
<1
The reductions of the copolymers P2 with TBTH afforded
good yields in the presence of substituents (phenyl, C=O)
capable of conjugative delocalization of a free radical on
the C(2) of the 1,3-dithiane ring, while in the absence of
such a possibility (product 2a), the yield dropped. In the
presence of stabilisation with two phenyl groups (P2d,e),
side products 3d, 3e, corresponding to the coupling of two
radicals, were isolated.
P2g 59.0
199.5
199.3
2g
4g
5g
24
25
<1
58.3
a 1,3-Dithiane carbon C(2).
b Ketone or ester C=O.
c The compounds of the series 2, 3, and 4 are known.
d Two superimposed signals.
Synlett 2003, No. 8, 1201–1203 ISSN 1234-567-89 © Thieme Stuttgart · New York