Entirely solvent-free procedure for the synthesis of distillable 1,3-dithianes using lithium tetrafluoroborate as a reusable catalyst

Article abstract of DOI:10.1055/s-2004-829084

Treatment of various types of aldehydes and ketones with 1,3-propanedithiol in the presence of a catalytic amount of lithium tetrafluoroborate at 25°C under solvent-free conditions followed by direct purification by distillation of the resulting mixture a

Full text of DOI:10.1055/s-2004-829084

1640
LETTER
Entirely Solvent-Free Procedure for the Synthesis of Distillable 1,3-Dithianes
Using Lithium Tetrafluoroborate as a Reusable Catalyst
S
olvent-free Proce
i
dure fo
y
r
the Synthes
o
is of
D
istilla
s
ble 1,3-D
h
ithianes i Kazahaya, Shinya Tsuji, Tsuneo Sato*
Department of Chemistry and Bioscience, Kurashiki University of Science and the Arts, Kurashiki 712-8505, Japan
Fax +81(86)4401062; E-mail: sato@chem.kusa.ac.jp
Received 26 March 2004
(Table 1, entry 1).11 The catalyst was quantitatively recov-
ered in the distilling flask. Even with 2 mol% of LiBF4,
this thioacetalization proceeded quantitatively, but took
longer to complete (entry 2). Substituted benzaldehydes
Abstract: Treatment of various types of aldehydes and ketones
with 1,3-propanedithiol in the presence of a catalytic amount of lith-
ium tetrafluoroborate at 25 °C under solvent-free conditions fol-
lowed by direct purification by distillation of the resulting mixture
affords the corresponding 1,3-dithianes in good to excellent yields. possessing electron-donating and electron-withdrawing
groups and acid-sensitive substrates like furfural12 using
Chemoselective protection of keto aldehydes is also successfully
achieved over the catalyst. The catalyst can be recovered and re-
the dithiol under such conditions provided the corre-
used.
Key words: chemoselectivity, 1,3-dithiane, Lewis acids, lithium
tetrafluoroborate, protecting groups
Table 1 LiBF4-Catalyzed Formation of 1,3-Dithianes from Carbo-
nyl Compounds under Solvent-Free Conditionsa
Entry
R1R2C=O
Time (h)
Yield (%)b
100
1,3-Dithianes have long been used as carbonyl protecting
groups1 and as masked acyl anions2 or methylene
functions3 in organic synthesis.4 They are generally pre-
pared by protic5 or Lewis acids,6 or sometimes solid acids7
catalyzed condensation of carbonyl compounds with 1,3-
propanedithiol in various organic solvents. The solvent-
free organic reactions are important not only for their sim-
plicity, but also as green and sustainable procedures.8
Moreover, in order to maximize these benefits, it is neces-
sary to carry out product isolation, separation, and purifi-
cation without using any organic solvent.9 Lithium
tetrafluoroborate (LiBF4) has recently attracted attention
as a mild and efficient Lewis acid catalyst due to its almost
neutral property, ease of handling, and the thermal stabil-
ity unlike lithium perchlorate.10 In this paper we wish to
disclose an entirely solvent-free procedure for the synthe-
sis of distillable 1,3-dithianes from their corresponding
carbonyl compounds and 1,3-propanedithiol catalyzed by
LiBF4 (Scheme 1).
1
C6H5CHO
1
5
1
3
3
2c
3
C6H5CHO
99
p-MeC6H4CHO
p-ClC6H4CHO
100
4
100
5
100
CHO
6d
5
100
O
CHO
7
8
6
5
100e
85f
75
CHO
CHO
Ph
Pr
9
n-C7H15CHO
i-C3H7CHO
t-C4H9CHO
(CH2)4C=O
(CH2)5C=O
Bu(Me)C=O
5
10
11
12
13
14
15
15
21
21
5
98
84
LiBF4 (10 mol%),
S R1
S R2
SH
SH
R1
R2
87
neat, 25 °C
+
O
86
then directly purified
by distillation
1.3 equiv
21
30
74
Scheme 1
79
O
When a mixture of 1,3-propanedithiol, benzaldehyde (1.3
equiv), and a catalytic amount of LiBF4 (10 mol%) was
stirred at 25 °C for 1 h, 2-phenyl-1,3-dithiane was exo-
thermically produced and isolated in 100% yield after di-
rect distillation of the resulting almost odorless mixture
16
Ph(Me)C=O
24
74
a Reaction conditions: R1R2C=O (6.5 mmol), 1,3-propanedithiol (5
mmol), LiBF4 (0.5 mmol), 25 °C, unless otherwise noted.
b Isolated yields of pure products after distillation.
c LiBF4 (0.1 mmol) was used.
SYNLETT 2004, No. 9, pp 1640–1642
2
2.
0
7.
2
0
0
4
d At 0 °C.
Advanced online publication: 29.06.2004
DOI: 10.1055/s-2004-829084; Art ID: U08704ST
© Georg Thieme Verlag Stuttgart · New York
e Z/E = 0/100.
f Z/E = 11/89.

LETTER
Solvent-Free Procedure for the Synthesis of Distillable 1,3-Dithianes
1641
sponding 1,3-dithianes in excellent yields (entries 3–6). A typical procedure is as follows (Table 1, entry 1): To a
Futhermore, a,b-unsaturated and aliphatic aldehydes were mixture of benzaldehyde (690 mg, 6.5 mmol) and LiBF4
cleanly and efficiently dithioacetalized at ambient tem- (46.9 mg, 0.5 mmol) 1,3-propanedithiol (541 mg, 5.0
peratures in good yields (entries 7–11). Interestingly, ster- mmol) was added dropwise with stirring over ten minutes
ically-hindered aldehydes such as mesitaldehyde and at 25 °C under N2. After the reaction mixture was stirred
pivalaldehyde were also applicable (entries 5 and 11). at the same temperature for one hour (completion of the
Similarly, lithium tetrafluoroborate catalyzed the protec- reaction was checked by GC), it was directly distillated by
tion of different types of cyclic (entries 12 and 13), ali- using a Kügelrohr apparatus at 0.5 mmHg with an oven
phatic (entry 14), a,b-unsaturated (entry 15), and aromatic temperature of 170–200 °C to give 2-phenyl-1,3-dithiane
ketones (entry 16) to afford the corresponding 1,3- (982 mg, 100%) as a white solid. LiBF4 remained in the
dithianes in good yields,13 although the time required for distilling flask as a white solid (47.9 mg, 102%) and was
the completion of the reaction was found to be longer used directly for the next reaction without any purifica-
compared to aldehydes. It is noteworthy that the double tion.
bond at the 2,3-position of isophorone remained unaffect-
In conclusion, we have demonstrated the use of lithium
tetrafluoroborate for the synthesis of 1,3-dithianes of a va-
ed under the conditions (entry 15).14
Because the conversion of aldehydes is faster than ke- riety of carbonyl compounds under solvent-free condi-
tones, as shown in Table 1, the present method can be tions where the catalyst could be readily recovered and
used for the chemoselective protection of aldehydes in the reused.16,17 Moreover, the relatively slow reaction rate of
presence of ketone function.15 For example, when 4- ketones allows for the chemoselective protection of alde-
acetylbenzaldehyde was allowed to react with the dithiol hydes in the presence of ketones. Works on other reac-
under the usual conditions, only the aldehyde group react- tions catalyzed by LiBF4 and related compounds are
ed and the corresponding 1,3-dithiane was selectively ob- currently underway in our laboratory.
tained in 85% yield. GC analysis of the crude product
showed the absence of any other by-products. Further-
more, the thioacetalization of 3-isopropenyl-6-oxoheptan-
References
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Groups in Organic Chemistry; McOmie, J. F. W., Ed.;
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Protecting Groups; Thieme: New York, 1994, 171–178.
(c) Greene, T. W.; Wuts, P. G. M. In Protective Groups in
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(2) For reviews, see: (a) Krief, A. In Comprehensive Organic
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(3) For a review, see: Pettit, G. R.; van Tamelen, E. E. Org.
React. 1962, 12, 356.
al also exhibited splendid selectivity towards the formyl
group (Scheme 2).
CHO
S
LiBF4 (10 mol%)
25 °C, neat, 3 h
S
O
+
HS SH
O
85%
91%
CHO
S
(4) For other synthetic applications, see: Luh, T.-Y. J.
Organomet. Chem. 2002, 653, 209; and references cited
therein.
(5) For a recent leading reference, see: Kobayashi, S.; Iimura,
S.; Manabe, K. Chem. Lett. 2002, 10.
S
LiBF4 (10 mol%)
25 °C, neat, 5 h
O
+
HS SH
O
(6) For recent leading references, see: (a) Rana, K. K.; Guin, C.;
Jana, S.; Roy, S. C. Tetrahedron Lett. 2003, 44, 8597; and
references cited therein. (b) Kamel, A.; Chouhan, G.
Tetrahedron Lett. 2003, 44, 3337. (c) Khan, A. T.; Mondal,
E.; Sahu, P. R.; Islam, S. Tetrahedron Lett. 2003, 44, 919.
(d) For dithioacetalization using LiOTf/neat: Firouzabadi,
H.; Eslami, S.; Karimi, B. Bull. Chem. Soc. Jpn. 2001, 74,
2401. (e) Firouzabadi, H.; Karimi, B.; Eslami, S.
Tetrahedron Lett. 1999, 40, 4055. (f)Fordithioacetalization
using LiBF4/CH3CN: Yadav, J. S.; Reddy, B. V. S.; Pandey,
S. K. Synlett 2001, 238. (g) For dithioacetalization using
LiClO4/diethyl ether: Saraswathy, V. G.; Sankararaman, S.
J. Org. Chem. 1994, 59, 4665. (h) Tietze, L. F.; Weigand,
B.; Wulff, C. Synthesis 2000, 69. (i) For dithioacetalization
using LiBr/neat: Firouzabadi, H.; Iranpoor, N.; Karimi, B.
Synthesis 1999, 58.
Scheme 2
Another advantage of this LiBF4-catalyzed 1,3-dithiane
synthesis is that the catalyst can be easily recovered quan-
titatively and reused. The activity of the recovered cata-
lyst did not decrease even after the fourth use (Table 2).
Table 2 Recovery and Reuse of LiBF4
SH
S
S
LiBF4 (10 mol%)
25 °C, neat, 1 h
+
PhCHO
Ph
SH
6.5 mmol
5 mmol
Run
1
2
3
4
(7) For recent leading references, see: (a) Hon, Y.-S.; Lee,
C.-F.; Chen, R.-J.; Huang, Y.-F. Synth. Commun. 2003, 33,
2829; and references cited therein. (b) Firouzabadi, H.;
Iranpoor, N.; Amani, K. Synthesis 2002, 59.
Yield (%)
100
98
97
98
Recovery of catalyst (%) quant
quant
quant
quant
Synlett 2004, No. 9, 1640–1642 © Thieme Stuttgart · New York

1642
K. Kazahaya et al.
LETTER
(15) Only a few methods are known in the literature for the
(8) For a recent review, see: Tanaka, K. Solvent-free Organic
Synthesis; Wiley-VCH: Weinheim, 2003.
chemoselective protection of aldehydes in the presence of
ketones: ref. 6c and references cited therein.
(9) Anastas, P. T.; Warner, J. C. In Green Chemistry: Theory
and Practice; Oxford: London, 1998, 115–119.
(10) For recent leading references, see: (a) Yadav, J. S.; Reddy,
B. V. S.; Vishmumurthy, P. Tetrahedron Lett. 2003, 44,
5691; and references cited therein. (b) Kazemi, F.; Kiasat,
A. R.; Ebrahim, S. Synth. Commun. 2003, 33, 999.
(c) Kazemi, F.; Kiasat, A. R.; Ebrahim, S. Synth. Commun.
2003, 33, 595.
(16) As far as we know, the present system is the first example for
the synthesis of 1,3-dithianes under entirely solvent-free
conditions, although our procedure is applicable for only
distillable such compounds. Though 1,3-dithiane synthesis
under solvent-free conditions has been reported in some
cases, unfortunately, all of these used organic solvents in the
work-up processes: (a) ref. 6d,e. (b) ref. 6i. (c) ref. 7b.
(d) Laskar, D. D.; Prajapati, D.; Sandhu, J. S. J. Chem. Res.,
Synop. 2001, 313. (e) Firouzabadi, H.; Iranpoor, N.;
Kohmareh, G. Synth. Commun. 2003, 33, 167.
(11) LiBF4 was the best catalyst among the lithium salts tested
under identical conditions: LiOTf (41%), LiCl (4%), LiClO4
(36%), LiBr (16%), LiI (39%).
(12) For a review, see: Gandini, A. Adv. Polym. Sci. 1977, 25, 47.
(13) It is important to note that ketones were efficiently
thioacetalized in our method, whereas LiBF4/MeCN has
been an ineffective reaction system, and the substrates
remained intact after prolonged reaction times.6f
(14) For example, see: Corey, E. J.; Shimoji, K. Tetrahedron Lett.
1983, 24, 169.
(17) 1,2-Ethanedithiol worked equally well under the same
reaction conditions. For example, treatment of benzaldehyde
(6.5 mmol) with 1,2-ethanedithiol (5 mmol) in the presence
of LiBF4 (0.5 mmol) at 25 °C for 1 h afforded 2-phenyl-1,3-
dithiolane in 99% yield.
Synlett 2004, No. 9, 1640–1642 © Thieme Stuttgart · New York