Molybdenum pentachloride (MoCl5) or molybdenum dichloride dioxide (MoO2Cl2): advanced catalysts for thioacetalization of heterocyclic, aromatic and aliphatic compounds

Article abstract of DOI:10.1016/j.tetlet.2008.03.048

A new, convenient and mild method for thioacetalization of heterocyclic, aromatic and aliphatic compounds catalyzed by MoCl₅ or MoO₂Cl₂ is described. This novel method is important for the synthesis of the difficult to prepare heterocyclic thioacetals such as the pterin thioacetals and it offers significant advantages such as high conversion, short reaction times and simplicity in operation.

Full text of DOI:10.1016/j.tetlet.2008.03.048

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3092–3096
Molybdenum pentachloride (MoCl ) or molybdenum dichloride
5
dioxide (MoO Cl ): advanced catalysts for thioacetalization
2
2
of heterocyclic, aromatic and aliphatic compounds
*
Shyamaprosad Goswami , Annada C. Maity
Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711 103, India
Received 24 November 2007; revised 7 March 2008; accepted 11 March 2008
Available online 14 March 2008
Abstract
A new, convenient and mild method for thioacetalization of heterocyclic, aromatic and aliphatic compounds catalyzed by MoCl
5
or
MoO Cl is described. This novel method is important for the synthesis of the difficult to prepare heterocyclic thioacetals such as the
2
2
pterin thioacetals and it offers significant advantages such as high conversion, short reaction times and simplicity in operation.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Heterocyclic aldehydes; 1,3-Propanedithiol; Thioacetalization; Heterocyclic thioacetals; Molybdenum pentachloride; Molybdenum
dichloride dioxide
1
. Introduction
the past 20 years owing to their interesting biochemistry
and the complexation of transition metals, for example,
molybdenum (present in nature as molybdenum cofactor ),
5
Thioketal or thioacetal protection of carbonyl groups is
of paramount importance in synthetic organic chemistry
tungsten and cobalt.
O
Mo
O
N
S
S
Co
S
S
S
N
N
S
N
N
N
N
O
HN
H
O
N
O
O
H
1
2
3
O
6
–10
and hence, the development of novel thionation reactions
remains of great interest. Heterocyclic molecules such as
pterin and quinoxaline containing alkene-1,2-dithio-
Although many different methods
have been
reported in the literature for the preparation of thioacetals,
the conversion of heterocyclic aldehydes to the correspond-
ing thioacetals has so far received comparatively little
1
,2
3,4
lates (dithiolenes 1, 2 and 3) have received attention over
1
1
12
13
success. Catalysts such as HCl, PTSA, BF –Et O,
3
2
1
4
15
ZnCl2 and AlCl3 have been reported for the prepara-
tion of thioketals and thioacetals, but these reagents fail
to produce heterocyclic thioacetals. Despite the wide range
of reagents available for the conversion of aldehydes to
*
Corresponding author. Tel.: +91 33 2668 4561 3x498; fax: +91 33 2668
2916.
E-mail address: spgoswamical@yahoo.com (S. Goswami).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.048

S. Goswami, A. C. Maity / Tetrahedron Letters 49 (2008) 3092–3096
3093
thioacetals, no attempt has been made to use molybdenum
2. Typical experiment for the synthesis of
quinoxalinthioacetal 5
pentachloride or molybdenum dichloride dioxide as a
catalyst. Recently, molybdenum dichloride dioxide was
found to be very reactive in the catalytic thioglycosyl-
ation of O-acetylated glycosides with the functionalized
To a stirred solution of quinoxaline aldehyde (500 mg,
3.16 mmol) and molybdenum pentachloride (10 mol %) or
molybdenum dichloride dioxide (5 mol %) in acetonitrile
(15 ml) cooled to 0–5 °C under a nitrogen atmosphere
was added 1,3-propanedithiol (340 mg, 3.15 mmol) drop-
wise over 5 min with stirring and the mixture was then stir-
red at room temperature for 1.5 h. Water (50 ml) was
added, and the organic product was extracted with methyl-
ene chloride (2 Â 50 ml). The organic layer was dried
(Na SO ) and concentrated. Column chromatography of
1
6
thiols in methylene chloride. Also, molybdenyl acetyl-
1
7
acetonate was found to be a good catalyst for the
formation of oxathiolane, dithiolane and dithiane
derivatives.
Fernandes et al. have shown that the high oxidation
state in the molybdenum complex [MoO Cl ] makes it a
2
2
highly effective catalyst for organic reductions, such as
1
8
the hydrosilylation of aldehydes and ketones, and the
2
4
1
9
reduction of imines, esters, sulfoxides and pyridine N-
the crude product on silica gel (100–200 mesh) and eluting
with 0.5% methanol in methylene chloride afforded 5 as a
brown crystalline solid (595 mg, 76%).
2
0
oxides, and for the epoxidation of double bonds and
2
1
the oxidation of alcohols to carbonyl compounds.
Consequently, we anticipated that MoCl or MoO Cl
2
5
2
might catalyze the thioacetal formation from aldehydes
as a result of the high oxidation states (+V or +VI) of
molybdenum in these catalysts. We thus set out to estab-
lish a method (Scheme 1) for the transformation of hetero-
cyclic, aromatic and aliphatic aldehydes to the
corresponding thioacetals using MoCl or MoO Cl as a
2
.1. Compound 4
1
Mp 138–142 °C. H NMR (CDCl , 300 MHz): d (ppm):
3.34 (br s, 1H, NH), 9.03 (s, 1H), 8.82 (s, 1H), 5.34 (s, 1H),
.13 (t, 2H, J = 4.61 Hz), 3.12, 3.02 (dd, 2H, J = 2.68,
.96 Hz), 2.10–2.00 (m, 2H), 1.36 (s, 9H). C NMR
3
1
3
2
13
5
2
2
catalyst. We reacted several aldehydes with 1,3-propanedi-
thiol in the presence of molybdenum pentachloride
(CDCl3, 100 MHz): 180.68, 159.36, 158.07, 154.12,
1
49.50, 141.64, 131.53, 54.45, 40.46, 27.0. MS (FAB): m/z
(
10 mol %) or molybdenum dichloride dioxide (5 mol %)
+
(%): 367 (M , 50%). Anal. Calcd for C H N O S : C,
15 21 5 2 2
in dry acetonitrile as solvent at room temperature under
a nitrogen atmosphere and obtained the corresponding
thioacetal in excellent yield within a few minutes. This
method is extremely useful for the synthesis of heterocyclic
thioacetals (especially pterinthioacetal 4) from the corres-
ponding aldehydes. This method was also effective with
acetals, for example, pterin or quinoxaline dimethylacetals
4
1
9.02; H, 5.75; S, 17.45. Found: C, 48.79; H, 5.64; N,
8.75; S, 17.46.
2
.2. Compound 5
Mp 118–120 °C. FT-IR (KBr, m): 2924, 1660, 1493, 1364,
À1
1
1
3
8
275, 1202, 1126, 984, 912, 853 cm . H NMR (CDCl ,
3
(
entries 8 and 9, Table 1). In these cases MoCl was found
5
00 MHz): d (ppm): 9.42 (s, 1H), 8.25–8.21 (m, 1H), 8.18–
.14 (m, 1H), 7.92–7.84 (m, 2H), 3.24 (t, 2H,
to be more effective than MoO Cl . In contrast, MoO Cl
2
2
2
2
was a more effective catalyst with free aldehydes. Table 1
shows that polynuclear aromatic aldehydes undergo rapid
transformation to the corresponding thioacetals in excel-
lent yields compared to other aldehyde substrates. The
reaction conditions and yields are summarized in Table
J = 9.64 Hz), 3.20 (d, 1H, J = 6.44 Hz), 2.86–2.77 (m,
1
3
2
1
1
1
H), 2.20–2.08 (m, 2H). C NMR (CDCl , 100 MHz):
3
92.62, 145.24, 144.58, 140.96, 132.40, 131.06, 130.35,
+
29.47, 37.50, 36.92, 29.56. MS (FIA): m/z (%): 247 (M
00%). Anal. Calcd for C H N S : C, 58.02; H, 4.87; N,
1
2
12
2 2
1
. All the prepared compounds were characterized by
1
13
11.28; S, 25.82. Found: C, 58.09; H, 4.82; N, 11.16; S, 25.76.
spectroscopic methods ( H NMR, C NMR, IR and
MS).
2
.3. Compound 6
In summary, we have developed a novel method for the
thioacetalization of heterocyclic, aromatic and aliphatic
aldehydes to the corresponding dithianes with 1,3-propane-
dithiol and MoO Cl or MoCl as catalysts in moderate to
Mp 127–128 °C. FT-IR (KBr, m): 2923, 1660, 1462,
À1
1
1232, 1112, 918 cm . H NMR (CDCl , 400 MHz): d
3
2
2
5
(ppm): 8.30 (d, 1H, J = 8.41 Hz), 8.25 (d, 1H,
excellent yields.
J = 6.40 Hz), 8.05 (d, 1H, J = 7.60 Hz), 7.88 (d, 1H,
J = 7.61 Hz), 7.79 (d, 1H, J = 7.20 Hz), 7.65 (d, 1H,
J = 7.20 Hz), 3.25, 3.17 (td, 2H, J = 4.21, 4.01 Hz), 2.87–
1
3
2
.78 (m, 2H), 2.18–2.13 (m, 2H).
100 MHz): 193.86, 151.59, 147.31, 137.40, 130.19, 129.50,
28.74, 127.72, 117.99, 117.10, 37.68, 31.15, 29.38. MS
C NMR (CDCl3,
1
0 mol% MoCl or 5 mol% MoO Cl
O
5
2
2
1
,3-propanedithiol
S
R
S
H
R
H
1
CH CN, rt
3
+
+
R = heterocyclic, aromatic,
aliphatic
(FIA): m/z (%): 248 (MH , 20); 265 (M À1+H O, 62).
2
Anal. Calcd for C H NOS : C, 63.12; H, 5.30; N, 5.66,
1
3
13
2
S, 25.92. Found: C, 63.04; H, 5.41; N, 5.82; S, 26.08.
Scheme 1.

3094
S. Goswami, A. C. Maity / Tetrahedron Letters 49 (2008) 3092–3096
Table 1
Thioacetalization of heterocyclic, aromatic and aliphatic aldehydes using MoCl
5
or MoO
2
Cl
2
as a catalyst
a
b
c
Entry
Substrate
Time MoO
2
Cl
2
/MoCl
5
Products
Yield (%) MoO
2
Cl
2
/MoCl
5
O
N
O
S
N
N
CHO
1
2/3.5 h
N
68/61
O
HN
O
HN
S
N
N
N
S
N
H
H
4
N
CHO
N
2
3
1.5/2 h
1.5/3 h
S
76/64
62/60
N
N
5
6
S
N
N
CHO
S
4
2/2.5 h
7
64/61
N
N
S
S
N
N
OHC
CHO
S
S
S
S
CHO
5
6
2/3.5 h
1/1.5 h
52/45
55/52
N
N
8
9
S
N
N
CHO
S
S
7
8
30 min/1.5 h
5/3.5 h
72/60
63/65
O
O
CHO
HN
10
S
O
OMe
OMe
N
N
O
4
5
N
H
N
OMe
N
N
OMe
9
4/3.5 h
70/76
92/82
S
1
0
1
CHO
5/15 min
S
1
1
CHO
S
S
1
8/25 min
90/84
12

S. Goswami, A. C. Maity / Tetrahedron Letters 49 (2008) 3092–3096
3095
Table 1 (continued)
a
b
c
Entry
Substrate
Time MoO
2
Cl
2
/MoCl
5
Products
Yield (%) MoO
2
Cl
2
/MoCl
5
F
F
S
CHO
12
30/45 min
74/62
S
1
3
S
O
H
1
1
3
4
2.5/1 h
62/55
56/52
S
O
O
H
1
4
S
O
CHO
HO
30/45 min
S
O
15
HO
a
b
c
Reactions were monitored by TLC analysis.
All the known compounds (8, 10 and 14 ) and unknown products were characterized by H NMR, C NMR, IR and mass spectroscopy.
Yields refer to those of isolated pure products after column chromatography on a silica gel.
10
10
22
1
13
2
.4. Compound 7
300 MHz): d (ppm): 9.48 (d, 1H, J = 8.54 Hz), 8.42 (s,
H), 8.32 (d, 1H, J = 8.61 Hz), 7.99 (t, 1H, J = 9.26 Hz),
1
Mp 212–214 °C. FT-IR (KBr, m): 2924, 2923, 1675,
7.57 (d, 2H, J = 6.24 Hz), 7.46 (t, 2H, J = 7.40 Hz), 6.70
(s, 1H), 3.33 (t, 2H, J = 12.0 Hz), 3.07, 3.01 (tt, 2H,
J = 3.39, 3.25 Hz), 2.35–2.14 (m, 2H). C NMR (CDCl3,
À1
1
1
3
2
3
(
(
412, 1230, 1156, 920, 802 cm
.
H NMR (CDCl3,
1
3
00 MHz): d (ppm): 8.25 (d, 2H, J = 8.31 Hz), 7.88 (d,
H, J = 8.25 Hz), 7.81 (d, 2H, J = 6.60 Hz), 5.76 (s, 2H),
100 MHz): 131.86, 131.40, 130.70, 129.61, 129.47, 128.82,
.15 (t, 4H, J = 5.56 Hz), 2.26–2.23 (m, 4H), 2.11–2.04
128.67, 128.48, 128.13, 127.66, 126.68, 125.21, 124.74,
+
+
m, 4H). MS (FIA): m/z (%): 441 (M +2+Na, 22); 311
124.60, 122.74. MS (FIA): m/z (%): 313 (M À1+H O,
2
100). Anal. Calcd for C H N S : C, 57.65; H, 4.84; N,
34); 191 (100).
2
0
20
2 4
6
.72; S, 30.78. Found: C, 57.59; H, 4.77; N, 6.52; S, 30.65.
2.8. Compound 13
2
.5. Compound 9
Mp 65–66 °C. FT-IR (KBr, m): 2933, 1487, 1456, 1275,
À1
1
Semisolid. FT-IR (KBr, m): 2923, 1662, 1591, 1454, 1282,
1232, 1182, 1089, 784 cm
.
H
NMR (CDCl ,
3
À1
1
1
(
213, 947, 840 cm
.
H NMR (CDCl , 400 MHz): d
400 MHz): d (ppm): 7.61 (t, 1H, J = 7.44 Hz), 7.23 (d,
1H, J = 6.89 Hz), 7.12 (t, 1H, J = 7.48 Hz), 7.02 (t, 1H,
J = 9.10 Hz), 3.09–3.03 (m, 2H), 2.88, 2.84 (tt, 2H,
3
ppm): 7.75 (d, 2H, J = 7.56 Hz), 7.70 (t, 2H,
J = 7.58 Hz), 7.34 (d, 1H, J = 7.40 Hz), 3.15–3.01 (m,
2
2
1
H), 2.80 (t, 2H, J = 7.22 Hz), 2.63 (s, 3H), 2.11–2.02 (m,
J = 3.42, 3.40 Hz), 2.13–2.09 (m, 1H), 1.94–1.83 (m, 1 H).
1
3
13
H).
C NMR (CDCl , 100 MHz): 146.98, 132.95,
C NMR (CDCl , 100 MHz): 159.89, 157.43, 129.74,
3
3
31.33, 129.82, 127.19, 31.87, 29.65, 29.65, 29.31. MS
126.14, 124.47, 115.17, 42.85, 31.95, 24.84. MS (FIA):
+
+
+
(
FIA): m/z (%): 212 (MH , 17); 229 (M +H O, 10).
m/z (%): 231 (M +H O, 35); 109 (58).
2
2
2
.6. Compound 11
2.9. Compound 15
Mp 195–197 °C. FT-IR (KBr, m): 2929, 1635, 1410,
Semi solid. FT-IR (KBr, m): 3384, 2916, 1675, 1422,
À1
1
À1
1
1
219, 1044, 834, 772 cm . H NMR (CDCl , 300 MHz):
1075, 1038, 882, 772 cm . H NMR (CDCl , 300 MHz):
3
3
d (ppm): 8.54 (d, 2H, J = 9.30 Hz), 8.31 (d, 2H,
J = 8.04 Hz), 8.21–8.15 (m, 3H), 8.05–8.00 (m, 2H), 6.22
d (ppm): 4.95 (d, 1H, J = 1.80 Hz), 3.99–3.74 (m, 2H),
3.74 (d, 1H, J = 4.23 Hz), 3.07 (br s, 1H), 2.98–2.86 (m,
(
s, 1H), 3.29 (t, 2H, J = 13.6 Hz), 3.06, 3.02 (tt, 2H,
2H), 2.73–2.65 (m, 2H), 2.35 (br s, 1H), 2.09–1.97 (m,
1
3
13
J = 3.52, 3.51 Hz), 2.31–2.06 (m, 2H). C NMR (CDCl3,
2H). C NMR (CDCl , 100 MHz): 72.60, 63.63, 47.76,
3
+
1
1
1
00 MHz): 132.21, 131.31, 131.21, 130.63, 127.86, 127.27,
25.99, 125.91, 125.44, 125.24, 125.16, 124.91, 124.75,
29.66, 28.41, 25.50. MS (ESI): m/z (%): 281 (MH , 40).
22.65, 48.92, 32.82, 25.37. MS (FIA): m/z (%): 337
Acknowledgements
+
(
M À1+H O, 21); 215 (100).
2
We thank DST [SR/S1/OC-13/2005], Govt. of India for
financial support. A.C.M. thanks UGC, Govt. of India for
a senior research fellowship. We appreciate mass spectral
help from Professor Thomas Schrader of Duisburg-Essen
University, Essen, Germany.
2
.7. Compound 12
Mp 178–180 °C. FT-IR (KBr, m): 2925, 1668, 1445,
À1
1
1
420, 1271, 1156, 889, 719 cm
.
H NMR (CDCl3,

3096
S. Goswami, A. C. Maity / Tetrahedron Letters 49 (2008) 3092–3096
References and notes
11. Pham-Huu, D. P.; Gizaw, Y.; BeMiller, J. N.; Petrus, L. Tetrahedron
003, 59, 9413.
2. Djerassi, C.; Gorman, M. J. Am. Chem. Soc. 1953, 75, 3704.
3. Nakata, T.; Nagao, S.; Mori, S.; Oishi, T. Tetrahedron Lett. 1985, 26,
461.
2
1
1
1
. Pilato, R. S.; Eriksen, K. E.; Greaney, M. A.; Stiefel, E. I.; Goswami,
S. P.; Kilpatrick, L.; Spiro, T. G.; Taylor, E. C.; Rheingold, A. R. J.
Am. Chem. Soc. 1991, 113, 9372.
6
1
4. Evans, D. V.; Truesdale, L. K.; Grimm, K. G.; Nesbitt, S. L. J. Am.
Chem. Soc. 1977, 99, 5009.
2
3
. Taylor, E. C.; Dotzer, R. J. Org. Chem. 1991, 56, 1816.
. Bradshaw, B.; Dinsmore, A.; Garner, C. D.; Joule, J. A. Chem.
Commun. 1998, 417.
1
1
1
5. Ong, B. S. Tetrahedron Lett. 1980, 21, 4225.
6. Weng, S. S.; Lin, Y. D.; Chen, C. T. Org. Lett. 2006, 8, 5633.
7. Rana, K. K.; Guin, C.; Jana, S.; Roy, S. C. Tetrahedron Lett. 2003,
4
5
6
7
. Dinsmore, A.; Garner, C. D.; Joule, J. A. Tetrahedron 1998, 54, 3291.
. Goswami, S. P. Heterocycles 1993, 35, 1551.
. De, S. K. Tetrahedron Lett. 2004, 45, 1035.
. Khan, A. T.; Mondal, E.; Sahu, P. R.; Islam, S. Tetrahedron Lett.
4
4, 8597.
1
8. Fernandes, A. C.; Fernandes, R.; Romao, C. C.; Royo, B. Chem.
Commun. 2005, 213.
2003, 44, 919.
1
2
2
2
9. Fernandes, A. C.; Romao, C. C. Tetrahedron Lett. 2005, 46, 8881.
0. Fernandes, A. C.; Romao, C. C. Tetrahedron 2006, 62, 9650.
1. Maignien, S.; Ait-Mohand, S.; Muzart, J. Synlett 1996, 439.
2. Juaristi, E.; Cuevas, G.; Vela, A. J. Am. Chem. Soc. 1994, 116,
8
9
. Kamal, A.; Chouhan, G. Tetrahedron Lett. 2002, 43, 1347.
. Samajdar, S.; Basu, M. K.; Becker, F. F.; Banik, B. K. Tetrahedron
Lett. 2001, 42, 4425.
10. Kamitori, Y.; Hojo, M.; Masuda, R.; Kimura, T.; Yoshida, T. J. Org.
5
796.
Chem. 1986, 51, 1427.