2,4,6-Trichloro-1,3,5-triazine catalyzed chemoselective transthioacetalization of aldehyde acetals and oxathioacetals

Article abstract of DOI:10.1007/s00706-006-0559-0

A mild and efficient transthioacetalization of aldehyde acetals and oxathioacetals was carried out using 2,4,6-trichloro-1,3,5-triazine as a mild and inexpensive catalyst. Chemoselective transacetalization is impressive as aldehyde O,O- and O,S-acetals ar

Full text of DOI:10.1007/s00706-006-0559-0

Monatshefte f€ur Chemie 138, 67–71 (2007)
DOI 10.1007/s00706-006-0559-0
Printed in The Netherlands
Short Communication
2,4,6-Trichloro-1,3,5-triazine Catalyzed
Chemoselective Transthioacetalization
of Aldehyde Acetals and Oxathioacetals
ꢀ
Babasaheb P. Bandgar , Neeta S. Joshi, and Sampada V. Bettigeri
Organic Chemistry Research Laboratory, School of Chemical Sciences,
Swami Ramanand Teerth Marathwada University, Nanded, Maharashtra, India
Received June 1, 2006; accepted (revised) August 3, 2006
Published online December 22, 2006 # Springer-Verlag 2006
Summary. A mild and efficient transthioacetalization of aldehyde acetals and oxathioacetals was
carried out using 2,4,6-trichloro-1,3,5-triazine as a mild and inexpensive catalyst. Chemoselective
transacetalization is impressive as aldehyde O,O- and O,S-acetals are converted into the corresponding
S,S-acetals in the presence of ketones or their acetals and oxathiocetals in nearly quantitative yields.
Keywords. Protection; Transthioacetalization; 2,4,6-Trichloro-1,3,5-triazine.
Introduction
The protection and subsequent deprotection of a functional group is a common
practice in a multi-step synthetic strategy and switchover of one protective group to
another one is also often required as demanded by their stability under the reaction
conditions in subsequent steps. Thus, a direct method for this transformation bypass-
ing the intermediate step of going back to the parent functionality is becoming
more important in order to improve the overall synthesis efficiency [1]. O,O-Ace-
tals, O,S-acetals, and S,S-acetals are important protecting groups for carbonyl com-
pounds in organic synthesis. However, S,S-acetals are superior protecting groups
than O,O-acetals and O,S-acetals because of their stability in acidic medium [2],
and they are also used in organic synthesis as acyl anion equivalent [3] as well as
intermediates for the conversion of carbonyl compounds to the parent hydrocar-
bons [4]. Therefore, conversion of O,O-acetals and O,S-acetals to S,S-acetals is an
important synthesis transformation. Various methods have been developed and they
ꢀ
Corresponding author. E-mail: bandgar_bp@yahoo.com

68
B. P. Bandgar et al.
are usually carried out under the catalysis of a variety of Lewis acids with different
amounts of loading, such as InCl3 (5 mol%) [5], MgBr2 (1.2 equiv.) [6], WCl6
(4–10 mol%) [7], ZrCl4 (3–5 mol%) [8], trichloroisocyanuric acid (10 mol%) [9],
silica chloride (200–300 mg=mmol) [10], and I2 (10 mol%) [11]. However, many
of these methods require long reaction times, expensive and hazardeous reagents,
and high catalyst loading, and thus lack generality. Accordingly, an improved al-
ternative procedure involving inexpensive and easily available catalyst with low
loading is desirable.
Recently, 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) has emerged as an
inexpensive and easily available reagent in organic synthesis [12]. As a part of our
continuing program [12n–p], we wish to report a new application of cyanuric
chloride as a mild and chemoselective catalyst for transthioacetalization of O,O-
acetals and O,S-acetals at room temperature (Scheme 1).
Scheme 1
Table 1. Transthiacetalization of acetals and oxathioacetals catalyzed by 2,4,6-trichloro-1,3,5-triazine
Entry
Substrate
Thiol=dithiol
Time=min
Yield=%
1
2
C6H5CH(OCH2)2
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)3SH
HS(CH2)3SH
HS(CH2)2SH
HS(CH2)2SH
C6H5SH
20
35
25
60
50
30
50
35
30
25
35
30
40
40
45
40
20
50
50
98 [14]
97 [16]
89 [13]
90 [9]
91 [11]
96
4-Cl–C6H4CH(OCH2)2
4-NO2–C6H4CHO(CH2)3O
4-Me–C6H4CHO(CH2)3O
4-OMe–C6H4CHO(CH2)2S
4-CN–C6H4CHO(CH2)2S
4-Br–C6H4CHO(CH2)2S
C6H5CH¼CH(OCH2)2
Furfuryl-CH(OCH2)2
3
4
5
6
7
97 [11]
98 [11]
90 [16]
94
8
9
10
11
12
13
14
15
16
17
18
19
Thiophene-CH(OEt)2
3,4-(OCH2O)C6H3CH(OEt)2
C5H11CH(OMe)2
97
94
C5H11CHO(CH2)2S
93 [15]
95 [20]
90 [16]
90 [16]
95 [17]
90
C6H13CH(OCH2CH2CH3)2
Cyclohexyl-(OCH2)2
Cyclohexyl-O(CH2)2S
C6H5SH
(C6H5)2-CO(CH2)2S
EtSH
2-CH2OTHP-Cyclopentyl-(OCH2)2
2-CH2OTBDMS-Cyclopentyl-(OCH2)2
HS(CH2)2SH
HS(CH2)2SH
91

Chemoselective Transthioacetalization
69
Results and Discussion
A mixture of O,O-acetal or O,S-acetal and thiol or dithiol in the presence of cy-
anuric chloride in DMF was stirred for a specified time at room temperature to
furnish the corresponding dithioacetals in excellent yields. The results are pre-
sented in Table 1.
The present method is applicable to open chain acetals, cyclic acetals, oxathio-
acetals of aliphatic, aromatic, and heterocylic aldehydes, and ketones furnishing the
corresponding dithioacetals in excellent yields. The presence of an electron-donat-
ing or electron-withdrawing group on the aromatic ring of acetals or oxathioacetals
does not make any difference in this transthioacetalization. Acetals or oxathioace-
tals of conjugated carbonyl compounds (Table 1, entry 8) are also converted to the
corresponding thioacetals without any isomerization. It is also important to note
that acetals or oxathioacetals of furfural and thiophene-2-aldehyde underwent
smooth transthioacetalization under the present reaction conditions which are other-
wise problematic under acidic conditions (Table 1, entries 9 and 10). Tolerance of a
variety of functional groups such as OTBDMS, OTHP, OMe, methylenedioxy, ester,
nitro, cyano, chloro, and bromo under the present reaction condition is also im-
Table 2. Chemoselective transthioacetalization
Entry
1
Substrate
Thiol=dithiol
Product (Yield=%)
Time=min
CH3(CH2)5CH(OCH2)2
þ
HS(CH2)2SH
CH3(CH2)5CH(SCH2)2 (90)
þ
45 [20]
CH3(OCH2)2CH2CH3
Cyclohexyl-(OCH2)2
þ
CH3C(SCH2)2CH2CH3 (0)
Cyclohexyl (SCH2)2 (90)
þ
2
3
4
5
6
7
8
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
40 [I6]
35 [14]
30 [13]
20 [14]
45 [16]
25 [14]
35 [16]
C6H5C(OCH2)2CH3
C6H5CH(OMe)2
þ
C6H5C(SCH2)2CH3 (0)
C6H5CH(SCH2)2 (96)
þ
C6H5C(CH3)(OMe)2
4-NO2C6H4CHO(CH2)2S
þ
C6H5C(CH3)C(SCH2)2 (0)
4-NO2C6H4CH(SCH2)2 (90)
þ
C6H5C(CH3)O(CH2)2S
4-ClC6H4CH(OCH2)3
þ
C6H5C(CH3)(SCH2)2 (0)
4-ClC6H4CH(SCH2)2 (0)
þ
C6H5CH(OMe)2
Cyclohexyl-(OCH2)2
þ
C6H5CH(SCH2)2 (95)
Cyclohexyl-(SCH2)2 (98)
þ
C6H5COCH2CH3
C6H5CH(OMe)2
þ
C6H5C(SCH2)2CH2CH3 (0)
C6H5CH(SCH2)2 (98)
þ
C6H5COCH3
C6H5C(SCH2)2(CH3) (0)
4-ClC6H4CH(SCH2)2 (97)
þ
4-ClC6H4CHO(CH2)2S
þ
C6H5CH2CH2COCH3
C6H5COCH2CH(OCH2)2
CH3COCH2CHO(CH2)2S
CH3COC6H4CH(OCH2)2
C6H5(CH2)2(SCH2)2CH3 (0)
C6H5COCH2CH(SCH2)2 (98)
CH3COCH2CH(SCH2)2 (97)
CH3COC6H4CH(SCH2)2 (97)
9
10
11
HS(CH2)2SH
HS(CH2)2SH
HS(CH2)2SH
35 [19]
25
30 [18]

70
B. P. Bandgar et al.
portant to mention. The most important advantage of the present methodology as
compared to the reported ones is the low catalytic amount (3 mol%) of cyanuric
chloride sufficient to push the reaction efficiently and on large scale.
Another important feature of this methodology is the impressive chemoselective
transthioacetalization of O,O-acetals or O,S-acetals of aldehydes in the presence of
ketones or O,O-acetals and O,S-acetals of ketones. The results are presented in
Table 2.
In conclusion, cyanuric chloride is found to be a mild, efficient, and chemose-
lective catalyst for transthioacetalization of acetals=oxathioacetals of aldehydes
in the presence of ketones or their acetals=oxathioacetals. General applicability,
operational simplicity, excellent yields, short reaction times, and mild reaction con-
ditions are attractive features of this method.
Experimental
IR spectra were recorded on a Bomen MB-104 FTIR spectrometer whereas 1H NMR were scanned on
an AC-300F NMR (300 MHz) instrument using CDCl3 as the solvent and TMS as internal standard.
Elemental analyses were made by Carlo-Erba EA1110 CNNO-S analyzer and agreed favourably with
the calculated values.
General Procedure
A mixture of 1 mmol O,O-acetal or 1 mmol O,S-acetal and 2.1 mmol thiol or 1.1 mmol dithiol in the
presence of a catalytic amount of cyanuric chloride (0.03 mmol) in 5 cm3 DMF was stirred at room
temperature for the specified time (Table 1). After completion of the reaction (TLC), the product was
extracted with 3ꢁ5 cm3 diethyl ether. The organic layer was washed with H2O, dried (Na2SO4), and
evaporated under vacuum to furnish the crude product, which was further purified by column chro-
matography (petroleum ether:ethyl acetate ¼ 9:1).
4-Cyanophenyl-1,3-dithiolane (Table 1, entry 6; C10H9NS2)
Mp 62ꢂC; IR (CHCl3): ꢀꢀ¼ 2225, 1658, 1640, 1490, 1454, 1265, 1230, 1195, 1062, 1018, 970 cmꢃ1
;
1H NMR (CDCl3, 300 MHz): ꢁ ¼ 5.50 (s, 1H), 2.80 (m, 4H), 7.10 (d, J ¼ 7.2 Hz, 2H), 7.28 (d,
J ¼ 7.2 Hz, 2H); MS: m=z ¼ 207 (Mþ).
2-Thiophene-1,3-dithiolane (Table 1, entry 10; C7H8S3)
1
Bp 115ꢂC; IR (CHCl3): ꢀꢀ¼ 1657, 1648, 1490, 1465, 1275, 1245, 1190, 1060, 1015 cmꢃ1; H NMR
(CDCl3, 300 MHz): ꢁ ¼ 3.30 (m, 4H), 5.60 (s, 1H) 6.10 (d, 2H), 7.15 (t, 1H); MS: m=z ¼ 188.141 (Mþ).
1-Hexanal-1,3-dithiane (Table 1, entry 12; C9H18S2)
1
Bp 165ꢂC; IR (CHCl3): ꢀꢀ¼ 2301, 1659, 1649, 1492, 1469, 1278, 1246, 1195, 1025 cmꢃ1; H NMR
(CDCl3, 300 MHz): ꢁ ¼ 1.86 (m, 1H), 2.10 (m, 1H), 2.98 (m, 4H), 4.40 (t, 3H) 0.80 (m, 9H); MS:
m=z ¼ 190.243 (Mþ).
2-Acetophenyl-1,3-dithiane (Table 2, entry 9; C11H12S2O)
1
Mp 70ꢂC; IR (CHCl3): ꢀꢀ¼ 1670cmꢃ1; H NMR (CDCl3, 300 MHz): ꢁ ¼ 3.76 (s, 2H), 4.20 (m, 1H),
3.20 (m, 4H), 7.15 (m, 5H); MS: m=z ¼ 190.243 (Mþ).
2-Acetylmethyl-1,3-dithiolane (Table 2, entry 10; C6H10S2O)
1
Bp 70ꢂC; IR (CHCl3): ꢀꢀ¼ 1718cmꢃ1; H NMR (CDCl3, 300 MHz): ꢁ ¼ 1.98 (s, 3H), 3.11 (m, 4H),
3.70 (s, 2H), 4.35 (m, 1H); MS: m=z ¼ 162.146 (Mþ).

Chemoselective Transthioacetalization
71
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