Generation of ortho-quinone methides upon thermal extrusion of sulfur dioxide from benzosultones

Article abstract of DOI:10.1016/j.tet.2005.06.087

3H-1,2-Benzoxathiole 2,2-dioxides (benzosultones) undergo thermal extrusion of sulfur dioxide to form ortho-quinone methides that enter Diels-Alder reaction with maleimides to form chroman 2,3-dicarboxylic acid derivatives.

Full text of DOI:10.1016/j.tet.2005.06.087

Tetrahedron 61 (2005) 8419–8422
Generation of ortho-quinone methides upon thermal extrusion
of sulfur dioxide from benzosultones
a,
b
Krzysztof Wojciechowski
*
and Karolina Dolatowska
a
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, PO Box 58, 01-224 Warszawa 42, Poland
b
Department of Chemistry, Technical University, ul. Koszykowa 75, 00-664 Warszawa, Poland
Received 21 April 2005; revised 2 June 2005; accepted 23 June 2005
Available online 18 July 2005
Abstract—3H-1,2-Benzoxathiole 2,2-dioxides (benzosultones) undergo thermal extrusion of sulfur dioxide to form ortho-quinone methides
that enter Diels–Alder reaction with maleimides to form chroman 2,3-dicarboxylic acid derivatives.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
oxyethene leading to 2,2-dimethoxychroman (6) (Scheme
). Such decomposition in methanol led to o-hydroxybenzyl
2
Thermal extrusion of sulfur dioxide from 1,3-dihydro-
benzo[c]thiophene 2,2-dioxides (1a) and 1,3-dihydro-2,1-
benzisothiazole 2,2-dioxides (benzosultams, 1b) is a well
established method for the generation of the corresponding
methyl ether (7) formed via addition of a nucleophile to
intermediate 5a. However, no experimental details of these
reactions were given.
1
quinodimethanes (ortho-xylylenes, 2a) and quinonemethyl-
eneimines (aza-ortho-xylylenes, 2b). These reactive inter-
2
mediates enter Diels–Alder reactions leading to tetrahydro-
naphthalenes (3a) and 1,2,3,4-tetrahydroquinolines (3b),
respectively (Scheme 1). There is also one report
concerning the synthesis of thiochromans (3c) via addition
of thioquinone methide (2c) generated via thermal extrusion
of SO from 1,2-benzodithiole 2,2-dioxide (1c).
3
2
Scheme 2.
The chemistry of ortho-quinone methides has been recently
reviewed by Van De Water and Pettus. These reactive
5
intermediates play an important role in numerous biological
processes. Thermal reactions were used for the generation
of o-quinone methides from such heterocycles as chro-
6
7
,8
9
10
mans, 4H-1,3-benzodioxins, 1,2-benzoxazines. Ther-
mal extrusion of SO2 from 4,4-bis(trifluoromethyl)-4H-
benzo-1,3,2-dioxathiin 2-oxide leading to the corresponding
Scheme 1.
1
1
quinone methide has also been described.
In the only report dealing with an application of the
analogous oxygen derivative 4a, namely the sultone of
2-hydroxytoluene-a-sulfonic acid, as a precursor of
o-quinone methide 5a, extrusion of SO upon photo-
2
4
chemical irradiation has been described. The intermediate
2. Results and discussion
5
a was trapped in a [4C2] cycloaddition with 1,1-dimeth-
In the present study we report our results on the thermal
extrusion of sulfur dioxide from 3H-1,2-benzoxathiole
Keywords: o-Quinone methide; Diels–Alder; Cycloaddition; Cheletropic
extrusion; Chroman.
*
2,2-dioxides (benzosultones, 4). Benzosultones can be
easily obtained from 2-hydroxytoluene-a-sulfonic acid
upon treatment with phosphorus oxychloride.
Corresponding author. Tel.: C48 22 343 2101; fax. C48 22 632 6681;
e-mail: kris@icho.edu.pl
1
2
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.087

8420
K. Wojciechowski, K. Dolatowska / Tetrahedron 61 (2005) 8419–8422
Scheme 3.
Table 1
Product
9
1
X
Y
R
R
Yield (%)
H
H
H
Cl
Cl
H
H
H
H
H
Cl
Cl
NO
NO
Ph
Ph
Me
Ph
Ph
Ph
Ph
H
Me
H
H
Me
H
37
32
64
58
32
41
40
10
11
12
13
14
15
2
2
Me
Heating of benzosultone 4a with N-phenylmaleimide
isolation proved impossible. Similarly, in the reaction with
2-phenoxyethyl vinyl ether, an electron rich alkene, no
cycloaddition product was formed. In all of these instances
large amounts of dimers and trimers of o-quinone methide
were formed.
(
(
NPMI, 8a) (1:1 mixture) in boiling 1,2-dichlorobenzene
180 8C) led to the formation of a mixture of products. MS
analysis of the crude reaction mixture revealed the presence
of products with molecular mass corresponding to dimers
and trimers of methylene quinone, as well as the expected
[
4C2] cycloadduct 9. Using a two- or three-fold excess of
In summary, we describe a novel method for the synthesis
of practically unknown chroman-2,3-dicarboxylic acid
derivatives. The synthesis was performed under neutral
conditions. In the only known report chroman-2,3-
dicarboxylates were obtained via addition of dimethyl
fumarate to ortho-quinone methides generated by a thermal
elimination of water from 2-hydroxybenzyl alcohols.
the NPMI, the amount of these by-products was diminished
and the cycloadduct 9 was formed in 37% yield. The
reactions of benzosultones 4b and 4c proceeded in a similar
way (Scheme 3, Table 1).
1
3
In reactions of quinonemethides 5 with 2-methyl-N-
phenylmaleimide (8b) two regioisomeric products can be
formed (Fig. 1). GC–MS analysis of the crude reaction
mixture revealed the formation of only one product with a
molecular mass corresponding to the expected cyclo-
addition product. The structure of these adducts was
3. Experimental
3.1. General remarks
1
deduced from the H NMR spectra. The spectra of
1
13
compounds 10, 13, and 15 revealed the presence of an
ABX system corresponding to 3a-methyl substituted
derivatives. The alternative structures 16 would show an
AB system of protons at C-9 and a singlet of hydrogen at
C-3a position.
Melting points are uncorrected. H and C NMR and
spectra were obtained with Varian Mercury 400 BB
instrument with TMS as internal standard. Coupling
constants J are given in Hz. IR were obtained using a
Perkin–Elmer 2000 FTIR instrument. Mass spectra (elec-
tron impact, 70 eV) were obtained on AMD 604 (AMD
Intectra GmbH, Germany) instrument. HRMS were
measured in the presence of perfluorokerosene as the
reference compound. Column chromatography was per-
formed using silica gel 240–400 mesh (Merck).
3
.2. Starting materials
Figure 1.
Starting benzosultones 4a and 4b were obtained from
the corresponding 2-hydroxybenzyl alcohols following the
known procedure.
Attempts to trap the generated quinone methides 5a–c with
other dienophiles were unsuccessful. When the sultones 4
were thermolysed in the presence of dimethyl maleate and
fumarate, and 2,3-dimethyl-N-phenylmaleimide, GC–MS
analysis showed only trace amounts of chromane-2,3-
dicarboxylates or the corresponding imide, but their
1
2
3.2.1. 3H-1,2-Benzoxathiole 2,2-dioxide (4a). Colorless
crystals. Mp 86–88 8C (lit., mp 86–87 8C). H NMR
1
4
1
(400 MHz, CDCl ): d 4.50 (s, 2H), 7.10 (d, JZ8.2 Hz, 1H),
3

K. Wojciechowski, K. Dolatowska / Tetrahedron 61 (2005) 8419–8422
8421
1
139 8C. H NMR (400 MHz, CDCl ): d 1.85 (s, 3H), 3.09
7
.20 (dd, JZ8.2, 7.6 Hz, 1H), 7.33 (d, JZ7.4 Hz, 1H), 7.40
3
1
3
(
dd, JZ7.6, 7.4 Hz, 1H). C NMR (100 MHz, CDCl ): d
(dd, JZ14.8, 6,7 Hz, 1H), 3.22 (dd, JZ14.8, 2.8 Hz, 1H),
3
1
3
5
cm ) n: 2999, 2945, 1477, 1463, 1364, 1213. MS (m/z, %):
1
0.2, 112.5, 119.3, 124.7, 125.8, 130.4, 151.0. IR (KBr,
3.32 (dd, JZ6.7, 2.8 Hz, 1H); 6.95–7.42 (m, 9H). C NMR
K1
(100 MHz, CDCl ): d 22.7, 25.3, 48.1, 79.3, 118.3, 123.6,
124.4, 126.2, 128.4, 128.7, 128.8, 129.1, 131.2, 153.61,
3
C
70 (M , 88), 106 (69), 78 (100).
K1
75.2, 175.4. IR (KBr, cm ): n 2965, 1717, 1595, 1494,
1485, 1396, 1234. MS (m/z, %): 293 (M , 66), 265 (4), 201
(11), 200 (28), 187 (18), 174 (50), 173 (14), 172 (13), 146
(24), 144 (11), 107 (15), 93 (8), 91 (26), 77 (27), 63 (13).
1
C
3
(
.2.2. 5,7-Dichloro-3H-1,2-benzoxathiole 2,2-dioxide
4b). Colorless crystals. Mp 139–141 8C. H NMR
1
(
400 MHz, CDCl ): d 4.56 (s, 2H), 7.24 (d, JZ1.4 Hz,
3
1
3
1
H), 7.43 (d, JZ1.4 Hz, 1H). C NMR (100 MHz, CDCl3):
d 51.0, 119.3, 120.2, 121.5, 124.1, 130.8, 146.2. IR (KBr,
HRMS calcd for C18
Elemental analysis calcd for C18
H, 5.15; N, 4.78. Found: C, 72.92; H, 5.55; N, 4.77.
H15NO
3
: 293.1052. Found: 293.1052.
H15NO
3
(293.32): C, 73.71;
K1
cm ) n: 3091, 2995, 2943, 1585, 1459, 1400, 1368, 1209,
C
163. MS (m/z, %): 238 (M , 46), 174 (100), 146 (38), 111
1
3
5
(
38), 75 (24). HRMS calcd for C H O S Cl : 237.9258.
7 4 3 2
3.3.3. 2-Methyl-9,9a-dihydro-3aH-chromeno[2,3-c]pyr-
role-1,3-dione (11). Colorless crystals. Mp 97–98 8C. H
Found 237.9262. Elemental analysis calcd for C H SO Cl
2
1
7
4
3
(
239.07): C, 35.17; H, 1.69. Found: C, 35.18; H, 1.93.
NMR (400 MHz, CDCl ): d 2.93 (s, 3H); 3.02 (dd; JZ15.0,
3
4
8
8
7
.7 Hz, 1H), 3.09 (dd, JZ15.0, 4.9 Hz, 1H), 3.47 (ddd; JZ
.7, 4.7, 4.9 Hz, 1H), 5.05 (d, JZ8.7 Hz, 1H), 6.99 (dd, JZ
.4, 7.3 Hz, 1H), 7.03 (d, JZ8.4 Hz, 1H), 7.12 (d, JZ
3
.2.3. 5-Nitro-3H-1,2-benzoxathiole 2,2-dioxide (4c).
To the solution of benzosultone (4a, 0.85 g, 5 mmol) in
concentrated sulfuric acid (10 mL) sodium nitrate (0.43 g,
5
mixture was stirred for 15 min at room temperature and then
poured into ice. The solid was separated, washed with water,
dissolved in dichloromethane and dried with MgSO . After
13
.2 Hz, 1H), 7.20 (dd, JZ7.3, 7.2 Hz, 1H). C NMR
mmol) was added in one portion at 5–10 8C. The reaction
(
1
100 MHz, CDCl ): d 24.7, 25.0, 41.7, 73.5, 118.2, 123.6,
3
K1
24.5, 128.5, 128.7, 153.5, 173.9, 176.8. IR (KBr, cm ) n:
2
(
959, 1702, 1484, 1435, 1384, 1343, 1322, 1284, 1225. MS
C
m/z, %): 217 (M , 56), 200 (5), 199 (2), 189 (2), 186 (23),
4
evaporation of the solvent product was recrystallized from
hexane–ethyl acetate (2:1).
160 (32), 132 (30), 131 (100), 111 (6), 91 (2), 77 (24).
HRMS calcd for C H NO : 217.0739. Found 217.0761.
1
2
11
3
Elemental analysis calcd for C H NO (217.22): C, 66.34;
1
2
11
3
Yield 0.86 g (80%). Colorless crystals. Mp 144–146 8C.
(
H, 5.11; N, 6.45. Found: C, 66.40; H, 5.24; N 6.24.
.3.4. 5,7-Dichloro-2-phenyl-9,9a-dihydro-3aH-chro-
meno[2,3-c]pyrrole-1,3-dione (12). Colorless crystals.
1
4
1
Lit., mp 148–150 8C). H NMR (400 MHz, CDCl ): d
3
1
3
4
.64 (s, 2H), 7.26–7.30 (m, 1H); 8.31–8.37 (m, 2H).
C
NMR (100 MHz): d 50.0, 113.2, 120.4, 122.0, 126.7, 144.3,
3
K1
54.8. IR (KBr, cm ): n 3114, 2947, 1593, 1531, 1475,
1
1
1
1
C
380, 1342, 1210. MS (m/z, %): 215 (M , 44), 151 (100),
35 (4), 121 (2), 93 (7), 79 (10), 74 (2), 65 (7).
Mp 212–214 8C. H NMR [400 MHz, (CD ) CO]: d 3.19–
3
2
3.24 (m, 2H), 3.91 (ddd, JZ8.7, 6.3, 5.6 Hz, 1H), 5.48 (d,
JZ8.7 Hz, 1H), 7.14–7.17 (m, 2H), 7.29–7.33 (m, 1H),
1
.39–7.48 (m, 4H). C NMR [100 MHz, (CD ) CO]: d
3
7
2
1
3
3 2
3.3. Cycloaddition of ortho-quinonemethides (general
procedure)
5.3, 41.9, 75.7, 124.4, 127.4, 128.0, 128.2, 129.0, 129.4,
29.7, 129.9, 132.9, 149.5, 172.8, 176.3. IR (KBr, cm ) n:
062, 1718, 1598, 1462, 1401, 1185. MS (m/z, %): 351 (11,
K1
Benzosultone 4a–c (1 mmol) and maleimide 8a–c (3 mmol)
were refluxed in 1,2-dichlorobenzene (5 mL) for 2 h. After
cooling, the reaction mixture was subjected to column
chromatography. The solvent was eluted with hexane–ethyl
acetate (50:1) and then the product was eluted with hexane–
ethyl acetate (5:1). The following compounds were obtained.
C
C
C
M C4), 349 (64, M C2), (100, M ), 329 (3), 319 (3),
2
2
57 (5), 255 (7), 230 (17), 228 (26), 202 (30), 201 (49),
00 (49), 199 (68), 173 (14), 165 (18), 136 (7), 93 (86).
3
5
HRMS calcd for C H NO Cl : 347.0116. Found:
11
1
7
3
2
3
47.0118. Elemental analysis calcd for C H NO Cl
17 11 3 2
(348.19): C, 58.64; H, 3.19; N, 4.02. Found: C, 58.82; H,
3
.42; N, 4.04.
3
.3.1. 2-Phenyl-9,9a-dihydro-3aH-chromeno[2,3-c]pyr-
1
role-1,3-dione (9). Colorless crystals. Mp 147–149 8C. H
NMR [400 MHz, (CD ) SO]: d 3.04 (dd, JZ15.1, 4.8 Hz,
3
2
3.3.5. 5,7-Dichloro-3a-methyl-2-phenyl-9,9a-dihydro-
3aH-chromeno[2,3-c]pyrrole-1,3-dione (13). Colorless
1
4
7
H), 3.07 (dd, JZ15.1, 7.0 Hz, 1H), 3.77 (ddd, JZ8.7, 7.0,
1
crystals. Mp 144–146 8C. H NMR (400 MHz, CDCl ):
.8 Hz, 1H), 5.29 (d, JZ8.7 Hz, 1H), 6.95–7.05 (m, 4H),
3
1
3
.20–7.24 (m, 2H), 7.31–7.50 (m, 3H).
C NMR
d 1.90 (s, 3H), 3.05 (dd, JZ15.0, 6.7 Hz, 1H), 3.25 (dd, JZ
15.0, 3.1 Hz, 1H), 3.34 (dd, JZ6.7, 3,1 Hz, 1H), 7.04–7.09
(m, 3H), 7.29 (d, JZ2.2 Hz, 1H), 7.34–7.45 (m, 3H). C
NMR (100 MHz, CDCl ): d 22.5, 25.2, 47.3, 80.2, 124.4,
[
100 MHz, (CD ) SO]: d 24.3, 41.3, 73.9, 117.6, 123.1,
3 2
1
3
1
1
1
25.4, 126.6, 128.2, 128.5, 128.6, 129.0, 131.6, 153.4,
K1
73.2, 176.5. IR (KBr, cm ): n 3042, 1721, 1708, 1585,
3
C
486, 1405, 1228, 1201. MS (m/z, %): 279 (M , 100), 251
126.0, 126.2, 127.3, 128.4, 128.9, 129.0, 129.2, 130.9,
148.1, 174.0, 174.4. IR (KBr, cm ): n 3063, 2963, 1716,
K1
(
9
5), 186 (14), 160 (26), 159 (12), 132 (35), 131 (83), 103 (6),
3 (41), 77 (11). HRMS calcd for C H NO : 279.0895.
C
1575, 1501, 1461, 1390, 1225. MS (m/z, %): 361 (M , 100),
1
7
13
3
Found: 279.0896. Elemental analysis calcd for C H NO
3
344 (4), 269 (6), 268 (13), 242 (23), 241 (6), 240 (4), 214
(13), 212 (2), 187 (61), 174 (2), 159 (3), 149 (2), 143 (7),
119 (4), 115 (6), 93 (37), 77 (5). HRMS calcd for
1
7
13
(
279.30): C, 73.11; H, 4.69; N, 5.02. Found: C, 72.99; H,
.90; N, 4.97.
4
3
5
C H NO Cl : 361.0272. Found: 361.0270. Elemental
1
8
13
3
2
3
[
.3.2. 3a-Methyl-2-phenyl-9,9a-dihydro-3aH-chromeno-
2,3-c]pyrrole-1,3-dione (10). Colorless crystals. Mp 137–
analysis calcd for C H NO Cl (362.21): C, 59.69; H,
18 13 3 2
3.62; N, 3.87. Found: C, 59.80; H, 3.77; N, 3.88.

8422
K. Wojciechowski, K. Dolatowska / Tetrahedron 61 (2005) 8419–8422
3
3
1
1
.3.6. 7-Nitro-2-phenyl-9,9a-dihydro-3aH-chromeno[2,
-c]pyrrole-1,3-dione (14). Colorless crystals. Mp 139–
References and notes
1
41 8C. H NMR [400 MHz, (CD ) SO]: d 3.20 (dd, JZ
1. For recent reviews on ortho-xylylenes see: Sadana, A. K.;
Saini, R. K.; Billups, W. E. Chem. Rev. 2003, 103, 1539–1602.
Mehta, G.; Kotha, S. Tetrahedron 2001, 57, 625–659. Segura,
J. L.; Martin, N. Chem. Rev. 1999, 99, 3199–3246.
2. For review on aza-ortho-xylylenes see: Wojciechowski, K.
Eur. J. Org. Chem. 2001, 3587–3605.
3
2
5.5, 5.8 Hz, 1H), 3.24 (dd, JZ15.5, 7.3 Hz, 1H), 3.80 (ddd,
JZ8.5, 7.3, 5.8 Hz, 1H), 5.43 (d, JZ8.5 Hz, 1H), 7.16–7.23
1
m, 2H); 7.29–7.35 (m, 1H); 7.34–7.51 (m, 5H). C NMR
3
(
[
400 MHz, (CD ) SO]: d 23.4, 42.7, 74.2, 124.3, 128.7,
3
2
1
1
1
3
25.5, 126.8, 127.8, 128.9, 129.0, 131.5, 142.3, 170.0,
K1
72.3, 175.7. IR (KBr, cm ): n 3077, 1722, 1709, 1594,
3. Hortmann, A. G.; Aron, A. J.; Bhattacharya, A. K. J. Org.
Chem. 1978, 43, 3374–3378.
C
514, 1401, 1343, 1242, 1182. MS (m/z, %): 324 (M , 100),
06 (5), 294 (6), 279 (5), 232 (4), 205 (15), 177 (43), 176
4. Chapman, O. L.; McIntosh, C. L.; Clardy, J. C. Chem.
Commun. 1971, 383–384.
5. Van De Water, R. W.; Pettus, T. R. R. Tetrahedron 2002, 58,
(68), 160 (9), 130 (20), 119 (16), 77 (14). HRMS calcd for
C H N O : 324.0746. Found: 324.0757.
1
7 12 2 5
5
367–5405.
3.3.7. 3a-Methyl-7-nitro-2-phenyl-9,9a-dihydro-3aH-
chromeno[2,3-c]pyrrole-1,3-dione (15). Colorless crys-
6. Pater, M. G. Angew. Chem., Int. Ed. 1989, 28, 555–570.
7. Paul, G. C.; Gajewski, J. J. J. Org. Chem. 1993, 58,
5060–5062.
1
tals. Yield 40%. Mp 155–156 8C. H NMR (400 MHz,
CDCl ): d 1.88 (s, 3H), 3.14 (dd, JZ7.3, 15.9 Hz, 1H), 3.40
8. Dorrestijn, E.; Pugin, R.; Nogales, M. V. C.; Mulder, P. J. Org.
Chem. 1997, 62, 4804–4810.
3
(
dd, JZ3.0, 15.9 Hz, 1H), 3.45 (dd, JZ3.0, 7.3 Hz, 1H),
7
.04–7.13 (m, 3H), 7.32–7.45 (m, 3H), 8.09–8.15 (m, 2H).
C NMR (100 MHz, CDCl ): d 22.7, 23.9, 46.4, 79.7,
9. Fixler, N.; Salez, H.; Demeunynck, M.; Lhomme, J. J. Chem.
Soc., Perkin Trans. 1 1995, 1649–1652.
1
3
3
1
1
1
3
18.7, 123.8, 124.6, 124.7, 126.0, 129.0, 129.2, 130.8,
K1
43.2, 158.4, 173.7, 174.1. IR (KBr, cm ): n 1704, 1485,
10. Yato, M.; Ohwada, T.; Shudo, K. J. Am. Chem. Soc. 1990, 112,
5341–5342.
C
436, 1284, 1225. MS (m/z, %): 338 (91, M ), 321 (11),
08 (8), 293 (7), 245 (7), 219 (33), 191 (21), 190 (36), 176
11. Sheppard, W. A. J. Org. Chem. 1968, 33, 3297–3306.
12. Zaborsky, O. R.; Kaiser, E. T. J. Am. Chem. Soc. 1966, 88,
3084–3087.
(100), 144 (24), 130 (16), 121 (14), 93 (52). HRMS calcd for
C H N O : 338.0903. Found: 338.0931. Elemental analy-
sis calcd for C H N O (338.32): C, 63.90; H, 4.17; N,
1
13. Hultzsch, K. J. Prakt. Chem. 1941, 158, 275–294.
14. Deacon, T.; Farrar, C. R.; Sikkel, B. J.; Williams, A. J. Am.
Chem. Soc. 1978, 100, 2525–2534.
1
8 14 2 5
8 14 2 5
8
.28. Found: C, 63.82; H, 4.14; N, 7.93.