Reactions of α,β-unsaturated N-benzenesulfonyl imine - N-[(2E)-3-phenyl-2-propen-1-ylidene]benzenesulfonamide with methyllithium

Article abstract of DOI:10.1002/jccs.201500082

α,β-Unsaturated N-benzenesulfonyl imine 1 was treated with 1.1 eq methyllithium to afford 1,2-addition adduct as a sole product. However, when compound 1 was treated with 2 eq MeLi, 1,2-addition product, benzenesulfonamide derivative 3 and 2H-1,2-benzothiazine 1,1-dioxide derivatives 4 and 5 were isolated.

Full text of DOI:10.1002/jccs.201500082

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Communication
Reactions of a,b-unsaturated N-benzenesulfonyl Imine - N-[(2E)-3-phenyl-2-propen-1-
ylidene]benzenesulfonamide with Methyllithium
Gon-Ann Lee,* Hsin-Yi Lee, Wei-Cheng Chen and Yen-Huei Lin
Department of Chemistry, Fu Jen Catholic University, Xinzhuang, New Taipei City 24205, Taiwan, ROC
(Received: Mar. 2, 2015; Accepted: May 18, 2015; Published Online: Jun. 5, 2015; DOI: 10.1002/jccs.201500082)
a,b-Unsaturated N-benzenesulfonyl imine 1 was treated with 1.1 eq methyllithium to afford 1,2-addition
adduct as a sole product. However, when compound 1 was treated with 2 eq MeLi, 1,2-addition product,
benzenesulfonamide derivative 3 and 2H-1,2-benzothiazine 1,1-dioxide derivatives 4 and 5 were isolated.
Keywords: Nucleophilic addition; a,b-Unsaturated sulfonyl imine; 1,2-Addition; Cyclization.
INTRODUCTION
Nucleophilic addition reaction to electron-deficient
was treated with 1.1 eq MeLi at -78 °C and stirred at rt for
24 h, only 1,2-addtion addition adduct 2 was obtained in
84% yield (Scheme 2).
olefins is one of the most important methods for C-C or
C-heteroatom formation in organic synthesis.1 The reac-
tions of a,b-unsaturated imine with different nucleophile
provide a convenient route for the preparation of func-
tionalized organic compounds2 and are increasingly being
used for the asymmetric synthesis to chiral compounds3
and natural products.4 However, the addition of organo-
lithium compounds to a,b-unsaturated imine tends to fa-
vour 1,2-addition for most substrates, and when successful,
1,4-addition will not afford.3b,3g In this paper, we reported
that the reaction of a,b-unsaturated N-benzenesulfonyl
imine with methyllithium. When two equivalents of MeLi
was added, not only afforded 1,2-addition product, but also
generated benzenesulfonamide derivatives and 2H-1,2-
benzothiazine 1,1-dioxide derivatives.
Reaction of Compound 1 with 1.1 eq MeLi
Scheme 2
However, when a,b-unsaturated N-benzenesulfonyl
imine 1 was treated with 2 eq MeLi at -78 °C and stirred at
rt for 24 h, four compounds, 2, 3, 4, and 5, were isolated in
yields of 41%, 18%, 7%, and 5%, respectively. The struc-
tures of compounds 3, 4, and 5 were confirmed by X-ray
crystallography (Scheme 3).
Reaction of Compound 1 with 2 eq MeLi
Scheme 3
RESULTS AND DISCUSSION
a,b-Unsaturated N-benzenesulfonyl imine 1 have
been successfully synthesized by the condensation reaction
of trans-cinnamaldehyde and benzenesulfonamide in tolu-
ene at refluxing temperature to give the important precur-
sor in 88% yield (Scheme 1).5
Synthesis of Compound 1
Scheme 1
The result shows that compound 3 was produced
from phenyl anion addition at conjugated C=C bond for
ring-closing reaction and followed by ring-opening reac-
tion to give compound 3.
When a,b-unsaturated N-benzenesulfonyl imine 1
* Corresponding author. Email:016850@mail.fju.edu.tw
Supporting information for this article is available on the www under http://dx.doi.org/10.1002/jccs.201500082
J. Chin. Chem. Soc. 2015, 62, 573-576
© 2015 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Communication
Lee et al.
Fig. 1. The X-ray crystal structure of 3.
Fig. 3. The X-ray crystal structure of 5.
Plausible mechanism for the formation of
Scheme 5
Compound 4
Fig. 2. The X-ray crystal structure of 4.
Compound 5 was formed from MeLi addition to
sulfonyl group to leave a phenyl anion6 due to the pKa of
Me-H is 487 and the pKa of Ph-H is 43.8 Phenyl anion un-
derwent 1,4-addition of 1 followed by ring-closing reac-
tion and oxidation to produce compound 5 (Scheme 6).
In conclusion, a,b-unsaturated N-benzenesulfonyl
imine reacted with 1.1 eq methyllithium will afford 1,2-ad-
dition adduct only. When 2 eq of MeLi was added, not only
afforded 1,2-addition product, but also formed benzene-
sulfonamide derivative 3 and 2H-1,2-benzothiazine 1,1-di-
oxide derivatives 4 and 5.
Plausible mechanism for the formation of
Scheme 4
Compound 3
Compound 4 was obtained from the formation of
benzylic anion which was attacked to another molecule and
followed by cyclization to give six-membered ring finally
hydration and oxidation to form compound 4.
EXPERIMENTAL
General information: Melting points were measured with
a Barloworld SMP3 melting point apparatus and were uncor-
574
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JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Reactions of a,b-Unsaturated N-benzenesulfonyl
2 (3.62 g, 84%). The NMR data are consistent with those reported
in the literature.10 1H NMR (300 MHz, CDCl3) d 7.91-7.87 (m,
2H), 7.50-7.14 (m, 8H), 6.32 (d, 1H, J = 15.8 Hz), 5.86 (dd, 1H, J
= 15.8, 6.7 Hz), 4.77 (s, 1H), 4.14-4.08 (m, 1H), 1.27 (d, 3H, J =
6.7 Hz); 13C NMR (75 MHz, CDCl3) d 141.2 (C), 136.3 (C), 132.5
(CH), 130.7 (CH), 130.1 (CH), 129.0 (CH), 128.5 (CH), 127.8
(CH), 127.2 (CH), 126.4 (CH), 51.8 (CH), 22.0(CH3). MS m/z
(%) 287 (M+, 13), 77 (100), 130 (45), 144 (45), 146 (62). HRMS
(EI) calcd for C16H17NO2S m/z 287.0980 (M+), found 287.0984.
Reaction of N-[(2E)-3-phenyl-2-propen-1-ylidene]-ben-
zenesulfonamide (1) with 2 eq Methyllithium: Methyllithium
(1.5 M in ether, 20 mL, 30 mmol) was added dropwise from a
dropping funnel to a stirred solution of compound 1 (4.08 g, 15
mmol) in 100 mL of dry THF at -78 °C. The mixture was allowed
to warm to rt and stirred for 24 h. The mixture was poured into a
400 mL beaker with 100 g of crushed ice and added 50 mL
CH2Cl2. The organic layer was separated and washed with water
and brine, and then dried over anhydrous MgSO4. After filtration,
the solvent was removed on a rotary evaporator and the residue
was purified by column chromatography and HPLC to give com-
pounds 2 (1.77 g, 41%), 3 (0.78 g, 18%), 4 (0.46 g, 7%), 5 (0.26 g,
5%). Compound 3: mp 111-112 °C; IR (neat, cm-1) 3034, 3275,
3061, 1950, 1715, 1557, 1492, 1467, 1453, 1329, 1157, 894, 759,
Plausible mechanism for the formation of
Scheme 6
Compound 5
rected. NMR spectra were measured in CDCl3 solution with a
Bruker AC-300 MHz NMR spectrometer, with CHCl3 (7.26 ppm)
as the internal standard. Carbon-13 NMR were measured in
CDCl3 solution on a 75 MHz NMR spectrometer and referenced
to CDCl3 (77.1 ppm). Chemical shifts (d) are expressed in ppm
downfield from tetramethylsilane. Coupling constants (J) are ex-
pressed in hertz (Hz). Mass spectra were measured with a
Finnigan/Thermo Quest MAT 95XL mass spectrometer. The ele-
mental analyses were recored on a Elementar vario EL III elemen-
tal analyzer. Infrared spectra were recorded on KBr pellets. Flash
chromatography was performed on silica gel (230 mesh). Column
chromatography was performed on silica gel (70-230 mesh). Sol-
vents are of reagent grade.
1
734, 703; H NMR (300 MHz, CDCl3) d 8.01-7.96 (m, 1H),
7.34-6.80 (m, 8H), 5.72 (q, 1H, J = 6.8 Hz), 4.64 (s, 2H), 3.90 (s,
2H), 2.02 (d, 3H, J = 6.8 Hz); 13C NMR (75 MHz, CDCl3) d 142.0
(C), 140.2 (C), 139.5 (C), 139.1 (C), 131.9 (CH), 129.1 (CH),
128.6 (CH), 127.2 (CH), 127.0 (CH), 126.4 (CH), 38.4 (CH2),
14.5 (CH3). MS m/z (%) 287 (M+, 7), 206 (32), 191 (100), 91 (33).
HRMS (EI) calcd for C16H17NO2S m/z 287.0980 (M+), found
287.0977. X-ray: CCDC 1051436. Compound 4: mp 193-195 °C;
IR (neat, cm-1) 3200, 3056, 2918, 2863, 1697, 1494, 1347, 1166,
769, 709, 597, 566; 1H NMR (300 MHz, CDCl3) d 7.78-7.75 (m,
1H), 7.74-6.23 (m, 14H), 4.85-4.70 (m, 1H), 4.10-4.00 (m, 1H),
3.17-3.10 (m, 1H), 3.08-2.91 (m, 2H), 2.70 (dd, 1H, J = 18.8, 3.1
Hz), 2.2 (s, 3H), 1.56 (d, 3H, J = 7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 209.1 (C), 140.0 (C), 137.1 (C), 136.5 (C), 131.4 (CH),
131.2 (CH), 130.5 (CH), 129.3 (CH), 128.2 (CH), 127.9 (CH),
127.4 (CH), 127.3 (CH), 127.2 (CH), 125.1 (CH), 55.1 (CH) 52.0
(CH), 47.0 (CH2), 46.1 (CH), 38.8 (CH), 30.6 (CH3), 19.0 (CH3).
MS m/z (%) 433 (M+, 1), 286 (61), 237 (43), 180 (30), 179 (100),
91 (28). HRMS (EI) calcd for C26H27NO3S m/z 433.1712 (M+),
found 433.1716. X-ray: CCDC 1051438. Compound 5: mp
160-162 °C; IR (neat, cm-1) 3240, 3032, 1697, 1493, 1309, 1168,
810, 774, 747, 696; 1H NMR (300 MHz, CDCl3) d 7.95-7.91 (m,
1H), 7.49-7.15 (m, 14H), 5.92 (s, 1H), 5.63 (s, 1H); 13C NMR (75
MHz, CDCl3) d 141.6 (C), 133.5 (C), 132.5 (C), 132.1 (CH),
Preparation of N-[(2E)-3-phenyl-2-propen-1-yli-
dene]-benzenesulfonamide (1):5 To a solution of trans-
cinnamaldehyde (26.4 g, 0.2 mol) and benzenesulfonamide (31.4
g, 0.2 mol) in 1 L toluene was stirred for 120 h at reflux under a
Dean-Stark trap. Toluene was removed on a rotary evaporator to
yield a pale yellow solid (47.7 g, 88%). The NMR data are consis-
tent with those reported in the literature.9
Reaction of N-[(2E)-3-phenyl-2-propen-1-ylidene]-ben-
zenesulfonamide (1) with 1.1 eq Methyllithium: Methyllithium
(1.5 M in ether, 11 mL, 16.5 mmol) was added dropwise from a
dropping funnel to a stirred solution of compound 1 (4.08 g, 15
mmol) in 100 mL of dry THF at -78 °C. The mixture was allowed
to warm to rt and stirred for 24 h. The mixture was poured into a
400 mL beaker with 100 g of crushed ice and added 50 mL
CH2Cl2. The organic layer was separated and washed with water
and brine, and then dried over anhydrous MgSO4. After filtration,
the solvent was removed on a rotary evaporator and the residue
was purified by flash column chromatography to give compound
J. Chin. Chem. Soc. 2015, 62, 573-576
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Communication
Lee et al.
3. (a) Hsieh, Y-T.; Lee, G.-H.; Wang, Y.; Luh, T.-Y. J. Org.
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129.6 (CH), 128.8 (CH), 127.7 (CH), 127.6 (CH), 127.0 (CH),
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C21H17NO2S m/z 347.0980 (M+), found 347.0989. X-ray: CCDC
1051439.
ACKNOWLEDGEMENTS
Financial support from the National Science Council
of the Republic of China (NSC 102-2113-M-030-007-
MY2) is gratefully acknowledged. We thank Professor M.
Shieh and Mr. T.-S. Kuo at NTNU for the X-ray structure
determination.
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J. Chin. Chem. Soc. 2015, 62, 573-576