Conversion of 3-nitroanilines into tricyclic systems: 1H-1-alkyl-8-X-2,2-dioxoisothiazolo[5,4,3-d,e]quinolines

Article abstract of DOI:10.1016/S0040-4020(01)00738-4

The route leading to the tricyclic 2,2-dioxoisothiazolo[5,4,3-d,e]quinolines from 3-nitroanilines has been described. The scope and limitation factors as well as some mechanistic features are discussed.

Full text of DOI:10.1016/S0040-4020(01)00738-4

TETRAHEDRON
Pergamon
Tetrahedron 57 :2001) 7899±7907
Conversion of 3-nitroanilines into tricyclic systems:
1H-1-alkyl-8-X-2,2-dioxoisothiazolo[5,4,3-d,e]quinolines
p
Â
Zbigniew Wrobel
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, PL-01-224 Warsaw, Poland
Received 12 February 2001; revised 15 June 2001; accepted 12 July 2001
AbstractÐThe route leading to the tricyclic 2,2-dioxoisothiazolo[5,4,3-d,e]quinolines from 3-nitroanilines has been described. The scope
and limitation factors as well as some mechanistic features are discussed. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results
In 1997 we reported the reaction of nitroarenes with some
allylic systems to obtain 4-substituted quinoline derivatives,
which took place in the presence of a base and Lewis acid.
The postulated transformation mechanism consisted in the
initial formation of a sH-adduct of a carbanion derived from
the allylic compound to the nitroaromatic system, followed
by its conversion to the nitroso compound, which
subsequently underwent intramolecular cyclization to the
®nal product.1±3 Recently we presented a communication4
describing the intramolecular version of this reaction,
namely direct transformation of N-alkyl-N-3-nitroaryl allyl-
sulfonamides 1 to tricyclic 1H-1-alkyl-8-X-2,2-dioxoiso-
thiazolo[5,4,3-d,e]quinolines 2. Small amounts of quino-
line N-oxides 3 accompanied formation of 2 :Scheme 1).4
Simple allyl sulfonamides 1a±h withan unsubstituted
terminal CC double bond, suitable for cyclization step
Table 1. Preparation of 1a±h from 4 via sulfonylation followed by alkyl-
ation withalkyl iodides
X
H
4
a
Timea
3 h
6
a
Yield :%)
76
R
Timea
2 h
1
Yield :%)b
Me
a
b
c
d
e
f
90
70
84
78
87
89
89
89
n-Buc 4 d
Allyld 1 d
Bnd
Me
2 d
2 d
Cl
b
1 d
b
55e
n-Buc 4 d
Me
MeO
c
d
3 h
3 h
c
d
76
90
Me
Me
2 h
1 d
g
h
Since 2 are expected to be useful intermediates in the syn-
thesis of pyrroloquinoline5 or pyridoquinoline6 type natural
products and some other fused nitrogen heterocycles7 we
undertook more detailed investigations of this transforma-
tion. Here we present a full report.
a
hˆhours, dˆdays.
Isolated.
3 equiv.
RCl and cat. KI.
3-Nitro N,N-di:prop-2-enylsulfonyl)aniline isolated in 20% yield as a
byproduct.
b
c
d
e
Scheme 1.
Keywords: 3-nitroanilines; sH-adducts; intramolecular cyclization; nitroso compounds; 1H-1-alkyl-8-X-2,2-dioxoisothiazolo[5,4,3-d,e]quinolines.
E-mail: wrobel@icho.edu.pl
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020:01)00738-4

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Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7900
Scheme 2. Reagents and conditions: :a) py., DCM, 2308C to rt; :b) K2CO3, KI :cat. for HalˆCl), DMF, rt.
Scheme 3. Reagents and conditions: :a) 2LDA, THF, TMEDA, 2788C; :b) DBU, LiBr, THF, rt.
Table 2. Preparation of 1i±l from 9 and carbonyl compounds in Horner±
bonds were synthesized from N-methyl-N-:3-nitrophenyl)-
methanesulfonamide 79 according to Scheme 3 :Table 2).
Wadsworth±Emmons reaction
R0
R00
1
Isolated yield :%)
Attempts to perform a direct addition of the lithiated 7 to
cyclohexanone were unsuccessful and led to mixture of
products. Alternatively 7 was treated with2 equiv. of
LDA and successively phosphorylated with diethyl chloro-
phosphate 8 according to the Craig procedure10 to give in
moderate 47% yield phosphonate 9 suitable for Horner±
Wadsworth±Emmons reaction. Condensation of 9 with
carbonyl compounds was accomplished under the modi®ed
Rathke conditions11 :DBU/LiBr/THF) to yield 1i±l. In this
case the unsaturated bond occurred mainly at a,b position to
SO2 group.
:CH2)4
Me
H
PhH
i
72
62
63
60
H
Ph
j
k
l
were synthesized from commercial 3-nitroanilines 4
:Scheme 2).
The sulfonylation of 4 withallylsulfonyl chloride 58 in the
presence of pyridine in dry dichloromethane :DCM) gave
N-:3-nitroaryl)prop-2-enyl sulfonamides 6 with55±90%
yield. The reaction proceeded smoothly and selectively
withmore nucleophilic nitroanilines :X ˆH, Me, MeO: 4a,
4c, 4d, respectively) whereas in the case of less nucleophilic
2-chloro-5-nitroaniline 4b it was slower and was accom-
panied withthe formation of bissulfonylated 3-nitro- N,N-
di:prop-2-enylsulfonyl)aniline. Alkylation of the sulfona-
mide nitrogen atom withan alkyl chloride or iodide was
performed in the presence of K2CO3 in DMF at room
temperature.9 KI was added as a catalyst in the case of
alkyl chlorides. NMR spectra revealed that both transfor-
mations occurred with the preservation of the terminal
double bond position.
N-:3-Nitrophenyl)prop-2-enyl sulfonamide 1a treated with
DBU and MgCl2 in DMSO underwent cyclization to 2a with
subsequent ®ve- and six-membered ring closure in moderate
yield. Quinoline N-oxide 3a was isolated as a byproduct
:Scheme 1 R0ˆR00ˆH).
1
The tricyclic structure of 2a was con®rmed by H NMR
spectrum.4 None of the signals derived from allylic part of
1a was observed. Instead, two new aromatic protons at 7.81
and 9.24 ppm could be observed withcoupling constant
Jˆ4.5 Hz characteristic for protons at positions 2 and 3 of
the quinoline ring. Also a four-proton pattern characteristic
for 1,3-disubstituted benzene ring in 1a was replaced in 2a
by eight signals in 7.69±7.85 ppm region with pattern
characteristic for ABX system.
Allyl sulfonamides 1i±l withsubstituted allylic double
Table 3. Cyclization of 1a in various conditions
Dimethyl sulfoxide turned out to be the solvent of choice
although other dipolar aprotic solvents such as DMF or
HMPA gave comparable results :Table 3).
Entry
Amount of MgCl2
Solvent
Timea
Yields :%)b
2a
3a
1
2
3
4
5
6
7
None
0.625
2.5
0.625
1.0
DMSO
DMSO
DMSO
DMF
MeCN
Py
HMPA
1 d
1 d
1 d
1 d
30 d
7d
3 h60
27
64
50
59
6
Traces
11
9
12
8
9
The reaction carried out in HMPA was faster than in DMSO
or DMF but the total yield of 2a and 3a was not higher. The
use of less polar solvents retarded the reaction and reduced
the yields of both products. Interestingly, despite the rather
poor material balance of the reaction :even in the best case)
only a little tarry material was observed. Presumably some
water-soluble side-products were formed which have not yet
been isolated. The optimum amounts of MgCl2 and DBU
were 0.6 and 5 equiv., respectively, as was found for similar
0.625
0.625
43
3
5 equiv. of DBU as a base.
hˆhours, dˆdays.
a
b
Isolated.

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Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7901
Table 4. Cyclization of 1a±j under optimized conditions
1
a
X
R
R0
R00
H
Procedurea
Timeb
2 :%)c
3 :%)c
H
Me
H
A
B
A
A
A
A
B
A
A
A
1 d
1 d :1 h
64
)
11
63
±
b
c
d
e
H
H
H
n-Bu
Allyl
Bn
H
H
H
H
H
H
H
H
1 d
1 d
1 d
1 d
64
61
70
41
57
52
21
14
33
7
8
7
9
11
Cl
Me
1 d :30 min)
1 d
60 d
±
f
g
h
Cl
Me
MeO
n-Bu
Me
Me
H
H
H
H
H
H
18
5
2 dd
±
±
14 de
1 d
i
H
H
Me
Me
:CH2)4
Me
A
B
A
B
35
27
1 d :30 min)
1 d
1 d :30 min)
35
28
63
±
±
j
H
k
l
H
H
Me
Me
H
Ph
PhA
H
1 d
46
23
f
A
2 h
31
16
a
b
c
d
e
f
A: 5 equiv. DBU, 0.625 equiv. MgCl2, DMSO solution rt, B: 1-st stage A, then re¯uxing with an excess of P:OEt)3.
dˆdays, hˆhours, time of re¯uxing with P:OEt)3 in parentheses.
Isolated.
Reaction at 808C, no reaction at 208C.
HMPA instead DMSO.
10l :3.5%) also isolated.
intermolecular processes.1±3 However, unlike the later ones
the reaction proceeded even in the absence of Lewis acid
although signi®cantly less effectively.
for completion. For XˆOMe, no reaction was observed
at room temperature. To accomplishthe transformation,
it was necessary to raise the temperature or replace
DMSO withHMPA. In suchconditions small amounts
of some other products were observed.
A variety of N-:3-nitroaryl)-N-methyl allylsulfonamides
1b±l were subjected to the cyclization reaction under opti-
mum conditions :Table 4).
4. The substitution of the allylic part of the molecule had
the dramatic in¯uence on the product 2 and 3 ratio,
although it had only little in¯uence on the overall rate
of the reaction. The introduction of substituents in both 2
and 3 positions resulted in the formation of substantial
amounts of quinoline N-oxide 3 which appeared to be
the main product in cyclization of the cyclohexylidene
derivative 1i. Unexpectedly 1l turned out to be the most
reactive substrate. Its full conversion was achieved in 2 h
:see Table 4). The formation of 2l and 3l was accompa-
nied by small amounts of 10l which could be considered
as an intermediate in the formation of 3l :see Scheme 4).
The results presented above lead to the following obser-
vations:
1. The reaction is of general character with respect to
substituents X, R, R0, and R00.
2. The reaction course :rate and 2/3 ratio) does not practi-
cally depend on R.
3. The substituent in the aromatic ring :X) has an impact on
the rate of the reaction rather than on the products ratio.
In the cases of XˆH and Cl the reaction was completed
within a day whereas for XˆMe, it needed several weeks
Since 3 are the oxidized forms of quinolines 2, some efforts
Scheme 4.

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Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7902
Table 5. In¯uence of oxygen on cyclization of 1j to 2j and 3j
subjected to the standard cyclization conditions was
consumed within 4 min :compared with several hours
needed for the conversion of 1a to 2a and 3a, Table 4)
giving 3a with69% yield :Scheme 5).
Conditions
2j :%)a
3j :%)a
b
25
59
9
35
21
50
Arc
O2
d
This means that 10a cannot be excluded as an intermediate
in the formation of 3a. Taking bothelectronic and steric
reasons into consideration one could expect the cyclization
of 13 to 2 to proceed even faster than 10 to 3, meaning that
the former cannot be the rate-limiting step in the trans-
formation of 1 to 2. The dominating impact of R on 2/3
ratio :see Table 4) is hard to explain without more infor-
mation about the oxidation step which precedes formation
of 3.
a
Isolated.
b
DMSO dried by distillation from CaH2, 100 ml of DMSO per 1 mmol of
1j, reaction at rt conducted until 1j was consumed :ca. 20 h, HPLC
control).
As in :b) but special grade Ar bubbled through the reaction mixture for 3
days prior to the addition of DBU and then until the end of the reaction
:ca. 20 h).
c
d
As in :c) but O2 used instead of Ar.
were undertaken to transform 3 in the crude mixtures of 2
and 3 to pure 2 thus improving the total yields of 2 and
simplifying the isolation procedure. In a control experiment
Further investigation on the mechanistic details of the reac-
tion as well as on application of 1H-1-alkyl-8-X-2,2-dioxo-
isothiazolo[5,4,3-d,e]quinolines as the intermediates in the
synthesis of other heterocyclic compounds are in progress.
12
it was found that pure 3a on action of re¯uxing P:OEt)3
gave 2a with90% isolated yield. Thus, some crude mixtures
of 2 and 3 after the cyclization step were re¯uxed with
excess of P:OEt)3 and then separated on silica gel :Table
4, procedure B).
3. Experimental
Melting points are uncorrected. The 1H and 13C NMR
spectra were recorded on Varian Gemini :200 MHz) in
CDCl3 solutions withTMS as an internal standard.
Chemical shifts were expressed in ppm, coupling constants
in hertz. The mass spectra were obtained on AMD-604
:AMD Intectra GmbH Germany) spectrometer withelectron
impact technique :70 eV). IR spectra were recorded on
Spectrum 2000 as ®lms or in KBr pellets. Silica gel :230±
400 mesh, Merck) was used for column chromatography.
All starting 3-nitroanilines were commercial. Allylsulfonyl
chloride 5 was prepared according to the literature.8
Mechanistic details of the reaction are under investigation.
Nevertheless the following general scheme seems plausible.
Deprotonation at the a position to SO2 group withDBU
followed by the intramolecular addition of carbanionic
centre of 11 to the nitroaromatic part of the molecule
would lead to sH-adduct 12.13 The loss of a molecule of
water :Lewis acid mediated) would lead to the nitroso
derivative 13. The intramolecular base-induced Ehrlich±
Sachs condensation14,15 of the latter :via intermediate 14)
would terminate the reaction leading to product 2. Th e
mechanism of formation of oxidized product 3 is not
clear. It may have been derived from nitro compound 10
:isolated from the reaction mixture in cyclization of 1l,
Table 4) which in turn could originate either from sH-adduct
12 or from the nitroso compound 13 as well as from 14 in a
spontaneous oxidation process. Unlike sH adducts13
aromatic nitroso compounds were not reported to undergo
spontaneous oxidation to the nitro compounds. The
oxidizing agent has not been recognized so far. It could
not have been DMSO since similar results were obtained
in DMF or HMPA. Experiments conducted in the presence
of oxygen or in inert atmosphere showed that oxygen is
involved in the formation of 3 :Table 5).
3.1. Sulfonylation of 3-nitroanilines 4 with allylsulfonyl
chloride 5 3general procedure)
To 3-nitro-4-X-aniline :25 mmol) dissolved in the mixture
of dry DCM :50 ml) and pyridine :ca. 30 mmol; 2.5 ml),
cooled to 2208C, allylsulfonyl chloride :ca. 27.5 mmol;
4 g) was added with stirring. The mixture was slowly heated
to the room temperature and stirred until the substrate was
consumed :TLC control). Then the mixture was poured onto
cold diluted aq. HCl solution, the layers were separated and
the aqueous layer was extracted with DCM :3£20 ml).
Combined organic layers were washed with water, dried
:MgSO4), the solvent was evaporated and the residue was
recrystallized or puri®ed on silica gel with hexane±ethyl
acetate mixture as eluent.
On the other hand, the potential intermediate in formation
of 3a, namely, 10a :RˆMe, XˆR0ˆR00ˆH), prepared
independently via condensation of cyclic sultam 159 with
acetaldehyde according to the described procedure,16
3.1.1. Compound 6a. From 4a; yield 76%; yellow crystals;
mp 104±1058C :AcOEt±hexane); [Found: C, 44.52; H,
4.14; N, 11.41%. C9H10N2O4S requires C, 44.62; H, 4.16;
N, 11.56%]: dH: 3.91 :dt, Jˆ7.2, 1.0 Hz, 2H), 5.35 :ddt, Jˆ
17.0, 2.4, 1.0 Hz, 1H), 5.50 :ddt, Jˆ10.0, 2.4, 1.0 Hz, 1H),
5.82±6.03 :m, 1H), 7.23 :broad s, n1/2ˆ4.75, 1H), 7.50±
7.64 :m, 2H), 8.00±8.10 :m, 2H); m/z :int. %): 242 :9.2),
179 :2.5), 178 :23.8), 177 :8.5), 151 :12.6), 131 :11.8), 117
:7.9), 105 :6.3), 91 :22.5); nmax :KBr): 1531.5, 1485.2,
1414.1, 1348.4, 1316.8, 1150.8, 1080.7.
Scheme 5. Reagents and conditions: :a) DMF, K2CO3 :cat.), rt, 1 h;
:b) DBU :5 equiv.), DMSO, rt, 4 min.
3.1.2. Compound 6b. From 4b: yield 55%; light-brown

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Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7903
crystals; mp 137±1388C :AcOEt); [Found: C, 39.10; H,
3.21; N, 10.14%. C9H9N2O4SCl requires C, 39.07; H,
3.28; N, 10.12%]; dH: 3.93 :ddt, Jˆ7.2, 1.6, 0.8 Hz, 2H),
5.32 :ddd, Jˆ17.0, 1.6, 0.8 Hz, 1H), 5.47 :ddt, Jˆ10.1, 1.6,
0.8 Hz, 1H), 5.80±6.01 :m,1H), 7.02 :broad s, n1/2ˆ4.50,
1H), 7.60 :d, Jˆ8.8 Hz, 1H), 7.98 :dd, Jˆ8.8, 2.6 Hz, 1H),
8.59 :d, Jˆ2.6 Hz, 1H); m/z :int. %): 278 :11.9), 276 :32.3),
214 :11.5), 213 :7.4), 212 :37.2), 211 :11.8), 187 :8.6), 185
:28.5), 178 :6.7), 177 :50.4), 168 :5.0), 167 :5.2), 166 :8.0),
165 :12.7); nmax :KBr): 1524.2, 1479.4, 1400.5, 1347.2,
1331.9, 1244.7, 1221.7, 1155.2, 1139.2, 1044.0; accompa-
nied with3-nitro- N,N-di:prop-2-enylsulfonyl)aniline: light-
yellow crystals; mp 109±1118C :AcOEt±hexane); dH: 4.22
:ddt, Jˆ13.8, 6.3 Hz, 1.1, 2H), 4.62 :ddt, Jˆ13.8, 7.0,
0.8 Hz, 2H), 5.62 :m, 2H), 5.68 :m, 2H), 5.82±6.02 :m,
2H), 7.70 :dd, Jˆ8.8, 0.5 Hz, 1H), 8.26 :dt, Jˆ8.8,
2.6 Hz, 1H), 8.33 :dd, Jˆ2.6, 0.5 Hz, 1H); nmax :KBr):
1529.7, 1379.8, 1351.0, 1227.0, 1156.1, 1063.9; m/z :int.
%): 380 :,1.0), 350 :,1.0), 318 :2.1), 276 :5.6), 337
:6.3), 225 :5.5), 217 :12.4), 212 :10.9), 211 :10.8):
LSIMS: 381 :M1H)1.
residue recrystallized. The mother liquor was puri®ed on
silica gel with hexane±ethyl acetate mixture as eluent.
3.2.1. Compound 1a. Light-yellow crystals; mp 668C, :aq.
MeOH); [Found: C, 46.90; H, 4.78; N, 11.06%.
C10H12N2O4S requires C, 46.87: H, 4.72; N, 10.93%]; dH:
3.44 :s, 3H), 3.83 :dt, Jˆ7.2, 1.0 Hz, 2H), 5.43 :ddd, Jˆ
16.9, 2.3, 1.1 Hz, 1H), 5.48 :ddt, Jˆ10.1, 2.3, 1.1 Hz, 1H),
5.80±6.01 :m, 1H), 7.57 :t, Jˆ8.1 Hz, 1H), 7.80 :ddd, Jˆ
8.1, 2.1, 1.0 Hz, 1H), 8.14 :ddd, Jˆ8.1, 2.1, 1.0 Hz, 1H),
8.22 :t, Jˆ2.1 Hz, 1H); m/z :int. %): 256 :20.3), 192 :7.8),
191 :10.1), 177 :15.0), 165 :37.9), 146 :12.5), 145 :14.5),
105 :35.9), 104 :23.7); nmax :KBr): 1641.3, 1578.9, 1531.6,
1479.0, 1347.3, 1313.0, 1261.5, 1179.5, 1150.2, 1088.5,
1052.9.
3.2.2. Compound 1b. Brown oil; [Found: C, 52.32; H, 6.28;
N, 9.51%. C13H18N2O4S requires C, 52.33; H, 6.08; N,
9.39%]; dH: major b,g isomer :.90%): 0.88 :t, Jˆ7.5 Hz,
3H), 1.24±1.52 :m, 4H), 3.73±3.81 :m, 4H), 5.44 :ddt, Jˆ
11.3, 2.4, 1.2 Hz, 1H), 5.50 :ddt, Jˆ4.7, 2.4, 1.2 Hz, 1H),
5.82±6.03 :m, 1H), 7.75 :ddd, Jˆ8.0, 2.1, 1.2 Hz, 1H), 8.16
:m, 2H); minor, a,b isomer :,10%): 1.94 :dd, Jˆ6.8,
1.6 Hz, 3H), 3.58±3.66 :m, 4H), 6.20 :ddd, Jˆ15.0, 3.3,
1.6 Hz, 1H), 6.61±6.79 :m, 1H), other signals overlapped
with those of the major isomer; m/z :int. %): 298 :17.5), 255
:26.8), 193 :8.6), 192 :9.2), 191 :74.7), 151 :19.8); nmax
:®lm): 1640.5, 1614.3, 1532.1, 1477.8, 1423.8, 1350.5,
1303.8, 1247.1, 1144.2, 1099.1, 1072.4.
3.1.3. Compound 6c. From 4c: yield 76%; light-yellow
crystals; mp 130±1358C :AcOEt±hexane); [Found: C,
46.67; H, 4.84; N, 11.00%. C10H12N2O4S requires C,
46.87; H, 4.72; N, 10.93%]: dH: 2.40 :s, 3H), 3.94 :dt, Jˆ
7.2, 1.2 Hz, 2H), 5.33 :ddd, Jˆ17.0, 2.3, 1.2 Hz, 1H), 5.49
:ddd, Jˆ10.1, 2.3, 1.2 Hz, 1H), 5.83±6.05 :m, 1H), 7.38 :d,
Jˆ8.4 Hz, 1H), 7.97 :dd, Jˆ8.4, 2.4 Hz, 1H), 8.39 :d, Jˆ
2.4 Hz, 1H); dC: 147.16, 136.33, 136.02, 131.69, 125.02,
124.92, 119.97, 115.70, 56.81, 18.25; :m/z, %): 257 :1.9),
256 :11.9), 192 :10.8), 177 :6.1), 175 :5.2), 165 :14.9), 163
:8.0), 151 :6.2), 146 :7.8), 145 :12.6), 144 :4.7), 117 :12.5);
3.2.3. Compound 1c. Brown oil; [Found: C, 51.40; H, 5.25;
N, 10.03%. C12H14N2O4S requires C, 51.05; H, 5.00; N,
9.92%]: dH: major b,g isomer :.96%): 3.84 :dt, Jˆ7.1,
1.0 Hz, 2H), 4.36 :dt, Jˆ6.3, 1.2 Hz, 2H), 5.11±5.21 :m,
2H), 5.45 :ddt, Jˆ13.3, 2.4, 1.2 Hz, 1H), 5.52 :ddt, Jˆ6.6,
2.4, 1.2 Hz, 1H), 5.68±6.05 :m, 2H), 7.53±7.62 :m, 1H),
7.70±7.76 :m, 1H), 8.13±8.19 :m, 2H); minor, a,b isomer
:traces): 1.96 :dd, Jˆ6.9, 1.7 Hz, 3H), 4.26 :dt, Jˆ6.2,
1.3 Hz, 2H), 6.18±6.28 :m, 1H), 6.65±6.83 :m, 1H); m/z
:int. %): 282 :6.1), 217 :3.5), 203 :6.5), 191 :16.9), 189
:5.9), 177 :15.9), 176 :8.7), 172 :5.9), 171 :8.4), 150
:6.2), 149 :20.3); nmax :KBr): 1641.8, 1613.4, 1532.0,
1480.1, 1422.6, 1351.3, 1227.4, 1197.6, 1153.2, 1067.4.
nmax :KBr): 1642.7, 1595.3, 1519.2, 1496.8, 1416.8, 1349.5,
1334.9, 1312.2, 1277.5, 1150.3, 1092.4.
3.1.4. Compound 6d. From 4d; yield 90%; dark-yellow
crystals; mp 126±1278C :AcOEt±hexane); [Found: C,
44.12; H, 4.54; N, 10.40%. C10H12N2O5S [272.05]: C,
44.11; H, 4.44; N, 10.29%]: dH: 3.87 :dt, Jˆ7.2, 1.2 Hz,
2H), 4.01 :s, 3H), 5.26 :ddt, Jˆ17.0, 2.4, 1.2 Hz, 1H),
5.43 :ddt, Jˆ10.2, 2.4, 1.2 Hz, 1H), 5.79±6.00 :m, 1H),
6.98 :d, Jˆ9.1 Hz, 1H), 6.99 :broad s, 1H), 8.06 :dd, Jˆ
9.1, 2.7 Hz, 1H), 8.46 :d, Jˆ2.7 Hz, 1H); m/z :int. %): 274
:4.9), 273 :9.9), 272 :79.3), 209 :4.8), 208 :41.3), 207 :6.0),
181 :18.2), 179 :12.2), 168 :10.5), 167 :100.0), 151 :12.2);
3.2.4. Compound 1d. Light-brown crystals; mp 127±1288C
:AcOEt±hexane); [Found: C, 58.01: H, 4.87; N, 8.41%.
C16H16N2O4S requires C, 57.83; H, 4.85; N, 8.43%]: dH:
major b,g isomer :.96%): 3.86 :dt, Jˆ7.2, 1.0 Hz, 2H),
4.93 :s, 2H), 5.44±5.57 :m, 2H), 5.88±6.09 :m, 1H),
7.21±7.26 :m, 5H), 7.48 :dd, Jˆ8.1, 0.3 Hz, 1H), 7.66
:ddd, Jˆ8.1, 2.1, 1.2 Hz, 1H), 8.06±8.12 :m 1H), 8.14±
8.17 :m, 1H); minor, a,b isomer :traces): 1.97 :dd, Jˆ6.9,
1.6 Hz, 3H), 4.81 :s, 2H), 6.28 :dq, Jˆ15.0, 1.6 Hz, 1H),
6.69±6.87 :m, 1H); m/z :int. %): 332 :2.5), 227 :7.6), 226
:14.9); nmax :KBr): 1527.9, 1455.5, 1344.1, 1300.1, 1247.6,
1221.3, 1140.7, 1061.9.
nmax :KBr): 1593.3, 1521.3, 1401.5, 1342.5, 1267.9, 1151.9,
1084.8.
3.2. Preparation of 1 by alkylation of 6 3general
procedure)
To the solution of 6 :10 mmol) in DMF :25 ml), K2CO3
:50 mmol, 6.9 g) was added :in some cases acompanied
withaddition of KI, 1 mmol, ca. 170 mg) followed by the
addition of alkyl halide :50 or 30 mmol, see Table 1). The
reaction ¯ask was stoppered and the mixture stirred
vigorously until the starting material was consumed :TLC
control). The mixture was poured into cold aq. HCl solution
and extracted withAcOEt :3 £50 ml). The combined
organic layers were washed with diluted NaCl solution,
3.2.5. Compound 1e. Light-yellow crystals; mp 83±848C
:AcOEt±hexane); [Found: C, 41.32; H, 3.88; N, 9.60%.
C10H11N2O4SCl requires C, 41.31; H, 3.81; N, 9.63%]: dH:
3.33 :s, 3H), 3.94 :dt, Jˆ7.1, 1.0 Hz, 2H), 5.49±5.60 :m,
2H), 5.90±6.10 :m, 1H), 7.67 :d, Jˆ8.3 Hz, 1H), 8.18 :dd,
Jˆ8.8, 2.6 Hz, 1H); m/z :int. %): 278 :5.2), 276 :13.4), 216
dried withMgSO , the solvent was evaporated and the
4

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Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7904
:6.2), 212 :19.1), 185 :10.4), 177 :20.5); nmax :KBr):
1522.1, 1473.5, 1353.9, 1337.8, 1206.7, 1189.9, 1139.3,
1088.3.
7.6 :t, 8.2, 1H), 7.89 :ddd, Jˆ8.2, 2.2, 1.1 Hz, 1H), 8.18
:ddd, Jˆ8.2, 2.2, 1.1 Hz, 1H), 8.36 :t, Jˆ2.2 Hz, 1H); m/z
:int. %): 367 :1.1), 321 :3.7), 302 :2.4), 293 :2.6), 215 :2.9),
159 :15.9), 153 :6.3), 152 :100.0); nmax :KBr): 1611.8,
1533.7, 1479.9, 1463.3, 1359.1, 1291.3, 1252.5, 1214.2,
1183.3, 1159.5, 1067.8, 1012.4.
3.2.6. Compound 1f. Light-yellow crystals; mp 60±618C
:AcOEt±hexane); [Found: C, 46.93; H, 5.30; N, 8.24%.
C13H17N2O4SCl requres C, 46.92; H, 5.15; N, 8.42%]: dH:
0.89 :t, Jˆ7.1 Hz, 3H), 1.23±1.52 :m, 4H), 3.68 :broad s,
2H), 3.90 :d, Jˆ7.1 Hz, 2H), 5.45±5.50 :m, 1H), 5.52±5.58
:m, 1H), 5.87±6.08 :m, 1H), 7.67 :d, Jˆ8.8 Hz, 1H), 8.19
:dd, Jˆ8.8, 2.7 Hz, 1H), 8.30 :d, Jˆ2.7 Hz, 1H); m/z :int.
%): 334 :1.6), 332 :4.6), 291 :13.0), 289 :34.2), 227 :34.8),
226 :10.5), 225 :77.6), 186 :24.7), 139 :12.5); nmax :KBr):
1528.4, 1469.1, 1343.4, 1203.5, 1142.5, 1081.3, 1048.3.
3.4. Synthesis of 1i±l by condensation of
phosphonosulfonamide 9 with carbonyl compounds
3general procedure)
Phosphonosulfonamide 9 :1830 mg, 5 mmol), LiBr :653 mg,
7.5 mmol) and the carbonyl compound :7.5 mmol) were
dissolved in dry THF and cooled to 2208C then treated
withDBU :900 ml, 6 mmol). The mixture turned deep-red
and yellow solid precipitated immediately. The cooling bath
was removed and the mixture stirred at rt until the starting 9
was consumed :TLC control). After pouring into ice-cold
aq. HCl solution, extraction withDCM :3 £50 ml), drying
the extracts with MgSO4 and evaporation of the solvent, the
residue was puri®ed on silica gel with hexane±ethyl acetate
mixture as eluent to yield products 1i±l.
3.2.7. Compound 1g. Light-yellow crystals; mp 70±718C
:MeOH); [Found: C, 48.87; H, 5.29; N, 10.40%.
C11H14N2O4S requires C, 48.88; H, 5.22; N, 10.36%]: dH:
2.53 :s, 3H), 3.29 :s, 3H), 3.93 :dt, Jˆ7.2, 1.1 Hz, 2H),
5.52±5.64 :m, 2H), 5.92±6.12 :m, 1H), 7.48 :dt, Jˆ8.3,
0.6 Hz, 1H), 8.13 :dd, Jˆ8.3, 2.3 Hz, 1H), 8.17 :d, Jˆ
2.3 Hz, 1H); dH: 147.49, 146.58, 140.83, 132.25, 125.48,
124.75, 123.72, 123.29, 55.87, 39.40, 18.86; m/z :int. %):
271 :4.9), 270 :36.9), 191 :12.3), 189 :11.2), 179 :14.2), 166
:10.7) 165 :100.0), 160 :12.7), 119 :81.7), 118 :38.6); nmax
:KBr): 1587.4, 1519.2, 1351.5, 1341.4, 1293.4, 1183.9,
1139.2, 1054.3.
3.4.1. Compound 1i. From 9 and cyclohexanone; yield
72%; yellow crystals, mp 61±628C; [Found: C, 54.46; H,
6.08; N, 8.96%. C14H18N2O4S requires C, 54.19; H, 5.85; N,
9.03%]: dH: 1.40±1.71 :m, 6H), 2.21 :t, Jˆ6.2 Hz, 2H),
2.46 :t, Jˆ6.2 Hz, 2H), 3.33 :s, 3H), 5.90 :s, 1H), 7.55
:ddd, Jˆ8.1, 7.7, 1.0 Hz, 1H), 7.79 :ddd, Jˆ8.1, 2.2,
1.1 Hz, 1H), 8.08±8.17 :m, 2H); m/z :int. %): 310 :18.3),
246 :15.4), 229 :13.0), 203 :18.1), 190 :19.3), 152 :44.5);
nmax :KBr): 1525.6, 1338.4, 1317.9, 1146.2, 1098.4.
3.2.8. Compound 1h. Light-brown crystals; mp 119±1208C
:aq. MeOH); [Found: C, 46.16; H, 5.05; N, 9.76%.
C11H14N2O5S requires C, 46.15; H, 4.93; N, 9.78%]: dH:
major b,g isomer: 3.27 :s, 3H), 3.85 :dt, Jˆ7.3, 1.0 Hz,
2H), 4.03 :s, 3H), 5.51±5.57 :m, 2H), 5.85±6.04 :m, 1H);
minor, a,b isomer: 6.23 :ddd, Jˆ15.0, 3.4, 1.7 Hz, 1H),
6.64±6.83 :m, 1H); aromatic part for bothisomers: 6.99±
7.04 :m, 1H), 8.22±8.27 :m, 2H); m/z :int. %): 287 :3.00),
286 :22.6), 182 :10.2), 181 :100.0), 166 :18.9), 165 :13.5),
136 :6.5), 135 :43.5); nmax :KBr): 1588.8, 1511.4, 1498.7,
1332.0, 1287.6, 1190.8, 1140.4, 1057.1, 1018.2.
3.4.2. Compound 1j. From 9 and Me2CO; yield 62%; light-
yellow oil; [Found: 48.83; H, 5.15; N, 10.42%.
C11H14N2O4S requires C, 48.88; H, 5.22; N, 10.36%]: dH:
major, a,b isomer: 1.94 :s, 3H), 1.95 :s, 3H), 3.32 :s, 3H),
5.94±5.97 :m, 1H); minor, b,g isomer: 1.94 :s, 3H), 3.45 :s,
3H), 3.76 :s, 2H), 5.06±5.09 :m, 1H): aromatic part for
both: 7.50±7.60 :m, 1H), 7.75±7.84 :m, 1H), 8.10±8.23
:m, 2H); m/z :int. %): 271 :3.6), 270 :25.8), 207 :6.4),
206 :40.7), 205 :6.8), 192 :7.8), 191 :68.5), 189 :4.6), 174
:8.6), 166 :9.2), 165 :100.0), 160 :12.4), 152 :27.9); nmax
:®lm): 1631.9, 1531.8, 1479.2, 1444.1, 1350.9, 1316.4,
1166.4, 1146.9, 1100.6, 1067.6.
3.3. Synthesis of phosphonosulfonamide 9 3similiar to
lit.10)
To the solution of LDA prepared from diisopropylamine
:12.4 ml, 88 mmol) and n-BuLi :8.8 ml of 10 M solution
in hexane, 88 mmol) in dry THF :350 ml) and TMEDA
:8 ml) a solution of N-methyl-N-3-nitrophenyl methane-
sulfonamide 79 :9.2 g, 40 mmol) in THF :50 ml) was
added quickly at 2708C under nitrogen. The dark-red
mixture was then stirred 5 min and treated with diethyl
chlorophosphate :2.7 ml, 15 mmol). After stirring for
10 min. at 2708C the mixture was quenched with aq. HCl
and extracted withDCM :3 £50 ml). Combined organic
extracts were washed with water, dried :MgSO4), the
solvent was evaporated and the residue chromatographed
on silica gel withDCM as eluent to yield the substrate
:1.86 g; 20% recovery) and product 9 :6.90 g; 47%).
3.4.3. Compound 1k. From 9 and PhCH2CHO: yield 63%;
yellow crystals; mp 858C :EtOH); [Found: C, 57.95; H,
4.52; N, 8.37%. C16H16N2O4S requires C, 57.82; H, 4.85;
N, 8.43%]: dH: 3.44 :s, 3H), 3.99 :dd, Jˆ6.5, 1.1 Hz, 2H),
6.15 :dt, Jˆ15.9, 7.4 Hz, 1H), 6.64 :dt, Jˆ15.9, 1.1 Hz, 1H),
7.28±7.37 :m, 5H), 7.51 :t, Jˆ8.2 Hz, 1H), 7.80 :ddd, Jˆ
8.2, 2.3, 1.0 Hz, 1H), 8.07 :ddd, Jˆ8.2, 2.3, 1.0 Hz, 1H),
8.19 :t, Jˆ2.3 Hz, 1H); LSIMS: 355 :M1Na)1; nmax :KBr):
1524.0, 1483.1, 1448.2, 1404.4, 1351.6, 1295.2, 1274.0,
1238.6, 1143.6, 1066.8.
3.4.4. Compound 1l. From 9 and PhCOMe; yield 60%; in
this case 10 equiv. of carbonyl compound and MeCN as a
solvent were used; yellow oil; [Found: C, 57.92; H, 4.92; N,
8.41%. C16H16N2O4S [332.39]: C, 57.82; H, 4.85; N,
8.43%]: two isomers :separated from a small sample); dH:
major, a,b isomer: 2.23 :d, Jˆ1.3 Hz, 3H), 3.39 :s, 3H),
3.3.1. Compound 9. Light-yellow crystals; mp 67±698C
:AcOEt±hexane); [Found: C, 39.21; H, 5.55; N, 7.41%.
C12H19N2O7SP requires C, 39.35; H, 5.23; N, 7.65%]: dH:
1.36 :dt, Jˆ7.1 Hz, 3JPHˆ0.6 Hz, 6H), 3.50 :s, 3H), 3.60 :d,
2
1JPHˆ17 Hz, 2H), 4.22 :dq, Jˆ7.1 Hz, JPHˆ8.3 Hz, 4H),

Â
Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7905
6.36 :q, Jˆ1.3 Hz, 1H), 7.33±7.44 :m, 5H), 7.57 :td, Jˆ8.2,
0.4 Hz, 1H), 7.8 :ddd, Jˆ8.2, 2.2, 1.1 Hz, 1H), 8.15 :ddd,
Jˆ8.2, 2.2, 1.1 Hz, 1H), 8.21 :td, Jˆ2.2, 0.4 Hz, 1H); m/z
:int. %): 332 :2.7), 270 :2.0), 269 :17.9), 268 :100.0), 253
:15.9), 210 :7.5); minor, b,g isomer: 3.25 :s, 3H), 4.27 :d,
Jˆ0.7 Hz, 2H), 5.54 :d, Jˆ0.7 Hz, 1H), 5.73 :d, Jˆ0.7 Hz,
1H), 7.28±7.35 :m, 5H), 7.46 :t, Jˆ8.1 Hz, 1H), 7.64 :ddd,
Jˆ8.1, 2.2,1.1 Hz, 1H), 7.85 :t, Jˆ2.2 Hz, 1H), 8.04 :ddd,
Jˆ8.2, 2.2, 1.1 Hz, 1H); m/z :int. %): 332 :0.5), 296 :2.6),
270 :12.0), 269 :14.9), 268 :78.9), 206 :12.7); nmax :®lm):
1604.4, 1573.4, 1531.4, 1479.2, 1444.4, 1351.2, 1167.7,
1148.8, 1100.7, 1067.4.
:5.7), 220 :12.3), 219 :100.0), 207 :8.5), 206 :60.9), 142
:21.6), 128 :48.1); nmax :KBr): 1621.0, 1594.6, 1470.2,
1410.1, 1364.6, 1326.5, 1208.5, 1157.1, 1137.5. Compound
3b: Light-brown crystals; mp 102±1038C :aq. EtOH);
[Found: C, 56.15; H, 5.13; N, 10.06%. C13H14N2O3S: C,
56.10; H, 5.07; N, 10.06%]: dH: 1.02 :t, Jˆ7.4 Hz, 3H),
1.42±1.60 :m, 2H), 1.82±1.97 :m, 2H), 3.81 :t, Jˆ7.5 Hz,
2H), 6.82 :d, Jˆ7.5 Hz, 1H), 7.68 :d, Jˆ6.4 Hz, 1H), 7.73
:dd, Jˆ8.9, 7.5 Hz, 1H), 7.92 :d, Jˆ8.9 Hz, 1H), 8.57 :d, Jˆ
6.4 Hz, 1H); m/z :int. %): 280 :6.0), 279 :16.4), 278 :100.0),
262 :11.7), 236 :8.80), 235 :10.7), 222 :63.2), 219 :15.3),
206 :9.9), 154 :19.1), 128 :18.3); nmax :KBr): 1632.7,
1562.1, 1499.1, 1431.6, 1391.7, 1326.5, 1225.0, 1170.9.
3.5. Reaction of 3-nitroarylallylsulfones 1 with DBU and
MgCl2
3.5.3. From the reaction of 1c. Compound 2c: Light-brown
crystals; mp 1128C :AcOEt±hexane); [Found: C, 58.29;
3.99; N, 11.40%. C12H10N2O2S: C, 58.52; H, 4.09; N,
11.37%]: dH: 4.44 :dt, Jˆ5.5, 1.6 Hz, 2H), 5.38 :ddt, Jˆ
10.2, 1.6, 1.0 Hz, 1H), 5.50 :ddt, Jˆ17.1, 1.6, 1.0 Hz, 1H),
5.92±6.11 :m, 1H), 6.79 :dd, Jˆ6.5, 1.4 Hz, 1H), 7.69±7.83
:m, 2H), 7.82 :d, Jˆ4.5 Hz, 1H), 9.25 :d, Jˆ4.5 Hz, 1H);
m/z :int. %): 248 :5.8), 247 :15.2), 246 :100.0), 206 :7.5),
182 :7.2), 181 :31.8), 155 :10.6), 154 :7.2), 142 :9.7), 128
:16.9); nmax :KBr): 1621.6, 1594.8, 1468.5, 1405.9, 1360.0,
1320.8, 1259.8, 1206.7, 1160.3, 1134.6. Compound 3c:
Yellow crystals; mp 174±1758C :MeOH); [Found: C,
55.09; H, 3.78; N, 10.69%. C12H10N2O3S requires C,
54.95; H, 3.84; N, 10.62%]: dH: 4.42 :dt, Jˆ5.6, 1.5 Hz,
2H), 5.40 :ddd, Jˆ10.2, 2.4 Hz, 1H), 5.50 :ddd, Jˆ16.1,
2.4, 1.5 Hz, 1H), 5.90±6.10 :m, 1H), 6.81 :d, Jˆ7.5 Hz,
1H), 7.70 :d, Jˆ6.3 Hz, 1H), 7.72 :dd, Jˆ8.9, 7.5 Hz,
1H), 7.93 :d, Jˆ8.9 Hz, 1H), 8.58 :d, Jˆ6.3 Hz, 1H); m/z
:int. %): 264 :3.1), 263 :6.9), 262 :46.5), 221 :6.7), 197
:4.6), 181 :8.3); nmax :KBr): 1631.0, 1561.1 1499.0,
1432.0, 1391.4, 1225.4, 1169.8, 1156.5, 1129.3, 1080.4.
Procedure A. Compound 1 :1 mmol) and MgCl2 :0.625
mmol, 60 mg) were dissolved in dry DMSO :10 ml), DBU
:746 ml, 5 mmol) was added in one portion, the reaction vial
stoppered and the mixture stirred for the time indicated in
Table 4 until the starting material disappeared :TLC
control). In the selected experiments :Scheme 5, Table 5)
Ar or O2 was bubbled through the reaction mixture for
indicated time prior to the addition of DBU and then during
the reaction. After completion, the mixture was poured into
saturated aq. NH4Cl solution and extracted withAcOEt
:3£20 ml). The combined extracts were washed with dil.
NaCl solution, dried withMgCl 2 the solvent was evaporated
and the residue separated on silica gel with hexane±ethyl
acetate mixture as eluent.
Procedure B. After performing procedure A, the crude
mixture was heated to re¯ux with triethylphosphite for
30 min to 1 h:Table 4). Teh volatiles were removed
under vacuum and the residue chromatographed on silica
gel withhexane±ethyl acetate mixture as eluent.
3.5.4. From the reaction of 1d. Compound 2d: Light-
brown crystals; mp 127±1288C :AcOEt±hexane); [Found:
C, 64.77; H, 3.97; N, 9.46%. C16H12N2O2S requires C,
64.85; H, 4.08; N, 9.45%]: dH: 4.99 :s, 2H), 6.54 :dd,
Jˆ6.2, 1.7 Hz, 1H), 7.30±7.45 :m, 3H), 7.47±7.55 :m,
2H), 7.60±7.73 :m, 2H), 7.86 :d, Jˆ4.5 Hz, 1H), 9.26 :d,
Jˆ4.5 Hz, 1H); m/z :int. %): 297 :5.6), 296 :28.0), 92 :7.3),
91 :100.0); nmax :KBr): 1624.3, 1595.8, 1482.2, 1468.9,
1266.9, 1317.2, 1211.1, 1158.2, 1139.5. Compound 3d:
Brown crystals; mp 181±1828C :AcOEt); [Found: C,
61.27; H, 3.83; N, 8.88%. C16H12N2O3S requires C, 61.53;
H, 3.87; N, 8.97%]: dH: 4.97 :s, 2H), 6.56 :d, Jˆ7.5 Hz,
1H), 7.33±7.52 :m, 5H), 7.58 :dd, Jˆ8.8, 7.5 Hz, 1H), 7.74
:d, Jˆ6.3 Hz, 1H), 7.89 :d, Jˆ8.8 Hz, 1H), 8.59 :d, Jˆ
6.3 Hz, 1H); m/z :int. %): 313 :3.1), 312 :15.5), 296 :3.4),
92 :8.2), 91 :100.0); nmax :KBr): 1633.3, 1604.4, 1559.3,
1498.2, 1456.1, 1432.5, 1391.1, 1361.5, 1316.6, 1291.3,
1172.8, 1147.4, 1127.7, 1074.6.
The following products were isolated:
3.5.1. From the reaction of 1a. Compound 2a: Yellow
crystals; mp 143±1448C :AcOEt±hexane); [Found: C,
54.62; H, 3.48; N, 12.76%. C10H8N2O2S requires C,
54.53; H, 3.66; N, 12.72%]: dH lit.4; m/z :int. %): 222
:5.7), 221 :12.4), 220 :100.0), 156 :9.9), 155 :78.6), 129
:40.6), 128 :55.3), 102 :19.7), 101 :19.2); nmax :KBr):
1626.3, 1597.2, 1466.1, 1362.5, 1315.1, 1277.4, 1192.4,
1153.7, 1135.3, 1036.1. Compound 3a: Light green crystals;
mp 228±2298C :MeOH); [Found: 50.66, H, 3.31; N,
11.95%. C10H8N2O3S requires C, 50.84; H, 3.41; N,
11.86%]: dH lit.4; m/z :int. %): 238 :5.3), 237 :11.1), 236
:100.0), 221 :5.0), 220 :26.6), 188 :35.5), 171 :8.8), 155
:17.5), 143 :9.8), 128 :16.1), 116 :19.1), 115 :12.3), 114
:7.8); nmax :KBr): 1631.8, 1561.3, 1498.8, 1462.4, 1418.1,
1388.5, 1322.1 1285.1, 1223.3, 1169.3, 1154.7.
3.5.5. From the reaction of 1e. Compound 3e: Pale-yellow
crystals; mp 214±2158C :AcOEt); [Found: C, 43.10; H,
2.72; N, 11.21%. C10H7N2O2SCl: C, 47.16; H, 2.77; N,
11.00%]: dH: 3.67 :s, 3H), 7.70 :s, 2H), 7.85 :d, Jˆ
4.5 Hz, 1H), 9.23 :d, Jˆ4.5 Hz, 1H); m/z :int. %): 257
:4.7), 256 :37.3), 255 :12.6), 254 :100.0), 191 :14.1), 190
:5.5), 189 :43.5), 163 :14.7), 162 :18.5), 155 :16.2); nmax
:KBr): 1616.2, 1595.0, 1469.6, 1437.0, 1405.7, 1349.2,
3.5.2. From the reaction of 1b. Compound 2b: Dark-green
crystals; mp 68±698C :CCl4±hexane); [Found: C, 59.64; H,
5.49; N, 10.65%. C13H14N2O2S requires C, 59.52; H, 5.38;
N, 10.68%]: dH: 1.01 :t, Jˆ7.3 Hz, 3H), 1.38±1.62 :m, 2H),
1.84±1.98 :m, 2H), 3.82 :t, Jˆ7.5 Hz, 2H), 6.78 :dd, Jˆ7.1,
0.8 Hz, 1H), 7.69 :dd, Jˆ8.8, 0.8 Hz, 1H), 7.79 :dd, Jˆ8.8,
7.1 Hz, 1H), 7.80 :d, Jˆ4.6 Hz, 1H), 9.23 :d, Jˆ4.6 Hz,
1H); m/z :int. %): 264 :4.9), 263 :12.9), 262 :81.5), 221

Â
Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7906
1321.9, 1247.4, 1207.8, 1168.0, 1142.3, 1114.6. Compound
3e: Yellow crystals; mp 252±2578C :dec., ClCH2CH2Cl±
AcOEt); [Found: 44.47; H, 2.31; N, 10.28%. C10H7N2O3SCl
requires C, 44.47; H, 2.61; N, 10.37%]: dH: 3.68 :s, 3H),
7.63 :d, Jˆ9.4 Hz, 1H), 7.74 :d, Jˆ6.4 Hz, 1H), 7.93 :d,
Jˆ9.4 Hz, 1H), 8.55 :d, Jˆ6.4 Hz, 1H); m/z :int. %): 272
:37.8), 271 :12.5), 270 :100.0), 256 :10.4), 254 :27.8); nmax
:KBr): 1564.7, 1490.7, 1372.3, 1328.9, 1223.3, 1201.9,
1166.8, 1139.4.
1490.8, 1473.3, 1405.8, 1348.8, 1314.7, 1301.0, 1204.6,
1156.0, 1129.5, 1080.2.
3.5.9. From the reaction of 1i. Compound 2i: Yellow
crystals; mp 1818C :EtOH); [Found: C, 61.12; H, 4.98; N,
10.21%. C14H14N2O2S requires C, 61.29; H, 5.14; N,
10.21%]: dH: 1.93±2.13 :m, 4H), 3,24 :t, Jˆ6.3 Hz, 2H),
3.33 :s, 3H), 3.38 :t, Jˆ6.3 Hz, 2H), 6.64 :d, Jˆ7.1 Hz, 1H),
7.53 :dd, Jˆ8.8 Hz, 0.8, 1H), 7.64 :dd, Jˆ8.8, 7.1 Hz, 1H);
m/z :int. %): 276 :6.3), 275 :16.7), 274 :100.0), 209 :22.1),
182 :11.5), 181 :7.2), 169 :6.0); nmax :KBr): 1627.2, 1602.9,
1594.2, 1482.6, 1466.5, 1432.4, 1364.4, 1353.3, 1320.3,
1278.4, 1240.2, 1215.5, 1186.8, 1151.7. Compound 3i:
Brown crystals; mp 203±2048C :EtOH); [Found: C,
57.83; H, 4.89; N, 9.61%. C14H14N2O3S requires C, 57.92;
H, 4.86; N, 9.65%]: dH: 1.85±2.10 :m, 4H), 3.12 :t, Jˆ
6.4 Hz, 2H), 3.32 :t, Jˆ6.4 Hz, 2H), 3.34 :s, 3H), 6.68 :d,
Jˆ7.5 Hz, 1H), 7.61 :dd, Jˆ8.8, 7.5 Hz, 1H), 7.88 :d, Jˆ
8.8 Hz, 1H); m/z :int. %): 292 :6.2), 291 :16.2), 290 :100.0),
275 :9.0), 274 :35.9), 273 :89.9), 272 :4.5), 227 :6.4), 226
:8.5), 225 :47.8), 224 :4.9), 210 :11.6), 209 :49.1), 208
:15.2); nmax :KBr): 1636.6, 1608.6, 1579.1, 1494.4,
1465.4, 1423.1, 1393.6, 1349.7, 1315.4, 1290.4, 1242.7,
1174.8, 1150.8, 1108.2, 1073.9.
3.5.6. From the reaction of 1f. Compound 2f: Light-brown
crystals; mp 107±1088C :AcOEt±hexane);[Found: C,
52.71; H, 4.42; N, 9.46%. C10H7N2O2SCl requires C,
52.61; H, 4.42; N, 9.44%]: dH: 1.00 :t, Jˆ7.3 Hz, 3H),
1.40±1.52 :m, 2H), 1.81±1.95 :m, 2H), 4.07±4.16 :m,
2H), 7.69 :s, 2H), 7.83 :d, Jˆ4.5 Hz, 1H), 9.22 :d, Jˆ
4.5 Hz, 1H); m/z :int. %): 298 :16.3), 297 :6.6), 296
:42.9), 255 :14.7), 254 :5.2), 253 :39.1), 242 :35.9), 241
:11.7), 240 :100.0), 189 :8.3), 176 :30.8); nmax :KBr):
1615.5, 1595.3, 1469.0, 1404.5, 1325.1, 1250.7, 1202.0,
1165.6, 1114.4. Compound 3f: Yellow crystals; mp 1748C
:AcOEt±hexane); [Found: C, 49.90; H, 4.15; N, 8.96%.
C13H13N2O3SCl requires C, 49.92; H, 4.19; N, 8.96%]: dH:
1.00 :t, Jˆ7.3 Hz, 3H), 1.38±1.61 :m, 2H), 1.78±1.96 :m,
2H), 4.07±4.15 :m, 2H), 7.62 :d, Jˆ9.4 Hz, 1H), 7.72 :d,
Jˆ6.4 Hz, 1H), 7.93 :d, Jˆ9.4 Hz, 1H), 8.55 :d, Jˆ6.4 Hz,
1H); m/z :int. %): 315 :4.0), 314 :25.2), 313 :10.1), 312
:64.1), 302 :6.2), 298 :5.9), 296 :15.2), 271 :12.9), 270
:5.0), 269 :33.4), 259 :8.2), 258 :37.4), 257 :11.8), 256
:100.0), 253 :14.5), 242 :12.6), 240 :34.6); nmax :KBr):
1627.0, 1586.1, 1565.3, 1495.1, 1470.1, 1434.9, 1398.1,
1365.6, 1336.1, 1286.0, 1217.6, 1185.0, 1164.6, 1142.7,
1070.4.
3.5.10. From the reaction of 1j. Compound 2j: Yellow
crystals; mp 147±1488C :aq. MeOH); [Found: C, 56.52;
H, 4.34; N, 11.84%. C11H10N2O2S requires C, 56.39; H,
4.30; N, 11.96%]: dH: 2.83 :s, 3H), 3,36 :s, 3H), 6.75 :dd,
Jˆ6.2, 1.8 Hz, 1H), 7.62±7.75 :m, 2H), 9.00 :s, 1H); m/z
:int. %): 236 :5.4), 235 :13.6), 234 :100.0), 186 :7.3), 185
:6.1), 170 :16.0), 169 :47.7), 155 :16.5), 142 :11.2); nmax
:KBr): 1610.0 1597.2, 1475.4, 1445.2, 1417.0, 1404.0,
1312.5, 1291.2, 1261.5, 1208.2, 1190.0, 1155.6, 1131.4,
1033.3. Compound 3j: Yellow crystals; mp 237±2388C
:MeOH); [Found: C, 52.70; H, 3.88; N, 11.09%.
C11H10N2O3S requires C, 52.79; H, 4.03; N, 11.19%]: dH:
2.72 :s, 3H), 3.35 :s, 3H), 6.76 :d, Jˆ7.4 Hz, 1H), 7.65 :dd,
Jˆ8.9, 7.4 Hz, 1H), 7.87 :d, Jˆ8.7 Hz, 1H), 8.41 :s, 1H); m/z
:int. %): 252 :5.8), 251 :13.7), 250 :100.0), 235 :3.2), 234
:22.9), 202 :23.8), 169 :15.1); nmax :KBr): 1636.4, 1604.3,
1588.3, 1491.2, 1470.1, 1431.5, 1394.5, 1384.1, 1365.0,
1313.9, 1299.5, 1219.4, 1159.0, 1105.0, 1059.7, 1034.3.
3.5.7. From the reaction of 1g. Compound 2g: Yellow
crystals; mp 222±2268C :AcOEt±hexane); [Found: C,
56.44; H, 4.27; N, 12.13%. C11H10N2O2S requires C,
56.40; H, 4.30; N, 11.96%]: dH: 2.64 :s, 3H), 3.52 :s, 3H),
7.58±7.75 :ABq: dAˆ7.72, dBˆ7.60, Jˆ8.8 Hz, 2H), 7.79
:d, Jˆ4.6 Hz, 1H), 9.16 :d, Jˆ4.6 Hz, 1H); m/z :int. %): 236
:5.5), 235 :12.8), 234 :100.0), 170 :11.4), 169 :81.4), 168
:9.6), 155 :25.5), 143 :9.8), 142 :24.0); nmax :KBr): 1588.6,
1483.6, 1463.8, 1413.0, 1401.7, 1344.9, 1314.0, 1249.3,
1216.7, 1197.3, 1155.4, 1131.6, 1064.6. Compound 3g:
Yellow crystals; mp 251±2528C :AcOEt); [Found: C,
52.05; H, 4.09; N, 11.10%. C11H10N2O3S requires C,
52.79; H. 4.03; N, 11.19%]: dH: 2.63 :s, 3H), 3.53 :s, 3H),
7.57 :d, Jˆ9.0 Hz, 1H), 7.69 :d, Jˆ6.3 Hz, 1H), 7.88 :d,
Jˆ9.0 Hz, 1H), 8.47 :d, Jˆ6.3 Hz, 1H); m/z :int. %): 251
:8.8), 250 :58.4), 235 :12.5), 234 :88.9), 202 :16.2), 186
:13.8), 173 :11.9), 170 :13.9), 169 :100.0), 168 :20.9),
155 :33.5); nmax :KBr): 1621.5, 1304.5, 1569.5, 1493.7,
1483.1, 1461.8, 1421.7, 1391.5, 1367.5, 1308.4, 1282.0,
1226.5, 1204.1, 1162.1, 1147.9, 1125.7, 1076.5.
3.5.11. From the reaction of 1k. Compound 2k: Yellow
crystals; mp 208±2098C :AcOEt); [Found: C, 64.81; H,
3.97; N, 9.55%. C16H12N2O2S requires C, 64.85; H, 4.08;
N, 9.45%]: dH: 3.40 :s, 3H), 6.75 :dd, Jˆ6.5, 1.5 Hz, 1H),
7.52±7.63 :m, 3H), 7.71±7.85 :m 2H), 8.13±8.19 :m, 2H),
8.24±8.26 :m, 1H); m/z :int. %): 297 :18.8), 296 :100.0),
232 :6.3), 231 :19.3), 204 :10.3); nmax :KBr): 1622.8,
1600.2, 1573.4, 1503.1, 1482.9, 1462.3, 1424.0, 1375.9,
1329.0, 1247.2, 1201.7, 1182.8, 1157.1. Compound 3k:
Light-orange crystals; mp 237±2388C :MEK); [Found: C,
61.22; H, 3.77; N, 8.83%. C16H12N2O3S requires C, 61.53;
H, 3.87; N, 8.97%]: dH: 3.40 :s, 3H), 6.82 :d, Jˆ7.5 Hz,
1H), 7.52±7.59 :m, 3H), 7.77 :dd, Jˆ8.9, 7.5 Hz, 1H),
7.85±7.90 :m, 2H), 7.91 :s, 1H), 8.01 :d, Jˆ8.9 Hz, 1H);
m/z :int. %): 313 :13.1), 312 :61.4), 311 :31.9), 298 :6.6),
297 :18.6), 296 :100.0), 248 :7.5), 247 :16.1), 232 :7.7), 231
:22.8), 219 :14.3). nmax :KBr): 1633.5, 1564.7, 1509.0,
1492.5, 1448.9, 1394.3, 1374.7, 1327.7, 1314.7, 1180.4,
1152.5, 1079.3.
3.5.8. From the reaction of 1h. Compound 2h: Yellow
crystals; mp 1788C :MeOH): [Found: C, 52.76; H, 3.94;
N, 11.16%. C11H10N2O3S requires C, 52.79; H, 4.03; N,
11.19%]: dH: 3.55 :s,1H), 4.03 :s, 3H), 7.63 :d, Jˆ9.3 Hz,
1H), 7.78 :d, Jˆ4.5 Hz, 1H), 7.80 :d, Jˆ9.3 Hz, 1H), 9.10
:d, Jˆ4.5 Hz, 1H); m/z :int. %): 286 :5.9), 252 :5.8), 251
:13.7), 250 :100.0), 235 :26.0), 185 :7.0), 181 :24.2), 172
:4.8), 171 :44.6), 166 :5.0); nmax :KBr): 1627.3, 1586.0,

Â
Z. Wrobel / Tetrahedron 57 /2001) 7899±7907
7907
3.5.12. From the reaction of 1l. Compound 2l: Green
crystals; mp 220±2228C :dec., 1,2-dichloroethane±
AcOEt±MeOH); [Found: C, 64.58; H, 3.74; N, 9.55%.
C16H12N2O2S requires C, 64.85; H, 4.08; N, 9.45%]: dH:
3.39 :s, 3H), 6.79 :dd, Jˆ6.3, 1.6 Hz, 1H), 7.51±7.67 :m,
3H), 7.71±7.82 :m, 2H), 7.91±7.97 :m, 2H), 9.26 :s, 1H);
m/z :int. %): 298 :6.5), 297 :19.1), 296 :100.0), 250 :6.9),
249 :4.8), 248 :7.5), 247 :6.4), 232 :18.9), 231 :36.2), 205
:10.5), 204 :18.7); nmax :KBr): 1619.6, 1590.2, 1574.4,
1522.2, 1499.2, 1445.7, 1468.0, 1408.7, 1319.3, 1222.0,
1191.2, 1155.5, 1136.3, 1090.2, 1036.1. Compound 3l:
Deep-red crystals; mp 195±2008C :1,2-dichloroethane±
AcOEt); dH: 3.37 :s, 3H), 6.81 :d, 1H), 7.59±7.65 :m,
3H), 7.70 :dd, Jˆ8.8, 7.4 Hz, 1H), 7.83±7.89 :m, 2H),
7.94 :d, Jˆ8.8 Hz, 1H), 8.69 :s, 1H); m/z :int. %): 314
:6.8), 313 :19.5), 312 :100.0), 297 :11.8), 296 :62.9), 264
:22.3), 248 :6.4), 247 :10.9), 232 :12.0), 231 :28.3), 219
:10.0), 204 :17.2); HRMS: calcd for C16H12N2SO3
[312.0569]; Found: 312.0568; nmax :KBr): 1631.8, 1601.3,
1580.0, 1564.7, 1489.6, 1469.5, 1431.3, 1444.6, 1393.6,
1359.9, 1322.1, 1232.3, 1211.4, 1187.6, 1164.6, 1153.6,
1136.1, 1098.1, 1039.3. Compound 10l: Yellow crystals;
mp 201±2028C :dec.); [Found: C, 58.11; H, 4.26; N,
8.30%. C16H14N2SO4 requires C, 58.17; H, 4.27; N,
8.48%]: dH: 2.74 :s, 3H), 3.28 :s, 3H), 6.36 :d, Jˆ9.2 Hz,
1H), 7.27±7.34 :m, 2H), 7.44±7.54 :m, 5H); m/z :int. %):
332 :6.3), 331 :18.8), 330 :100.0), 301 :2.7), 300 :13.8), 266
:10.1), 265 :7.2), 238 :3.5), 237 :5.4), 236 :26.9), 235 :8.9),
221 :11.3), 220 :39.4), 219 :19.8), 218 :14.9); nmax :KBr):
1620.0, 1605.0, 1590.4, 1522.0, 1467.7, 1444.3, 1418.7,
1339.2, 1319.3, 1300.7, 1269.5, 1193.9, 1162.2, 1125.0,
1100.1.
2.42 :d, Jˆ7.6 Hz, 3H), 3.22 :s, 3H), 6.89 :dd, Jˆ8.0,
1.3 Hz, 1H), 7.1 :q, Jˆ7.6 Hz, 1H), 7.32 :dd, Jˆ8.2,
1.3 Hz, 1H), 7.41 :q, Jˆ8.1 Hz, 1H); m/z :int. %): 256
:6.1), 255 :12.4), 254 :100.0), 237 :11.2), 236 :6.3), 220
:9.2), 173 :16.0), 161 :8.1), 160 :5.7), 148 :7.0), 147
:7.8), 145 :13.7); nmax :KBr): 1639.9, 1606.7, 1525.6,
1469.3, 1449.8, 1362.6, 1329.3, 1304.2, 1203.6, 1169.0,
1154.6, 1121.6.
3.5.14. Conversion of 10a to 3a. 10a :254 mg, 1 mmol) and
MgCl2 :60 mg, 0.625 mmol) were dissolved in DMSO
:10 ml), DBU :746 ml, 5 mmol) was added, the mixture
was stirred for 4 min at rt, and then quenched with saturated
aq. NH4Cl solution. After work up followed by ¯ash
chromatography 3a was isolated :162 mg, 69%).
Acknowledgements
This search was funded by the State Committee of Scienti®c
ResearchGrant No. PBZ 6.01.
References
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Â
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according to the described procedure.16 Sultam 159
:1140 mg, 5 mmol) was dissolved in dry DMF :6 ml),
K2CO3 :30 mg) and the large excess of acetaldehyde
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was poured onto ice-cold aq. dil. HCl, extracted withAcOEt
:3£30 ml), extracts washed with water, dried with MgSO4
and the solvent was evaporated. The residue containing the
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:560 mg, 44%): light-brown crystals; mp 139±1428C :aq.
MeOH); [Found: C, 47.28; H, 3.96; N, 10.82%.
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Â
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Â
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