Ring opening of 2-substituted 4-nitrothiophenes with pyrrolidine. Access to new functionalized nitro-unsaturated building blocks

Article abstract of DOI:10.1016/S0040-4020(01)00765-7

The reaction conditions of the ring-opening processes of 3-nitrothiophene 7a and of 3-nitrobenzo[b]thiophene 7b with pyrrolidine and silver nitrate were optimized as well as those of the subsequent S-methylation of the ensuing silver enethiolates 8a and 8b to 4-methylthio-2-nitro-1-pyrrolidino-1,3-butadiene 9a and 1-(2-methylthiophenyl)-1-nitro-2-pyrrolidinoethylene 9b. Under such conditions 2-X-substituted 4-nitrothiophenes 7c-i consistently gave good yields of the corresponding 4-methylthio-2-nitro-1-pyrrolidino-4-X-1,3-butadienes 9c-i. The nitroenamine derivatives 9a-i were then reacted with p-tolylmagnesium bromide to furnish moderate to good yields of 4-methylthio-2-nitro-1-(p-tolyl)-4-X-1,3-butadienes 10a,c-i and 1-(2-methylthiophenyl)-1-nitro-2-(p-tolyl)ethylene 10b. Stereochemistry of the interesting building blocks 9a-i and 10a-i was assigned on the grounds of ¹H NMR data and NOE experiments.

Full text of DOI:10.1016/S0040-4020(01)00765-7

TETRAHEDRON
Pergamon
Tetrahedron 57 32001) 8159±8165
Ring opening of 2-substituted 4-nitrothiophenes with pyrrolidine.
Access to new functionalized nitro-unsaturated building blocks
Carlo Dell'Erba,a Antonella Gabellini,a Marino Novi,a,p Giovanni Petrillo,a Cinzia Tavani,a
Barbara Cosimellib and Domenico Spinellib
aDipartimento di Chimica e Chimica Industriale, Via Dodecaneso 31, 16146 Genova, Italy
bDipartimento di Chimica Organica `A.Mangini', Via S.Donato 15, 40127 Bologna, Italy
Received 4 April 2001; revised 26 June 2001; accepted 19 July 2001
AbstractÐThe reaction conditions of the ring-opening processes of 3-nitrothiophene 7a and of 3-nitrobenzo[b]thiophene 7b with pyrro-
lidine and silver nitrate were optimized as well as those of the subsequent S-methylation of the ensuing silver enethiolates 8a and 8b to
4-methylthio-2-nitro-1-pyrrolidino-1,3-butadiene 9a and 1-32-methylthiophenyl)-1-nitro-2-pyrrolidinoethylene 9b. Under such conditions
2-X-substituted 4-nitrothiophenes 7c±i consistently gave good yields of the corresponding 4-methylthio-2-nitro-1-pyrrolidino-4-X-1,3-
butadienes 9c±i. The nitroenamine derivatives 9a±i were then reacted with p-tolylmagnesium bromide to furnish moderate to good yields
of 4-methylthio-2-nitro-1-3p-tolyl)-4-X-1,3-butadienes 10a,c±i and 1-32-methylthiophenyl)-1-nitro-2-3p-tolyl)ethylene 10b. Stereo-
chemistry of the interesting building blocks 9a±i and 10a±i was assigned on the grounds of 1H NMR data and NOE experiments.
q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
1,4-disubstituted 2,3-dinitro-1,3-butadienes 3 have proved
to be interesting building blocks allowing the attainment
of a variety of target molecules, both in the aliphatic and
in the heteroaromatic series.6
The reactions of 3,4-dinitrothiophene 1 with secondary
aliphatic amines in ethanol afford 1,4-bis3dialkylamino)-
2,3-dinitro-1,3-butadienes 2 via a ring-opening process
with extrusion of hydrogen sulphide.1,2 Employing the
diethylamino derivative 3Scheme 1, in 2: RˆEt) we have
shown that, by reaction with Grignard reagents, it is possible
to replace the two amino groups with the residue 3alkyl,
aryl, vinyl) of the organometallic reagent.2±5 The ensuing
Related ring-opening processes of the nitrothiophene
moiety include the reactions of 2-nitrothiophene 34) that
undergoes ring opening by treatment with amines and silver
nitrate in ethanol 3Scheme 1).7 Unlike the case of dinitro-
thiophene 1, in the reaction with 4 a carbon±sulphur bond is
retained in the ring-opened product and the resulting silver
butadienethiolates 35) can be S-methylated with excess
methyl iodide to afford the interestingly functionalized
butadienes 6.
Under the same conditions employed for 4, also 3-nitro-
thiophene 7a8 and 3-nitrobenzo[b]thiophene 7b9 have
been shown to consistently react, e.g. with pyrrolidine and
silver nitrate 3Scheme 2), to eventually afford the corre-
sponding ring-opening S-methylated products 9a and 9b.
In spite of the demonstrated substantial utility of the products
arising from the initial ring opening of 1, the processes on
nitrothiophenes above have surprizingly received little atten-
tion with regard to the possible synthetic exploitation of the
ensuing derivatives. In our opinion this may be also due to not
fully satisfactory yields of the processes leading to the poten-
tial building blocks of structure related to 6 and 9.
Scheme 1.
Keywords: nitrothiophenes; ring-opening reactions; functionalized nitro-
butadienes.
Corresponding author. Address: C.N.R. Centro di Studio per la Chimica
p
dei Composti Cicloalifatici e Aromatici, Via Dodecaneso 31, 16146
Genova, Italy. Tel.: 139-010-353-6103; fax: 139-010-362-4337;
e-mail: novi@chimica.unige.it
While similar researches are in progress on a-nitrothio-
phene systems, we report herein on our optimization of
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020301)00765-7

8160
C.Dell'Erba et al./ Tetrahedron 57 /2001) 8159±8165
Scheme 2. a: XˆYˆH; b: X,Yˆ
YˆH; i: XˆCN, YˆH.
; c: XˆPhS, YˆH; d: XˆPhSO2, YˆH; e: XˆMeS, YˆH; f: XˆMeSO2, YˆH; g: XˆMeCO, YˆH; h: XˆCOOMe,
the ring-opening reaction of 7a with pyrrolidine and silver
nitrate and on the extension of such conditions to 7b and to
2-substituted 4-nitrothiophenes 37c±i). The ensuing nitro-
enamines 39a±i) have been successively reacted with
p-tolylmagnesium bromide as a ®rst example of their,
hitherto-unknown and expectedly wide, utilization as
synthetic building blocks.
reported above).
ꢀ1†
As a further check of the above standard procedure, the
3-nitrobenzo[b]thiophene 7b gave, in front of a reported
35% yield,9 62% yield of the ring-opened product 9b,
along with 21% of unreacted 7b: a substantial increase in
yield which, while supporting the previous results, has
encouraged further researches on the use of the ring-opening
reactions of the b-nitrothiophene system with pyrrolidine as
a source of interesting unsaturated building blocks.
2. Results and discussion
2.1. Ring-opening reactions of nitrothiophenes 7a±i with
pyrrolidine and silver nitrate
The reaction of 3-nitrothiophene 7a with pyrrolidine
39 mol equiv.) and silver nitrate 31.1 mol equiv.) was ®rst
carried out as reported in the literature.8 After 30 h at
room temperature, the resulting silver butadienethiolate 8a
was ®ltered, washed with ethanol, ether, dried and reacted
with excess methyl iodide. Through the described workup
31E,3Z)-4-methylthio-2-nitro-1-pyrrolidino-1,3-butadiene
9a was isolated in a yield 330%) in good agreement with the
reported one 324%).
Our ring-opening procedure with pyrrolidine and silver
nitrate was extended to nitrothiophenes 7c±i and the results
obtained are collected in Table 1 together with those
relevant to the above mentioned reactions on 7a and 7b.
Inspection of such results suggests that the procedure may
be of quite general applicability since satisfactory yields of
the expected nitrobutadienes 9c±i were obtained. The data
of Table 1 also suggest that the conversion of 7 into 9 could
possibly be further optimized since variable amounts of
unreacted nitrothiophene were recovered.
In order to test whether the yield of 9a could be improved by
a proper choice of the experimental conditions, we carried
out several successive experiments on the above reaction on
7a with modi®cations both of the reaction 3solvent, time
and, in particular, the 7a±amine±AgNO3 molar ratio) and
the operative variables 3use of sonication, puri®cation of the
intermediate 8a). The best conditions eventually found
required the treatment of 7a and AgNO3 32.0 mol equiv.)
in absolute ethanol with 2.2 mol equiv. of pyrrolidine at
room temperature. The use of sonication in an ultrasonic
cleaner during the ®rst 30 min of reaction generally assured
precipitation of a crystalline silver butadienethiolate. After
standing overnight in the dark, from the reaction mixture
most of the ethanol was evaporated under vacuum and
excess methyl iodide added to the crude still-wet residue.
After the standard workup, column chromatography
allowed isolation of 11% of unreacted 7a and 64% of the
ring-opened product 9a, a value corresponding to a 72%
yield based on the reacted nitrothiophene.
In this regard, it is necessary to stress that during the ring-
opening step, the unreacted 7 cannot be detected by TLC
and that only after the methylation of the intermediate silver
enethiolate 8 the thiophene substrate can be recovered by
chromatography. In our opinion, the incomplete conversion
of some experiments is due to the fact that in the ®rst step of
Table 1. Results of the ring-opening reactions of nitrothiophene derivatives
7a±i with pyrrolidine and silver nitrate and of the subsequent methylation
step
Entry
Substrate
Product
Yield 3%)a
Recovd. 7 3%)
1
2
3
4
5
6
7
8
9
7a
7b
7c
7d
7e
7f
7g
7h
7i
9a
9b
9c
9d
9e
9f
9g
9h
9i
64 372)
62378)
59 379)
79 388)
52370)
54 389)
45 389)
48 389)
58 367)
11
21
25
10
26
39
49
46
13
It is noteworthy that the employment of two moles of amine
per mole of 7a perfectly matches the stoichiometric amount
required by Eq. 31). However, while such stoichiometry
requires one mole of AgNO3, the use of two moles of it in
our best conditions was dictated by the fact that an experi-
ment, carried out with a 7a±amine±AgNO3 molar ratio of
1:2.2:1, furnished, at the same time of the standard
reaction, a signi®cantly lower yield of 9a based on the
reacted 7a 348%, to be compared with the 72% value
Ring-opening reaction: [7]ˆ0.17 M; [AgNO3]<0.34 M 3satd. solution);
[pyrrolidine]ˆ0.37 M in absolute ethanol, room temperature, overnight.
Methylation step: on crude silver enethiolate 8 with excess MeI, room
temperature, 2h.
a
Isolated yields, average values of at least two independent reactions.
Yields calculated on the amount of 7 consumed are reported in
parenthesis.

C.Dell'Erba et al./ Tetrahedron 57 /2001) 8159±8165
8161
the procedure some thiophene 7 remains adsorbed on the
precipitated enethiolate 8. On the other hand, it should be
recalled that in control experiments the use of longer times
of sonication and/or of reaction in the ®rst 3ring opening)
step resulted in a substantial decrease in the absolute and
relative yields of 9 with concomitant increase in the amount
of tarry material produced.
moderate to good in dependence of the nature of the func-
tionalized vinyl bonded at C32) of the 2-nitroenamine
system of 9a±i.
The regioselectivity of the reaction leading to 10a±i from
9a±i proved to be satisfactory when considering the
presence in the latter substrates of groups which can
potentially react with the Grignard reagent15,16 in
competition with the nitroenamine system. Actually, the
lower yields of entries 7±9 suggest the intervention of
competitive processes whose exact nature is at the
moment unclear since not well de®ned by-products could
be isolated from the somewhat complex ®nal reaction
mixtures. Studies aimed at the optimization of the yields
of the above cited reactions, in particular that with 9g, are
planned.
Finally, it should also be mentioned that the reactions of
Table 1 were generally performed starting from 1.4 to
1.5 mmol of 7. The scale-up of the experiments generally
resulted in a decrease in the absolute yield of 9 so that
reactions carried out in duplicate or triplicate were to be
preferred to a single scaled-up experiment.
2.2. Reactions of the unsaturated derivatives 9a±i with p-
tolylmagnesium bromide
2.3. Stereochemical assignments
A common feature of the unsaturated building blocks 9a±i
is the presence of a tert-nitroenamine function whose
potentiality in synthesis is well known.10±12 A particularly
interesting aspect of the latter are the reactions with organo-
metallic reagents which, after acidic quenching, result in an
overall substitution of the dialkylamino group with the
residue of the employed organometal.2±5,13
As regard the stereochemistry of the nitrovinyl system of
compounds 9 and 10 an 3E)-con®guration can be con®dently
assigned on the grounds of the marked deshielding of the
nitrovinylic protons cis to the nitrogroup2±4 3average values:
d 8.5 and 8.1 ppm for compounds 9 and 10, respectively).
The preferential 3E)-con®guration of tert-nitroenamines is
well documented10,12 and, consistently, compounds 9b±i
show chemical shift values, for the nitrovinylic protons, in
good agreement with the H±C31) proton of 1-pyrrolidino-2-
nitro-4-methylthio-1,3-butadiene 9a, to which a 31E)-
Because of the importance of C±C bond forming processes,
as a ®rst approach to the study of the behavior of the poly-
functionalized derivatives 9a±i, we investigated on their
reactions with p-tolylmagnesium bromide. The results
obtained from the reactions of 9a±i with 1.1 mol equiv. of
p-tolylmagnesium bromide in THF at 2788C 3Scheme 3,
Table 2) show that it is possible to approach the new nitro-
vinyl derivatives 10a±i where the tolyl replaces the parent
pyrrolidine moiety of 9a±i. The yields of 10a±i were from
con®guration has been attributed.8 On the basis of the H
1
NMR data of nitrobutadiene systems structurally related to 9
and 10,17 moreover, a moderate up®eld shift 3ca. 0.2±
0.3 ppm) is expected for H±C31) protons on going from
an 3E)-1-pyrrolidino-2-nitro- to an 3E)-1-3p-tolyl)-2-nitro-
vinyl system. Consistently enough, compounds 10 show
signals for the nitrovinyl protons with an average shielding
of 0.4 ppm with respect to the corresponding pyrrolidino
derivative 9. The preference for 3E)-con®guration in
1-aryl-2-nitrovinyl systems arising from substitution by
Grignard reagents of the dialkylamino group of nitro-
enamines is, on the other hand, well assessed.2±4
Scheme 3. 3i) p-MeC6H4MgBr, THF, 2788C; 3ii) H3O1 quenching.
In the 1-pyrrolidino-9 and in the 1-3p-tolyl)-2-nitro-4-
methylthio-4-X-1,3-butadienes 10 the con®guration at the
remaining C33)±C34) double bonds of 9a, 9c,d,f±i, 10a and
10c,d,f±i had to be assigned. As far as 9a and 10a 3XˆH)
are concerned, the JH±C33),H±C34) values of 9.8 and 10.5 Hz
3for 9a and 10a, respectively) proved that the two protons
are cis related. Such a result, while con®rming the 31E,3E)
con®guration of 9a already reported,8 suggests no signi®-
cant inversion of con®guration at the C33)±C34) double
bond during the transformation of 9a into 10a by action of
the Grignard reagent. The fact that the cis-relation between
H±C33) and X±C34) of the parent thiophenes 7c,d,f±i is
retained both in the ring-opening products 9c,d,f±i and in
their derivatives 10c,d,f±i is in agreement with the absence
of NOE between the H±C33) and the MeSC34), as ascer-
tained by NOEDIF experiments. The only NOE's observed
were in the experiments performed on 9e and on 10e show-
ing NOE between H±C33) and one MeS group 3cis-relation)
while the effect on the second MeS 3trans-relation) was, as
expected, negligible.
Table 2. Yields of 10a±i from the reactions of the unsaturated derivatives
9a±i with p-tolylmagnesium bromide in THF at 2788C
Entry
Substrate
Product
Yield 3%)a
1
2
3
4
5
6
7
8
9
9a
9b
9c
9d
9e
9f
9g
9h
9i
10a
10b
10c
10d
10e
10f
10g
10h
10i
84b
94
78
66
86
85
39
57
60
[9]<[p-TolylMgBr]<0.08 M; quenching into ice±CH2Cl2 with HCl equi-
molar with Grignard.
a
Isolated yields: average values of at least two independent reactions.
Depending on workup conditions, in some cases traces of the isomer
b
31E,3E)-10a have been detected 31H NMR, Ref. 14) in mixed chromato-
graphic fractions.

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C.Dell'Erba et al./ Tetrahedron 57 /2001) 8159±8165
3. Conclusion
quent methylation reactions of the intermediates 8 were
performed according to the following general procedure.
In conclusion, the ring-opening reactions of 2-substituted
4-nitrothiophenes with pyrrolidine and silver nitrate and
the subsequent treatment of the ensuing nitroenamines 9
with Grignard reagents to afford nitrovinyl derivatives 10
A mixture of b-nitrothiophene derivative 7 31.4 mmol) and
silver nitrate 30.48 g, 2.8 mmol) in absolute ethanol 38.5 ml)
was sonicated under argon until complete dissolution of 7
3ca. 10 min; some silver nitrate remained undissolved). The
¯ask was disaerated with argon and pyrrolidine 30.26 ml,
3.1 mmol) was added by syringe, cooling with an external
ice bath. After further 30 min of sonication, the reaction
mixture was left to stand overnight at room temperature in
the dark. Most of the solvent was evaporated under reduced
pressure to leave a dark yellowish still-wet precipitate. The
reaction was cooled to 08C and excess methyl iodide 35 ml)
was added by syringe and the reaction mixture allowed to
reach room temperature. After 2h, the reaction was diluted
with acetone and ®ltered from a grey precipitate, which was
washed with acetone. The clear ®ltrate was evaporated
under reduced pressure to leave a residue that was dissolved
in dichloromethane and chromatographed on a silica gel
column 3dichloromethane and then a gradient of the latter
with ethyl acetate). Some unreacted b-nitrothiophene
derivative 7 was eluted ®rst followed by the nitrovinyl-
pyrrolidine 9.
represent
a convenient access to polyfunctionalized
building blocks of possibly wide potentiality in synthesis,
as highlighted by the presence of groups whose interesting
reactivity is well known: the nitroenamine,2±5,10±13 nitro-
vinyl,18±24 ketene S,S- and S,SO2-acetal moieties15,25±29 as
well as the captodative30±32 vinyl systems of a-methylthio-
a,b-unsaturated ketones, esters and nitriles.16,33,34
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded on a Varian Gemini
200 spectrometer with TMS as internal reference; chemical
shifts are expressed as d ppm. Melting points were deter-
mined on a BuÈchi 535 apparatus and are uncorrected. Silica
gel 230±400 mesh was used for column chromatography.
Sonication was performed at room temperature with a
Bransonic Ultrasonic Cleaner Model 2510. All solvents
were distilled before use; petroleum ether and light
petroleum refer, respectively, to the fraction with bp 40±
60 and 80±1008C. Tetrahydrofuran 3THF) was puri®ed by
standard methods and distilled over potassium benzo-
phenone ketyl before use. Pyrrolidine was dried and
distilled over potassium hydroxide before use. The thio-
phene derivatives 7a,35 7b,36 7c,37 7d,37 7f,38,39 7g,40 7h,41
and 7i,42 were synthesized according to known procedures.
p-Tolylmagnesium bromide 3ca. 1 M in THF) was
prepared using standard procedures and titrated just before
use.43 All other commercially available reagents were used
as-received.
4.2.1. 01E,3Z)-4-Methylthio-2-nitro-1-pyrrolidino-1,3-
butadiene 09a). Yellow solid, mp 79.2±80.38C 3petroleum
1
ether±dichloromethane) 3lit.8 24% yield, mp 80±818C); H
NMR 3CDCl3) d 1.98 34H, m), 2.31 33H, s), 3.18 32H, m),
3.72 32H, m), 6.26 31H, d, Jˆ9.8 Hz), 6.36 31H, d,
Jˆ9.8 Hz), 8.41 31H, s); 13C NMR 3CDCl3) d 17.16,
24.89, 25.62, 49.14, 54.68, 116.82, 120.60, 132.13, 145.56.
4.2.2. 0E)-1-02-Methylthiophenyl)-1-nitro-2-pyrrolidino-
ethylene 09b). Yellow solid, mp 122.5±123.58C 3petroleum
ether±dichloromethane) 3lit.9 35% yield, no physical, spec-
troscopic or analytical data reported); nmax 3Nujol) 1612,
1
1485, 1395, 1263, 1217 cm21; H NMR 3CDCl3) d 1.82
34H. m), 2.43 33H, s), 2.70 32H, m), 3.66 32H, m), 7.20
33H, m), 7.38 31H, m), 8.67 31H, s); 13C NMR 3CDCl3) d
15.00, 24.35, 25.95, 47.85, 55.07, 122.24, 123.94, 124.03,
129.76, 130.00, 133.36, 142.19, 145.90; Anal. Calcd for
C13H16N2O2S: C, 59.1; H, 6.1; N, 10.6%. Found: C, 59.3;
H, 6.3; N, 10.5%.
4.1.1. 2-Methylthio-4-nitrothiophene 07e). To a solution
of 3,4-dinitrothiophene44 31.24 g, 7.1 mmol) in methanol
325 ml) was added, under magnetic stirring and cooling
with an external ice bath, commercial sodium methane-
thiolate 31.0 g, 14.3 mmol). The reaction was kept at room
temperature until TLC revealed disappearance of the parent
substrate 3ca. 2h). The reaction mixture was poured into ice/
water and extracted with dichloromethane. The combined
extracts were washed with water, dried 3Na2SO4), ®ltered
and evaporated under reduced pressure. The oily residue
was chromatographed on a silica gel column using a
gradient of petroleum ether and diethyl ether as eluant.
The 2-methylthio-4-nitrothiophene was thus obtained in
45% yield as an oil which solidi®ed in the refrigerator:
mp 24.0±25.08C 3lit.45 21±228C); 1H NMR 3CDCl3) d
2.55 33H, s), 7.55 31H, d, Jˆ1.6 Hz), 8.20 31H, d,
Jˆ1.6 Hz); 13C NMR 3CDCl3) d 21.17, 124.05, 128.38,
140.82, 148.01.
4.2.3.
01E,3E)-4-Methylthio-2-nitro-4-phenylthio-1-
pyrrolidino-1,3-butadiene 09c). Yellow solid, mp 132.2±
132.88C 3petroleum ether±dichloromethane); nmax 3Nujol)
1
1622, 1580, 1438, 1398, 1274 cm21; H NMR 3CDCl3) d
1.97 34H, m), 2.23 33H, s), 3.20 32H, m), 3.70 32H, m), 6.70
31H, s), 7.33 33H, m), 7.50 32H, m), 8.42 31H, s); 13C NMR
3CDCl3) d 16.42, 24.55, 25.85, 49.40, 55.36, 120.52,
124.75, 127.73, 129.29, 131.20, 134.01, 136.87, 145.83.
Anal. Calcd for C15H18N2O2S2: C, 55.9; H, 5.6; N, 8.7%.
Found: C, 55.5; H, 5.6; N, 8.6%.
4.2.4. 01E,3E)-4-Methylthio-2-nitro-4-phenylsulfonyl-1-
pyrrolidino-1,3-butadiene 09d). Yellow solid, mp 132.3±
133.38C 3petroleum ether±dichloromethane); nmax 3Nujol)
1605, 1567, 1413, 1307, 1266, 1084 cm21 1H NMR
;
4.2. Ring opening of b-nitrothiophenes 7a±i and access
to nitrovinylpyrrolidines 9a±i
3CDCl3) d 1.83 33H, s), 2.00 34H, m), 2.94 32H, m), 3.80
32H, m), 7.57 33H, m), 8.01 32H, m), 8.20 31H, s), 8.52 31H,
s); 13C NMR 3CDCl3) d 17.58, 24.47, 25.84, 51.69, 55.73,
The ring opening of the b-nitrothiophenes 7 and the subse-

C.Dell'Erba et al./ Tetrahedron 57 /2001) 8159±8165
8163
118.68, 128.70, 129.03, 133.46, 136.64, 136.71, 139.48,
147.35. Anal. Calcd for C15H18N2O4S2: C, 50.8; H, 5.1; N,
7.9%. Found: C, 50.6; H, 5.3; N, 8.1%.
same temperature until disappearance of the substrate 3ca.
15±45 min): the progress of the reaction being monitored by
TLC. Quenching of the reactions was performed by pouring
the reaction solution, with vigorous shaking, into a mixture
of dichloromethane with ice/water containing 1.1 mmol of
HCl. After extraction with dichloromethane, the organic
phase was washed with water, dried 3Na2SO4) and concen-
trated in a rotary evaporator under reduced pressure. The
products 10 were usually obtained in quite pure form by
chromatography of the residue on a silica gel column eluted
with a gradient of dichloromethane and diethyl ether.
4.2.5. 01E)-4,4-Bis0methylthio)-2-nitro-1-pyrrolidino-1,3-
butadiene 09e). Yellow solid, mp 60.9±61.88C 3petroleum
ether); nmax 3Nujol) 1614, 1566, 1393, 1256, 1232 cm21; 1H
NMR 3CDCl3) d 1.96 34H, m), 2.31 33H, s), 2.43 33H, s),
3.17 32H, m), 3.70 32H, m), 6.32 31H, s), 8.47 31H, s); 13C
NMR 3CDCl3) d 16.43, 16.96, 24.53, 26.03, 49.25, 54.87,
117.05, 120.26, 139.35, 146.17. Anal. Calcd for
C10H16N2O2S2: C, 46.1; H, 6.2; N, 10.8%. Found: C, 46.1;
H, 6.2; N, 10.8%.
4.3.1. 01E,3Z)-4-Methylthio-2-nitro-1-0p-tolyl)-1,3-buta-
diene 010a). Yellow oil, nmax 3Nujol) 1638, 1604, 1550,
1
1517, 1436, 1316, 1305, 1180 cm21; H NMR 3CDCl3) d
4.2.6. 01E,3E)-4-Methylsulfonyl-4-methylthio-2-nitro-1-
pyrrolidino-1,3-butadiene 09f). Yellow solid, mp 81.5±
82.58C 3petroleum ether±diethyl ether); nmax 3Nujol)
2.27 33H, s), 2.39 33H, s), 6.46 31H, d, Jˆ10.5 Hz), 6.60
31H, d, Jˆ10.5 Hz), 7.21 and 7.47 32H each, AA0BB0,
Jˆ8.2Hz), 8.05 31H, s); 13C NMR 3CDCl3) d 17.62,
21.66, 114.61, 128.45, 129.56, 130.95, 134.67, 138.66,
141.46, 144.10. Anal. Calcd for C12H13NO2S: C, 61.3; H,
5.6; N, 6.0%. Found: C, 61.1; H, 5.8; N, 6.0%.
1610, 1566, 1410, 1260, 1305, 1082 cm21 1H NMR
;
3CDCl3) d 2.05 34H, m), 2.24 33H, s), 3.09 and 3.16 35H
in all, partly overlapping m and s), 3.84 32H, m), 7.97 31H,
s), 8.54 31H, s); 13C NMR 3CDCl3) d 17.54, 24.54, 25.88,
40.56, 51.67, 55.87, 118.62, 135.25, 135.71, 147.20. Anal.
Calcd for C10H16N2O4S2: C, 41.1; H, 5.5; N, 9.6%. Found:
C, 40.9; H, 5.6; N, 9.6%.
4.3.2.
0E)-1-02-Methylthiophenyl)-1-nitro-2-0p-tolyl)-
ethylene 010b). Yellow solid, mp 56.2±57.08C 3petroleum
ether); nmax 3Nujol) 1636, 1605, 1584, 1515, 1435, 1323,
1
1310, 1184 cm21; H NMR 3CDCl3) d 2.31 33H, s), 2.42
4.2.7. 03Z,5E)-3-Methylthio-5-nitro-6-pyrrolidino-3,5-
hexadien-2-one 09g). Yellow oil, nmax 3Nujol) 1673,
33H, s), 6.98 and 7.06 32H each, AA0BB0, Jˆ8.5 Hz), 7.25
32H, m), 7.41 31H, app d, Jˆ6.8 Hz), 7.5231H, m), 8.30
31H, s); 13C NMR 3CDCl3) d 15.90, 21.51, 125.93, 126.91,
128.24, 129.66, 130.34, 130.77, 131.08, 131.16, 136.40,
140.13, 141.86, 147.10. Anal. Calcd for C16H15NO2S: C,
67.3; H, 5.3; N, 4.9%. Found: C, 67.0; H, 5.1; N, 4.8%.
1
1612, 1560, 1471, 1408, 1275, 1148, 1087, 1017 cm21; H
NMR 3CDCl3) d 2.01 34H, m), 2.17 33H, s), 2.53 33H, s),
2.98 32H, m), 3.81 32H, m), 7.68 31H, s), 8.52 31H, s); 13C
NMR 3CDCl3) d 16.53, 24.45, 25.77, 27.32, 50.78, 55.29,
119.86, 132.44, 137.02, 148.05, 196.19. Anal. Calcd for
C11H16N2O3S: C, 51.5; H, 6.3; N, 10.9%. Found: C, 51.3;
H, 6.5; N, 11.0%.
4.3.3. 01E,3E)-4-Methylthio-2-nitro-4-phenylthio-1-0p-
tolyl)-1,3-butadiene 010c). Yellow solid, mp 96.4±97.08C
3petroleum ether±dichloromethane); nmax 3Nujol) 1631,
4.2.8. Methyl 02Z,4E)-2-Methylthio-4-nitro-5-pyrroli-
dino-2,4-pentadienoate 09h). Waxy yellow solid, nmax
1
1603, 1547, 1514, 1439, 1316, 1292, 1179 cm21; H NMR
3Nujol) 1717, 1621, 1540, 1410, 1273, 1123, 1036 cm21
;
3CDCl3) d 2.20 33H, s), 2.40 33H, s), 6.45 31H, s), 7.22 32H,
half AA0BB0, Jˆ8.0 Hz), 7.40 35H, m), 7.55 32H, m), 7.96
31H, s); 13C NMR 3CDCl3) d 16.52, 21.64, 120.21, 128.57,
128.98, 129.47, 129.67, 130.84, 132.50, 132.65, 135.07,
141.63, 144.43, 145.29. Anal. Calcd for C18H17NO2S2: C,
62.9; H, 5.0; N, 4.1%. Found: C, 62.7; H, 5.0; N, 4.2%.
1H NMR 3CDCl3) d 2.01 34H, m), 2.25 33H, s), 3.02 32H,
m), 3.79 and 3.85 35H in all, partly overlapping m and s),
7.80 31H, s), 8.51 31H, s); 13C NMR 3CDCl3) d 16.94, 24.51,
25.84, 50.70, 52.74, 55.23, 119.85, 128.03, 133.45, 148.03,
165.37. Anal. Calcd for C11H16N2O4S: C, 48.5; H, 5.9; N,
10.3%. Found: C, 48.2; H, 6.1; N, 10.1%.
4.3.4. 01E,3E)-4-Methylthio-2-nitro-4-phenylsulfonyl-1-
0p-tolyl)-1,3-butadiene 010d). Yellow solid, mp 81.5±
82.58C 3petroleum ether±dichloromethane); nmax 3Nujol)
4.2.9. 02Z,4E)-2-Methylthio-4-nitro-5-pyrrolidino-2,4-
pentadienenitrile 09i). Yellow solid, mp 124.0±125.08C
3petroleum ether±dichloromethane); nmax 3Nujol) 2216,
1
1633, 1608, 1516, 1502, 1322, 1313, 1185, 1153 cm21; H
1
1613, 1580, 1397, 1244, 1220 cm21; H NMR 3CDCl3) d
NMR 3CDCl3) d 2.21 33H, s), 2.39 33H, s), 7.15 and 7.24
32H each, AA0BB0, Jˆ8.3 Hz), 7.66 33H, m), 8.01 33H in
all, partly overlapping s and m), 8.15 31H, s); 13C NMR
3CDCl3) d 17.86, 21.68, 127.87, 128.70, 129.23, 129.98,
130.98, 134.04, 134.75, 138.06, 138.46, 141.62, 142.97,
146.27. Anal. Calcd for C18H17NO4S2: C, 57.6; H, 4.6; N,
3.7%. Found: C, 57.4; H, 4.7%; N, 3.7%.
2.04 34H, m), 2.48 33H, s), 3.04 32H, m), 3.80 32H, m), 7.31
31H, s), 8.44 31H, s); 13C NMR 3CDCl3) d 16.56, 24.55,
25.84, 50.58, 55.27, 109.38, 115.24, 118.82, 132.85 and
147.79. Anal. Calcd for C10H13N3O2S: C, 50.2; H, 5.5; N,
17.6%. Found: C, 50.4; H, 5.6; N, 17.7%.
4.3. Reactions of nitrovinylpyrrolidines 9a±i with p-
tolylmagnesium bromide
4.3.5.
01E)-4,4-Bis0methylthio)-2-nitro-1-0p-tolyl)-1,3-
butadiene 010e). Yellow solid, mp 69.5±70.88C 3petroleum
ether); nmax 3Nujol) 1643, 1605, 1547, 1514, 1506, 1317,
A solution of nitrovinylpyrrolidines 9 31 mmol) in THF
312ml) was cooled to 2788C under magnetic stirring.
The calculated amount of a ca. 1 M solution of p-tolyl-
magnesium bromide 31.1 mmol) in THF was slowly added
by syringe and the reaction mixture left under stirring at the
1
1311, 1185 cm21; H NMR 3CDCl3) d 2.24 33H, s), 2.39
33H, s), 2.49 33H, s), 6.30 31H, s), 7.22 and 7.43 32H each,
AA0BB0, Jˆ8.2Hz), 7.95 31H, s); 13C NMR 3CDCl3) d
16.46, 16.85, 21.60, 114.65, 129.14, 129.68, 130.78,

8164
C.Dell'Erba et al./ Tetrahedron 57 /2001) 8159±8165
3. Dell'Erba, C.; Mele, A.; Novi, M.; Petrillo, G.; Stagnaro, P.
Tetrahedron 1992, 48, 4407±4418.
134.65, 141.47, 144.63, 146.83. Anal. Calcd for
C13H15NO2S2: C, 55.5; H, 5.4; N, 5.0%. Found: C, 55.3;
H, 5.5; N, 5.0%.
4. Dell'Erba, C.; Novi, M.; Petrillo, G.; Spinelli, D.; Tavani, C.
Tetrahedron 1996, 52, 3313±3326.
4.3.6. 01E,3E)-4-Methylsulfonyl-4-methylthio-2-nitro-1-
0p-tolyl)-1,3-butadiene 010f). Yellowish solid, mp 119.5±
121.08C 3petroleum ether±dichloromethane); nmax 3Nujol)
5. Dell'Erba, C.; Mugnoli, A.; Novi, M.; Pertici, M.; Petrillo, G.;
Tavani, C. Eur.J.Org.Chem. 1999, 431±435.
6. Dell'Erba, C.; Mugnoli, A.; Novi, M.; Pani, M.; Petrillo, G.;
Tavani, C. Eur.J.Org.Chem. 2000, 903±912and previous
papers in the series.
1
1641, 1604, 1519, 1510, 1317, 1295, 1190, 1145 cm21; H
NMR 3CDCl3) d 2.27 33H, s), 2.41 33H, s), 3.16 33H, s), 7.27
and 7.36 32H each, AA0BB0, Jˆ8.4 Hz), 7.86 31H, s), 8.20
31H, s); 13C NMR 3CDCl3) d 17.68, 21.68, 40.44, 127.82,
130.13, 131.15, 134.48, 138.44, 141.57, 143.18, 145.01.
Anal. Calcd for C13H15NO4S2: C, 49.8; H, 4.8; N, 4.5%.
Found: C, 49.9; H, 5.0; N, 4.3%.
7. Guanti, G.; Dell'Erba, C.; Leandri, G.; Thea, S. J.Chem.Soc.,
Perkin Trans.1 1974, 2357±2360.
8. Surage, S. S.; Kumaran, G.; Rajappa, S.; Rajalakshmi, K.;
Pattabhi, V. Tetrahedron 1997, 53, 8531±8540.
9. Surage, S. S.; Rajappa, S. Tetrahedron Lett. 1998, 39, 7169±
7172.
4.3.7. 03Z,5E)-3-Methylthio-5-nitro-6-0p-tolyl)-3,5-hexa-
dien-2-one 010g). Yellow solid, mp 71.2±71.68C
3petroleum ether); nmax 3Nujol) 1660, 1630, 1582, 1480,
10. Rajappa, S. Tetrahedron 1981, 37, 1453±1480.
11. Fuji, K.; Node, M. Synlett 1991, 603±610.
12. Rajappa, S. Tetrahedron 1999, 55, 7065±7114.
13. Severin, T.; Scheel, D.; Adhikary, P. Chem.Ber. 1969, 102,
2966±2971.
1
1425, 1306, 1260, 1125 cm21; H NMR 3CDCl3) d 2.11
33H, s), 2.40 33H, s), 2.56 33H, s), 7.23 32H, half AA0BB0,
Jˆ8.0 Hz), 7.35 33H in all, s and half AA0BB0 partly over-
lapping, Jˆ8.0 Hz), 8.1231H, s); 13C NMR 3CDCl3) d
16.05, 21.66, 27.63, 127.63, 128.30, 129.92, 130.98,
137.20, 142.46, 143.34, 146.25, 196.48. Anal. Calcd for
C14H15NO3S: C, 60.6; H, 5.5; N, 5.1%. Found: C, 60.2; H,
5.4; N, 5.0%.
14. For the 31E,3E)-10a isomer: 1H NMR 3CDCl3) 2.37 and 2.39
36H in all, two partly overlapping s), 6.16 31H, d, Jˆ15.5 Hz),
6.98 31H, d, Jˆ15.5 Hz), 7.22 and 7.43 32H each, AA0BB0,
Jˆ8.1 Hz), 7.68 31H, s).
15. GroÈbel, B.-T.; Seebach, D. Synthesis 1977, 357±402.
16. Kobayashi, K.; Tanaka, H.; Takabatake, H.; Kitamuna, T.;
Nakahashi, R.; Morikawa, O.; Hisatoshi, K. Bull.Chem.
Soc.Jpn 1999, 72, 1071±1074.
4.3.8. Methyl 02Z,4E)-2-methylthio-4-nitro-5-0p-tolyl)-
2,4-pentadienoate 010h). Yellow solid, mp 67.1±67.78C
3petroleum ether); nmax 3Nujol) 1721, 1640, 1605, 1502,
17. Compare for instance 3Ref. 3): 3E,E)-1,4-bis3pyrrolidino)-2,3-
dinitro-1,3-butadiene [dH±C31)ˆdH±C34)ˆ8.70 ppm] with 3E,E)-
1434, 1325, 1293, 1246, 1186, 1058 cm21 1H NMR
;
1,4-bis3p-tolyl)-2,3-dinitro-1,3-butadiene [dH±C31)ˆdH±C34)
ˆ
3CDCl3) d 2.20 33H, s), 2.40 33H, s), 3.91 33H, s), 7.24
and 7.36 32H each, AA0BB0, Jˆ8.0 Hz), 7.59 31H, s), 8.11
31H, s); 13C NMR 3CDCl3) d 16.35, 21.63, 53.08, 128.31,
129.89, 129.98, 130.99, 137.32, 137.77, 142.36, 143.23,
164.43. Anal. Calcd for C14H15NO4S: C, 57.3; H, 5.2; N,
4.8%. Found: C, 57.1; H, 5.2; N, 4.9%.
8.50 ppm].
18. Perekalin, V. V.; Lipina, E. S.; Berestovitskaya, V. M.;
Efremov, D. A. Nitroalkenes, Conjugated Nitro Compounds;
Wiley: New York, 1994.
19. Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979,
33, 1±18.
20. Barrett, A. G.; Graboski, G. G. Chem.Rev. 1986, 86, 751±762.
21. Seebach, D.; Imwinkelried, R.; Weber, T. EPC syntheses with
C,C bond formation via acetals and enamines. Schefford, R.,
Ed.; Modern Synthetic Methods; Vol. 4; Springer: Berlin,
1986; pp. 220±240.
4.3.9. 02Z,4E)-2-Methylthio-4-nitro-5-0p-tolyl)-2,4-penta-
dienenitrile 010i). Yellow solid, mp 118.2±118.78C 3light
petroleum); nmax 3Nujol) 2227, 1632, 1603, 1499, 1310,
1
1290, 1213, 1185, 1043 cm21; H NMR 3CDCl3) d 2.41
and 2.42 33H each, two s partly overlapped), 7.26 33H in
all, s and half AA0BB0 partly overlapping, Jˆ8.4 Hz), 7.35
32H, half AA0BB0, Jˆ8.4 Hz), 8.22 31H, s); 13C NMR
3CDCl3) d 16.65, 21.76, 114.27, 119.78, 127.66, 129.85,
130.16, 130.96, 139.02, 140.87, 143.13. Anal. Calcd for
C13H12N2O2S: C, 60.0; H, 4.6; N, 10.8%. Found: C, 60.0;
H, 4.7; N, 10.9%.
22. Kabalka, G. W.; Varma, R. S. Org.Prep.Proced.Int. 1987,
19, 283±328.
23. Rosini, G.; Ballini, R. Synthesis 1988, 833±847.
24. Pecunioso, A.; Galoppini, E.; Menicagli, R. Tetrahedron
1990, 46, 7497±7508.
25. Tominaga, Y.; Matsuda, Y. J.Heterocycl.Chem. 1985, 22,
937±949.
26. Dieter, R. K. Tetrahedron 1986, 42, 3029±3096.
27. Kolb, M. Synthesis 1990, 171±190.
Acknowledgements
28. Junjappa, H.; Ila, H.; Asokan, C. V. Tetrahedron 1990, 46,
5423±5506.
The authors wish to thank the University of Genova, the
University of Bologna and C.N.R. for ®nancial support to
this research.
29. Braverman, S.; Cherkinsky, M.; Nov, E.; Sprecher, M.
Tetrahedron 1999, 55, 2353±2362 and references therein.
Â
30. Viehe, H. G.; Merenyi, R.; Stella, L.; Janousek, Z. Angew.
Chem., Int. Ed. Engl. 1979, 18, 917±932.
Â
31. Viehe, H. G.; Janousek, Z.; Merenyi, R.; Stella, L. Acc.Chem.
Res. 1985, 18, 148±154.
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