Chemistry of polyhalogenated nitrobutadienes, part 5: Synthesis and reactions of dichloromethyl nitrovinylidene ketones of heterocycles

Article abstract of DOI:10.1055/s-2007-982554

An easy access to dichloromethyl nitrovinylidene ketones of five-membered heterocycles is presented starting from nitroperchlorobutadiene. These complex ketones are valuable starting materials for novel product structures in versatile reactions such as selective reductions, substitutions to give α-nitroacryl cyanides, fragmentations by means of an alkoxide, as well as ring-cleavage/ring-closure steps by the action of hydrazine. Some of the products show biological activity in crop protection. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-982554

LETTER
1507
Chemistry of Polyhalogenated Nitrobutadienes, Part 5: Synthesis and
Reactions of Dichloromethyl Nitrovinylidene Ketones of Heterocycles
S
ynthesis andRea
i
c
tions
o
k
f
D
ichlorom
t
ethyl
N
o
itrovinylide
r
K
etones of
HA
eterocycles . Zapol’skii,a Jan C. Namyslo,a Mimoza Gjikaj,b Dieter E. Kaufmann*a
a
Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
Fax +49(5323)722834; E-mail: dieter.kaufmann@tu-clausthal.de
b
Institute of Inorganic and Analytical Chemistry, Clausthal University of Technology, Paul-Ernst-Str. 4, 38678 Clausthal-Zellerfeld,
Germany
Received 16 March 2007
1. Me2NH,
MeOH
2. HCl,
Abstract: An easy access to dichloromethyl nitrovinylidene ke-
tones of five-membered heterocycles is presented starting from ni-
troperchlorobutadiene. These complex ketones are valuable starting
materials for novel product structures in versatile reactions such as
selective reductions, substitutions to give a-nitroacryl cyanides,
fragmentations by means of an alkoxide, as well as ring-cleavage/
ring-closure steps by the action of hydrazine. Some of the products
show biological activity in crop protection.
Cl
Cl
XH
X
Y
X
Y
HY
MeOH
Cl
Cl
O2N
Cl
Cl
O
O2N
O2N
Cl
Cl
Cl
Cl
2
3
(X = Y = NH, 85%)1e
7
(80%)
(60%)
1
Key words: nitro compound, haloalkene, ketone, cyclization, het-
erocycle
8
(X = NH,
Y = N-CP, 45%)
CP =
4
5
(X = Y = NMe, 65%)
9
(45%)
N
Cl
Polyhalogeno-1,3-butadienes bearing at least one nitro
group are in general valuable starting materials for the
synthesis of highly functionalized heterocycles,1–3 with 2-
nitropentachloro-1,3-butadiene (1) being one of the most
prominent members of this relatively new class of
synthetic building blocks. In the present paper, 1 serves
as starting material for the highly substituted butenones
7–11.
(X = NH,
Y = S,
10 (50%)
11 (90%)
60%)1e
6
(X = Y = S, 92%)1b
Scheme 1
The structure of the dichloromethyl nitrovinylidene ke-
tone of imidazolidine 7 (Figure 1) was additionally prov-
en by an X-ray analysis.4 The almost-planar structure, the
downfield-shifted 1H NMR signals [d = 9.12 (2 NH), 7.35
(1 CH) ppm in DMSO-d6], and the low solubility even in
DMSO indicate that threefold H-bonding with the carbo-
nyl and the nitro group must be important. The trichloro-
vinyl compounds 2, 3, 5, and 6 were converted
exclusively into the corresponding ketones 7, 8, 10, and
11, respectively, but the imidazolidine 4 gave 2,3,3-
trichloroacrylic acid (12) with 30% yield in addition to the
main product 9 (Scheme 2). Arylamides of 12 are known
for their herbicidal activity.5 With respect to the above
mentioned hydrolysis of 2–6, it is worth noting that the
detour comprising the initial use of the secondary amine
has been proved to be essential, as the direct hydrolysis by
means of 10% water in dimethyl sulfoxide even at 90 °C
gave only poor yields of 7–11 (about 10–30%).
In the course of our recent studies, 1 was first treated with
1,2-bisnucleophilic reagents leading to the formation of
five-membered saturated N,N1e-, N,S1e-, or S,S1b-hetero-
cycles, i.e. the imidazolidines 2–4, the thiazolidine 5, or
the dithiolane 6, respectively (Scheme 1).
Thus, in the case of N,N-bisnucleophiles a very good
yield of the cyclization product was obtained applying
ethylenediamine (85% of 2), whereas the N,N-dimethyl
derivative as well as N-(2-chloro-5-pyridylmeth-
yl)ethane-1,2-diamine furnished the corresponding
product with 65% and 45% yield, respectively. Although
the thiazolidine 5 was already formed with 60% yield, the
dithiolane was obtained almost quantitatively (92%).
Subsequently, the trichlorovinyl compounds 2–6 were
subjected to a methanolic solution of dimethylamine
(fourfold excess), which attacked the tertiary CCl-posi-
tion of the trichloro-nitroallylidene unit. Thus, enamines
were formed as intermediates and – by means of hydro-
chloric acid in methanol – directly transformed into the
corresponding enols and, subsequently, into the tauto-
merization products 7–11.
2.065 Å
H
O
N
O
N
2.135 Å
H
N
Cl
O
H
Cl
2.048 Å
SYNLETT 2007, No. 10, pp 1507–1512
1
8
.0
6
.2
0
0
7
Advanced online publication: 07.06.2007
DOI: 10.1055/s-2007-982554; Art ID: G06907ST
© Georg Thieme Verlag Stuttgart · New York
Figure 1 Structure of nitrobutenone 74

1508
V. A. Zapol’skii et al.
LETTER
1. Me2NH
2. HCl
O
OH
Cl
S
S
MeN
O2N
NMe
EtONa, EtOH
73%
+
9
Cl
Cl
Cl
MeOH
Cl
O2N
S
S
17
Cl
O
O2N
4
45%
12 30%
H
HS(H2C)2S
O2N
N2H4·H2O,
MeOH
N
Cl
11
Cl
Scheme 2
N
75%
The carbonyl group within 7–11 allowed for diverse suc-
cessive chemistry, ranging from reductive 1,2-additions
with borohydrides over 1,4-additions via an intermediate
hydrazone and to SN reactions with the azide ion in the
chlorinated a-position. In detail, the first reaction of the
ketones 10 and 11 was the reduction by means of one
equivalent of sodium borohydride in ethanol at 0 °C.
Thus, as expected, the alcohols 13 and 14 were formed in
80% and 98% yield, respectively. Furthermore, applying
an excess of the reducing agent (2.3 equiv, 10–15 °C, 1 h)
to the dithiolane derivative 11, the allylidene double bond
was reduced as well (35% yield of 15). Alternatively, 15
could be obtained by direct reduction of the unsaturated
butanol 14 with 50% yield (Scheme 3).
N
18
NH2
Scheme 4
A conceivable mechanistic pathway for the reaction
cascade to 18 is shown in Scheme 5. It comprises cleav-
age of the dithiolane ring by attack of the terminal amino
nitrogen in I after initial formation of the hydrazone, pre-
sumably following a first addition to the twofold-activat-
ed Michael system. It is noteworthy that a different type
of dithiolane ring cleavage under basic conditions had
been observed before.1b
H
HS(H2C)2S
S
S
S
S
N
NH2
N2H4·H2O
N
HN
S
O
N
O2N
O2N
O2N
OH
Cl
Cl
O2N
Cl
80%
Cl
11
Cl
Cl
Cl
1 equiv
NaBH4
I
II
X
Y
Cl
13
O
H
H
N
HS(H2C)2S
O2N
HS(H2C)2S
O2N
O2N
EtOH
N
N2H4·H2O
1 equiv
NaBH4
S
S
N
S
S
N
Cl
Cl
– HCl
– HCl
OH
Cl
OH
Cl
10 (X = NH,
Y = S)
11 (X = Y = S)
98%
EtOH
50%
Cl
O2N
O2N
N
HN
NH2
NH2
Cl
15
Cl
14
18
III
Scheme 5 Proposed reaction mechanism for the formation of 18
Scheme 3
Thus, the resulting pyrazole (i.e. intermediate II) is, pre-
sumably, attacked by a second hydrazine molecule substi-
tuting one CCl group of the dichloromethyl unit, leading
to the depicted structure III. Examples for such conver-
sions of a dichloromethylcarbonyl group are rare in the
literature.7a Two further intramolecular cyclizations
affording substituted 1H-pyrazoles are known.7b,c Like-
wise, corresponding dibromo8a–c or difluoro9a–f com-
pounds have been published to serve as starting materials
for comparable reactions. In our case, its rich substitution
pattern makes 18 a promising candidate for subsequent
chemistry. In addition, the primary amino group of the
hydrazone 18 was selectively acylated under standard
conditions to give 19 with 95% yield.
According to proton NMR spectroscopy, the prepared
nitrobutan-2-ol 15 consisted of a 5:1 mixture of the
erythro- and threo-isomers which proved inseparable by
column chromatography. In addition, the allylic hydroxyl
group of 15 was easily acylated under standard conditions
to give 16 with 95% yield.
Reaction of dithiolane 11 with the O-nucleophile sodium
ethoxide led selectively to a C–C bond-cleavage reaction
yielding 2-nitromethylene-1,3-dithiolane6 (17) via a pri-
mary 1,2-addition reaction. Presumably, this reaction
goes through an unstable 2-nitroacrylic acid which easily
decarboxylates to give the dithioketene acetal 17.
An unexpected reaction occurred when 11 was treated
with the N-nucleophile hydrazine yielding the structurally
interesting pyrazole 18 (Scheme 4).
However, not only the aforementioned heterocycles 10
and 11, but also the imidazoles 7–9 exhibit an interesting
potential for further conversions. Again we started with
the sodium borohydride reduction, whereupon 7 gave the
Synlett 2007, No. 10, 1507–1512 © Thieme Stuttgart · New York

LETTER
Synthesis and Reactions of Dichloromethyl Nitrovinylidene Ketones of Heterocycles
1509
expected alcohol 20 in 55% yield. Unexpectedly, but at
last similar to the formation of 17, the chloropyridylmeth-
yl derivative 8 afforded 1-(2-chloropyridin-5-ylmethyl)-
2-(nitromethylene)imidazolidine (21)10 under C–C bond
cleavage, a substance with remarkable insecticidal activi-
ty.11a–d A nitroalcohol was not formed at all. When 7 was
reacted with an excess of sodium azide, the a-nitroacrylic
acid cyanide 22 was formed with 35% yield via nucleo-
philic substitution and dehydrochlorination along with
evolution of nitrogen gas (Scheme 6). In case of the N,N-
dimethyl derivative 9 the reaction with sodium azide
stopped at the stage of the bisazido compound 23 (75%
yield), but prolonged reaction time at 90–95 °C furnished
the expected acid cyanide 24 in 40% yield, too. Both
substitution patterns are novel.
Acknowledgment
We gratefully acknowledge Bayer AG, Leverkusen, for financial
support and Chemetall GmbH, Frankfurt am Main, for chemicals.
We thank Dr. H. Frauendorf, University of Göttingen, Germany, for
HRMS data.
References and Notes
(1) (a) Kaberdin, R. V.; Potkin, V. I.; Zapol’skii, V. A. Russ.
Chem. Rev. 1997, 66, 827. (b) Zapol’skii, V. A.; Namyslo,
J. C.; Adam, A. E. W.; Kaufmann, D. E. Heterocycles 2004,
63, 1281. (c) Zapol’skii, V. A.; Nutz, E.; Namyslo, J. C.;
Adam, A. E. W.; Kaufmann, D. E. Synthesis 2006, 2927.
(d) Zapol’skii, V. A.; Namyslo, J. C.; Blaschkowski, B.;
Kaufmann, D. E. Synlett 2006, 3464. (e) Zapol’skii, V. A.;
Namyslo, J. C.; Gjikaj, M.; Kaufmann, D. E. ARKIVOC
2007, (i), 76.
(2) Ibis, C. Bull. Soc. Chim. Belg. 1996, 105, 317.
(3) Zapol’skii, V. A.; Potkin, V. I.; Nechai, N. I.; Kaberdin, R.
V.; Pevzner, M. S. Russ. J. Org. Chem. 1997, 33, 1461.
(4) Crystal Data for 7 have been deposited with the Cambridge
Crystallographic Data Center (CCDC 632420) and may be
obtained free of charge from The Director, CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK [fax:+44 (1223)336033; e-
mail: fileserv@ccdc.ac.uk or www.ccdc.cam.ac.uk].
(5) Molchanov, L. V.; Kadyrov, C. S.; Ayupova, A. T. Chem.
Nat. Compd. 1981, 17, 357.
Cl
HN
NH
N
N
NaBH4,
EtOH
NaBH4,
EtOH
OH
Cl
O2N
R = R' = H
55%
R = H,
R' = CP
Cl
20
HN
60%
RN
NR'
NO2
21
O
(6) (a) Hirai, K.; Ishiba, T.; Sugimoto, H. Chem. Pharm. Bull.
1972, 20, 1711. (b) Schaumann, E.; Scheiblich, S.; Wriede,
U.; Adiwidjaja, G. Chem. Ber. 1988, 121, 1165.
O2N
Cl
Cl
RN
NR'
N
N
7 (R = R' = H)
(c) Shibuya, I.; Taguchi, Y.; Tsuchiya, T.; Oishi, A.; Katoh,
E. Bull. Chem. Soc. Jpn. 1994, 67, 3048. (d) Terang, N.;
Mehta, B.; Ila, H.; Junjappa, H. Tetrahedron 1998, 54,
12973.
NaN3,
DMF
NaN3,
DMF
O
8 (R = H, R' = CP)
O
O2N
O2N
R = R' = H 9 (R = R' = Me)
R = R' = Me
75%
(7) (a) Roedig, A.; Becker, H.-J. Justus Liebigs Ann. Chem.
1955, 597, 214. (b) Takahashi, M.; Zheng, M.; Oshida, T.;
Narahara, K. J. Heterocycl. Chem. 1994, 31, 205.
(c) Chowdhury, S. K. D.; Sarkar, M.; Mahalanabis, K. K.
J. Chem. Res., Synop. 2003, 11, 746.
(8) (a) Chattaway, F. D.; Lye, R. J. Proc. R. Soc. London, Ser. A
1932, 135, 282. (b) Chattaway, F. D. J. Chem. Soc. 1933,
1624. (c) Chattaway, F. D.; Parkes, G. D. J. Chem. Soc.
1935, 1005.
N3
23
N3
N
22 (R = R' = H, 35%)
24 (R = R' = Me, 40%)
90–95 °C
DMF
Scheme 6
(9) (a) Linderman, R. J.; Kirollos, S. K. Tetrahedron Lett. 1989,
30, 2049. (b) Saloutin, V. I.; Fomin, A. N.; Pashkevich, K. I.
Bull. Acad. Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1985,
34, 135. (c) Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.;
Carter, J. S.; Collins, P. W.; Docter, S.; Graneto, M. J.; Lee,
L. F.; Malecha, J. W.; Miyashiro, J. M.; Rogers, R. S.;
Rogier, D. J.; Yu, S. S.; Anderson, G. D.; Burton, E. G.;
Cogburn, J. N.; Gregory, S. A.; Koboldt, C. M.; Perkins, W.
E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson,
P. C. J. Med. Chem. 1997, 40, 1347. (d) Tsuji, K.; Konishi,
N.; Spears, G. W.; Ogino, T.; Nakamura, K.; Tojo, T.; Ochi,
T.; Shimojo, F.; Senoh, H.; Matsuo, M. Chem. Pharm. Bull.
1997, 45, 1475. (e) Filyakova, V. I.; Karpenko, N. S.;
Kuznetsova, O. A.; Pashkevich, K. I. Russ. J. Org. Chem.
1998, 34, 381. (f) Li, J.; DeMello, K. M. L.; Cheng, H.;
Sakya, S. M.; Bronk, B. S.; Rafka, R. J.; Jaynes, B. H.;
Ziegler, C. B.; Kilroy, C.; Mann, D. W.; Nimz, E. L.; Lynch,
M. P.; Haven, M. L.; Kolosko, N. L.; Minich, M. L.; Li, C.;
Dutra, J. K.; Rast, B.; Crosson, R. M.; Morton, B. J.; Kirk,
G. W.; Callaghan, K. M.; Koss, D. A.; Shavnya, A.; Lund,
L. A.; Seibel, S. B.; Petras, C. F.; Silvia, A. Bioorg. Med.
Chem. Lett. 2004, 14, 95.
Although there are papers dealing with corresponding
transformations of the -CCl3,12a–c the chlorosulfenyl-
dichloromethyl,12d the nitrodichloromethyl,12e the C–
CCl2N,12f,g or the C=CCl212h group into a nitril, to the best
of our knowledge, this is the first report of the correspond-
ing conversion of a CHCl2 unit that is activated by an
adjacent carbonyl substituent.
In conclusion, we have developed an efficient two-step
synthesis of dichloromethyl nitrovinylidene ketones of
five-membered heterocycles starting from a nitroperchlo-
robutadiene.13 These unsaturated ketones have proved to
be valuable, highly substituted precursors for successive
reactions such as reductions of the carbonyl group, C–C
bond-cleavage reactions, SN reactions at the gem-dichlo-
romethyl group or cascade reactions under ring cleavage
of the original heterocycle followed by construction of a
new one. Unsaturated, nitro-substituted b-halohydrines,
acyldiazides, acrylic cyanides and pyrazoles bearing a
novel substitution pattern are easily accessible this way.
Synlett 2007, No. 10, 1507–1512 © Thieme Stuttgart · New York

1510
V. A. Zapol’skii et al.
LETTER
(10) Kagabu, S.; Moriya, K.; Shibuya, K.; Hattori, Y.; Tsuboi, S.;
Shiokawa, K. Biosci. Biotechnol. Biochem. 1992, 56, 362.
(11) (a) Zhang, N.; Tomizawa, M.; Casida, J. E. J. Med. Chem.
2002, 45, 2832. (b) Shiokawa, K.; Moriya, K.; Shibuya, K.;
Hattori, Y.; Tsuboi, S.; Kagabu, S. J. Biosci. Biotechnol.
Biochem. 1992, 56, 1364. (c) Kagabu, S.; Nishiwaki, H.;
Sato, K.; Hibi, M.; Yamaoka, N.; Nakagawa, Y. Pest
Manage. Sci. 2002, 58, 483. (d) Fischer, R.; Jeschke, P.;
Erdelen, C.; Lösel, P.; Reckmann, U.; Kaufmann, D.;
Zapol’skii, V. (Bayer AG); WO 03/040129A1, 2003.
(12) (a) Soulen, R. L.; Clifford, D. B.; Crim, F. F.; Johnston, J. A.
J. Org. Chem. 1971, 36, 3386. (b) Belen’kii, L. I.;
General Procedure for the Synthesis of 2-Nitrobuten-3-
ones 7–11
A suspension of 5.00 mmol of the heterocycles 2–6 in 20 mL
MeOH each was treated with 2.25 g (20.0 mmol) of a 40%
solution of Me2NH in H2O. The mixture was then kept at 45–
50 °C for the required reaction time, according to TLC
(typically 2–10 h). After cooling to 5 °C, excessive amine
was neutralized with concentrated HCl. Stirring at 30–70 °C
(3–6 h, TLC monitoring), recooling to r.t., and adding of
H2O (100 mL) then yielded a precipitate which was washed
twice with H2O (2 × 20 mL) and Et2O (2 × 20 mL), in detail:
1,1-Dichloro-3-(imidazolidin-2-ylidene)-3-nitropropan-
2-one (7)
Reaction times: 6 h with Me2NH, 5 h with HCl at 40–45 °C;
80% yield; mp 169–170 °C. 1H NMR (DMSO-d6): d = 3.69
(br s, 4 H, NCH2CH2N), 7.35 (s, 1 H, Cl2CH), 9.12 (br s,
2 H, NH). 13C NMR (DMSO-d6): d = 43.6 (2 CH2), 70.9
(CHCl2), 113.6 (CNO2), 159.6 (NHCNH), 180.4 (C=O).
HRMS (ESI) [M + H]+: m/z calcd for C6H7Cl2N3O3:
239.9937; found: 239.9937.
Brokhovetskii, D. B.; Krayushkin, M. M. Tetrahedron 1991,
47, 447. (c) Garuti, L.; Roberti, M.; Pession, A.; Leoncini,
E.; Hrelia, S. Bioorg. Med. Chem. Lett. 2001, 11, 3147.
(d) Phillips, W. G.; Ratts, K. W. J. Org. Chem. 1972, 37,
1526. (e) Hall, R. H.; Jordaan, A.; Malherbe, M. J. Chem.
Soc., Perkin Trans. 1 1980, 126. (f) Khlebnikov, A. F.;
Novikov, M. S.; Kusei, E. Yu.; Kopf, J.; Kostikov, R. R.
Russ. J. Org. Chem. 2003, 39, 559. (g) Kosinskaya, I. M.;
Pinchuk, A. M.; Shevchenko, V. I. J. Gen. Chem. USSR
(Engl. Transl.) 1971, 41, 101. (h) Kristol, D.; Shapiro, R.
J. Org. Chem. 1973, 38, 1470.
1,1-Dichloro-3-{1-[(2-chloro-5-pyridyl)methyl]imid-
azolidin-2-ylidene}-3-nitropropan-2-one (8)
Reaction times: 10 h with Me2NH, 5 h with HCl at 40–45 °C;
60% yield; mp 171–173 °C. 1H NMR (DMSO-d6): d = 3.87
(br s, 4 H, NCH2CH2N), 4.46 (br s, 2 H, NCH2), 7.49 (s, 1 H,
CHCl2), 7.56 (d, 1 H, J = 8.3 Hz, H-3aryl), 7.76 (dd, 1 H,
J = 8.3, 2.4 Hz, H-4aryl), 8.33 (d, 1 H, J = 2.4 Hz, H-6aryl),
10.31 (br s, 1 H, NH). 13C NMR (DMSO-d6): d = 42.8, 46.6,
47.9 (3 CH2), 69.5 (CHCl2), 107.5 (CNO2), 124.6
(CCl=CH), 129.9 (CHCCH), 140.0 (CH), 150.0 (N=CH),
150.3 (NCCl), 162.5 (NCNH), 175.4 (C=O). HRMS (ESI)
[M + H]+: m/z calcd for C12H11Cl3N4O3: 364.9970; found:
364.9971.
(13) Experimental Details
1H NMR and 13C NMR spectra were obtained on a BRUKER
Avance 400. Proton spectra were referenced to TMS; 13
C
NMR spectra refer to the solvent signal at d = 77.0 ppm.
Spectra in DMSO-d6 were referenced to d = 2.50 ppm (1H)
and 39.7 ppm (13C), respectively. High-resolution mass
spectra were measured with a Bruker Daltonik APEX IV FT
Ion Cyclotron Resonance mass spectrometer with
electrospray ionization.
1-(2-Chloro-5-pyridylmethyl)-2-(2,3,3-trichloro-1-nitro-
allylidene)imidazolidine (3)
1,1-Dichloro-3-(1,3-dimethylimidazolidin-2-ylidene)-3-
nitropropan-2-one (9)
To a solution of 7.19 g (38.7 mmol) N-(2-chloro-5-pyridyl-
methyl)ethane-1,2-diamine in 30 mL MeOH was added a
solution of 5.00 g (18.4 mmol) 1,1,2,4,4-pentachloro-3-
nitro-1,3-butadiene (1) in 5 mL MeOH at –40 °C within 5
min. The resulting mixture was kept at –40 °C for 1 h, then
1 h at r.t. The precipitate was sucked off, washed with H2O
(3 × 20 mL), MeOH (1 × 10 mL), and Et2O (2 × 20 mL).
Drying in vacuo yielded 3.19 g (45%) of imidazolidine 3, mp
174–175 °C. 1H NMR (DMSO-d6): d = 3.78 (br s, 4 H,
NCH2CH2), 4.56 (br s, 2 H, H2CCaryl), 7.54 (d, J = 8.3 Hz, 1
H, H-3aryl), 7.77 (dd, J = 8.3, 2.4 Hz, 1 H, H-4aryl), 8.35 (d,
J = 2.4 Hz, 1 H, H-6aryl), 9.41 (br s, 1 H, NH). 13C NMR
(DMSO-d6): d = 42.7, 49.5, 51.0 (3 CH2), 103.3 (CNO2),
124.4 (CH), 125.3, 125.6 (CCl=CCl2), 131.5 (Cquat), 137.9
(CH), 147.9 (N=CH), 149.6 (NCCl), 159.8 (NCNH). HRMS
(ESI) [M + H]+: m/z calcd for C12H10Cl4N4O2: 382.9631;
found: 382.9632.
Reaction times: 6 h with Me2NH, 6 h with HCl at 35–40 °C;
45% yield; mp 150–151 °C. 1H NMR (DMSO-d6): d = 2.86
(s, 6 H, NCH3), 3.91 (br s, 4 H, NCH2CH2), 7.54 (s, 1 H,
CHCl2). 13C NMR (DMSO-d6): d = 33.6 (CH3), 49.1 (2
CH2), 69.8 (CHCl2), 106.4 (CNO2), 161.9 (NCN), 175.3
(C=O). HRMS (ESI) [M + H]+: m/z calcd for C8H11Cl2N3O3:
268.0250; found: 268.0252.
As a side product, trichloroacrylic acid (12) was isolated:
After the aforementioned acidic hydrolysis the mixture was
treated with an excess of 10% NaHCO3 in H2O at 10 °C and
set to pH 9. The usual extraction as described above then
gave 9, whereas the basic aqueous solution was acidified
with HCl, extracted with CH2Cl2 (2 × 20 mL), washed with
H2O (2 × 10 mL) and dried over anhyd Na2SO4. Evaporation
of the solvent yielded 12 (30%), mp 71–73 °C (lit.14 73–
74 °C). 1H NMR (CDCl3): d = 11.0 (br s, 1 H, COOH). 13
C
NMR (CDCl3): d = 121.7 (CCl), 134.6 (CCl2), 165.8 (C=O).
1,1-Dichloro-3-nitro-3-(thiazolidin-2-ylidene)propan-2-
one (10)
2-(2,3,3-Trichloro-1-nitroallylidene)-1,3-dimethyl-
imidazolidine (4)
In analogy to the preparation of 3, the dissolved nitro-
perchlorobutadiene (1) was added to a solution of N,N¢-
dimethylethane-1,2-diamine (85% in H2O) in 20 mL MeOH.
After completion of the reaction, 200 mL of cold H2O was
added. Then, the aqueous phase was extracted with CHCl3
(3 × 20 mL). The organic layer was washed twice with H2O
and dried over anhyd CaCl2. Removal of the solvent in vacuo
afforded a crude product that was reprecipitated with Et2O
(20 mL). Drying in vacuo again yielded 3.43 g (65%)
imidazolidine 4, mp 122–124 °C. 1H NMR (CDCl3):
d = 3.00 (s, 6 H, NMe), 3.86 (br s, 4 H, NCH2). 13C NMR
(CDCl3): d = 35.4 (CH3), 49.8 (CH2), 99.6 (CNO2), 120.9,
125.4 (CCl=CCl2), 162.0 (NCN). HRMS (ESI) [M + H]+:
m/z calcd for C8H10Cl3N3O2: 285.9914; found: 285.9913.
Reaction times: 2 h with Me2NH, 3 h with HCl at 65–70 °C;
50% yield; mp 130–131 °C. 1H NMR (DMSO-d6): d = 3.31
(t, 2 H, J = 8.6 Hz, SCH2), 4.07 (t, 2 H, J = 8.6 Hz, NCH2),
7.36 (s, 1 H, CHCl2), 10.83 (br s, 1 H, NH). 13C NMR
(DMSO-d6): d = 29.0 (SCH2), 51.7 (NCH2), 70.8 (CHCl2),
120.7 (CNO2), 173.9 (HNCS), 180.1 (C=O). HRMS (ESI)
[M + H]+: m/z calcd for C6H6Cl2N2O3S: 256.9549; found:
256.9550.
1,1-Dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitropropan-
2-one (11)
Reaction times: 3 h with Me2NH, 3 h with HCl at 30–35 °C;
90% yield; mp 140–141 °C. 1H NMR (CDCl3): d = 3.58 (m,
4 H, CH2), 7.12 (s, 1 H, CHCl2). 13C NMR (DMSO-d6):
d = 38.3, 39.1 (2 SCH2), 69.0 (CHCl2), 133.0 (CNO2), 180.3
Synlett 2007, No. 10, 1507–1512 © Thieme Stuttgart · New York

LETTER
Synthesis and Reactions of Dichloromethyl Nitrovinylidene Ketones of Heterocycles
1511
(SCS), 187.4 (C=O). HRMS (EI) [M + H]+: m/z calcd for
C6H5Cl2NO3S2: 273.9161; found: 273.9162.
1,1-Dichloro-3-nitro-3-(thiazolidin-2-ylidene)propan-2-
ol (13)
CHCl2). 13C NMR (CDCl3): d = 20.4 (CH3), 38.1, 39.2 (2
SCH2), 70.5 (CHCl2), 76.2 (CHO), 130.4 (CNO2), 169.2
(C=O), 173.3 (SCS). HRMS (ESI) [M + Na]+: m/z calcd for
C8H9Cl2NO4S2: 339.9242; found: 339.9242
To a solution of 0.30 g (1.17 mmol) nitrobutenone 10 in 20
mL EtOH at 0 °C was added 0.049 g (1.30 mmol) NaBH4
within 2 min. The resulting mixture was kept at 0 °C for 10
min and for additional 15 min at 10 °C. After addition of 50
mL cold H2O and neutralization with 5% HCl, the
precipitate that was formed was sucked off and washed with
H2O (3 × 20 mL). Drying in vacuo yielded 0.24 g (80%)
nitrobutenol 13; mp 122–124 °C. 1H NMR (DMSO-d6):
d = 3.13 (t, 2 H, J = 8.6 Hz, SCH2), 3.86 (t, 2 H, J = 8.6 Hz,
NCH2), 5.33 (br s, 1 H, CHCNO2), 6.35 (d, 1 H, J = 5.2 Hz,
CHCl2), 7.15 (br s, 1 H, OH), 8.90 (br s, 1 H, NH). 13C NMR
(DMSO-d6): d = 28.4 (SCH2), 50.3 (NCH2), 74.1, 75.0
[CH(OH)CHCl2], 116.8 (CNO2), 169.5 (HNCS). HRMS
(ESI) [M + H]+: m/z calcd for C6H8Cl2N2O3S: 258.9705;
found: 258.9707.
2-(Nitromethylene)-1,3-dithiolane (17)
To a solution of 0.30 g (1.09 mmol) nitrobutenone 11 in 20
mL EtOH at r.t. was added 0.15 g (2.20 mmol) NaOEt. The
resulting mixture was kept at r.t. for 1 d. After cooling to
10 °C, addition of 60 mL cold H2O and neutralization with
concd HCl, the resulting precipitate was sucked off and
washed with H2O (2 × 20 mL). Drying in vacuo afforded
0.13 g (73%) dithiolane 17, mp 105–106 °C (lit.6a,c 105–
106 °C). 1H NMR (CDCl3): d = 3.54 (br s, 4 H, SCH2), 7.57
(s, 1 H, CH). 13C NMR (CDCl3): d = 36.8, 38.7 (2 SCH2),
124.0 (CHNO2), 167.4 (SCS).
3-Hydrazonomethyl-5-(2-mercaptoethyl)sulfanyl-4-
nitro-1H-pyrazol (18)
A suspension of 0.30 g (1.09 mmol) 11 in 15 mL MeOH was
treated with 0.27 g (5.45 mmol) N2H4·H2O (64% in H2O) at
r.t. The resulting mixture was stirred for 5 h at the same
temperature. Then the precipitate was sucked off, washed
twice with H2O and once with MeOH (10 mL each portion).
After drying in vacuo 0.20 g (75%) pyrazole 18 was
obtained; mp 216–218 °C. 1H NMR (DMSO-d6): d = 2.64
(br s, 1 H, SH), 2.82 (m, 2 H, HSCH2), 3.27 (m, 2 H,
CSCH2), 8.03 (s, 1 H, N=CH), 8.20 (br s, 2 H, NH2), 13.83
(br s, 1 H, NH). 13C NMR (DMSO-d6): d = 23.7 (HSCH2),
33.5 (CSCH2), 122.1 (N=CH), 127.0 (CNO2), 140.9 (N=C),
145.3 (NHCS). HRMS (ESI) [M + H]+: m/z calcd for
C6H9N5O2S2: 248.0270; found: 248.0271.
1,1-Dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitropropan-
2-ol (14)
Preparation as described for 13; 98% yield; mp 135–136 °C.
1H NMR (CDCl3): d = 3.58 (m, 4 H, CH2), 4.00 (d, 1 H,
J = 10.5 Hz, OH), 5.11 (dd, 1 H, J = 10.5, 8.7 Hz, CHOH),
6.23 (d, 1 H, J = 8.7 Hz, CHCl2). 13C NMR (CDCl3):
d = 38.0, 39.4 (2 SCH2), 72.5 (CHCl2), 78.5 [CH(OH)],
132.2 (CNO2), 173.4 (SCS). HRMS (ESI) [M + Na]+: m/z
calcd for C6H7Cl2NO3S2: 297.9137; found: 297.9139.
1,1-Dichloro-3-(1,3-dithiolan-2-yl)-3-nitropropan-2-ol
(15)
(1) Starting from nitropropanol 14 in analogy to the
synthesis of 13, 152 mg, 50% yield.
Acetic Acid [5-(2-Mercapto-ethylsulfanyl)-4-nitro-1H-
pyrazol-3-ylmethylene]hydrazide (19)
(2) Directly from nitropropanone 11 under modified
conditions: To a suspension of 0.30 g (1.09 mmol)
nitrobutenone 11 in 20 mL EtOH at 0 °C was added 0.045 g
(1.20 mmol) NaBH4 within 2 min. The resulting mixture was
kept at 0 °C for 10 min and at 10 °C for 15 min. In contrast
to the reaction described above, in this case another portion
(0.045 g, 1.20 mmol) of NaBH4 was added, and the mixture
was kept at 10 °C for additional 60 min. After addition of 50
mL cold H2O, neutralization with 5% HCl, and extraction
with CH2Cl2 (3 × 20 mL), the organic layer was washed with
H2O and dried over anhyd CaCl2. Evaporation of the solvent
and column chromatography (PE–EtOAc, 10:1) yielded a
yellow oil, 106 mg (35%) of 15 as a mixture of erythro- und
threo-isomers (5:1 ratio according to NMR). 1H NMR
(CDCl3): d (major isomer) = 3.29 (m, 5 H, SCH2CH2S, OH),
4.49 (m, 1 H, CHOH), 4.89 (dd, 1 H, J = 10.2, 8.1 Hz,
CHNO2), 5.18 (d, 1 H, J = 10.2 Hz, SCHS), 5.81 (d, 1 H,
J = 8.1 Hz, CHCl2); d (minor isomer) = 3.29 (m, 5 H,
SCH2CH2S, OH), 4.49 (m, 1 H, CHOH), 4.92 (dd, 1 H,
J = 8.5, 6.0 Hz, CHNO2), 5.25 (d, 1 H, J = 8.5 Hz, SCHS),
6.12 (d, 1 H, J = 6.0 Hz, CHCl2). 13C NMR (CDCl3): d
(major isomer) = 37.9, 38.7 (SCH2CH2S), 50.6 (SCHS), 72.5
(CHCl2), 76.0 (CHOH), 90.5 (CHNO2); d (minor isomer) =
37.8, 38.7 (SCH2CH2S), 49.9 (SCHS), 73.0 (CHCl2), 77.3
(CHOH), 91.7 (CHNO2). HRMS (ESI) [M + Na]+: m/z calcd
for C6H9Cl2NO3S2: 299.9293; found: 299.9295.
A solution of 0.20 g (0.81 mmol) pyrazole 18 in 15 mL Ac2O
was kept at 20 °C for 3 h. The precipitate was sucked off,
washed with H2O (2 × 10 mL) and MeOH (1 × 10 mL) and
dried in vacuo yielding 0.22 g (95%) pyrazole 19
(Z:E = 1:0.4); mp 213–215 °C. 1H NMR (DMSO-d6): d
(major isomer) = 2.24 s (3 H, CH3), 2.66 br s (1 H, SH), 2.85
m (2 H, HSCH2), 3.30 m (2 H, CSCH2), 8.36 s (1 H,
1JC,H = 178 Hz, N=CH), 11.75 (br s, 1 H, NH), 14.43 (br s, 1
H, NH); d (minor isomer) = 2.00 s (3 H, CH3), 2.66 br s (1
H, SH), 2.85 m (2 H, HSCH2), 3.30 (m, 2 H, CSCH2), 8.59
(s, 1 H, 1JC,H = 177 Hz, N=CH), 11.92 (br s, 1 H, NH), 14.61
(br s, 1 H, NH). 13C NMR (DMSO-d6): d (major isomer) =
20.3 (CH3), 23.7 (HSCH2), 33.7 (CSCH2), 129.4 (N=CH),
133.4 (CNO2), 138.2, 146.0, 172.9 (CO); d (minor isomer) =
21.9 (CH3), 23.7 (HSCH2), 33.6 (CSCH2), 129.3 (N=CH),
133.3 (CNO2), 138.0, 146.0, 166.4 (CO). HRMS (EI) [M +
H]+: m/z calcd for C8H11N5O3S2: 290.0382; found: 290.0376
1,1-Dichloro-3-(imidazolidin-2-ylidene)-3-nitropropan-
2-ol (20)
Compound 20 was prepared as described for thiazolidine 13;
55% yield; mp 134–136 °C. 1H NMR (DMSO-d6): d = 3.61
(br s, 4 H, 2 CH2), 5.14 (d, 1 H, J = 5.1 Hz, CHOH), 6.29 (d,
1 H, J = 5.1 Hz, CHCl2), 6.70 (br s, 1 H, OH), 8.54 (br s, 2
H, NH). 13C NMR (DMSO-d6): d = 43.4 (2 CH2), 73.9, 75.1
(CHCl2CH), 106.4 (CNO2), 159.8 (NHCNH). HRMS (ESI)
[M + H]+: m/z calcd for C6H9Cl2N3O3: 242.0094; found:
242.0095.
1,1-Dichloro-3-(1,3-dithiolan-2-ylidene)-3-nitropropan-
2-yl Acetate (16)
1-(2-Chloropyridin-5-ylmethyl)-2-(nitromethyl-
ene)imidazolidine (21)
A mixture of 0.30 g (1.09 mmol) nitrobutenol 14 and 0.18 g
(2.18 mmol) NaOAc in 10 mL Ac2O were stirred for 4 h
under reflux. After cooling to r.t. the mixture was diluted
with 60 mL cold H2O. The resulting precipitate was sucked
off and washed thoroughly with H2O (5 × 20 mL). Drying in
vacuo yielded 0.33 g (95%) acetate 16, mp 119–120 °C. 1H
NMR (CDCl3): d = 2.15 (s, 3 H, CH3), 3.58 (m, 4 H, CH2),
6.39 (d, 1 H, J = 8.8 Hz, CHO), 6.54 (d, 1 H, J = 8.8 Hz,
To a solution of 0.50 g (1.37 mmol) imidazolidine 8 in 20
mL EtOH at 0 °C was added 0.055 g (1.44 mmol) NaBH4
within 1 min. After 10 min at this temperature, the mixture
was diluted with 100 mL cold H2O and neutralized with 5%
HCl. The resulting precipitate was sucked off, washed with
H2O (3 × 20 mL), and dried in vacuo. Imidazolidine 21 was
obtained in 60% yield, 0.21 g; mp 163–164 °C (lit.15 166–
Synlett 2007, No. 10, 1507–1512 © Thieme Stuttgart · New York

1512
V. A. Zapol’skii et al.
LETTER
CH2Cl2 (6 × 20 mL). The organic layer then was washed
with H2O and dried over CaCl2. Evaporation of the solvents
afforded 0.38 g (75%) azide 23 (starting from 0.50 g, 1.86
mmol of 9), mp 123–125 °C. 1H NMR (DMSO-d6): d = 2.87
(s, 6 H, 2 × CH3), 3.91 (br s, 4 H, 2 CH2), 6.20 (s, 1 H, CH).
13C NMR (DMSO-d6): d = 33.8 (2 CH3), 49.1 (2 CH2), 75.1
(CH), 107.9 (CNO2), 161.9 (NCN), 178.2 (C=O). HRMS
(ESI) [M + H]+: m/z calcd for C8H11N9O3: 282.1058; found:
282.1059.
167 °C). 1H NMR (DMSO-d6): d = 3.58 (m, 4 H,
NCH2CH2NH), 4.49 (s, 2 H, CH2Caryl), 6.77 (s, 1 H,
CHNO2), 7.54 (d, 1 H, J = 8.1 Hz, H-3aryl), 7.78 (dd, 1 H,
J = 8.1, 1.5 Hz, H-4aryl), 8.37 (d, 1 H, J = 1.5 Hz, H-6aryl),
8.90 (br s, 1 H, NH). 13C NMR (DMSO-d6): d = 42.7
(NHCH2), 45.4, 48.2 (CH2NCH2), 96.0 (CHNO2), 124.6
(CH), 131.6 (Cquat), 139.4 (CH), 149.4 (N=CH), 149.8 (CCl),
158.7 (NHCN).
3-(Imidazolidin-2-ylidene)-3-nitro-2-oxopropionitrile
(22)
3-(1,3-Dimethylimidazolidin-2-ylidene)-3-nitro-2-oxo-
propionitrile (24)
To a solution of 0.50 g (2.08 mmol) imidazolidine 7 in 10
mL DMF was added 0.81 g (12.46 mmol) NaN3 in one
portion at r.t. After stirring for 1 d, 70 mL cold H2O was
added. On treatment with concd HCl a precipitate appeared
that was sucked off and washed with H2O (2 × 20 mL) and
MeOH (2 × 5 mL). Drying in vacuo yielded 0.13 g (35%)
22; mp 255–257 °C. 1H NMR (DMSO-d6): d = 3.70 (br s, 4
H, 2 × CH2), 10.03 (br s, 2 H, NH). 13C NMR (DMSO-d6):
d = 43.5 (2 CH2), 112.2, 116.3 (CN, CNO2), 158.0
(NHCNH), 165.0 (C=O). HRMS (ESI) [M + H]+: m/z calcd
for C6H6N4O3: 183.0513; found: 183.0513.
A solution of 0.30 g (1.09 mmol) azide 23 in 10 mL DMF
was treated with additional 0.14 g (2.18 mmol) NaN3 and
then was heated to 90–95 °C for 10 h. Work-up as described
for 23 gave 0.09 g (40%) nitrile 24; mp 175–177 °C. 1H
NMR (DMSO-d6): d = 2.89 (s, 6 H, 2 CH3), 3.93 (br s, 4 H,
2 CH2). 13C NMR (DMSO-d6): d = 34.1 (2 CH3), 49.4 (2
CH2), 112.6, 115.3 (CN, CNO2), 159.6 (NCN), 164.2 (C=O).
HRMS (ESI) [M + H]+: m/z calcd for C8H10N4O3: 211.0826;
found: 211.0826.
(14) Ol’dekop, Y. A.; Kaberdin, R. V. J. Org. Chem. USSR (Engl.
Transl.) 1975, 11, 288.
(15) Kagabu, S.; Yokoyama, A. K.; Iwaya, K.; Tanaka, M.
Biosci. Biotechnol. Biochem. 1998, 62, 1216.
1,1-Diazido-3-(1,3-dimethylimidazolidin-2-ylidene)-3-
nitropropan-2-one (23)
The preparation followed the protocol for 22, but after
addition of concd HCl the mixture was extracted with
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