S-methyl methaneimidothioates as enamine precursors. A simple procedure for synthesis of 2-nitroenamines

Article abstract of DOI:10.1055/s-1998-2017

2-Nitroalken-1-amines are prepared by condensation of substituted nitromethanes with S-methyl methaneimidothioates in the absence of solvent.

Full text of DOI:10.1055/s-1998-2017

139
SHORT PAPERS
S-Methyl Methaneimidothioates as Enamine Precursors. A Simple Procedure for
Synthesis of 2-Nitroenamines
Kathleen A. Turner
CSIRO Molecular Science, Private Bag 10, Clayton South MDC, Clayton, Victoria 3169, Australia
Fax +61(3)95438160
Received 22 April 1997; revised 9 June 1997
Abstract: 2-Nitroalken-1-amines are prepared by condensation of
substituted nitromethanes with S-methyl methaneimidothioates in the
absence of solvent.
convenient and general synthesis of 2-nitroenamines from
substituted nitromethanes and S-methyl methaneimido-
thioates, which allows considerable variation of the sub-
stituents on the enamino nitrogen and the 2-position of the
double bond is now presented. The nitromethanes are
available from the corresponding acetonitriles17 and the
S-methyl methaneimidothioates can be readily prepared
from the amines18 or isothiocyanates19 via the correspond-
ing thioformamides.20The reaction provides the (Z)-alkene
exclusively. However, it should be noted that these com-
pounds are photosensitive and readily undergo isomeri-
sation to a mixture of E- and Z-isomers in solution.
Key words: nitromethanes, imidothioates, nitroalkenamines, con-
densation, solvent free
2-Nitroenamines are of considerable importance due to
their utility as synthetic intermediates1-3and their phar-
macological properties.4 Popular strategies for prepa-
ration of 2-nitroenamines are reaction of a 2-halo-,5,6
2-alkylthio-,7 2-alkylsulfinyl-8 or 2-alkoxynitroethene9
with an amine or transamination.10 This method requires
prior preparation of the appropriate precursor, which in
many cases is not trivial. Other approaches include con-
densation of orthoformates10 and amide acetals11 with
nitromethanes. Specific procedures for preparation of
2,2-diamino-12–14and 2-amino-2-thionitroethenes15,16 are
also available. Most of these reactions are somewhat re-
strictive in their outcome, requiring a nitromethane bear-
ing an additional activating group, or nitromethane itself.
The scope of this reaction is demonstrated by the data inTa-
ble 1. Avariety of aromatic and heterocyclic nitromethanes
provide the corresponding nitroenamines in good yields. It
may be noted however that ortho-substitution requires
longer reaction times and reduces the yield of product. Al-
though aliphatic nitromethanes do provide the desired
products the reaction is much slower and results in consid-
erably decreased conversion. Various aromatic and hetero-
cyclic S-methyl methaneimidothioates are well-tolerated.21
Given the dearth of existing procedures for preparing
nitroenamines bearing aryl groups on the double bond, a
2-Nitroalken-1-amines-3; General Procedure:
The S-methyl methaneimidothioate (5.0 mmol) was added to the ni-
tromethane (2.0 mmol). The resulting mixture was stirred at r.t. until
it solidified then left to stand for the remainder of the reaction time
Table 1. 2-Nitroenamines 3 Prepared
Product
R1
R2
Reaction Time
(h)
Yielda (%)
mp (°C)
Molecular Formulab
3a
3b
3c
3d
3e
3f
Ph
Ph
48
100
94
93
87
38
86
89
87
82
75
118–121
161–163
151–154
121–123
103–104
171–174 (dec.)
158–160c
195–198
143–145
161–163
C14H12N2O2
C14H11ClN2O2
C15H14N2O3
C12H10N2O2S
C9H10N2O2
4-ClC6H4
4-MeOC6H4
2-thienyl
Me
Ph
2
Ph
24
Ph
2
Ph
64 days
4-ClC6H4
2-thienyl
4-ClC6H4
2-thienyl
2-MeOC6H4
thiazol-2-yl
thiazol-2-yl
3-pyridyl
3-pyridyl
Ph
24
C11H8ClN3O2S
C9H7O2N3S2
C13H10ClN3O2
C11H9N3O2S
C15H14N2O3
3g
3h
3i
2
6
1
3j
13 days
a Yield of isolated product based on 1.
b Satisfactory microanalyses obtained: C ± 0.27, H ± 0.14, N ± 0.26, Cl ± 0.45, S ± 0.14.
c Partial sublimation.

140
Short Papers
SYNTHESIS
Table 2. Spectral Data of (Z)-2-Nitroenamines 3a
Product
IR (KBr)
1H NMR (CDCl3/TMS)
d, J (Hz)
Partial 13C NMR (CDCl3)b
d
MS (eV)
m/z (%)
n (cm-1)
3a
3256,
1642,
1491,
1386,
1310,
1167
6.96–7.49 (m, 10H), 7.55
(d, J = 14, 1H, H1), 11.00 (br d,
J = 14, 1H, NH)
117.3 (2C, C2¢, C6¢), 125.4
(C4¢), 128.2 (C4²), 128.4 (2C,
C2², C6²), 129.9 (4C, C3¢, C5¢,
C3², C5²), 139.3 (C1)
240 (M+, 100), 223 (M+-OH, 74),
193 (M+-NO2H, 62)
3b
3c
3d
3e
3f
3244,
1643,
1496,
1378,
1326,
1172
7.03–7.47 (m, 9H), 7.58 (d, J = 13, 117.5 (2C, C2¢, C6¢), 125.7
1H, H1), 11.03 (d, J = 13, 1H, NH) (C4¢), 128.6 (2C, C2², C6²),
130.1 (2C, C3¢, C5¢), 131.2 (2C,
276 (M+, 27), 274 (M+, 74), 257
(M+-OH, 24), 227 (M+-NO2H,
31), 193 (M+-NO2-Cl, 100)
C3², C5²), 139.3 (C1)
3244,
1643,
1495,
1380,
1325,
1177
3.83 (s, 3H, CH3O), 6.90–7.45 (m, 55.3 (CH3), 113.9 (2C, C2², C6²), 270 (M+, 100), 253 (M+-OH, 22),
9H), 7.56 (d, J = 14, 1H, H1),
10.99 (d, J = 14, 1H, NH)
117.3 (2C, C2¢, C6¢), 125.3 (C4¢), 224 (M+-NO2, 71), 209 (M+-NO2-
130.0 (2C, C3¢, C5¢), 131.4 (2C,
C3², C5²), 138.8 (C1) 159.6
(C4²)
CH3, 40)
3239,
1637,
1486,
1387,
1319,
1145
7.02 (dd, J = 4, 5, thienyl-H4²),
7.06–7.28 (m, 4H, Ph-H, thienyl-
H), 7.28–7.57 (m, 3H, Ph-H,
thienyl-H), 7.83 (d, J = 14, 1H,
H1), 11.18 (br d, J = 14, 1H, NH)
117.7 (2C, C2¢, C6¢), 125.6
(C4¢), 126.0, 126.4, 126.7 (C3¢¢,
C4², C5²), 130.1 (2C, C3¢, C5¢),
139.2 (C1)
246 (M+, 100), 200 (M+-NO2, 79),
167 (86), 77 (C6H5+, 85)
3284,
1656,
1484,
1401,
1334,
1152
2.17 (s, 3H, H3), 6.94–7.63
(m, 6H, Ph-H, H1), 10.90 (br d,
J = 12, 1H, NH)
16.4 (CH3), 117.1 (2C, C2¢, C6¢),
178 (M+, 100), 161 (M+-OH, 15),
125.1 (C4¢), 130.0 (2C, C3¢, C5¢), 130 (M+-NO2H-H, 66), 104
137.6 (C1)
(C6H5NCH, 47), 77 (C6H5, 58)
3246,
1628,
1501,
1405,
1300,
1181
7.00 (dd, J = 1, 3, 1H, thiazolyl-
113.8 (C5¢), 128.7 (2C, C2²,
281 (M+, 32), 234 (M+-NO2H,
H5¢), 7.30–7.54 (m, 5H, ArH, thia- C6²), 131.4 (2C, C3², C5²), 135.8 100), 200 (M+-NO2-Cl, 30)
zolyl-H4¢), 8.05 (d, J = 12, 1H,
H1), 11.13 (br d, 1H, NH)
(C4¢), 140.2 (C1), 160.7 (C2¢)
3g
3h
3231,
1630,
1500,
1397,
1308,
1179
7.00 (d, J = 4, 1H, thiazolyl-H5¢),
7.06 (t, J = 4, 1H, thienyl-H4²),
7.21 (d, J = 4, 1H, thienyl-H),
7.44 (d, J = 4, 2H, thiazolyl-H4¢,
thienyl-H), 8.30 (br s, 1H, H1),
11.22 (br s, 1H, NH)
114.0 (C5¢), 126.6, 127.3, 127.7
(C3², C4², C5²), 135.7 (C4¢),
140.3 (C1), 160.4 (C2¢)
253 (M+, 91), 206 (M+-NO2H,
100), 122 (M+-NO2H-C4H4S, 38)
3242,
1651,
1480,
1392,
1331,
1167
7.32–7.57 (m, 7H, ArH, pyridyl-H, 124.1 (C4¢), 124.3 (C5¢), 128.8
H1), 8.47 (dd, J = 1, 3, 1H, pyridyl- (2C, C2², C6²), 131.4
H5¢), 8.56 (d, J = 3Hz, 1H, pyridyl- (2C, C3², C5²), 138.1 (C2¢),
H2¢), 10.87 (br d, J = 13, 1H, NH) 139.8 (C1), 146.7 (C6¢)
277 (M+, 33), 275 (M+, 100), 258
(M+-OH, 37), 240 (M+-Cl, 19),
229 (M+-NO2, 59), 194 (M+-NO2-
Cl, 40)

February 1998
SYNTHESIS
141
Table 2. (continued)
Product
IR (KBr)
1H NMR (CDCl3/TMS)
d, J (Hz)
Partial 13C NMR (CDCl3)b
d
MS (eV)
m/z (%)
n (cm–1)
3i
3200,
1646,
1470,
1335,
1151
7.06 (ddd, J = 1, 2, 3, 1H, thienyl-
H4), 7. 12–7.65 (m, 4H, thienyl-
H3, -H5, pyridyl-H4¢,-H6¢), 7.77
(d, J = 13, 1H, H1), 8.48 (dd,
J = 1, 3, 1H, pyridyl-H5¢), 8.57
(d, J = 2, 1H, pyridyl-H2¢), 10.98
(br d, J = 13, 1H, NH)
124.3 (2C, C4¢, C5¢), 126.5,
126.7, 127.3 (C3², C4², C5²),
138.0 (C2¢), 139.9 (C1), 146.8
(C6¢)
247 (M+, 77), 201 (M+-NO2, 100)
3j
3238,
1649,
1501,
1488,
1353,
1164
3.82 (s, 3H, CH3O), 6.92–7.46
(m, 9H, Ph-H), 7.52 (d, J = 13,
1H, H1), 10.97 (br d, J = 13, 1H,
NH)
55.5 (CH3), 110.9 (C3²), 117.0
(2C, C2¢, C6¢), 120.3 (C6²),
124.9 (C4¢), 129.8 (2C, C3¢, C5¢),
130.5 (C5²), 131.8 (C4²), 139.0
(C1), 158.0 (C2²)
270 (M+, 100), 224 (M+-NO2,
38), 209 (M+-NO2-CH3, 58)
1
a The products are assigned the Z configuration on the basis of the H NMR shift of H1, which is shielded in the Z-isomer relative to the
E-isomer. For example, in the E-isomers of 3a and 3i H1 resonates at d = 8.85 and 8.86, respectively,
b Only the more intense peaks are quoted as the compounds undergo partial isomerisation during collection of 13C data. This results in peaks of
similar intensity to that of most of the quaternary carbons in the molecules casting doubt on assignment of these peaks.
(see Table 1). The crude material was then subjected to radial chro-
matography on silica gel [CH2Cl2/petroleum spirit (bp 40–60°C)
(1:1) elution]. The eluate containing the major yellow/orange band
was concentrated under reduced pressure to give the product as yel-
low to red crystals. Alternatively, the crude product was recrystallised
from MeOH and the mother liquors subjected to radial chromatogra-
phy as described above.
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potential for reaction of imidothioates substituted at C1, but
yields may be variable.