An efficient approach to novel 5,5-disubstituted dithiohydantoins via a- cyano-a(dihalogenomethyleneamino)alkanoic acid esters

Article abstract of DOI:10.1055/s-1998-2175

Convenient syntheses of 5,5-disubstituted 2,4-dithiohydantoins 7 and α- [bis(alkylthio)methyleneimino]-α-cyanoalkanoic acid esters 8 via α-cyano- α-(dichloromethyleneimino)alkanoic acid esters 4 by conversion with sulfides and thiolates are described. The mechanism of the formation of 7 is investigated.

Full text of DOI:10.1055/s-1998-2175

SYNTHESIS
October 1998
1437
An Efficient Approach to Novel 5,5-Disubstituted Dithiohydantoins via α-Cyano-α-
(dihalogenomethyleneamino)alkanoic Acid Esters
Marco Bergemann, Richard Neidlein*
Pharmazeutisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany
Received 18 February 1998; revised 23 March 1998
Dedicated to Prof. Dr. Gottfried Heinisch, Innsbruck, on the occasion of his 60th birthday with best wishes
Abstract: Convenient syntheses of 5,5-disubstituted 2,4-dithiohy-
dantoins
alkanoic acid esters
7
and α-[bis(alkylthio)methyleneimino]-α-cyano-
via α-cyano-α-(dichloromethylene-
8
imino)alkanoic acid esters 4 by conversion with sulfides and thi-
olates are described. The mechanism of the formation of 7 is
investigated.
Key words: α-cyano-α-isocyanoalkanoic acid esters, α-cyano-α-
(dihalogenomethyleneimino)alkanoic acid esters, 2,4-dithiohy-
dantoins
In previous communications we have reported the synthe-
sis of α-cyano-α-isocyanoalkanoic acid esters 2 (Scheme
1) and their synthetic applications.1 Esters 2 proved to be
versatile intermediates and allowed for the facile synthe-
ses of various heterocyclic compounds.2
2, 3, 4
R1
R2
a
b
c
CH3
C2H5
C6H5–CH2
CH3–C6H4–CH2
t-C4H9
t-C4H9
t-C4H9
t-C4H9
d
Scheme 2
that can be stored at –25°C, but are very sensitive to hy-
drolysis.
Dihalogeno isocyanides react with sulfides to give
isothiocyanates.4–8 Upon reaction of α-cyano-α-(dibro-
momethyleneimino)alkanoic acid esters 3 with ammoni-
um sulfide in acetone the chlorine atoms were not substi-
tuted by sulfur, but dibromide 3 was reduced to esters 2
with formation of elemental sulfur. The reduction of 3 to
2 had been achieved in earlier work by the use of magnes-
ium metal (Scheme 3).1, 9–11
Scheme 1
α-Cyano-α-isocyanoalkanoic acid esters 2 react like sim-
ple isocyanides3 rapidly and selectively with bromine to
give the pure α-cyano-α-(dibromomethyleneimino)al-
kanoic acid esters 3 at 0°C in quantitative yields (Scheme
2). This reaction has not only synthetic value, but is also a
convenient method for a titrimetric analysis of α-cyano-
α-isocyanoalkanoic acid ester solutions. Because of the
instability of 2 in pure form at room temperature, the
compounds are best stored in dichloromethane solution at
–25°C and used in this form for further reactions. On
treatment of 3 with an excess of bromine no further reac- Scheme 3
tion was observed.1
α-Cyano-α-(dichloromethyleneimino)alkanoic acid es-
The reaction of 2 with a dilute solution of chlorine in carb-
on tetrachloride at 0°C gave the α-cyano-α-(dichloro-
methyleneimino)alkanoic acid esters 4 accompanied by a
large number of byproducts resulting from chlorination of
the alkyl side chains. Pure dichloro isocyanides 4 could be
obtained (Scheme 2) in high yields under modified reac-
tion conditions (–78°C, more diluted solutions, use of
carefully dried silica gel during chromatographic work-
up). Compounds 4 are colourless, weakly viscous liquids
ters 4, however, showed different behaviour in their re-
action with ammonium sulfide. 5-Alkoxycarbonyl-5-
alkyl-2,4-dithiohydantoins 7 were isolated from the re-
action mixtures in good yields (Scheme 4). Other syn-
theses of 5,5-dialkyl-substituted 2,4-dithiohydantoins
have been described in literature.12–14 If sodium sulfide
was used instead of ammonium sulfide the yields of 7
were lower.

SYNTHESIS
Papers
1438
If thiolates are used instead of sulfides, the chlorine atoms
in 4 are substituted by alkylthio groups as expected,16
leading to very stable α-[bis(alkylthio)methyleneimino]-
α-cyanoalkanoic acid esters 8 (Scheme 6). Addition of
hydrogen sulfide ions (HS–) or alkyl sulfide ions (RS–) to
solutions of 8 gave no further reaction, even under more
drastic conditions.
5, 6, 7
R1
R2
8
R1
R2
R3
a
b
c
CH3
C2H5
C6H5–CH2
t-C4H9
t-C4H9
t-C4H9
a
b
c
CH3
C2H5
C6H5–CH2
t-C4H9
t-C4H9
t-C4H9
C2H5
C2H5
C2H5
Scheme 4
Scheme 6
The unexpected formation of these reaction products can
be explained by discussing the results of further investiga-
tions. The first step of the postulated mechanism is the
substitution of the chlorine atoms by sulfide, leading to α-
cyano-α-isothiocyanatoalkanoic acid esters 5 (Scheme 5).
Subsequent nucleophilic attack of the hydrogen sulfide
ion (HS–) on the carbon atom of the isothiocyanato group
followed by cyclization leads to intermediate 6. Base-cat-
alyzed rearrangement with intermediate ring opening
could give the stable 2,4-dithiohydantoins 7. This type of
rearrangement mechanism has also been proposed by Car-
rington.15
In summary, a simple and efficient method for preparation
of 5-alkoxycarbonyl-5-alkyl-2,4-dithiohydantoins 7 and
α-[bis(alkylthio)methyleneimino]-α-cyanoalkanoic acid
esters 8 is presented and the high synthetic potential of α-
cyano-α-isocyanoalkanoic acid esters 2 has been demon-
strated.
All reactions were carried out under argon in flame-dried glassware.
CH2Cl2 was freshly distilled from CaH2; Et2O, THF and benzene
were distilled from Na/benzophenone before use. Silica gel (60–
200 mesh) for column chromatography (CC) was obtained from ICN-
Biomedicals. Mps were determined on a Reichert melting point mi-
croscope and are uncorrected. UV-vis spectra were recorded as
MeCN solutions on a Hewlett Packard HP 8453 UV-vis ChemStation
and Hewlett Packard HP 8452A diode array spectrophotometer, λ in
nm (log ε). IR spectra were recorded as KBr pellets or films on a
Perkin–Elmer PE 1600 FT-IR spectrophotometer, ν in cm–1. 1H NMR
spectra were recorded on Bruker WM-250 (at 250.13 MHz), Bruker
AM-360 (at 360.12 MHz) and Varian XL 300 spectrometers (at
299.95 MHz), δ in ppm rel. to TMS, J in Hz. 13C NMR spectra were
obtained at 62.89 MHz, at 90.56MHz and at 75.43 MHz on the same
spectrometers (the degree of substitution was determined by J-modu-
lated spin-echo experiments). MS were performed on a Varian MAT-
311 A mass spectrometer at 70 eV, m/z (rel.%). Elemental analyses
were obtained on a Foss-Heraeus Vario EL; all compounds gave sat-
isfactory analyses (C, H, S ±0.3%).
Chlorination of α-Cyano-α-isocyanoalkanoic Acid Esters 2a–d;
General Procedure:
Scheme 5
A solution of α-cyano-α-isocyanoalkanoic acid esters 2 (1 mmol) in
CH2Cl2 was dried for several days over activated molecular sieve 4A
at –25°C. To these solutions of 2 (concentration 0.05 mol/L) was
added a stoichiometric amount of chlorine solution in CCl4 (concen-
tration 0.05 mol/L) at –78°C under argon with stirring. After 30 min
at –78°C the mixture was warmed to r.t. and the solvent evaporated
in vacuo at max 20°C. The residue was purified by flash chromatog-
raphy on dry silica gel (6 × 1 cm, silica gel dried at 160°C/1.2 ×
10–2 mbar, 2 h) with CH2Cl2. Evaporation of the solvent yielded the
The unstable intermediate 5 was also obtained by reaction
of dichloride 4 with gaseous hydrogen sulfide (H2S) and
sodium hydrogen carbonate in acetone and was identified
spectroscopically. Solutions of 5 gave 2,4-dithiohydan-
toin 7 after reaction with one equivalent of ammonium
sulfide. This observation provides additional support for
the proposed mechanism.

SYNTHESIS
FAB-MS (matrix NBA): m/z (%) = 342 (2) [M+ + H], 285 (5) [M+ +
October 1998
1439
corresponding α-cyano-α-(dichloromethyleneimino)alkanoic acid
esters 4 as colourless liquids, which can be stored at –25°C.
+
+
H – C4H8], 105 (40) [CH3C7H6 ], 57 (100) [C4H9 ].
HRMS (C16H1835Cl37ClN2O2) [m/z]: 340.0745 (calcd 340.0745).
tert-Butyl α-Cyano-α-(dichloromethyleneimino)propanoate (4a):
Reaction of 2a (180 mg, 1 mmol) in CH2Cl2 with chlorine in CCl4
(10 mL, 0.1 mmol/mL) gave 4a as a colourless oil. Excess of chlorine
leads to alkyl chlorinated products; yield: 188 mg (75%).
5-Alkoxycarbonyl-5-alkyldithiohydantoins 7a–c; General Proce-
dure:
To a solution of α-cyano-α-(dichloromethyleneimino)alkanoic acid
esters 4 in pure anhyd acetone (10 mL) was added 20% aq (NH4)2S
(2 mmol, 685 mg, 0.68 mL) under stirring. The mixture turned yellow
and a white precipitate (NH4Cl) was formed. After stirring for 60 min
at r.t. the solvent was evaporated in vacuo at max 30°C and water
(20 mL) and benzene (15 mL) were added. The organic layer was sep-
arated and the aqueous layer washed with benzene (15 mL). The com-
bined benzene layers were dried (Na2SO4), filtered and the solvent
evaporated in vacuo. The crude products, yellow oils were purified by
column chromatography on silica gel (20 × 3 cm) with hexane/EtOAc
(3:1) as eluent. The yellow oils which remained after evaporation of
the solvents crystallized in a few minutes. Recrystallization from tol-
uene yielded dithiohydantoins 7 as large yellow crystals.
IR (film): ν = 2963 (s), 2902 (m), 2266 (w, -CN), 1752 (s, CO), 1644
(s), 1372 (m), 1260 (s), 1127 (s), 803 cm–1 (s).
1H NMR (CDCl3): δ = 1.54 [s, 9H, C(CH3)3], 1.97 (s, 3H, CH3).
13C NMR (CDCl3): δ = 26.2 (CH3), 27.6 [C(CH3)3], 62.1 (C–CO),
85.9 [C(CH3)3], 115.3 (-CN), 134.7 (-NCCl2), 163.4 (CO).
MS (EI, –20°C): m/z (%) = 235 (3) [M+ – CH3], 149 (28) [M+
–
+
CO2C4H9], 57 (100) [C4H9 ].
HRMS (C9H1235Cl37ClN2O2) [m/z]: 250.0276 (calcd 250.0277)
tert-Butyl 2-Cyano-2-(dichloromethyleneimino)butanoate (4b):
Reaction of 2b (194 mg, 1 mmol) in CH2Cl2 with chlorine in CCl4
(10 mL, 0.1 mmol/mL) gave 4b as a colourless oil; yield: 217 mg
(82%).
IR (film): ν = 2983 (m), 2942 (m), 2872 (w), 2255 (s, -CN), 1750 (s,
CO), 1643 (s), 1459 (m), 1372 (m), 1255 (m), 1155 (m), 905 (m), 837
(m), 790 cm–1 (m).
5-tert-Butoxycarbonyl-5-methyl-2,4-dithiohydantoin (7a):
Reaction of 4a (251 mg, 1 mmol) with 20% aq (NH4)2S (685 mg,
0.68 mL, 2 mmol) gave 7a as light yellow cubic crystals; yield:
173 mg (70%); mp 136–138 ˚C (toluene); Rf (hexane/EtOAc 3:1) =
0.31.
1H NMR (CDCl3): δ = 1.16 (t, 3J = 7.3 Hz, 3H, CH2CH3), 1.54 [s, 9H,
C(CH3)3], 2.24 (q, 2H, CH2CH3).
13C NMR (CDCl3): δ = 8.6 (CH2CH3), 27.6 [C(CH3)3], 33.5
(CH2CH3), 67.0 (C–CO), 85.6 [C(CH3)3], 114.4 (-CN), 135.2
(NCCl2), 162.8 (CO).
IR (KBr): ν = 3439 (m, NH), 3241 (s, NH), 3151 (s, NH), 2978 (m),
2935 (m), 1730 (s, CO), 1528 (s, CS–NH), 1430 (s), 1370 (s), 1231
(m), 1122 (s), 909 (m), 836 (m), 776 (m), 610 cm–1 (m).
1H NMR (CDCl3): δ = 1.47 [s, 9H, C(CH3)3], 1.77 (s, 3H, CH3), 8.08
(s, 1H, NHa), 10.00 (s, 1H, NHb).
MS (EI, –20°C): m/z (%) = 249 (2) [M+ – CH3], 163 (21) [M+
–
+
CO2C4H9], 57 (100) [C4H9 ].
HRMS (C10H1435Cl37ClN2O2) [m/z]: 264.0432 (calcd 264.0433).
13C NMR (CDCl3): δ = 24.2 (CH3), 27.6 [C(CH3)3], 79.2 (C-CO),
84.8 [C(CH3)3], 163.9 (CO), 181.0 (CS–NH), 201.3 (NH–CS–
NH).
tert-Butyl 2-Cyano-2-(dichloromethyleneimino)-3-phenylpro-
panoate (4c):
Reaction of 2c (256 mg, 1 mmol) in CH2Cl2 with chlorine in CCl4
(10 mL, 0.1 mmol/mL) gave 4c as a colourless oil; yield: 291 mg
(89%).
MS (EI, 96°C): m/z (%) = 246 (4) [M+], 146 (30) [M+ – CO2C4H9],
+
57 (100) [C4H9 ].
HRMS (C9H14N2O2S2) [m/z]: 246.0496 (calcd 246.0497).
UV-vis (MeCN): λ (log ε) = 232 (3.83), 302 nm (4.37).
IR (film): ν = 3066 (w), 3034 (m), 2981 (s), 2933 (m), 2262 (m, -CN),
1748 (s, CO), 1640 (s), 1497 (m), 1456 (s), 1372 (s), 1258 (s), 1151
(s), 907 (s), 834 (s), 737 (m), 700 cm–1 (s).
5-tert-Butoxycarbonyl-5-ethyl-2,4-dithiohydantoin (7b):
Reaction of 4b (265 mg, 1 mmol) with 20% aq (NH4)2S (685 mg,
0.68 mL, 2 mmol) gave 7b as yellow cubic crystals; yield: 151 mg
(58%); mp 143°C (toluene); Rf (hexane/EtOAc 3:1) = 0.38.
IR (KBr): ν = 3428 (m, NH), 3280 (s, NH), 3103 (s, NH), 2978 (m);
2934 (m), 1727 (s, CO), 1526 (s, CS–NH), 1432 (s), 1372 (s), 1275
(m), 1127 (s), 985 (m), 838 (m), 787 (m), 656 cm–1 (m).
1H NMR (CDCl3): δ = 1.42 [s, 9H, C(CH3)3], 3.43 (d, 2J = 13.5 Hz,
2
1H, Ph–CHaHb), 3.50 (d, J = 13.5 Hz, 1H, Ph–CHaHb), 7.31–7.39
(m, 5H, arom H).
13C NMR (CDCl3): δ = 27.5 [C(CH3)3], 45.2 (Ph–CH2), 67.1 (C–CO),
86.0 [C(CH3)3], 114.3 (-CN), 128.0/128.2/130.6/132.1 (arom C),
134.8 (-NCCl2), 162.2 (CO).
1H NMR (CDCl3): δ = 0.94 (t, 3J = 7.4 Hz, 3H, CH2CH3), 1.47 [s, 9H,
FAB-MS (matrix NBA): m/z (%) = 328 (4) [M+ + H], 271(52) [M+ +
3
+
+
C(CH3)3], 2.22 (m, J = 7.4 Hz, 2H, CH2CH3), 8.18 (s, 1H, NHa),
H – C4H8], 91 (84) [C7H7 ], 57 (100) [C4H9 ].
HRMS (C15H1635Cl37ClN2O2) [m/z]: 326.0589 (calcd 326.0589)
10.08 (s, 1H, NHb).
13C NMR (CDCl3): δ = 7.7 (CH2CH3), 27.6 [C(CH3)3], 31.7
(CH2CH3), 83.4 (C–CO), 84.8 [C(CH3)3], 163.4 (CO), 181.3 (CS–
NH), 199.7 (NH–CS–NH).
tert-Butyl 2-Cyano-2-(dichloromethyleneimino)-3-(p-tolyl)pro-
panoate (4d):
MS (EI, 112°C): m/z (%) = 260 (4) [M+], 160 (60) [M+ – CO2C4H9],
+
57 (100) [C4H9 ].
Reaction of 2d (270 mg, 1 mmol) in CH2Cl2 with chlorine in CCl4
(10 mL, 0.1 mmol/mL) gave 4d as a colourless oil. Excess of chlorine
leads to alkyl chlorinated products; yield: 307 mg (90%).
IR (film): ν = 3022 (m), 2982 (s), 2933 (m), 2872 (w), 2262 (s,-CN),
1748 (s, CO), 1640 (s), 1516 (s), 1372 (s), 1259 (s), 1152 (s), 906 (s),
834 cm–1 (s).
HRMS (C10H16N2O2S2) [m/z]: 260.0653 (calcd 260.0653).
UV-vis (MeCN): λ (log ε) = 232 (3.80), 302 nm (4.38).
5-Benzyl-5-tert-butoxycarbonyl-2,4-dithiohydantoin (7c):
Reaction of 4c (327 mg, 1 mmol) with 20% aq (NH4)2S (685 mg,
0.68 mL, 2 mmol) gave 7a as yellow to orange cubic crystals; yield:
242 mg (75%); mp 153–155 °C (toluene); Rf (hexane/EtOAc 3:1) = 0.36.
IR (KBr): ν = 3430 (m, NH), 3175 (s, NH), 3056 (m), 2982 (m), 2938
(m), 1747 (s, CO), 1542 (s, CS–NH), 1427 (s), 1251 (s), 1152 (m),
1101 (s), 985 (m), 840 (m), 702 cm–1 (m).
1H NMR (CDCl3): δ = 1.45 [s, 9H, C(CH3)3], 2.34 (s, 3H, C6H4CH3),
3.38 (d, 2J = 13.4 Hz, 1H, CH3C6H4–CHaHb), 3.46 (d, 2J = 13.4 Hz,
1H, CH3C6H4–CHaHb), 7.12 – 7.26 (m, 4H, arom H).
13C NMR (CDCl3): δ = 21.1 (C6H4CH3), 27.5 [C(CH3)3], 44.8
(CH3C6H4CH2), 67.2 (C–CO), 85.9 [C(CH3)3], 114.4 (-CN), 129.0/
129.7/130.0/137.8 (aromC), 139.3 (-NCCl2), 162.4 (CO).

SYNTHESIS
Papers
1440
1H NMR (CDCl3): δ = 1.45 [s, 9H, C(CH3)3], 3.21 (d, 2J = 13.7 Hz,
1H, Ph–CHaHb), 3.70 (d, 2J = 13.7 Hz, 1H, Ph–CHaHb), 7.2 – 7.4 (m,
5H, arom H), 7.95 (s, 1H, NHa), 9.99 (s, 1H, NHb).
MS (EI, 46°C): m/z (%) = 316 (0.3) [M+], 215 (27) [M+ – CO2C4H9],
57 (100) [C4H9 ].
HRMS (C14H24N2O2S2) [m/z]: 316.1278 (calcd 316.1279).
+
13C NMR (CDCl3): δ = 27.6 [C(CH3)3], 44.1 (Ph–CH2), 83.0 (C–CO),
85.1 [C(CH3)3], 127.8/128.6/130.1/132.7 (arom C), 162.8 (CO),
180.9 (CS–NH), 198.8 (NH–CS–NH).
tert-Butyl 2-[Bis(ethylthio)methyleneimino]-2-cyano-3-phenyl-
propanoate (8c):
MS (EI, 124°C): m/z (%) = 322 (4) [M+], 222 (29) [M+ – CO2C4H9],
+
+
Reaction of 4c (327 mg, 1 mmol) in acetone (10 mL) with sodium
(51 mg, 2.2 mmol) in abs MeOH (5 mL) and EtSH (149 mg, 0.177
mL, 2.4 mmol) gave 8c as yellow oil, which crystallized in a few days
as light yellow needles. The crystals were washed with a small
amount of pentane and recrystallized from Et2O; yield: 114 mg
(30%); mp 82–83°C (Et2O); Rf (CH2Cl2) = 0.80.
IR (film): ν = 3088 (w), 3064 (w), 3032 (m), 2976 (s), 2930 (m), 2872
(m), 2236 (m, -CN), 1739 (s, CO), 1549 (s), 1455 (m), 1370 (s), 1255
(s), 1152 (s), 932 (s), 840 (m), 736 (m), 701 cm–1 (s).
91 (45) [C7H7 ], 57 (100) [C4H9 ].
HRMS (C15H18N2O2S2) [m/z]: 322.0811 (calcd 322.0810).
UV-vis (MeCN): λ (log ε) = 234 (3.79), 304 nm (4.30).
α-[Bis(ethylthio)methyleneimino]-α-cyanoalkanoic Acid Esters
8a–c; General Procedure:
To a solution of sodium (51 mg, 2.2 mmol) in anhyd MeOH were
added at 0°C EtSH (149 mg, 0.177 mL, 2.4 mmol). A solution of the
corresponding α-cyano-α-(dichloromethyleneimino)alkanoic acid
ester 4 in pure anhyd acetone was added to the EtS– solution at 0°C
under stirring over a period of 10 min. The solution turned slightly
yellow and a white precipitate (NaCl) was formed. After stirring at r.t.
for 24 h the mixture was adsorbed on silica gel (2 g) and was purified
by column chromatography on silica gel (20 × 3 cm) eluting with
CH2Cl2. Evaporation of the solvent yielded the α-[bis(ethylthio)me-
thyleneimino]-α-cyanoalkanoic acid esters 8 as colourless oils, the
benzyl derivative 8c crystallized. The products can be stored at –25°C
for an extended period of time and they have a characteristic onion-
like smell.
IR (KBr): ν = 3066 (w), 3029 (m), 2980 (s), 2933 (m), 2872 (m), 2233
(m, -CN), 1739 (s, CO), 1546 (s), 1456 (m), 1370 (s), 1254 (s), 1152
(s), 944 (s), 737 (m), 700 cm–1 (s).
1H NMR (CDCl3): δ = 1.26 (t, 3J = 7.3 Hz, 3H, SCH2CH3), 1.35 (t, 3J
= 7.3 Hz, 3H, SCH2CH3), 1.43 [s, 9H, C(CH3)3], 3.03 (m, 3J = 7.3 Hz,
3
2
2H, SCH2CH3), 3.13 (m, J = 7.3 Hz, 2H, SCH2CH3), 3.43 (d, J =
2
13.3 Hz, 1H, Ph–CHaHb), 3.52 (d, J = 13.3 Hz, 1H, Ph–CHaHb),
7.25–7.42 (m, 5H, arom H).
13C NMR (CDCl3): δ = 13.9 (SCH2CH3), 14.8 (SCH2CH3), 26.5
(SCH2CH3), 27.4 [C(CH3)3], 28.9 (SCH2CH3), 46.9 (Ph–CH2), 65.9
(C–CO), 84.4 [C(CH3)3], 116.6 (-CN), 127.6/128.1/131.1/134.0
(arom C), 165.3 (CO), 169.1 [NC(SEt)2].
MS (EI, 70°C): m/z (%) = 378 (1.5) [M+], 287 (18) [M+ – C7H7], 277
+
(27) [M+ – CO2C4H9], 261 (30) [M+ – C7H7 – CN], 91 (17) [C7H7 ],
tert-Butyl 2-[Bis(ethylthio)methyleneimino]-2-cyanopropanoate
(8a):
Reaction of 4a (251 mg, 1 mmol) in acetone (10 mL) with sodium
(51 mg, 2.2 mmol) in abs MeOH (5 mL) and pure EtSH (149 mg,
2.4 mmol, 0.177 mL) gave 8a as a colourless oil; yield: 181 mg
(60%); Rf (CH2Cl2) = 0.53.
+
57 (100) [C4H9 ].
HRMS (C19H26N2O2S2) [m/z]: 378.1434 (calcd 378.1436).
Reaction of tert-Butyl 2-Cyano-2-(dibromomethyleneimino)bu-
tanoate (3b) with Ammonium Sulfide:
IR (film): ν = 2977 (s), 2932 (m), 2872 (m), 2236 (w, -CN), 1741 (s,
CO), 1552 (s), 1449 (m), 1370 (m), 1256 (s), 1160 (s), 1126 (s), 952
(m), 841 cm–1 (s).
To a solution of 3b (354 mg, 1 mmol) in pure acetone (10 mL) was
added 20% aq (NH4)2S (343 mg, 1 mmol, 0.34 mL) over a period of
15 min. After stirring at r.t. for 45 min the solvent was evaporated in
vacuo at max 20°C. The residue was purified by column chromatog-
raphy on silica gel (10 × 1 cm) eluting with CH2Cl2. Spectroscopic
data of the resulting product were identical to those of tert-butyl 2-
cyano-2-isocyanobutanoate (2b); yield: 122 mg (63%).
1H NMR (CDCl3): δ = 1.28 (t, 3J = 7.4 Hz, 3H, SCH2CH3), 1.37 (t, 3J
= 7.4 Hz, 3H, SCH2CH3), 1.49 [s, 9H, C(CH3)3], 1.93 (s, 3H, CH3),
3
3
2.99 (m, J = 7.4 Hz, 2H, SCH2CH3), 3.17 (m, J = 7.4 Hz, 2H,
SCH2CH3).
13C NMR (CDCl3): δ = 13.7 (SCH2CH3), 14.9 (SCH2CH3), 26.5
(SCH2CH3), 27.7 [C(CH3)3], 27.8 (CH3), 28.7 (SCH2CH3), 60.8 (C–
CO), 84.0 [C(CH3)3], 117.6 (-CN), 166.4 (CO), 168.4 [NC(SEt)2].
MS (EI, 20°C): m/z (%) = 302 (0.01) [M+], 201 (18) [M+ – CO2C4H9],
We thank BASF AG, Bayer AG, and Hoechst AG, the Fonds der Che-
mischen Industrie, as well as the Deutsche Forschungsgemeinschaft
for support of this work. Thanks go to Hewlett Packard for providing
UV/VIS spectrometers. We would also like to thank Dr. W. Kramer
and Ms. U. Hertle for NMR spectra, Mr. H. Rudy and Mr. P. Weyrich
for elemental analysis and mass spectra. Dr. R. Faust and Dr. Th.
Lindel are warmly thanked for many helpful discussions and Dr. M.
Winter for help with the manuscript.
+
57 (100) [C4H9 ].
HRMS (C13H22N2O2S2) [m/z]: 302.1121 (calcd 302.1123).
tert-Butyl 2-[Bis(ethylthio)methyleneimino]-2-cyanobutanoate
(8b):
Reaction of 4b (265 mg, 1 mmol) in acetone (10 mL) with sodium
(51 mg, 2.2 mmol) in abs MeOH (5 mL) and EtSH (149 mg, 0.177
mL, 2.4 mmol) gave 8b as a colourless to light yellow oil; yield: 199
mg (63%); Rf (CH2Cl2) = 0.55.
IR (film): ν = 2976 (m), 2932 (m), 2876 (w), 2236 (s, -CN), 1739 (s,
CO), 1543 (s), 1456 (m), 1370 (s), 1251 (m), 1156 (m), 965 (m), 927
(m), 840 (m), 738 cm–1 (m).
(1) Bergemann, M.; Neidlein, R. Synthesis 1996, 8, 975
(2) Bergemann, M.; Neidlein, R. Helv. Chim. Acta 1998, in press
(3) Nef, I. U. Liebigs Ann. Chem. 1892, 270, 267.
Nef, I. U. Liebigs Ann. Chem. 1894, 280, 291.
Nef, I. U. Liebigs Ann. Chem. 1894, 280, 297.
Neidlein, R.; Haussmann, W. Chem. Ber. 1966, 99, 239.
Neidlein, R.; Haussmann, W. Angew. Chem. 1965, 77, 506;
Angew. Chem., Int. Ed. Engl. 1965, 4, 521.
Neidlein, R.; Haussmann, W. Angew. Chem. 1965, 77, 733;
Angew. Chem., Int. Ed. Engl. 1965, 4, 745.
(4) Kühle, E.; Anders, B.; Zumach, G.; Klauke, E.; Tarnow, H.
Angew. Chem. 1969, 81, 18; Angew. Chem., Int. Ed. Engl. 1969,
8, 20.
1H NMR (CDCl3): δ = 1.17 (t, 3J = 7.4 Hz, 3H, CH2CH3), 1.30 (t, 3J
= 7.4 Hz, 3H, SCH2CH3), 1.38 (t, 3J = 7.4 Hz, 3H, SCH2CH3), 1.51
[s, 9H, C(CH3)3], 2.22 (m, 3J = 7.4 Hz, 2H, CH2CH3), 3.02 (m, 3J =
7.4 Hz, 2H, SCH2CH3), 3.18 (m, 3J = 7.4 Hz, 2H, SCH2CH3).
13C NMR (CDCl3): δ = 8.8 (CH2CH3), 13.9 (SCH2CH3), 14.9
(SCH2CH3), 26.5 (SCH2CH3), 27.8 [C(CH3)3], 28.7 (SCH2CH3), 35.0
(CH2CH3), 65.5 (C–CO), 84.1 [C(CH3)3], 116.7 (-CN), 165.8 (CO),
168.9 [NC(SEt)2].

SYNTHESIS
October 1998
1441
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