An approach to biologically important S-heterocycles, dithiocarbamyls, and their relevant phosphono derivatives

Article abstract of DOI:10.1002/jhet.5570420114

The feasibility of insertions of carbanions between two sulfur atoms has been reported when 5-(4-chlorophenyl)-4-cyano-1,2-dithiol-3-thione (1) and tetramethylthiuram disulfide (17) were allowed to react with unsaturated 2a,b and active phosphonium salts

Full text of DOI:10.1002/jhet.5570420114

Jan-Feb 2005
103
An Approach to Biologically Important S-Heterocycles,
Dithiocarbamyls, and their Relevant Phosphono Derivatives
Maha D. Khidre, Azza A. Kamel and Wafaa M. Abdou
Department of Pesticide Chemistry, National Research Centre, Dokki, Cairo, Egypt
Received June 9, 2004
The feasibility of insertions of carbanions between two sulfur atoms has been reported when 5-(4-
chlorophenyl)-4-cyano-1,2-dithiol-3-thione (1) and tetramethylthiuram disulfide (17) were allowed to react
with unsaturated 2a,b and active phosphonium salts 11a,b. The reactions afforded, mainly, 1,3-dithiols 4a,b
and 14a,b together with substituted thiophenes 10a,b and 16a,b. Reactions of 1 and 17 with α-alkylth-
iomethyl phosphonates 24a,b afforded the phosphonates 25a,b and 26a,b, respectively.
J. Heterocyclic Chem., 42, 103 (2005).
Literature reports the synthesis and utility of many thiol
attack led to the formation of zwitterion 3a, which, subse-
quently, could follow two different pathways: i)
Intramolecular cyclization and hydrolysis yielding 4a with
concomitant elimination of triphenylphosphine oxide.
Similar insertion reaction has been reported previously for
the reaction of cis-disulfides with active ylides [6b,c], dia-
zomethane [7c], and very recently [8a] for the reaction of 1
with diethyl vinylphosphonate. ii) Extrusion of triph-
enylphosphine sulfide from 3a followed by thiophilic
addition of a second ylide species 2a affording the ylide 6a
via 5a. The latter step is presumably invoked by the
and dithiol derivatives as insecticides, fungicides and seed
protectants [1-3] as well as being useful as antioxidants
and in volcanization processes [4]. In addition, they are
known to possess therapeutic values in controlling dis-
eases, such as pneumonea [5]. For these reasons, the chem-
istry of the sulfur-sulfur bond continues to be an active
area of research from both a mechanistic and a synthetic
point of view. The mechanism of nucleophilic attack by
carbenoids, carbenes and phosphorus ylides on the S-S
linkage in dithiols, followed by substitution reaction at the
heteroatomic center (S, N, …etc), has been a major point
of interest for research in the last three decades [6,7]. For
the past few years, one of our research directions has cen-
tered on the synthesis of thiols, dithiols and phosphory-
lated sulfur compounds, derived from the reactions of
acyclic and cyclic cis-disulfides with P(III) and P(V)
reagents [8]. Preliminary results in a screening assay of
selected synthesized compounds showed pesticidal and
pharmacological activity. The work described in this arti-
cle involved the reactions of 5-(4-chlorophenyl)-4-cyano-
1,2-dithiol-3-thione (1) and tetramethylthiuram disulfide
(17) with unsaturated- 2a,b and active-11a,b phosphonium
salts as well as the phosphonate carbanions 24a,b. The
reactions, depicted in Schemes 1- 7, led to the synthesis of
the title compounds: new S-heterocycles, dithiocarbamyls
and their phosphono derivatives, for biological evaluation.
The results are compared and discussed, together with
other published researchs in this area.
Reaction of 1,2-dithiol (1) with vinyltriphenylphospho-
nium bromide (2a, 2 molar amounts) in a mixture of 40 ml
of dimethylformamide (DMF) and 10 ml of LiOH (0.5 M)
yielded 6-(4-chlorophenyl)-5-cyano-2-methyl (4H)-1,3-
dithiacyclohexene-4-thione (4a, 43%) and 5-(4-chloro-
phenyl)-6-methyl-(4H)-4-oxothienothiapyran (10a, 21%)
(Scheme 1). The products 4a and 10a were obtained in
similar ratio, irrespective of the number of mole equiva-
lents of 2a that was used.
The formation of 4a and 10a could be attributed to ini-
tial attack by the carbanion center of 2a on the cleaved -S-
S-linkage, initiated by the alkaline medium [6c,e]. This

104
M. D. Khidre, A. A. Kamel and W. M. Abdou
Vol. 42
α-electron-withdrawing substituent, CN group [9]. Further
attack of the ylide on the carbon-nitrogen triple bond [10]
and ring closure afforded dihydroazaphosphete 7a. The
phosphineimine 8a, which resulted from opening of the
four membered ring in 7a would lead to the formation of
the iminothiapyran 9a. Finally, the product 10a is regarded
as an oxidation form of 9a through the hydrolysis. An
analogous transformation is known for the imino function,
in an alkaline solution to the keto-structure [11].
A similar treatment of 1 with 2 equivalents of allyltriph-
enylphosphonium bromide (2b) in a mixture of 40 ml of
DMF containing 10 ml of LiOH (0.5 M) afforded the
analogs 4b (47%) and 10b (18%) according to Scheme 2,
which followed the same patterns discussed above.
Furthermore, the electrophilic attack of thiocarbonyl group
in 1 at the central atom of the allyl moiety in 2b (Scheme 2,
pathway ii) has been amply documented [12], and we have
evoked it on several occasions to rationalize our experi-
mental findings [13].
In a systematic study, the reaction of 1 with methyli-
dene-(12a) and ethylidenetriphenylphosphoranes (12b),
prepared in situ from the corresponding phosphonium bro-
mide 11a (or 11b), proceeded smoothly under the same
conditions (with 2a,b) to give the substituted thiophenes
16a (16%) and 16b (17%) in addition to 1,3-dithiols 14a
(52%) and 14b (50%) as shown in Scheme 3. Structures of
the new compounds were delineated from elemental analy-
ses and their spectroscopic properties.
When tetramethylthiuram disulfide (17) was treated, at
room temperature, with an equimolar amount of 2a,b in a
mixture of CH Cl and aqueous LiOH (0.5 M) (1:4, ratio)
α-ω-(bis-dimethyldithiocarbamyl)alkene 19 (or 20) was
obtained in a yield as high as ~ 70%. Rationalization of the
reaction of Scheme 4 is that reagent 2 attacks the disulfide
bond as an electrophile and that an ylide-like species 18 is
produced then rearranges. The ylide intermediate 18 is
reminiscent of that reported [7c] in the reaction of aryl
2
2
disulfides with the Simmons-Smith reagent (ICH ZnI).
2
A noteworthy contrast exists between the present behavior
of unsaturated and active phosphonium salts 2a,b and 11a,b
with 1,2-dithiol 1 and those reported previously [8c] for the
behavior of resonance stabilized ylides toward the same sub-
strate, 1 in toluene. Thus, the results of the former investiga-
On the contrary, bis(dimethyldithiocarbamyl)alkanes
22a,b (~ 62%) - and not the ylides 23 [6c] -were obtained
by treating 17 with alkylidenephosphoranes 12a,b, pre-
pared in situ from the corresponding bromide salt, under
the conditions previously mentioned, 17 with 2a,b.
Identification of the insertion products was confirmed by
combustion analysis, as well as by mass and NMR spec-
troscopy. The above result can be fully explained by
tion [8c] indicated that ylides of the type (Ph P=CHCOR',
3
R'= OMe, OEt, Ph, Me) reacted with 1 mainly at the thiocar-
bonyl group or further with the nitrile function in the second
step whereas compounds derived from an insertion reaction
at the -S-S- linkage were the common major products in the
present four studied reactions (Schemes 1, 2 and 3).

Jan-Feb 2005
An Approach to Biologically Important S-Heterocycles,
105
assuming that the reaction of 17 with 12a,b occurs accord-
ing to Scheme 5. Step A is the expected nucleophilic attack
by reagent 12 on the disulfide bond leading to the ylide 21.
Step B is a known reaction of thiocarbamyl anion; since
the sulfur anion is the most powerful nucleophile present
in the reaction mixture [6c], which undergo a substitution
reaction to afford the final products 22a,b, and does not
abstract a hydrogen atom from 21 giving the ylide 23).
Scheme 5 that represent the course of the reactions of 17
with active phosphorus ylides 12a,b, are in line with what
has been previously explored by Field and Banks [6b].
cis-configuration to the CN group, and could readily elim-
inate the trans-isomer, which would predict a singlet in the
range δ 2.23-2.25 for a free H C-S [16].
3
On the other hand, when the disulfide 17 was allowed to
react with the Wittig-Horner reagents 24a,b, under the
same reaction conditions, the phosphonate 26a (65%) or
26b (60%) was obtained (Scheme 7). Compounds 26a,b
are considered to proceed through an initial nucleophilic
attack by the carbanion center in the phosphoryl carnanion
24a (or 24b) on the S-S linkage in 17 leading to an elusive
1:1 intermediate species A, which in turn undergoes dis-
placement reaction with a second molecule of 17, under
thiuram-sulfide ion yielding the products 26a,b.
Next, the reactions of cis-disulfides 1 and 17 with
α-alkylthiomethyl phosphonates 24a,b were investigated
with regard to the synthesis of new phosphonate deriva-
tives with potential biological activity. The synthesis of
phosphono substituted-S-compounds should be of great
interest as many of them have been reported to possess
antibiotic, antineoplastic, antiviral or herbicidal attributes
[14]. Treatment of 1 with an equivocal amount of diethyl
α-alkylthiomethyl phosphonates 24a,b in an alcoholic
NaOEt at room temperature afforded the phosphonate 25a
(46%) or 25b (50%), advantageously (Scheme 6).
Compound 25 is somewhat compromised as occurring
through condensation of the carbanion ion with thioxocar-
Selective examples of the synthesized products: 4a, 10b,
14b, 20, 22a, 25a,b and 26a,b were screened against boll-
worms (cotton). The observed activities of the tested pests
were compared with the activity of triazophos (Hostathion®)
against the pests. Phosphorylated compounds 25a,b and
26a,b showed significant activity toward all tested pests. The
active products will be subjected to further screening under
different factors, and full results will be published together
with other results elsewhere.
bon-3 in 1 and extrusion of a molecule of H S (Perkin-
2
type condensation) [8a,15].
The spectroscopic results demonstrated that in the case
of the olefin 25 no isomeric phosphonates arose.
Molecular models indicate, in fact, the existence of steric
crowding between the nitrile substituent and the phospho-
EXPERIMENTAL
rus moiety [P(O)(OEt) ] in the transition state leading
2
stereospecifically to one isomer that has the nitrile and
thioalkyl groups in the cis-form. Furthermore, the assign-
ment of stereochemistry to compounds 25a,b was based on
H NMR, which showed two singlets at δ 2.27 and 2.28
ppm whose peak area integrated to 3 protons, and are
Melting points are uncorrected. The IR spectra were recorded
on Perkin Elmer 317 Grating IR spectrophotometer, using KBr
1
13
disc. The H and C NMR spectra were measured on a Jeol-270
1
31
MHz instrument using SiMe as an internal reference. The
P
4
NMR spectra were recorded relative to external H PO (85%)
3
4
assigned to the methyl group (S-CH ). The splitting of the
3
with a Varian CFT-20 instrument. The mass spectra were per-
formed at 70 eV on a Shimadzu GCS-QP 1000 EX spectropho-
tometer provided with a data system. The appropriate precautions
in handling moisture-sensitive compounds were observed.
methyl signal is in support with the suggested cis-structure
of 25. Finally, the data recorded (deshielded shift) for the
splitted signal of the H C-S protons in 25a suggested its
3

106
M. D. Khidre, A. A. Kamel and W. M. Abdou
Vol. 42
Solvents were dried by standard techniques. Light petroleum
refers to the fraction 40-60 °C.
phy, which was developed with light petroleum containing
increasing amounts of ethyl acetate. Pure light petroleum eluted
colorless crystals of triphenylphosphine (TLC), mp 77-80 °C.
The fraction (9.5:5, v/v) yielded colorless needles of triph-
enylphosphine sulfide (ca 50%), mp 162 °C.
General Procedure for the Reaction of 1,2-Dithiols 1 and 17 with
Phosphonium Bromides 2a, 2b, 11a and 11b.
To a stirred solution of two mol equiv of the appropriate salt 2a,
2b, 11a or 11b and one molar equivalent of 1 [17] in 40 ml DMF,
freshly prepared 10 ml (0.5 M) of LiOH was added in one portion
to the mixture. The two-phase system was stirred at r.t. up to the
consumption of the starting dithiol (~12 h for salts 2a and 11a and
for ~24 h for 2b and 11b). The mixture was then extracted with
5-(4-Chlorophenyl)-6-ethyl-2-methyl-(4H)-4-oxothienoth-
iapyran (10b).
Compound 10b was obtained (9:1, v/v) as colorless crystals
-1
(170 mg, 18%), mp 191-193 °C (acetone); IR 1670 cm (CO),
1
H NMR (CDCl ): δ 1.15 (t, J = 7.6 Hz, 3H, 6CCH ), 1.42 (s, 3H,
3
3
CHCl (2 X 100 ml). The combined organic extracts were back-
2-CH ), 2.73 (q, J = 7.6 Hz, 2H, CH ), 6.28 (s, 1H, 3-H), 7.45,
3
3
2
washed with 30 ml H O, dried, and the solvent was evaporated in
the presence 7 g (Kieselgel 60, particle size 0.2- 0.5 mm; E. Merk,
Darmstadt) and packed with light petroleum.
7.47 (2d, J = 8.1 Hz, 2H, 3'-H, 5'-H), 7.78, 8.0 (2d, J = 8.1 Hz,
2
13
2H, 2'-H, 6'-H); C NMR (CDCl ): δ 13.3, 14.7 (2 x CH ), 28.4
3
3
(6-CH ), 125.6 (1'-C), 128.8, 129.2 (2'-C, 3'-C, 5'-C, 6'-C), 138.6
2
(4'-C), 114.8 (3-C), 139.4 (2-C), 137.7 (6-C), 141.6 (5-C), 175.4
Reaction of 1 with Vinyltriphenylphosphonium Bromide (2a).
+
(CO); ms: m/z (EI) (%) 321 (14), 320 (M , 23), 305 (9), 290 (12),
+
+
+
According to the general procedure: A mixture of 0.8 g (2.97
mmoles) of 1 and 2.19 g (5.94 mmoles) of 2a in 40 ml DMF con-
taining 10 ml (0.5 M) of LiOH was refluxed for 12 h. After the
usual workup, the residue was applied to column chromatogra-
phy, which was developed with light petroleum containing
increasing amounts of ethyl acetate. The fraction (9.5:5, v/v)
yielded colorless needles of triphenylphosphine sulfide (ca 68%),
mp 162 °C.
237 (44), 209 [(M - ClC H ), 100], 111 (33), 75 (C H , 18).
6
4
6 3
Anal. Calcd. for C H ClOS (320.8): C, 59.89; H, 4.08; Cl,
16 13
2
11.05; S, 19.99. Found: C, 59.8; H, 4.03; Cl, 11.11; S, 19.88%.
6-(4-Chlorophenyl)-5-cyano-2-ethyl-(4H)-1,3-dithiacyclohex-
ene-4-thione (4b).
Compound 4b was obtained (7:3, v/v) as straw yellow crystals
(435 mg, 47 %), mp 142-144 °C (EtOH); IR 2220 (CN), 1485
-1
1
cm (C=S); H NMR (CDCl ): δ 0.92 (t, J = 6.8 Hz, 3H, CH ),
3
3
5-(4-Chlorophenyl)-6-methyl-(4H)-4-oxothienothiapyran (10a).
Compound 10a was obtained (9:1, v/v) as colorless crystals
3.21-3.26 (m, 2H, CH ), 4.62 (t, J = 8.1 Hz, 1H, 2-H), 7.45, 7.47
2
(2d, J = 8.1 Hz, 2H, 3'-H, 5'-H), 7.72, 7.75 (2d, J = 8.1 Hz, 2H, 2'-
-1
1
13
(182 mg, 21%), mp 168-170 °C (MeCN); IR 1654 cm (CO); H
H, 6'-H); C NMR (CDCl ): δ 13.8 (CH ), 24.2 (CH ), 38.5 (2-
3
3
2
NMR (CDCl ): δ 1.54 (s, 3H, CH ), 6.41 (d, J = 4.4 Hz, 1H, 3-
C), 108.9 (5-C), 118.4 (CN), 126.1 (1'-C), 129.4, 129.6 (2'-C, 3'-
C, 5'-C, 6'-C), 137.8 (4'-C), 143.2 (6-C), 188.6 (C=S); ms: m/z
3
3
H), 7.44, 7.47 (2d, J = 8.1 Hz, 2H, 3'-H, 5'-H), 7.57 (d, J = 4.4 Hz,
13
+
+
1H, 2-H), 7.75, 7.78 (2d, J = 8.1 Hz, 2H, 2'-H, 6'-H); C NMR
(EI) (%) 312 (17), 311 (M , 31), 271 (18), 155 (ClC H CS ,
6
4
+
(CDCl ): δ 14.8 (CH ), 126.7 (1'-C), 129.3, 129.8 (2'-C, 3'-C, 5'-
100), 111 (ClC H , 30), 75 (16). The fraction 6:4, v/v gave
3
3
6
4
C, 6'-C), 139.8 (4'-C), 113.4 (3-C), 124.9 (2-C), 127.6 (9-C),
139.3 (6-C), 141.3 (5-C), 151.2 (8-C), 171.6 (C=O); ms: m/z (EI)
triphenylphosphine oxide (60%), mp 156 °C.
Anal. Calcd. for C H ClNS (311.9): C, 50.06; H, 3.23; Cl,
11.37; N, 4.49; S, 30.84. Found: C, 49.99; H, 3.17; Cl, 11.43; N,
4.45; S, 30.91%.
13 10
3
+
+
(%) 293 (16), 292 (M , 29), 277 (18), 223 (37), 181 [(M -
+
ClC H ), 100], 111 (33), 75 (20).
6
4
Anal. Calcd. For C H ClOS (292.8): C, 57.43; H, 3.1; Cl,
14
9
2
Reaction of 1 with Phosphonium Salts 11a and 11b.
12.11; S, 21.9. Found: C, 57.49; H, 3.15; Cl, 12.07; S, 21.83%.
A mixture of 0.8 g (2.97 mmoles) of 1 and 2.12 g (5.94 mmoles)
of methyl- (11a) or 2.21 g (5.94 mmoles) of ethyltriphenylphos-
phonium bromide (11b) in 40 ml DMF containing 10 ml (0.5 M) of
LiOH was refluxed for 10 h. After the usual workup, the residue
was applied to a column chromatography, which was developed
with light petroleum containing increasing amounts of ethyl
acetate. Pure light petroleum eluted colorless crystals of triph-
enylphosphine, mp 77-80 °C. The fraction (9.5:5, v/v) yielded col-
orless needles of triphenylphosphine sulfide (ca 62%), mp 162 °C.
6-(4-Chlorophenyl)-5-cyano-2-methyl-(4H)-1,3-dithiacyclohex-
ene-4-thione (4a).
Compound 4a was obtained (7:3, v/v) as straw yellow crystals
(380 mg, 43%), mp 126-128 °C (CH Cl ); IR 2218 (CN), 1488
2
2
-1
1
cm (C=S); H NMR (CDCl ): δ 1.46 (d, J = 8.4 Hz, 3H, CH ),
3
3
4.55 (q, J = 8.4 Hz, 1H, 2-H), 7.45, 7.47 (2d, J = 8.1 Hz, 2H, 3'-H,
13
5'-H), 7.59, 7.66 (2d, J = 8.1 Hz, 2H, 2'-H, 6'-H); C NMR
(CDCl ): δ 13.5 (CH ), 30.3 (2-C), 108.2 (5-C), 117.3 (CN), 126.3
3
3
(1'-C), 129.1, 129.7 (2'-C, 3'-C, 5'-C, 6'-C), 139.5 (4'-C), 141.6 (6-
4-(4-Chlorophenyl)-3-cyano-2-methylthiophene (16a).
+
C), 192.4 (C=S); ms: m/z (EI) (%) 298 (29), 297 (M , 53), 271
+
(18), 155 (ClC H CS , 100), 111 (30), 75 (16). The fraction 6:4,
Compound 16a was obtained (8:2, v/v) as colorless needles
6
4
-1
1
v/v gave triphenylphosphine oxide (54%), mp 156 °C.
(110 mg, 16 %), mp 164-166 °C (CHCl ); IR 2198 cm (CN), H
3
Anal. Calcd. for C H ClNS (297.8): C, 48.39; H, 2.71; Cl,
NMR (CDCl ): δ 1.38 (s, 3H, CH ), 7.41, 7.42 (2d, J = 8.1 Hz,
12
8
3
3
3
11.90; N, 4.70; S, 32.30. Found: C, 48.44; H, 2.75; Cl, 11.82; N,
4.66; S, 32.36%.
2H, 3'-H, 5'-H), 7.58, 7.61 (2d, J = 8.1 Hz, 2H, 2'-H, 6'-H), 7.79
13
(s, 1H, 5-H); C NMR (CDCl ): δ 14.8 (CH ), 110.4 (3-C),
3
3
118.2 (CN), 122.6 (5-C), 125.8 (1'-C), 129.3, 129.8 (2'-C, 3'-C,
5'-C, 6'-C), 138.4 (4'-C), 139.2 (2-C); ms: m/z (EI) (%) 234 (37),
233 (M , 62), 218 (14), 207 (29), 192 (23), 111 (100), 75 (19).
Reaction of 1 with Allyltriphenylphosphonium Bromide (2b).
+
According to the general procedure: A mixture of 0.8 g (2.97
mmoles) of 1 and 2.28 g (5.94 mmoles) of 2b in 40 ml DMF con-
taining 10 ml (0.5 M) of LiOH was refluxed for 30 h. After the
usual workup, the residue was applied to a column chromatogra-
Anal. Calcd. for C H ClNS (233.7): C, 61.67; H, 3.45; Cl,
12
8
15.17; N, 5.99; S, 13.72. Found: C, 61.59; H, 3.38; Cl, 15.24; N,
5.93; S, 13.77%.

Jan-Feb 2005
An Approach to Biologically Important S-Heterocycles,
107
6-(4-Chlorophenyl)-5-cyano-4-methylidene-1,3-dithiacyclohex-
16 Hz, 2 x 1H, CH=CH), 6.81 (d, Z-isomer, J = 12 Hz, 2 x
ene (14a).
1H). The mixture of the isomers were re-dissolved in CH Cl
2 2
and kept at 0 °C for 2 days. The solvent was decanted and the
procedure was repeated with fresh CH Cl . Crystals that sepa-
Compound 14a was obtained (6:4, v/v) as light yellow crystals
2
2
(410 mg, 52 %), mp 192-194 °C (MeCN); IR 2222 (CN), 1619
rated out were collected and proved to be the major isomer E-
19 (0.4 g, 37%), m.p. 114-116 °C; IR 1616 (HC=CH), 1487
-1
1
cm (C=C, exocyclic); H NMR (CDCl ): δ 2.78 (s, 2H, 2-CH ),
3
2
5.76 (s, 2H, =CH ), 7.42, 7.44 (d, J = 8.1 Hz, 2H, 3'-H, 5'-H),
2
-1
1
cm (C=S); H NMR (CDCl ): δ 3.27, 3.45 [2s, 2 x 6H,
13
3
7.58, 7.61 (d, J = 8.1 Hz, 2H, 2'-H, 6'-H); C NMR (CDCl ): δ
3
2N(CH ) ], 6.64 (d, J = 16 Hz, 2 x 1H, CH=CH-homotopic);
3 2
29.1 (2-C), 107.1 (=CH ), 110.2 (5-C), 117.6 (CN), 126.2 (1'-C),
2
13
C NMR (CDCl ): δ 31.7, 33.8 (2s, 2 x [N(CH ) ]), 130.4,
3
3 2
129.2, 129.8 (2'-C, 3'-C, 5'-C, 6'-C), 139.1 (4'-C), 139.7 (6-C),
131.8 (CH=CH), 191.2, 191.5 (2x C=S); ms: m/z (EI) (%) 266
+
149.7 (4-C); ms: m/z (EI) (%) 266 (10), 265 (M , 18), 249 (33),
+
(M , 11), 88 (100).
+
155 (100, ClC H CS ), 111 (41), 75 (22).
6
4
Anal. Calcd. for C H N S (266.47): C, 36.06; H, 5.29; N,
8
14 2 4
Anal. Calcd. for C H ClNS (265.8): C, 54.23; H, 3.03; Cl,
12
8
2
10.51; S, 48.13. Found: C, 36.13; H, 5.24; N, 10.43; S, 48.21%.
13.34; N, 5.27; S, 24.13. Found: C, 54.29; H, 3.11; Cl, 13.28; N,
5.35; S, 24.23%.
1,3-(bis-Dimethyldithiocarbamyl)allene (20).
4-(4-Chlorophenyl)-3-cyano-2-ethyl-5-methylthiophene (16b).
Compound 16b was obtained (8:2, v/v) as colorless needles
Compound 20, 793 mg (68%) of (E and Z isomers) was
obtained (from 17 + 2b) as yellow crystals after chromato-
graphic separation (hexane/AcOEt, 7:3, v/v). The mixture of
diastereomers 20 is tested first by H NMR spectrum whereby
they present in ratio 3:1. Likewise with 19, fractional crystal-
-1
1
(132 mg, 17 %), mp 178-180 °C (CHCl ); IR 2200 cm (CN), H
3
1
NMR (CDCl ): δ 0.92 (t, J = 7.4 Hz, 3H, C-CH ), 1.46 (s, 3H, 5-
3
3
CH ), 2.72 (q, J = 7.4 Hz, 2H, 2-C-CH ), 7.45, 7.46 (2d, J = 8.1
3
2
lization from CH Cl afforded a pure sample of the major iso-
2
2
Hz, 2H, 3'-H, 5'-H), 7.71, 7.73 (2d, J = 8.1 Hz, 2H, 2'-H, 6'-H);
mer E-20 (315 mg, 27 %), m.p. 126-128 °C; IR 1622 (HC=CH),
13
C NMR (CDCl ): δ 12.8 (C-CH ), 14.6 (CH ), 24.8 (CH ),
3
3
3
2
-1
1
1485 cm (C=S); H NMR (CDCl ): δ 3.40, 3.45 [2s, 2 x 6H,
3
110.1 (3-C), 118.1 (CN), 126.3 (1'-C), 128.7, 129.3 (2'-C, 3'-C,
5'-C, 6'-C), 139.4 (4'-C), 138.8, 139.6, 139.9 (2-C, 4-C, 5-C); ms:
a
2N(CH ) ], 3.86 (d, J = 6.5 Hz, 2H, CH S), 5.93 (m, 1H, CH ),
3 2
2
b
13
6.52 (d, J = 16.5 Hz, 1H, CH ); C NMR (CDCl ): δ 24.7
(CH ), 31.3, 31.6, 33.5, 34.1 (4s, 2 x [N(CH ) ]), 120.6 (=CH ),
126.7 (=CH ), 188.3, 190.6 (2 x C=S); ms: m/z (EI) (%): 280
(M , 16), 88 (100).
+
3
m/z (EI) (%) 262 (32), 261 (M , 56), 245 (33), 231 (21), 205
a
2
3 2
(44), 111 (100), 75 (24).
b
Anal. Calcd. for C H ClNS (261.8): C, 64.24; H, 4.62; Cl,
14 12
+
13.54; N, 5.35; S, 12.25. Found: C, 64.31; H, 4.66; Cl, 13.48; N,
5.40; S, 12.31%.
Anal. Calcd. for C H N S (280.5): C, 38.54; H, 5.75; N,
9
16 2 4
9.99; S, 45.73. Found: C, 38.46; H, 5.66; N, 10.03; S, 45.67%.
6-(4-Chlorophenyl)-5-cyano-4-ethylidene-1,3-dithiacyclohexene
(14b).
bis-(Dimethyldithiocarbamyl)methane (22a).
Compound 22a, 688 mg (65%) was obtained (from 17 + 11a)
as straw yellow crystals after chromatographic separation
(hexane/AcOEt, 8:2, v/v), m.p. 138-140 °C (cyclohexane); IR
Compound 14b was obtained (7:3, v/v) as pale yellow needless
-
(435 mg, 50%), mp 198-201 °C (EtOH); IR 2218 (CN), 1622 cm
1
1
(C=C, exocyclic); H NMR (CDCl ): δ 1.34 (d, J = 7.3 Hz, 3H,
3
-1
1
1484 cm (C=S); H NMR (CDCl ): δ 3.12, 3.28 [2s, 2 x 6H,
2-C.CH ), 1.95 (d, J = 6.8 Hz, 3H, 4-C=C.CH ), 4.51 (q, J = 7.3
3
3
3
13
2N(CH ) ], 4.21 (s, 2H, SCH ); C NMR (CDCl ): δ 22.8
Hz, 1H, 2-H), 5.89 (q, J = 6.8 Hz, 1H, =CH), 7.46, 7.48 (2d, J =
3 2
2
3
(CH S), 31.4, 33.6 (NCH ), 190.8, 192.4 (C=S); ms: m/z (EI)
8.3 Hz, 2H, 3'-H, 5'-H), 7.68, 7.78 (2d, J = 8.3 Hz, 2H, 2'-H, 6'-
2
3
+
13
(%) 254 (M , 14), 88 (100).
H); C NMR (CDCl ): δ 14.2, 18.3 (2 x CH ), 33.2 (2-C), 110.9
3
3
Anal. Calcd. for C H N S (254.46): C, 33.04; H, 5.55; N,
(5-C), 116.8 (=CH), 117.9 (CN), 139.6 (6-C), 147.4 (4-C), 126.6
(1'-C), 129.2, 129.8 (2'-C, 3'-C, 5'-C, 6'-C), 139.4 (4'-C); ms: m/z
7
14 2 4
11.0; S, 50.41. Found: C, 33.09; H, 5.48; N, 11.07; S, 50.47%.
+
(EI) (%) 294 (13), 293 (M , 25), 278 (11), 267 (24), 263 (18),
bis-(Dimethyldithiocarbamyl)ethane (22b).
+
155 (100, ClC H CS ), 111 (37), 75 (15).
6
4
Compound 22b, 720 mg (60%) was obtained (from 17 + 11b)
as sandy yellow crystals after chromatographic separation
(hexane /AcOEt, 8:2, v/v), m.p. 126-128 °C (MeCN); IR 1484
Anal. Calcd. for C H ClNS (293.8): C, 57.23; H, 4.12; Cl,
12.07; N, 4.77; S, 21.83. Found: C, 57.29; H, 4.18; Cl, 12.14; N,
4.68; S, 21.79%.
14 12
2
-1
1
cm (C=S); H NMR (CDCl ): δ 1.26 (d, J = 6.8 Hz, 3H, CH ),
3
3
Reaction of Tetramethylthiuram Disulfide (17) with
Phosphonium Salts 2a,b and 11a,b.
13
3.23, 3.27 [2s, 2 x 6H, 2N(CH ) ], 4.88 (q, 1H, SCH); C NMR
3 2
(CDCl ): δ 15.3 (CH ), 30.1 (SCH), 31.3, 33.8 (NCH ), 194.2,
3
3
3
+
196.2 (C=S); ms: m/z (EI) (%) 268 (M , 13), 88 (100).
A mixture of 1.0 g (4.16 mmoles) of 17 [18] and 4.2 mmoles of
2a (1.55 g), 2b (1.61 g), 11a (1.5 g) or 11b (1.56 g) in 40 ml of
CH Cl containing 10 ml (0.5 M) of LiOH solution was stirred at
Anal. Calcd. for C H N S (268.49): C, 35.79; H, 6.01; N,
8
16 2 4
10.43; S, 47.77. Found: C, 35.84; H, 6.04; N, 10.37; S, 47.85%.
2
2
r.t. for 12-24 h (TLC). Following the same procedure and workup
were used in the general procedure, compounds 19, 20, 22a and
22b were obtained.
Reaction of 1 and 17 with α-Alkylthiomethyl Phosphonates
24a,b.
Compounds 25a, 25b, 26a and 26b were prepared by adding a
solution of 3 mol equiv of NaOEt in 30 ml absolute ethanol to a
stirred solution of one mol equiv of 24a or 24b in 20 ml EtOH at
-10 °C. Stirring is continued for 20 min and a solution of 0.8 g
(2.97 mmoles) of 1 (or 0.8 g, 3.33 mmoles of 17) in 20 ml EtOH
is then added at -10 °C. After stirring for 1 h at 0 °C, and further
1,2-(bis-Dimethyldithiocarbamyl)ethylene (19).
Compound 19, 756 mg (70%) of (E/Z ratio, 3:1) was
obtained (from 17 + 2a) as yellow crystals after chromato-
graphic separation (hexane /AcOEt, 7:3, v/v), H NMR
1
(CDCl ): δ 3.42 (br, 12H, 2N(CH ) ], 6.65 (d, E-isomer, J =
3
3 2

108
M. D. Khidre, A. A. Kamel and W. M. Abdou
Vol. 42
13
for ~ 12 h (TLC) at r.t., the solvent is concentrated to its half in
2H, SCH ), 4.12, 4.18 (2q, 2 x 2H, 2OCH ); C NMR (CDCl ): δ
2
2
3
vacuo and then poured onto ice, extracted with CHCl , dried and
14.7, 15.6, 15.9 (OCCH , SCCH ), 28.6 (SCH ), 31.1, 31.5, 33.4,
3
3
3
2
evaporated. The residue is then purified by chromatography
(light petroleum /AcOEt gradient as eluents).
33.7 (NCH ), 38.2 (d, J = 99.5 Hz, CP), 62.8 (OCH ), 190.2,
3
CP
2
31
191.7 (2 x C=S); P NMR (CDCl ): δ 18.86 ppm, ms: m/z (EI) (%)
3
+
450 (M , 28), 435 (9), 389 (13), 313 (41), 137 (55), 88 (100).
5-(4-Chlorophenyl)-4-cyano-(3H)-1,2-dithiol-3-(α-diethylphos-
phorylmethylene)thiomethyl (25a).
Anal. Calcd. for C H N O PS (450.67): C, 34.65; H, 6.04;
13 27
2
3
5
N, 6.22; P, 6.87; S, 35.58. Found: C, 34.56; H, 6.11; N, 6.29; P,
Compound 25a, 592 mg (46%) was obtained (7:3, v/v) as yel-
6.93; S, 35.52%
.
low fine needles, m.p. 150-152 °C (MeCN); IR 2210 (CN), 1254
-1
1
(P=O), 1030 cm (P-O-C); H NMR (CDCl ): δ 1.22, 1.26 (2dt,
3
J
= 7.2, J = 4.8 Hz, 6H, 2OC-CH ), 2.27 (d, J = 4.2 Hz,
REFERENCES AND NOTES
HH
HP 3 HP
3H, SCH ), 4.09, 4.18 (2q, J = 8.7, 2 x 2H, 2-OCH ), 7.42, 7.77
3
2
13
(2d, J = 8.2 Hz, 2 x 2H, H-Ar); C NMR (CDCl ): δ 13.5
[1] M. B. Green, G. S. Hartley and T. F. West, Chemicals for
Crop Protection and Pest Control, Pergamon Press, New York, 1977,
Chapter 13, p 114-128.
[2a] T. Al-Nakib, M. J. Meegan and M. L. Burke, J. Chem.
Research (S), 170 (1994); (M), 1042 (1994); [b] E. Drouhet and B.
Dupont, Arzneim-Forsch/Drug Research, 42, 705 (1992).
[3] E. R. Cole, Nature, 198, 1083 (1963); Chem. Abstr., 59,
11311 (1963).
[4a] C. J. Olander and S. Sunner, Pure & Appl. Chem., 2, 117
(1961); [b] T. Gessner, Rubber Chem. Technol., 35, 659 (1962); Chem.
Abstr., 57, 13945 (1962); [c] J. P. Chupp, J. J. D'Amico and K. L.
Ieschinsky, J. Org. Chem., 43, 3553 (1978).
[5] C. Mannich and Ph. Fresenins, Arch. Pharm., 274, 461
(1936); Chem. Abstr., 31, 1952 (1937).
[6a] P. K. Srivastava, L. Field and M. M. Grenan, J. Med. Chem.,
18, 798 (1975); [b] L. Field and C. H. Banks, J. Org. Chem., 40, 2774
(1975); [c] R. Galli, J. Org. Chem., 52, 5340 (1987); [d] N. M. Yousif,
K. Z. Gadalla and S. M. Yassin, Phos. Sulf. and Silicon, 60, 261
(1991); [e] C. G. Krespan, J. Am. Chem. Soc., 83, 3434 (1961).
[7a] B. Movassaagh, M. M. Lakouraj and Z. Fadaei, J. Chem.
Research (S), 350 (2000); [b] T. B. Christensen and K. Daasbjerg, Acta
Chem. Scand., 51, 307 (1997); [c] S. Tamayaki and S. Oae, Bull.
Chem. Soc. (Jpn), 45, 960 (1972).
[8a] W. M. Abdou, M. D. Khidre and A. A. Kamel, Heterocycl.
Comm., 10, 217 (2004); [b] W. M. Abdou, Phos. Sulf. and Silicon, 144,
393 (1999); [c] W. M. Abdou and N. A. F. Ganoub, Phos. Sulf. and
Silicon, 105, 63 (1995); [d] W. M. Abdou, I. T. Hennawy and Y. O. El-
Khoshnieh, J. Chem. Research (S), 50 (1995); (M), 442 (1995); [e] W.
M. Abdou and I. T. Hennawy, Phos. Sulf. and Silicon, 89, 105 (1994);
[f] W. M. Abdou, E. S. M. A. Yakout and M. M. Said, Int. Sulfur
Letters, 17, 33 (1993); [g] W. M. Abdou and E. S. M. A. Yakout,
Tetrahedron, 49, 6411 (1993).
3
(SCH ), 18.32 (OCCH ), 63.3 (OCH ), 110.4 (4-C), 118.1 (CN),
3
3
2
121.5 (d, J = 122.8 Hz, =C-P), 126.5, 129.3, 129.6, 139.5,
CP
31
141.2 (C'-Ar), 151.3 (3-C); P NMR (CDCl ): δ 17.84 ppm, ms:
m/z (EI) (%) 432 (18), 433 (M , 33), 407 (16), 386 (15), 360
(31), 396 (28), 349 (55), 155 (100, ClC H CS ).
3
+
+
6
4
Anal. Calcd. for C
H ClNO PS (433.94): C, 44.29; H,
16 17 3 3
3.95; Cl, 8.17; N, 3.23; P, 7.14; S, 22.17. Found: C, 44.35; H,
3.99; Cl, 8.24; N, 3.18; P, 7.22; S, 22.10%.
5-(4-Chlorophenyl)-4-cyano-(3H)-1,2-dithiol-3-(α-diethylphos-
phorylmethylene)thioethyl (25b).
Compound 25b, 665 mg (50%) was obtained (7:3, v/v) as pale
yellow needles, m.p. 143-145 °C (cyclohexane); IR 2218 (CN),
-1
1
1282 (S-S), 1254 (P=O), 1030 cm (P-O-C); H NMR (CDCl ):
3
δ 1.13, 1.24 (2dt, J = 7.2, J = 4.6 Hz, 6H, OCCH ), 1.35 (t,
HH
HP
3
J
= 6.8 Hz, SCCH ), 3.98 (q, J = 4.2 Hz, 2H, SCH ), 4.11,
HH
3 HP 2
4.23 (2q, J = 8.7, 2 x 2H, 2-OCH ), 7.43, 7.76 (2d, J = 8.1 Hz, 2 x
2
13
2H, H-Ar); C NMR (CDCl ): δ 14.3, 15.1 (2CH ), 29.4
3
3
(SCH ), 62.4 (OCH ), 111.2 (4-C), 118.4 (CN), 128.8 (d, J =
2
2
CP
124.8 Hz, =C-P), 126.1, 130.2, 130.5, 139.1, 141.5 (C'-Ar), 151.5
31
(3-C); P NMR (CDCl ): δ 18.3 ppm, ms: m/z (EI) (%) 446
3
+
(14), 447 (M , 24), 421 (9), 386 (21), 360 (33), 310 (37), 249
(58), 155 (100, ClC H CS ).
+
6
4
Anal. Calcd. for C
H ClNO PS (447.97): C, 45.58; H,
17 19 3 3
4.28; Cl, 7.91; N, 3.13; P, 6.91; S, 21.47. Found: C, 45.53; H,
4.21; Cl, 7.84; N, 3.22; P, 6.97; S, 21.52%.
bis-(Dimethyldithiocarbamyl)thiomethyl-α-diethylphosphoryl-
methane (26a).
[9a] P. Metzner, Synthesis, 12, 1185 (1992); [b] A. Thuiller,
Phosphorus and Sulfur, 23, 253 (1985).
[10a] H. J. Bestmann and R. Zimmerman, Org. Phosphorous
Comp., 3, 1 (1972); [b] E. Ciganek, J. Org. Chem. 35, 3631 (1970).
[11] J. Vicente, M. T. Chicote, J. Fernandez-Baeza and F. Lahoz,
J. Inorg. Chem. 30, 3617 (1991).
[12a] P. D. Croce and D. J. Pocar, J. Chem. Soc. Perkin Trans 1,
619 (1976); [b] E. Zbiral, Tetrahedron Lett., 5107 (1970).
[13a] W. M. Abdou, M. A. I. Salem and A. A. Sediek, Monatsh.
für Chem., 134, 1373 (2003); [b] W. M. Abdou, M. A. I. Salem and A.
A. Sediek, J. Chem. Soc. (Jpn), 75, 2481 (2002); [c] W. M. Abdou, A.
F. M. Fahmy and A. A. Kamel, Eur. J. Org. Chem. 1696 (2002).
[14] K. Issleib, Nachr. Chem. Tech. Lab. 35, 1037 (1987).
[15a] A. Rieker, W. Rundel and H. Z. Kessler, Z. Naturforsch. 24,
547 (1969); [b] L. S. Boulos and E. S. M. A. Yakout, Phosphorus,
Sulfur and Silicon, 84, 35 (1993); [c] W. M. Abdou and N. A. Ganoub,
Synth. Comm. 28, 3579 (1998).
Compound 26a, 942 mg (65%) was obtained (8:2, v/v) as col-
orless crystals, m.p. 170-172 °C (EtOH); IR 1484 (C=S), 1256
-1
1
(P=O), 1080 cm (P-O-C); H NMR (CDCl ): δ 1.32, 1.37 (2dt,
3
J
= 7.2, J = 4.6 Hz, 6H, 2 x OCCH ), 3.24, 3.35 (2s, 2 x 6H,
HH
HP 3
2N(CH ) ], 2.42 (s, 3H, SCH ), 4.15, 4.22 (2q, J = 11.5, 2 x 2H,
3 2
3
13
2OCH ); C NMR (CDCl ): δ 14.2 (SCH ), 15.2, 15.4
2
3
3
(OCCH ), 31.2, 31.6, 33.24, 33.29 [2N(CH ) ], 38.5 (d, J = 98
3
3 2
CP
31
Hz, CP), 61.6 (OCH ), 188.3 (C=S); P NMR (CDCl ): δ 22.4
ppm, ms: m/z (EI) (%) 436 (M , 23), 389 (30), 299 (22), 252
2
3
+
(55), 137 (62), 88 (100).
Anal. Calcd. for C H N O PS (436.65): C, 33.01; H, 5.77;
12 25
2
3
5
N, 6.42; P, 7.09; S, 36.72. Found: C, 32.96; H, 5.69; N, 6.35; P,
7.03; S, 36.78%.
bis-(Dimethyldithiocarbamyl)thioethyl-α-diethylphosphoryl-
methane (26b).
[16] P. M. Silverstein, G. C. Bassler and T. C. Morril,
Spectroscopic Identification of Organic Compounds, New York, Wiley
and Sons: 1981.
[17] C. Trebaul and J. Teste, Bull. Soc. Chim. (France), 2456
(1969).
Compound 26b, 900 mg (60%) was obtained (8:2, v/v) as color-
less crystals, m.p. 152-154 °C (from benzene); IR 1485 (C=S), 1260
-1
1
(P=O), 1055 cm (P-O-C); H NMR (CDCl ): δ 1.24, 1.37 (2dt,
3
J
= 7.2, J = 4.6 Hz, 2 x 3H, 2 x OCCH ), 1.41 (t, J = 6.8 Hz,
HH
HP 3
3H, SCCH ), 2.89, 3.12 [2s, 2 x 6H, 2N(CH ) ], 4.27 (q, J = 6.8 Hz,
[18] J. V. Braun, Ber. 35, 817 (1902).
3
3 2