Tetraphenylphosphonium allyldithiocarbimates derived from Morita-Baylis-Hillman adducts: Synthesis, characterization, crystal structure and antifungal activity

Article abstract of DOI:10.1016/j.molstruc.2015.10.097

Botrytis blight is a very destructive disease caused by Botrytis spp., infecting flowers, trees, vegetables and fruits. Twelve new compounds were prepared by the reaction of potassium N-aryl-sulfonyldithiocarbimates with Morita-Baylis-Hillman derivatives

Full text of DOI:10.1016/j.molstruc.2015.10.097

Journal of Molecular Structure 1106 (2016) 130e140
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Tetraphenylphosphonium allyldithiocarbimates derived from Morita-
Baylis-Hillman adducts: Synthesis, characterization, crystal structure
and antifungal activity
, *,
Eder C. Tavares a 1, Mayura M.M. Rubinger a, Eclair V. Filho a, Marcelo R.L. Oliveira a,
b
c
d
d
ꢀ
Dorila Pilo-Veloso , Javier Ellena , Silvana Guilardi , Rafael A.C. Souza ,
e
ꢀ
Laercio Zambolim
a Departamento de Química, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
b Departamento de Química e ICEx, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil
c
~
~
~
Instituto de Física de Sao Carlos, Universidade de Sao Paulo, 13560-970 Sao Carlos, SP, Brazil
d
^
^
Instituto de Química, Universidade Federal de Uberlandia, 38408-100 Uberlandia, MG, Brazil
e Departamento de Fitopatologia e CCA, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Botrytis blight is a very destructive disease caused by Botrytis spp., infecting flowers, trees, vegetables
and fruits. Twelve new compounds were prepared by the reaction of potassium N-aryl-sulfonyldithio-
carbimates with Morita-Baylis-Hillman derivatives bearing phenyl and furyl groups. These are the first
examples of allyldithiocarbimate anions and were isolated as tetraphenylphosphonium salts. The new
compounds were characterized by HRMS, NMR and Infrared spectroscopy. Further, the structures of
three allyldithiocarbimates were determined by single crystal X-ray diffraction. The compounds are
isostructural and crystallize in the space group P21/c of the monoclinic system, and the allyldithio-
carbimate anions present Z configuration. All the compounds were active against Botrytis cinerea. The
best results were achieved with the tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-(methoxycarbonyl)
Received 13 July 2015
Received in revised form
27 October 2015
Accepted 28 October 2015
Available online 2 November 2015
Keywords:
Dithiocarbimates
Morita-Baylis-Hillman adducts
Antifungal activity
allyl-(4-chlorophenylsulfonyl)dithiocarbimate (IC50 38 mM).
© 2015 Elsevier B.V. All rights reserved.
Botrytis cinerea
Crystal structure of allyldithiocarbimates
1. Introduction
Yadav and co-workers have reported an efficient and highly
stereoselective eco-friendly synthetic protocol that involves the
nucleophilic displacement (SN20) of MBH acetates by dithiocarba-
mate anions [4]. It was demonstrated that allyldithiocarbamates
are efficiently prepared from MBH bromides in isopropyl alcohol
rather than from acetates in water [5].
The Morita-Baylis-Hillman (MBH) reaction is one of the most
powerful protocols for carbonecarbon bond formation and can
result in densely functionalized molecules. The MBH adducts can
undergo several synthetic organic transformations, constituting
valuable building blocks for the syntheses of natural products and
other organic materials [1,2].
Unlike the dithiocarbamates, the dithiocarbimates (RNCS22ꢀ) are
dianions (Fig. 1b) and, to the best of our knowledge, there are no
descriptions in the literature on the use of these anions as nucle-
ophiles in organic reactions or as useful organic synthetic in-
termediates. Nevertheless, the literature reports the synthesis and
characterization of their metal complexes or disulfides derivatives
[6e10]. It has been demonstrated that zinc complexes with
dithiocarbimates [6,7] and tin-organometallic dithiocarbimates
[8,9] inhibit the growth of Colletotrichum gloeosporioides.
Organic dithiocarbamates (R2NCS-2) are a versatile class of
monoanionic 1,1-dithio ligands (Fig. 1a), whose derivatives have
been extensively studied in different fields, playing pivotal roles in
agriculture as fungicides, and in the rubber industry as vulcaniza-
tion accelerators [3].
* Corresponding author.
Encouraged by these findings and in line with other ongoing
projects aiming to expand the scope of the synthetic applications of
MBH adducts and dithiocarbimates, taking into account that the
E-mail address: eder@unifei.edu.br (E.C. Tavares).
Present Address: Instituto de Física e Química, Universidade Federal de Itajuba,
1
ꢀ
ꢀ
37500-903 Itajuba, MG, Brazil.
http://dx.doi.org/10.1016/j.molstruc.2015.10.097
0022-2860/© 2015 Elsevier B.V. All rights reserved.

E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
131
1 mmol of the bromide 2 or the acetate 4 in acetone (2 mL) was
added dropwise to a stirring solution of the appropriate N-R-sul-
fonyldithiocarbimate potassium salt (1.2 mmol) in acetone:water
1:1 (10 mL). The mixture (monitored by TLC) was stirred for 15 min
at room temperature. Then, water (5 mL) was added and the
product was extracted with ethyl acetate (3 ꢁ 20 mL). The organic
phase was concentrated under reduced pressure and the residue
was dissolved in water. Tetraphenylphosphonium chloride
(1 mmol) was added to this aqueous solution and the yellow solid
thus formed was filtered, washed with distilled water and dried
under reduced pressure for one day.
Fig. 1. General formulae of the (a) dithiocarbamate and (b) dithiocarbimate anions.
development of new agrochemicals for efficient crop protection is
of utmost importance, we have employed the MBH acetates and
bromides in nucleophilic displacement protocols either in SN2 or
SN20 fashions with various N-aryl-sulfonyldithiocarbimates.
Herein we report the synthesis of a series of tetraphenylphos-
phonium allyldithiocarbimates and a study of their activity against
Botrytis cinerea. Botrytis blight, also known as the gray mold dis-
ease, caused by Botrytis spp., affects more than 200 plant species,
including flowers, trees, leafy vegetables and fruits [11,12]. The new
compounds were characterized by HR-ESI-MS, infrared and NMR
spectroscopies and the proposed structures were supported by X-
ray diffraction experiments. To the best of our knowledge, these are
the first examples of allyldithiocarbimates, being a novel promising
class of antifungals for the control of plant diseases.
All the NMR spectra for compounds 5aef and 6aef showed the
expected signals for the tetraphenylphosphonium cation at: 1H
NMR (300 MHz, CDCl3) d
: 7.58e7.66 (m*, 8H), 7.71e7.78 (m, 8H),
7.84e7.90 (m, 4H); and 13C NMR (75 MHz, CDCl3)
d: 117.7 (d,
2
3
1JCeP ¼ 89 Hz), 131.0 (d, JCeP ¼ 12.8 Hz), 134.6 (d, JCeP ¼ 9.8 Hz),
136.0 (d, 4JCeP ¼ 3.0 Hz). (*Signal superimposed to the H-3 signal in
most spectra).
2.2.1. Tetraphenylphosphonium (Z)-2-(methoxycarbonyl)-3-
phenylallyl- (phenylsulfonyl)dithiocarbimate (5a)
Yield ¼ 96%; mp ¼ 52.8e54.4 ꢂC; IR (ATR, cmꢀ1) nmax 3055, 2947,
1703, 1622, 1595, 1483, 1435, 1362, 1263, 1138, 1107, 1082, 941, 752,
719, 685, 557, 523; 1H NMR (Allyldithiocarbimate signals, 300 MHz,
2. Experimental
CDCl3) d
: 3.72 (s, 3H, OCH3), 4.20 (s, 2H, H-1), 7.22e7.33 (m, 6H, H-30,
H-40, H-50, H-6, H-7, H-8), 7.53 (d, 2H, J5,6 ¼ J9,8 ¼ 6.0 Hz, H-05, H-9),
2.1. Methods and materials
7.58e7.66 (m*, 1H, H-3), 7.97 (d, 2H, J6 ,5 ¼ J2 ,3 ¼ 6.0 Hz, H-2 , H-6 );
0
0
0
0
0
The 1H and 13C NMR spectra were recorded on a Varian Mercury
300 instrument (300 MHz and 75 MHz, respectively), using
deuterated chloroform as a solvent and tetramethylsilane (TMS) as
internal standard. COSY, HETCOR and NOEDIF experiments were
performed for structural characterization of the reaction products.
Infrared spectra were recorded on a Varian 660-IR, equipped with
GladiATR (Attenuated Total Reflection) scanning from 4000 to
500 cmꢀ1. Uncorrected Melting points were obtained from MQAPF-
301 melting point apparatus (Microquimica, Brazil). High-
resolution mass spectra were recorded on a Shimadzu LCMS-IT-
TOF liquid chromatography mass spectrometer under electro-
spray ionization (ESI). Thin layer chromatography analysis was
conducted on aluminum precoated silica gel plates. Column chro-
matography was performed on silica gel (230e400 mesh). The N-R-
sulfonyldithiocarbimate potassium salts dihydrate, with the gen-
eral formula K2(ReSO2N]CS2).2H2O, where R ¼ C6H5, 4-FC6H4, 4-
ClC6H4, 4-BrC6H4, 4-IC6H4, 4-CH3C6H4, were prepared from the
sulfonamides as described in the literature (Scheme 1) [13e18].
13C NMR (Allyldithiocarbimate signals, 75 MHz, CDCl3)
d: 33.4 (C-1),
52.7 (OCH3), 127.5 (C-2), 127.8 (C-20, C-60), 128.1 (C-30, C-50), 128.8 (C-
6, C-8), 129.0 (C-7), 130.4 (C-5, C-9), 130.5 (C-40), 135.1 (C-4),141.5 (C-
3), 143.9 (C-10), 168.5 (C]O), 201.8 (C]N); HRMS (ESI) m/z calcd for
C
18H16NO4Sꢀ3 406.0241, found 406.0252.
2.2.2. Tetraphenylphosphonium (Z)-2-(methoxycarbonyl)-3-
phenylallyl-(4-fluorophenylsulfonyl)dithiocarbimate (5b)
Yield ¼ 98%; mp ¼ 57.8e59.1 ꢂC; IR (ATR, cmꢀ1) nmax 3057, 2949,
1703, 1587, 1487, 1435, 1362, 1265, 1138, 1107, 1082, 939, 833, 721,
687, 523; 1H NMR (Allyldithiocarbimate signals, 300 MHz, CDCl3)
d
:3.72 (s, 3H, OCH3), 4.20 (s, 2H, H-1), 6.95 (t, 2H,
J3 ,2 ¼ J5 ,6 ¼ J3 ,5 ,F ¼ 9.0 Hz, H-30, H-50), 7.22e7.33 (m, 3H, H-6, H-7,
H-8), 7.52 (d, 2H, J5,6 ¼ J9,8 ¼ 6.0 Hz, H-5, H-9), 7.58e7.66 (m*, 1H, H-
3), 7.95e7.99 (m, 2H, H-20, H-60); 13C NMR (Allyldithiocarbimate
0
0
0
0
0
0
0 0
signals, 75 MHz, CDCl3) d: 33.8 (C-1), 52.3 (OCH3), 114.6 (d, JC3 ,C5 -
¼ 22 Hz, C-30, C-50), 127.6 (C-2), 128.8 (C-6, C-8), 129.0 (C-7), 130.4
F
(C-5, C-9),130.7 (d, JC2 ,C6 -F ¼ 9.0 Hz, C-20, C-60), 135.1 (C-4), 140.0 (d,
Morita-Baylis-Hillman (MBH) adducts (Compounds
1
and 3,
0
0
JC1 -F ¼ 2.3 Hz, C-10),141.5 (C-3),164.0 (d, JC4 -F ¼ 246.8 Hz, C-40),168.5
(C]O), 202.2 (C]N); HRMS (ESI) m/z calcd for C18H15FNO4S3-
424.0147, found 424.0163.
Scheme 2) were prepared by the reaction of methyl acrylate with
benzaldehyde or furfural, catalyzed by trimethylamine [19], and
were converted into the bromide (2) [20,21] and acetate (4) de-
rivatives, as described in the literature.
0
0
2.2.3. Tetraphenylphosphonium (Z)-2-(methoxycarbonyl)-3-
phenylallyl-(4-chlorophenylsulfonyl)dithiocarbimate (5c)
2.2. General procedure for the syntheses of
tetraphenylphosphonium allyldithiocarbimates (5aef and 6aef)
Yield ¼ 99%; mp ¼ 61.9e62.5 ꢂC; IR (ATR, cmꢀ1) nmax 3059,
2949, 1703,1622, 1583, 1483, 1435, 1363, 1265, 1140, 1107, 1082, 945,
816, 748, 721, 687, 557, 523; 1H NMR (Allyldithiocarbimate signals,
The syntheses of the new compounds 5aef and 6aef were
performed by the following general procedure: A solution of
300 MHz, CDCl3) d: 3.72 (s, 3H, OCH3), 4.20 (s, 2H, H-1), 7.22e7.34
(m, 5H, H-30, H-50, H-6, H-7, H-8), 7.51e7.62 (m, 2H, H-5, H-9), 7.66
(s*, 1H, H-3), 7.84e7.92 (m, 2H, H-20, H-60); 13C NMR (Allyldithio-
carbimate signals, 75 MHz, CDCl3) d: 33.8 (C-1), 52.4 (OCH3), 127.5
(C-2), 127.9 (C-20, C-60), 128.8 (C-6, C-8), 129.0 (C-7), 129.9 (C-30, C-
50), 130.4 (C-5, C-9), 135.1 (C-4),136.4 (C-40), 141.6 (C-3), 142.4 (C-10),
168.5 (C]O), 202.6 (C]N); HRMS (ESI) m/z calcd for C18H15ClNO4S3-
439.9852, found 439.9871.
Scheme 1. Preparation of potassium N-R-sulfonyldithiocarbimates.

132
E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
Scheme 2. Preparation of the Morita-Baylis-Hillman derivatives.
2.2.4. Tetraphenylphosphonium (Z)-2-(methoxycarbonyl)-3-
phenylallyl-(4-bromophenylsulfonyl)dithiocarbimate (5d)
13C NMR (Allyldithiocarbimate signals, 75 MHz, CDCl3)
d: 33.7 (C-1),
52.3 (OCH3), 112.9 (C-6), 116.4 (C-5), 124.0 (C-2), 127.8 (C-20, C-60),
128.0 (C-3), 128.1 (C-30, C-50), 130.5 (C-40), 143.9 (C-10), 144.6 (C-7),
150.9 (C-4), 168.3 (C]O), 202.4 (C]N); HRMS (ESI) m/z calcd for
Yield ¼ 99%; mp ¼ 63.5e65.1 ꢂC; IR (ATR, cmꢀ1) nmax 3053,
2949, 1703, 1622, 1574, 1435, 1362, 1265, 1138, 1107, 1082, 943, 721,
687, 557, 523; 1H NMR (Allyldithiocarbimate signals, 300 MHz,
C
16H14NO5S-3 396.0040, found 396.0078.
CDCl3)
d
: 3.72 (s, 3H, OCH3), 4.20 (s, 2H, H-1), 7.22e7.032 (m, 3H, H-6,
0
0
0
0
0
H-7, H-8), 7.37e7.40 (d, 2H, J3 ,2 ¼ J5 ,6 ¼ 9.0 Hz, H-3 , H-5 ), 7.51 (d,
2H, J5,3 ¼ J9,8 ¼ 6.0 Hz, H-5, H-9), 7.55e7.65 (m*, 1H, H-3), 7.82e7.86
(m, 2H, H-20, H-60); 13C NMR (Allyldithiocarbimate signals, 75 MHz,
2.2.8. Tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-
(methoxycarbonyl)allyl-(4-fluorophenylsulfonyl)dithiocarbimate
(6b)
CDCl3)
d
: 33.8 (C-1), 52.3 (OCH3), 124.9 (C-40), 127.5 (C-2), 128.8 (C-
Yield ¼ 88%; mp ¼ 140.9e141.2 ꢂC; IR (ATR, cmꢀ1) nmax 3056,
2948, 1698, 1633, 1585, 1490, 1434, 1357, 1263, 1213, 1135, 1106,
1083, 954, 935, 829, 755, 721, 690, 561, 539, 524, 512; 1H NMR
6, C-8), 129.0 (C-7), 130.1 (C-20, C-60), 130.3 (C-5, C-9), 130.8 (C-30, C-
50), 135.1 (C-4), 141.5 (C-3), 143.1 (C-10), 168.4 (C]O), 202.5 (C]N);
HRMS (ESI) m/z calcd for C18H15BrNO4S-3 485.9326, found 485.9347.
(Allyldithiocarbimate signals, 300 MHz, CDCl3)
d: 3.69 (s, 3H,
OCH3), 4.34 (s, 2H, H-1), 6.38 (s, 1H, H-6), 6.90 (s, 1H, H-5), 6.92 (t,
0
0
0
0
2.2.5. Tetraphenylphosphonium (Z)-2-(methoxycarbonyl)-3-
phenylallyl-(4-iodophenylsulfonyl)dithiocarbimate (5e)
2H, J3 ,2 ¼ J5 ,6 ¼ 6.0 Hz, H-30,H-50), 7.41 (s, 1H, H-3), 7.45 (s, 1H, H-
7),7.99 (t, 2H, J2 ,3 ¼ J6 ,5 ¼ 6.0 Hz, H-20,H-60); 13C NMR (Allyldi-
0
0
0
0
Yield ¼ 94%; mp ¼ 69.7e72.1 ꢂC; IR (ATR, cmꢀ1) nmax 3057, 2947,
thiocarbimate signals, 75 MHz, CDCl3) d: 33.7 (C-1), 52.3 (OCH3),
1705, 1435, 1363, 1263, 1140, 1107, 1080, 943, 723, 688, 557, 525; 1H
NMR (Allyldithiocarbimate signals, 300 MHz, CDCl3) d: 3.72 (s, 3H,
OCH3), 4.20 (s, 2H, H-1), 7.21e7.33 (m, 3H, H-6, H-7, H-8), 7.48 (d,
112.8 (C-6), 114.5 (d, JC3 ,C5 -F ¼ 22 Hz, C-30, C-50), 116.3 (C-5), 124.1
0
0
(C-2), 127.9 (C-3), 130.7 (d, JC2 ,C6 -F ¼ 9.0 Hz, C-20, C-60), 140.0 (C-10),
0
0
144.6 (C-7), 150.9 (C-4), 164.0 (d, JC4 -F ¼ 246.8 Hz, C-40), 168.2 (C]
0
2H, J2 ,3 ¼ J6 ,5 ¼ 9.0 Hz, H-20, H-60), 7.54e7.65 (m, 4H, H-5, H-9, H-
O), 202.7 (C]N); HRMS (ESI) m/z calcd for C16H13FNO5S-3 413.9945,
0
0
0
0
30, H-50), 7.68 (s*, 1H, H-3); 13C NMR (Allyldithiocarbimate signals,
found 413.9961.
75 MHz, CDCl3) d
: 33.8 (C-1), 52.5 (OCH3), 97.8 (C-40), 127.5 (C-2),
128.8 (C-6, C-8), 129.1 (C-7), 129.9 (C-20, C-60), 130.3 (C-5, C-9), 135.1
(C-4), 137.0 (C-30, C-50), 141.8 (C-3), 143.2 (C-10), 168.4 (C]O), 202.9
(C]N); HRMS (ESI) m/z calcd for C18H15INO4S-3 531.9208, found
531.9217.
2.2.9. Tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-
(methoxycarbonyl)allyl-(4-chloro phenylsulfonyl)dithiocarbimate
(6c)
Yield ¼ 89%; mp ¼ 131.8e133 ꢂC; IR (ATR, cmꢀ1) nmax 3056,
2944, 1698, 1633, 1581, 1475, 1434, 1357, 1261, 1135, 1106, 1083, 954,
937, 750, 723, 561, 524; 1H NMR (Allyldithiocarbimate signals,
2.2.6. Tetraphenylphosphonium (Z)-2-(methoxycarbonyl)-3-
phenylallyl-(4-methylphenylsulfonyl)dithiocarbimate (5f)
300 MHz, CDCl3) d: 3.67 (s, 3H, OCH3), 4.33 (s, 2H, H-1), 6.37 (m, 1H,
Yield ¼ 91%; mp ¼ 58.6e60.0 ꢂC; IR (ATR, cmꢀ1) nmax 3055,
H-6), 6.85 (d, 1H, J5,6 ¼ 3.0 Hz, H-5), 7.19 (d, 2H, J3 ,2 ¼ J5 ,6 ¼ 9.0 Hz,
0
0
0
0
2947, 1703, 1435, 1362, 1263, 1136, 1105, 1082, 935, 719, 685, 559,
H-30, H-50), 7.39 (bs, 1H, H-3), 7.43 (s, 1H, H-7), 7.82e7.91 (m, 2H, H-
523; 1H NMR (Allyldithiocarbimate signals, 300 MHz, CDCl3)
d
: 2.31
20, H-60); 13C NMR (Allyldithiocarbimate signals, 75 MHz, CDCl3)
d:
(s, 3H, CH3), 3.72 (s, 3H, OCH3), 4.20 (s, 2H, H-1), 7.11 (d, 2H,
33.7 (C-1), 52.3 (OCH3),112.8 (C-6),116.4 (C-5),123.9 (C-2),127.8 (C-
3), 127.9 (C-20, C-60), 129.8 (C-30, C-50), 136.4 (C-40), 142.4 (C-10),
144.7 (C-7), 150.8 (C-4), 168.2 (C]O), 203.1 (C]N); HRMS (ESI) m/z
calcd for C16H13ClNO5S3- 429.9650, found 429.9692.
J3 ,2 ¼ J5 ,6 ¼ 6.0 Hz, H-30, H-50), 7.22e7.33 (m, 3H, H-6, H-7, H-8),
7.53 (d, 2H, J5,3 ¼ J9,8 ¼ 6.0 Hz, H-5, H-9), 7.57e7.66 (m*, 1H, H-3),
7.85e7.89 (m, 2H, H-20, H-60); 13C NMR (Allyldithiocarbimate sig-
0
0
0
0
nals, 75 MHz, CDCl3) d: 21.7 (CH3), 33.7 (C-1), 52.3 (OCH3), 127.7 (C-
2), 128.2 (C-20, C-60), 128.4 (C-30, C-50), 128.8 (C-6, C-8), 129.0 (C-7),
130.4 (C-5, C-9), 135.1 (C-4), 140.5 (C-40), 141.1 (C-3), 141.3 (C-10),
168.5 (C]O), 201.4 (C]N); HRMS (ESI) m/z calcd for C19H18NO4S3-
420.0398, found 420.0415.
2.2.10. Tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-
(methoxycarbonyl)allyl-(4-bromo phenylsulfonyl)dithiocarbimate
(6d)
Yield ¼ 76%; mp ¼ 116.0e118.2 ꢂC; IR (ATR, cmꢀ1) nmax 3052,
2944, 1698, 1631, 1573, 1471, 1434, 1355, 1261, 1135, 1106, 1079, 950,
935, 721, 559, 524; 1H NMR (Allyldithiocarbimate signals, 300 MHz,
2.2.7. Tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-
(methoxycarbonyl)allyl-(phenylsulfonyl)dithiocarbimate (6a)
Yield ¼ 79%; mp ¼ 111.2e112.4 ꢂC; IR (ATR, cmꢀ1) nmax 3118,
3055, 2947, 1699, 1437, 1360, 1263, 1135, 1105, 1082, 951, 935, 719,
686, 557, 523; 1H NMR (Allyldithiocarbimate signals, 300 MHz,
CDCl3) d: 3.68 (s, 3H, OCH3), 4.34 (s, 2H, H-1), 6.38 (bs, 1H, H-6), 6.86
(d, 1H, J5,6 ¼ 3.0 Hz, H-5); 7.36e7.45 (m, 4H, H-30, H-50, H-3, H-7),
7.83e7.85 (m, 2H, H-20, H-60); 13C NMR (Allyldithiocarbimate signals,
75 MHz, CDCl3)
d 33.7 (C-1), 52.3 (OCH3), 112.7 (C-6), 116.4 (C-5),
CDCl3)
d
: 3.70 (s, 3H, OCH3), 4.36 (s, 2H, H-1), 6.37e6.39 (m, 1H, H-
123.9 (C-2), 125.0 (C-20, C-60), 127.9 (C-3), 130.0 (C-30, C-50), 130.8 (C-
40), 142.9 (C-10), 144.7 (C-7), 150.8 (C-4), 168.2 (C]O), 203.2 (C]N);
HRMS (ESI) m/z calcd for C16H13INO5S-3 473.9145, found 473.9164.
6), 6.91e6.92 (m, 1H, H-5), 7.28e7.31 (m, 3H, H-30, H-40, H-50), 7.43
(s, 1H, H-3), 7.44e7.45 (m, 1H, H-7), 7.98e8.02 (m, 2H, H-20, H-60);

E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
133
2.2.11. Tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-
(methoxycarbonyl)allyl-(4-iodo phenylsulfonyl)dithiocarbimate
(6e)
inhibition at the concentrations tested. The diameter of the fungus
colony was measured with a vernier caliper every 24 h from the
first day of incubation. The inhibition of the colony growth was
calculated as follows: Inhibition % ¼ 100 (Cc ꢀ Cs)/Cc, where Cc is
the average growth of the control and Cs is the average growth of
the fungus in contact with the substance in test. Data were trans-
ferred into a graphic program (OriginPro8), and sigmoidal dos-
eeresponse curves were determined, furnishing the IC50 values for
each compound.
Yield ¼ 83%; mp ¼ 60.3e61.2 ꢂC; IR (ATR, cmꢀ1) nmax 3052,
2948, 1698, 1621, 1565, 1471, 1434, 1359, 1278, 1263, 1139, 1106,
1079, 941, 721, 686, 557, 522; 1H NMR (Allyldithiocarbimate signals,
300 MHz, CDCl3) d: 3.69 (s, 3H, OCH3), 4.34 (s, 2H, H-1), 6.38 (bs,1H,
H-6), 6.86 (d, 1H, J5,6 ¼ 3.0 Hz, H-5), 7.41 (s, 1H, H-3), 7.45 (bs, 1H, H-
7), 7.56e7.63 (m, 2H, H-20, H-60), 7.68e7.76 (m, 2H, H-30, H-50); 13C
NMR (Allyldithiocarbimate signals, 75 MHz, CDCl3) d: 33.7 (C-1),
52.3 (OCH3), 98.6 (C-10), 112.7 (C-6), 116.4 (C-5), 124.0 (C-2), 127.9
(C-3), 130.0 (C-20, C-60), 136.8 (C-30, C-50), 143.6 (C-40), 144.7 (C-7),
150.9 (C-4), 168.2 (C]O), 203.2 (C]N); HRMS (ESI) m/z calcd for
3. Results and discussion
3.1. Synthesis and characterization
C
16H13INO5S-3 521.9006, found 521.9077.
Six N-R-sulfonyldithiocarbimate potassium salts, with the gen-
eral formula K2(ReSO2N]CS2).2H2O, where R ¼ C6H5, 4-FC6H4, 4-
ClC6H4, 4-BrC6H4, 4-IC6H4, 4-CH3C6H4, were prepared from the
respective primary sulfonamides in reaction with carbon disulfide
and potassium hydroxide in N,N-dimethylformamide (DMF), as
shown in Scheme 1, following synthetic procedures described in
the literature [13e18].
2.2.12. Tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-
(methoxycarbonyl)allyl-(4-methyl phenylsulfonyl)dithiocarbimate
(6f)
Yield ¼ 77%; mp ¼ 126.9e128.2 ꢂC; IR (ATR, cmꢀ1) nmax 3047,
2947, 1699, 1435, 1361, 1259, 1136, 1107, 1082, 951, 721, 689, 561,
522; 1H NMR (Allyldithiocarbimate signals, 300 MHz, CDCl3)
d
: 2.28
(s, 3H, CH3), 3.67 (s, 3H, OCH3), 4.32 (s, 2H, H-1), 6.35e6.37 (m, 1H,
The reaction of benzaldehyde or furfural with methyl acrylate in
methanol, catalyzed by trimethylamine (Scheme 2), furnished the
MBH adducts 1 and 3 [19]. Two different approaches were neces-
sary in order to prepare the allyldithiocarbimates from the adducts
1 and 3 in high yields. The MBH adduct 1 was converted into the
bromide derivative (2) by the addition of lithium bromide and
sulfuric acid in acetonitrile (Scheme 2) [20,21]. The MBH adduct 3
was acetylated in reaction with acetic anhydride in the presence of
0
0
0
0
H-6), 6.90 (d, 1H, J5,6 ¼ 3.0 Hz, H-5), 7.08 (d, 3H, J3 ,2 ¼ J5 ,6 ¼ 6.0 Hz,
H-30, H-50), 7.40 (s,1H, H-3), 7.41 (d,1H, J7,6 ¼ 3.0 Hz, H-7), 7.81e7.88
(m, 2H, H-20, H-60); 13C NMR (Allyldithiocarbimate signals, 75 MHz,
CDCl3) d: 21.7 (CH3), 33.8 (C-1), 52.3 (OCH3), 112.9 (C-6), 116.4 (C-5),
124.0 (C-2), 128.0 (C-3), 128.2 (C-20, C-60), 128.4 (C-30, C-50), 140.6
(C-10), 141.0 (C-40), 144.6 (C-7), 150.9 (C-4), 168.3 (C]O), 202.1 (C]
N); HRMS (ESI) m/z calcd for
C
17H16NO5S-3 410.0196, found
410.0224.
4-(dimethylamino)pyridine (DMAP), yielding the acetate 4
(Scheme 2) [27e29].
2.3. X-ray crystallography
The compounds 2 and 4 were the key intermediates for the
syntheses of the target compounds (Scheme 3). The reaction of 2
and 4 with the potassium N-R-sulfonyldithiocarbimates in aqueous
acetone at room temperature were quite fast (10e15 min). The
potassium allyldithiocarbimates thus obtained were of very diffi-
cult purification. Thus, precipitating the allyldithiocarbimates as
tetraphenylphosphonium salts furnished the stable new com-
pounds 5aef and 6aef, in high yields (91e96% and 76e89%,
respectively).
The tetraphenylphosphonium allyldithiocarbimates 5aef and
6aef are yellow solids. They are soluble in acetonitrile, dime-
thylformamide, dimethyl sulfoxide, ethanol, methanol, chloroform
and dichloromethane, being insoluble in water and diethyl ether.
Liquid chromatography mass spectrometry (LCMS-IT-TOF) experi-
ments were performed under electrospray ionization (ESI) for
compounds 5aef and 6aef. All spectra in the negative-ion acqui-
sition mode showed the expected peaks for the allyldithiocarbi-
mate anions, thus confirming the proposed formulae.
The yellow colored single crystals of the compounds 6a, 6b and
6f suitable for X-ray diffraction studies were grown by slow evap-
oration from their solutions in acetone/water. The X-ray measure-
ments were carried out on an Enraf-Nonius FR590 Kappa-CCD
single crystal diffractometer using graphite monochromated MoK
a
radiation (0.71073 Å) at 293.0(2) K. The Bruker AXS Collect software
was used for data collection and for indexing the reflections and
determining the unit cell parameters. The collected data were
processed using HKL Denzo-Scalepack program [22]. The structures
were solved by direct methods using SIR-92 program [23] and
refined by full-matrix least squares calculations using SHELXL-2014
[24]. All non-hydrogen atoms were refined in the anisotropic
approximation against F2 of all reflections. Hydrogen atoms in their
calculated positions were refined using a riding model. Structural
representations were drawn using ORTEP-3 [25] and MERCURY
[26]. The program WinGX [25] was used to prepare materials for
publication. The crystal parameters of compounds 6a, 6b and 6f are
shown in Table 1.
The
are observed around 1260 cmꢀ1 and 970 cmꢀ1, respectively
(Table 2) [13e18]. The low value for the CN is due to the highly
CN band
nCN and nasymCS2 bands of the potassium dithiocarbimates
n
2.4. Biological assay
conjugated NCS2 system (Scheme 4, structures A-C). The n
was shifted to ca. 1360 cmꢀ1 in the spectra of 5aef and 6aef while
the nasymCS2 band had an opposite shift, to 954e935 cmꢀ1. An in-
crease in the double bond character of the CN bond of the allyldi-
thiocarbimates becomes evident from the analysis of the canonical
The antifungal activity of the new compounds against B. cinerea
was evaluated by the Poisoned food technique [6]. Discs of mycelia
of the fungus (diameter of 6 mm) were placed at the center of Petri
dishes containing 15 mL of the culture medium (PDA) homoge-
neously mixed with dimethyl sulfoxide (0.6 mL), Tween 80 (0.6 mL)
and the tested compounds 5aef and 6aef. Each treatment con-
sisted of four repetitions and the dishes were incubated at 22 ꢂC for
three days. The control (negative check treatment) was prepared
with PDA, dimethyl sulfoxide and Tween 80. A positive check
treatment was prepared following the same procedure using the
fungicide zinc bis(dimethyldithiocarbamate) and showed 100%
structures shown in Scheme 4. The shift of the
nCN band is
consistent with the greater importance of the canonical form E
when compared to the structure C (Scheme 4). Thus, a greater
double bond character for the C]N implies in a reduced double
bond character for the CeS bonds. With respect to the MBH moiety,
the band due to the
6aef was observed in the expected range of ca. 1700 cmꢀ1
The integration curves of the 1H NMR signals in the spectra of
a,b-unsaturated carbonyl group of 5aef and
.

134
E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
Table 1
Crystallographic data and details of diffraction experiments for the compounds 6a, 6b and 6f.
6a
6b
6f
Empirical formula
Formula weight (g molꢀ1
Temperature (K)
Crystal system
C40H34NO5PS3
735.83
293(2)
Monoclinic
P21/c
C40H33FNO5PS3
753.82
293(2)
Monoclinic
P21/c
C41H36NO5PS3
749.86
293(2)
Monoclinic
P21/c
)
Space group
Unit cell dimensions (Å,º)
a
16.3253(3)
16.2315(4)
16.2843(3)
b
13.8281(3)
13.8335(3)
13.7939(4)
c
17.7201(4)
17.8261(3)
18.1143(4)
b
112.547(1)
3694.5(1), 4
1.323
0.289
112.518(1)
3697.5(1), 4
1.354
0.294
111.249(1)
3792.3(2), 4
1.313
0.283
Volume (Å3), Z
Calculated density (g cmꢀ3
m
)
(mmꢀ1
)
F(000)
Crystal size (mm)
range (º)
1536
1568
1568
0.434 ꢁ 0.317 ꢁ 0.193
2.946 to 27.479
ꢀ21.19; ꢀ17.17; 0.23
16511
0.392 ꢁ 0.298 ꢁ 0.165
2.917 to 27.502
21,-19; 17,-17; 21,-23
21601
0.369 ꢁ 0.244 ꢁ 0.163
2.914 to 27.499
ꢀ21.19; 0.17; 0.23
15962
q
Limiting indices
Reflections collected
Independent reflections
Goof
8462 [R(int) ¼ 0.0782]
8468 [R(int) ¼ 0.085]
8681 [R(int) ¼ 0.075]
0.890
0.916
0.909
Data/restraints/parameters
8462/0/451
8468/0/460
8681/0/460
R indices [I > 2
s
(I)]
R ¼ 0.0496, wR ¼ 0.1125
R ¼ 0.0852, wR ¼ 0.1245
0.453 and ꢀ0.269
R ¼ 0.0493, wR ¼ 0.1188
R ¼ 0.0860, wR ¼ 0.1315
0.411 and ꢀ0.291
R ¼ 0.0535, wR ¼ 0.1308
R ¼ 0.0918, wR ¼ 0.1450
0.509 and ꢀ0.335
R indices (all data)
Largest diff. peak and hole (e Aꢀ3
)
h
i
ꢀ
ꢀ
ꢀ
ꢁ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ2 1=2
ꢂ
2
2
2
ꢀ
ꢀ
ꢀ
ꢀ
R ¼ SðjjF0j ꢀ jFcjÞ=S F0 ; wR ¼ Sw F0 ꢀ Fc =Sw F0
.
Scheme 3. Syntheses of the allyldithiocarbimates and numbering for the NMR attributions.
5aef and 6aef were consistent with a 1:1 proportion between the
tetraphenylphosphonium cation and the allyldithiocarbimate
anion. The signals of the dithiocarbimate moiety in the spectra of
the allyldithiocarbimates showed approximately the same chemi-
cal shifts as those presented by the parent potassium dithiocarbi-
mates [13e18]. The main differences were observed in their 13C
NMR spectra, where the carbon signals of the N]CS2 group of the
With respect to the MBH moieties in compounds 6aef, two
signals assigned to the sp2-CH2-methylenic hydrogens (
6.43 and
6.72) [28] in the 1H NMR spectrum of the MBH acetate 4 were
d
substituted by one signal at ca.
d 4.3 in the spectra of 6aef, a
characteristic chemical shift for the sp3-CH2-S group (H-1, Scheme
3). In addition, the signal of H-3, now bonded to a sp2 carbon atom,
was shifted from ca.
d 6.3 in the spectrum of 4 to the range of
compounds 5aef and 6aef (
field if compared with the spectra of the potassium dithiocarbi-
mates ( ca. 225) [13e16]. This fact is also consistent with the
d
201.4e203.2) was shifted to higher
d
7.4e7.7, and thus became superimposed to the tetraphenylphos-
phonium hydrogen signals in most spectra of the allyldithiocarbi-
mates. The H-1 and H-3 signals of the bromide 2 are observed at
d
greater double bond character of the CN bond in the allyldithio-
carbimates (Scheme 4).
d
4.41 and 7.84, respectively [21], shifting to higher field at
d
d 4.20
and 7.4e7.7 in the spectra of 5aef. COSYand HETCOR experiments

E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
135
Table 2
Comparison of diagnostic infrared bands and NMR signals observed in the spectra of compounds 5aef and 6aef and the parent potassium dithiocarbimates (K2Laef) and MBH
derivatives 2 and 4.
Compounds
Infrared (cmꢀ1
CN
)
13C NMR (
d)
1H NMR (
H1
d)
n
nasymCS2
nC ¼ O
N¼C
H3
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
K2La [13]
K2Lb [16]
K2Lc [15]
K2Ld [15]
K2Le [14]
K2Lf [15]
2 [21]
4 [28,29]
1362
1362
1363
1362
1363
1362
1360
1357
1357
1355
1359
1361
1255
1259
obscured
obscured
1280
1260
e
941
939
945
943
943
935
951
954
954
950
941
951
971
977
960
955
971
955
e
1703
1703
1703
1703
1705
1703
1699
1698
1698
1698
1698
1699
e
201.8
202.2
202.6
202.5
202.9
201.4
202.4
202.7
203.1
203.2
203.2
202.1
225.7
225.3
225.7
225.7
225.6
225.2
e
4.20
4.20
4.20
4.20
4.20
4.20
4.36
4.34
4.33
4.34
4.34
4.32
e
7.58e7.66
7.58e7.66
7.66
7.55e7.65
7.68
7.57e7.66
7.43
7.41
7.39
7.36e7.45
7.45
7.40
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
1718
1720
4.41
6.43/6.72
7.84
6.3
e
e
e
Scheme 4. Resonance structures for dithiocarbimates dianions (AeC) and substituted dithiocarbimates monoanions (DeE).
confirmed the assignments of the NMR signals. Diagnostic infrared
bands and NMR spectral data of the titled molecules are compared
with those of parent potassium dithiocarbimates (K2Laef) and
MBH derivatives 2 and 4 in Table 2.
In order to investigate the stereochemistry around C2]C3 of
compounds 6aef, NOE difference spectroscopy experiments were
performed. The aromatic hydrogen signal of H-5 showed NOE en-
hancements upon irradiation of H-1, indicating that they were
located on the same side of the double bond, thus establishing the
(Z)-stereochemistry for the allyldithiocarbimates. NOEDIFF data for
compounds 5aef also confirmed that the (Z)-stereochemistry
found in the parent bromide 2 was preserved in the products.
C2eC8eO3eO4eC9 and the aromatic ring. The torsion angles
around the bonds S1eC10 and C1eC2, which describe the orienta-
tion
of
the
three
fragments
in
relation
to
the
S1eNeC10eS2eS3eC1, is similar in all compounds (Table 3). The
dihedral angles between the planes of the furan ring and the phenyl
ring are 13.45 (1)ꢂ, 10.30 (1)ꢂ and 7.52(1)ꢂ for the compounds 6a, 6b
and 6f, respectively.
The NeC10 bond in the compounds 6a, 6b and 6f have a double
bond character [distance of ca. 1.323(3) Å] and is slightly longer
than the value of 1.279 Å, for a typical double N(sp2) ¼ C(sp2) bond
[30]. Further, the C10eS3 bond lengths, in the range of 1.755(2)-
1.763(2) Å, show that the carbon-sulfur bonds are considerably
shorter than a CeS single bond (ca. 1.815 Å) and the C10eS2 [in the
range 1.682(2)-1.686(2) Å] is slightly longer than a typical C]S
double bond (For example 1.602(1) Å in the thioformaldehyde)
[31]. These observations confirm the importance of the canonical
forms (D) and (E) for the substituted dithiocarbimates monoanions
(Scheme 4) and agree with the spectroscopic data.
In the three compounds, the bond lengths of C2eC3 (ca.
1.344 Å), C4eC5 (ca. 1.347 Å) and C6eC7 (ca. 1.322 Å) are consistent
with normal C]C double bond (1.34 Å). The distances of C2eC8 in
the methoxycarbonyl group in the range of 1.486e1.489 Å are
shorter than a normal CeC single bond (1.54 Å). The C8eO3 double
bonds are in the range of 1.186e1.192 Å and the C8eO4 (ca. 1.338 Å)
bonds present intermediate character. The C9eO4 bond lengths (ca.
3.2. X-ray crystallography
The crystal structures of three tetraphenylphosphonium allyl-
dithiocarbimates (6a, 6b and 6f) were determined. The compounds
are isostructural and crystallize in the space group P21/c of the
monoclinic system with four molecules in the unit cell. There are
one anion and one cation in the asymmetric unit (Figs. 2e4). The
results confirm the (Z)-stereochemistry for the allyldithiocarbimate
anions. Selected bond lengths and torsion angles are given in
Table 3.
There are four planar fragments in the allyldithiocarbimate
anions:
S1eNeC10eS2eS3eC1,
C2eC3eC4eC5eC6eC7eO5,

136
E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
Fig. 2. An ORTEP drawing of 6a with atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
Fig. 3. An ORTEP drawing of 6b with atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
Fig. 4. An ORTEP drawing of 6f with atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.

E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
137
Table 3
1.456 Å) are consistent with the expected value for a CeO single
bond. Similar behavior is observed for related compounds [32,33].
The bond lengths and angles in the tetraphenylphosphonium
cation are similar and are comparable to those found in other
structures with the same cation [10,34,35]. The phosphorus atom
exhibit a distorted tetrahedral geometry, the CeP distances ranging
from 1.791(2) Å to 1.802(2)Å and the angles CePeC ranging from
107.23(9)ꢂ to 111.7(1)ꢂ. The CeC bond lengths in the four phenyl
rings range from 1.358(4) Å to 1.407(3) Å. In the crystals of com-
pounds 6a, 6b and 6f the packing appears to be controlled by the
extended zig-zag chains of PPhþ4 cations and the anions occupy the
channels between these chains. Similar behavior is observed in
other tetraphenylphosphonium salts [34].
Selected bond lengths (Å) and torsion angles (ꢂ) for compounds 6a, 6b and 6f.
Compound
6a
6b
6f
Bond lengths
S(1)dO(1)
S(1) eO(2)
S(1) eN
S(1)dC(10)
S(2)dC(10)
S(3)dC(10)
1.437 (2)
1.441 (2)
1.610 (2)
1.776 (2)
1.686 (2)
1.756 (2)
1.826 (2)
1.327 (3)
1.443 (2)
1.439 (2)
1.609 (2)
1.773 (2)
1.685 (2)
1.755 (2)
1.822 (2)
1.324 (3)
1.440 (2)
1.441 (2)
1.614 (2)
1.776 (2)
1.682 (2)
1.763 (2)
1.824 (2)
1.319 (3)
S(3)dC(1)
NeC(10)
Torsion angles
C(10) eS(1)dNdC(10)
NeS(1) eC(10) eC(20)
NeS(1) eC(10) eC(60)
S(3) eC(1) eC(2) eC(3)
S(3) eC(1) eC(2) eC(8)
ꢀ60.5 (2)
ꢀ31.3 (2)
153.9 (2)
87.2 (2)
ꢀ60.4 (2)
ꢀ31.6 (2)
155.0 (2)
88.3 (2)
ꢀ59.1 (2)
ꢀ31.3 (2)
153.7 (2)
89.5 (2)
The crystal packing in all structures is mainly determined by the
electrostatic interactions between oppositely charged ions. More-
over, there are two short CeH/O intramolecular contacts involving
the oxygen atoms O4 and O5, CeH/O intermolecular interactions
between cations and anions involving the oxygen atoms O1 and O2,
ꢀ89.1 (2)
ꢀ89.0 (2)
ꢀ87.7 (2)
and CeH/ interactions between cations. The CeH/
p p interactions
Table 4
form chains along the b axis. In the compound 6b there is one
additional CeH/O intermolecular interaction between the cation
and the anion involving O1, and in the compounds 6b and 6f there
Geometric parameters for intra- and intermolecular interactions in compounds 6a,
6b and 6f.
DonoreH/Acceptor
d(DeH)
d(H/A)
d(D/A)
<(DHA)
are also CeH/
O intermolecular interactions between anions
(Table 4). In all crystals, the CeH/O intermolecular interactions
form zigzag chains in the b axis direction. In the compounds 6b and
6f, there are also CeH/O intermolecular interactions between
anions along the c axis (Figs. 5e7).
Compound 6a
C1eH1A/O5
C3eH3/O4
0.97
0.93
0.93
0.93
0.93
2.36
2.27
2.52
2.57
2.85
2.992(3)
2.692(3)
3.143(3)
3.492(3)
3.598(3)
116.0
106.7
124.5
172.1
139.0
C16eH16/O1i
C33eH33/O2ii
C25eH25/Cg3iii
Compound 6b
C1eH1A/O5
C3eH3/O4
3.3. Antifungal assay
0.97
0.93
0.93
0.93
0.93
0.93
0.93
2.37
2.27
2.59
2.59
2.55
2.60
2.83
2.926(3)
2.693(3)
3.478(3)
3.182(3)
3.156(3)
3.520(3)
3.592(3)
116.6
107.5
159.0
121.9
123.5
172.4
140.0
Botrytis blight, caused by B. cinerea is the most important post-
harvest disease affecting strawberry, causing serious economic
losses [11]. Therefore, and because it has a short life cycle with
abundant sporulation, B. cinerea is an excellent model for new
antifungals prospection. Thus, the new compounds 5aef and 6aef
were evaluated for their in vitro activity against B. cinerea using the
Poisoned food method [6,36] at various concentrations. The effects
of the compounds on the mycelial growth of B. cinerea after 3 days
of incubation are summarized in Tables 5 and 6.
The best model to describe the influence of the concentration of
the allyldithiocarbimates in the growth of B. cinerea was the
sigmoidal curve, as exemplified in Figs. 8 and 9.
The concentrations of the compounds to inhibit 50% of the
colony growth with respect to the control (IC50) could be calculated
C3eH3/O2iv
C15eH15/O1v
C16eH16/O1v
C33eH33/O2vi
C25eH25/Cg3vii
Compound 6f
C1eH1A/O5
C3eH3/O4
0.97
0.93
0.93
0.93
0.93
0.93
2.38
2.26
2.60
2.51
2.59
2.83
2.928(3)
2.688(3)
3.474(3)
3.151(3)
3.484(3)
3.587(3)
115.5
107.1
156.7
125.9
161.5
139.0
C3eH3/O2viii
C15eH15/O1ix
C33eH33/O2x
C25eH25/Cg3xi
Symmetry codes: (i) 1 ꢀ x, ꢀ1/2 þ y, 1/2 ꢀ z; (ii) x,ꢀ1 þ y,z; (iii) 1 ꢀ x, 1/2 þ y, 1/
2 ꢀ z; (iv) ꢀx, 1/2 þ y, ꢀ1/2 ꢀ z; (v) 1 ꢀ x, 1/2 þ y, 1/2 ꢀ z; (vi) x, 1 þ y, z; (vii)
1 ꢀ x, ꢀ1/2 þ y, 1/2 ꢀ z; (viii) 3 ꢀ x, ꢀ1/2 þ y, 5/2 ꢀ z; (ix) 2 ꢀ x, ꢀ1/2 þ y, 3/2 ꢀ z; (x)
x, ꢀ1 þ y, z; (xi) ꢀx, ꢀ1/2 þ y, 1/2 ꢀ z. Cg3 is the C11eC16 ring.
Fig. 5. Blue dashed lines indicate CeH/O intermolecular interactions. Green dashed lines indicate CeH/p interactions along the b axis. (For interpretation of the references to color
in this figure legend, the reader is referred to the web version of this article.)

138
E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
Fig. 6. Packing diagram of 6b, viewed down the b axis. Dashed lines indicate CeH/O intermolecular interactions.
Fig. 7. Packing diagram of 6f, viewed down the b axis. Dashed lines indicate CeH/O intermolecular interactions.
Table 5
Inhibition of Botrytis cinerea growth by the allyldithiocarbimates 5aef at different concentrations on the third day of incubation at 22 ꢂC and the 50% inhibitory concentration
(IC50) obtained from nonlinear regression analysis of the sigmoidal doseeresponse curves.
Substances
Inhibition (%)a, concentration (mM)
IC50 (mM)
0.03
0.05
0.10
0.30
0.50
5a
5b
5c
5d
5e
5f
29.8 ( 1.4)
35.9 ( 1.6)
26.7 ( 2.6)
26.7 ( 1.5)
15.0 ( 1.3)
28.9 ( 1.3)
41.4 ( 1.4)
41.5 ( 1.4)
37.5 ( 1.6)
37.1 ( 1.3)
36.9 ( 1.3)
40.8 ( 1.4)
49.3 ( 1.5)
47.3 ( 1.7)
52.5 ( 1.5)
50.4 ( 1.5)
40.7 ( 1.4)
49.1 ( 1.4)
68.3 ( 1.5)
65.7 ( 1.5)
68.3 ( 1.6)
72.7 ( 1.6)
65.5 ( 1.7)
70.5 ( 1.5)
82.9 ( 2.0)
86.5 ( 1.7)
79.7 ( 1.6)
78.3 ( 1.7)
76.8 ( 1.6)
80.8 ( 1.6)
100
130
94
95
130
98
a
Inhibition (%) ¼ 100(Cc-Cs)/Cc, were Cc is the average growth of the control and Cs is the average growth diameter of the fungus colony in contact with the substance in
test.
from the equations obtained from the doseeresponse curves for
each compound (Tables 5 and 6). From these results, it is clear that
the compounds 6aef, bearing the furan substituent, exhibited
higher activities than those with the phenyl group (5aef). On the
other hand, the changes in the dithiocarbimate moieties had little
effect on the magnitude of the activity within each group of

E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
139
Table 6
Inhibition of Botrytis cinerea growth by the allyldithiocarbimates 6aef at different concentrations on the third day of incubation at 22 ꢂC and the 50% inhibitory concentration
(IC50) obtained from nonlinear regression analysis of the sigmoidal doseeresponse curves.
Substances
Inhibition (%)a, concentration (mM)
IC50 (mM)
0.02
0.04
0.06
0.10
0.12
6a
6b
6c
6d
6e
6f
27.6 ( 1.4)
37.3 ( 2.4)
28.1 ( 1.5)
27.0 ( 3.3)
30,8 ( 2.0)
28.8 ( 1.4)
45.7 ( 0.7)
49.5 ( 0.9)
50.9 ( 1.1)
46.3 ( 0.9)
44.6 ( 2.4)
43.1 ( 0.1)
56.4 ( 0.5)
57.6 ( 2.2)
59.3 ( 1.2)
56.0 ( 0.5)
55.1 ( 0.8)
52.5 ( 1.3)
65.1 ( 1.3)
64.5 ( 1.7)
64.4 ( 2.5)
64.4 ( 1.4)
62.4 ( 1.2)
60.8 ( 2.2)
68.0 ( 1.4)
64.9 ( 1.7)
66.7 ( 2.1)
65.5 ( 2.0)
62.8 ( 1.4)
64.1 ( 1.5)
47
41
38
46
49
56
a
Inhibition (%) ¼ 100(Cc-Cs)/Cc, were Cc is the average growth of the control and Cs is the average growth diameter of the fungus colony in contact with the substance in
test.
ambient conditions [6]. Deposition of a white solid is observable in
their solutions after a few days at room temperature and, therefore,
their biological assays are not satisfactorily reproducible. The bro-
mide 2 and the acetate 4 were much less active than the allyldi-
thiocarbimates. At the concentration of 0.5 mmol Lꢀ1 they inhibited
the growth of B. cinerea in 44% and 22%, respectively, while com-
pounds 5aef and 6aef inhibitions were above 76% at this con-
centration. Thus, the presence of the dithiocarbimate moieties in
compounds 5aef and 6aef proved to be important for the observed
activity.
80
70
60
50
40
30
20
Consequently, the combination of sulfonyldithiocarbimates
with MBH derivatives may represent an advantageous strategy to
achieve higher efficiency in the antifungal activity. The best results
of the series 6aef, and in particular of the compound 6c indicated
that allyldithiocarbimates bearing
a furan ring and a 4-
chlorophenyl group can be possible prototypes for new antifun-
gals, especially for the control of Botrytis blight.
-1.6
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
log concentration (mmol.L-1)
4. Conclusion
Fig. 8. Sigmoidal doseeresponse curve e Inhibition (%) of Botrytis cinerea by com-
pound 5c at different concentrations on the third day of incubation at 22 ꢂC in com-
parison with the control.
In summary, the reaction of Morita-Baylis-Hillman derivatives
with potassium N-aryl-sulfonyldithiocarbimates and tetraphenyl-
phosphonium chloride allowed the syntheses of twelve tetraphe-
nylphosphonium allyldithiocarbimates in high yields. The reactions
were very stereoselective, producing exclusively the Z isomers, as
confirmed by NOE difference spectroscopy and by single crystal X-
ray diffraction measurements. The new compounds (5aef and
6aef) inhibit the growth of B. cinerea and are considerably more
active than the parent potassium sulfonyldithiocarbimates and the
MBH derivatives 2 and 4. A furan ring and a 4-chlorophenyl group
in the structures of the allyldithiocarbimates enhance their activity,
70
60
50
40
30
20
10
leading to IC50 values as low as 38 mM. Thus, the allyldithiocarbi-
mate salts are a new group of biologically active substances with
potential application as agrochemicals.
Acknowledgment
We are grateful to the Conselho Nacional de Desenvolvimento
ꢀ
~
ꢁ
Científico e Tecnologico (CNPq), Fundaçao de Amparo a Pesquisa de
-2.2
-2.0
-1.8
-1.6
-1.4
-1.2
-1.0
-0.8
-0.6
~
Minas Gerais (FAPEMIG) and Coordenaçao de Aperfeiçoamento de
log concentration (mmol.L-1)
Pessoal de Nível Superior (CAPES) for research fellowships and
financial support.
Fig. 9. Sigmoidal doseeresponse curve e Inhibition (%) of Botrytis cinerea by com-
pound 6c at different concentrations on the third day of incubation at 22 ꢂC in com-
parison with the control.
Supplementary material
Details on data collection, refinement and crystallographic data
in CIF format for structures 6a, 6b and 6f have been deposited at the
Cambridge Crystallographic Data Centre, CCDC 1061693 (com-
pound 6a), CCDC 1061694 (compound 6b) and CCDC 1061695
(compound 6f). Copies of this information may be obtained free of
compounds. Nevertheless, compounds 5c and 6c bearing the 4-
chlorophenyl groups were slightly more active within both groups.
Although the parent potassium dithiocarbimates (RSO2N]
CS2K2) are active as antifungals, they are not very stable at the

140
E.C. Tavares et al. / Journal of Molecular Structure 1106 (2016) 130e140
2119e2126.
charge from The Director, CCDC, 12 Union Road, Cambridge, CB2
1EZ, UK (fax: þ44 1223 336 033; email: deposit@ccdc.cam.ac.uk or
www: http://www.ccdc.cam.ac.uk).
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[17] J. Janczak, M.M.M. Rubinger, M.R.L. Oliveira, L.C. Alves, Acta Cryst. C68 (2012)
m312em316.
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