p-Aromatic Isothiocyanates: Synthesis and Anti Plant Pathogen Activity

Article abstract of DOI:10.1134/S1070363218060348

In this study, a series of p-aromatic isothiocyanates are prepared by reacting p-aromatic amines with carbon disulphide and further treating with molecular iodine to yield corresponding isothiocyanate derivatives. The structures of newly synthesized compounds are confirmed by IR, NMR, and MS data. Activity of the products against plant pathogenic fungi and bacteria is tested and the structure-activity relationship is approached. p-Nitrophenyl isothiocyanate most efficiently inhibits Rhizoctonia solani and Erwinia carotovora. The order of seven aromatic isothiocyanates antifungicidal activity is following: p-nitrophenyl > p-methoxyphenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > phenyl > p-fluorophenyl. For antibacterial activity, the order was p-nitrophenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > p-fluorophenyl > phenyl > p-methoxyphenyl. The present study indicates that some of the compounds exhibit promising antimicrobial activity and can be used as an alternative to the traditional synthetic fungicides for controlling R. solani and E. carotovora.

Full text of DOI:10.1134/S1070363218060348

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 6, pp. 1252–1257. © Pleiades Publishing, Ltd., 2018.
p-Aromatic Isothiocyanates:
Synthesis and Anti Plant Pathogen Activity1
J. Tanga, J. Niua, W. Wanga, H. Huoa, J. Lia, L. Luoa, and Y. Caoa*
a College of Plant Protection, China Agricultural University, Beijing, 100193 China
*e-mail: caoysong@126.com; caoys@cau.edu.cn
Received April 15, 2018
Abstract—In this study, a series of p-aromatic isothiocyanates are prepared by reacting p-aromatic amines with
carbon disulphide and further treating with molecular iodine to yield corresponding isothiocyanate derivatives.
The structures of newly synthesized compounds are confirmed by IR, NMR, and MS data. Activity of the
products against plant pathogenic fungi and bacteria is tested and the structure-activity relationship is
approached. p-Nitrophenyl isothiocyanate most efficiently inhibits Rhizoctonia solani and Erwinia carotovora.
The order of seven aromatic isothiocyanates antifungicidal activity is following: p-nitrophenyl > p-methoxy-
phenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > phenyl > p-fluorophenyl. For antibacterial
activity, the order was p-nitrophenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > p-fluorophenyl >
phenyl > p-methoxyphenyl. The present study indicates that some of the compounds exhibit promising anti-
microbial activity and can be used as an alternative to the traditional synthetic fungicides for controlling R.
solani and E. carotovora.
Keywords: aromatic isothiocyanates, antimicrobial activity, structure-activity relationship
DOI: 10.1134/S1070363218060348
INTRODUCTION
lower stems of plants [21, 22]. Erwinia carotovora is a
Gram-negative rod-shaped bacterium that thrives alone
or aggregates into pairs and chains [23]. Li and co-
workers [16] determined that longer-chain ITC
derivatives toxicity was influenced by steric hindrance.
Antibacterial activity of ITCs was moderately
influenced by increased hydrophobicity [16].
Over the recent years, the new strategies for plant
disease management have led to development of
botanical fungicides [1–4]. Glucosinolates (GLs), the
secondary metabolites of Brassicales plants, and their
enzymatic hydrolysis attracted close attention [5, 6].
Isothiocyanates (ITCs) exhibit biological activity
against various bacteria [7], fungi [8], nematodes [9],
viruses [10], insects, and weeds [11, 12]. Minor
changes in ITCs structures can result in significant
impact on their bioactivity [13–16]. Hansch and co-
authors [17] studied structure-activity relationships for
ITC and indicated that substituents could influence
isothiocyante “function” [17]. It was determined that
n-pentyl-ITC was 22-fold more toxic than its highly
branched isomer [18]. Toxicity of p-butylphenyl and
p-bromophenyl ITCs was more pronounced than that of
phenyl ITC [19]. p-Hydroxyphenyl ITC demonstrated
higher antiviral activity than phenyl ITC [20].
Up to date, little research is performed on activity
of different para substituted aromatic ITCs against
plant pathogenic bacteria and fungi. The current study
targeted creating a highly active antimicrobial
compound and an efficient approach to structure-
activity relationship. For this purpose seven new
aromatic ITCs were synthesized and tested for
antifungal and antibacterial activities against R. solani
and E. carotovora.
RESULTS AND DISCUSSION
Synthesis of ITCs involved reaction of p-aromatic
amines with carbon disulfide in the presence of TEA
and treatment of the salts thus obtained by iodine
(Scheme 1). The process conditions (temperature, time
of iodine addition and solvents) were optimized. It was
determined that the optimal reaction temperature was
Rhizoctonia solani is a plant pathogenic fungus
with a wide host range all over the world. It causes
serious plant loss by attacking primarily roots and
1 The text was submitted by the authors in English.
1252

p-AROMATIC ISOTHIOCYANATES
1253
Scheme 1. Synthetic route to isothiocyanates.
H
NEt3
N
S
NHEt3
R
R
+ CS2
NH2
S
ACN
S
S
Iodine
NEt3
Iodine
NEt3
H
H
R
N C
S
R
N C
S
S
C N
R
R = H, CH3, CH3CH2, OCH3, F, Cl, NO2.
below 5°C. In order to avoid ITCs direct reacting with
amines, the process temperature should not exceed 50°C.
The effect of iodine addition time on the yield of the
products was studied over a period of 5 to 60 min.
Iodine addition to the suspension of dithiocarbamate
salt must be carried out over a period of 20 min.
Among the solvents, ACN, DMF, MeOH, and EtOH,
the most efficient one was determined to be ACN.
Aromatic substrates containing various substituents in
para position gave ITCs in high yields (89–98%), even
with electron-withdrawing substituents (NO2, F, Cl)
attached to the aromatic ring. Structures of the
synthesized compounds were characterized by IR,
NMR and mass spectra (Table 1).
Efficacy of ITCs against mycelial growth of R.
solani. According to the present study p-nitrophenyl
ITC displayed the highest activity against R. solani
(Table 2). The percent inhibition of mycelial growth
was 37.92 and 94.17% at concentrations of 5.0 and
25.0 µg/mL, respectively. p-Fluorophenyl ITC demon-
strated the lowest activity, 50.3% at 100.0 µg/mL. At
Table 1. Characteristic data for the synthesized compounds
Found, %
Molecular Molecular Yield,
EI-MS 1H NMR,
Calculated, %
R
IR, ν, cm–1
formula
weight
%
[M]+
δ, ppm
C
H
N
C
H
N
Phenyl
C7H5NS
135.19
98 61.95 3.72 10.31 62.19 3.73 10.36 135.0 7.13–7.37 m 3062, 2936 (CH),
(5H)
2098(NCS), 1615
(CS)
p-Methylphenyl C8H7NS
p-Methoxyphenyl C8H7NOS
149.21
165.21
163.24
95 64.20 4.72 9.37 64.39 4.73 9.39 149.0 2.32 d (3H), 3061, 2930 (CH),
2175 (NCS), 1493
(CS)
7.13 m (5H)
92 57.93 4.26 8.45 58.16 4.27 8.48 165.0 3.78 s (3H), 3066, 2905 (CH),
6.83 m (2H), 2115 (NCS), 1503
(CS)
7.13 m (2H)
p-Ethylphenyl
C9H9NS
94 66.24 5.54 8.61 66.22 5.56 8.58 163.0 1.37 t (3H), 3012, 2957 (CH),
2.62 d (2H), 2098(NCS), 1501
7.14 t (2H), (CS)
7.42 t (2H)
p-Fluorophenyl C7H4FNS
153.18
93 54.79 2.62 9.11 54.89 2.63 9.14 153.0 7.09–7.37 m 2125 (NCS), 1487
(4H)
(CS)
p-Chlorophenyl C7H4ClNS 169.63
91 49.38 2.37 8.23 49.56 2.38 8.26 169.0 7.09–7.37 m 3021 (CH2), 2125
(4H)
(NCS), 1501 (CS),
726 (Ph)
p-Nitrophenyl
C7H4N2O2S 180.18
89 46.54 2.23 15.51 46.66 2.24 15.55 180.0 7.37 d (2H), 2930 (Ar-H), 2135
8.25 d (2H) (NCS), 1530 (CS),
1145 (NO)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 6 2018

1254
TANG et al.
Table 2. Percentage inhibition of mycelial growth of R. solani by ITCs
p-Methylphenyl p- Methoxyphenyl p-Ethylphenyl p-Fluorophenyl p-Chlorophenyl p-Nitrophenyl
Phenyl
20.0 12.03aa 5.0
12.29a
5.0
17.92a
38.33b
52.92c
10.0 12.65a 15.0 12.92a
20.0 37.16b 25.0 27.08b
50.0 67.06c 50.0 32.92b
10.0 10.56a 5.0 37.92a
20.0 19.10b 10.0 75.83b,c
50.0 52.24c 15.0 82.83c
80.0 93.62d 20.0 91.40d
50.0 34.91b 10.0 13.56a
80.0 54.81c 20.0 28.07b
100.0 68.31d 50.0 68.63c
120.0 84.01e 100.0 79.25c
10.0
15.0
25.0
50.0
69.17d 100.0 78.32d 100.0 50.30c
86.67e 150.0 84.29d 150.0 70.70d 100.0 98.59d 25.0 94.17d
a Mean values followed by same letters within the same column were not significantly different according to the LSD test (P < 0.05).
the highest concentrations, all screened compounds
exhibited significant fungistatic efficiency ranged from
70.70 to 98.59%.
critically on their hydrophobic content, which is
typically quantified by the n-octanol/water partition
coefficient [25]. Hydrophobicity (log P) of ITCs was
measured using an octanol-aqueous shake-flask
method [26]. log P Values of seven screened ITCs
ranged from 3.20 to 4.43 (Table 3). In the present study,
activity of ITCs against R. solani became moderately
intensive with the hydrophobicity increasing. This
indicated that hydrophobicity favored antifungal
activity of ITCs against R. solani, and suggested that
the transport of ITCs to the target sites of R. solani
could involve hydrophobicity transport mechanisms.
The toxic potency related to various aromatic
substituent attached to the aromatic ring was determined
to have the following order: p-nitrophenyl > p-meth-
oxyphenyl > p-chlorophenyl > p-methylphenyl > p-ethyl-
phenyl > phenyl > p-fluorophenyl (Table 3).
In general, toxicity of chemicals is related to a
hydrophobicity term, an electronic term and a steric
term [24]. We hypothesize that all the ITCs are
Michael-type acceptors, that can set off the Michael
addition reaction with the cellular thiols, and this can
be considered as the molecular mechanism of action.
Antimicrobial activity of the compounds depends
The derivatives with an electron-withdrawing
substituent should be more activity against R. solani
than those with electron-donating substituent, because
of electronic effect. Comparison of the molecular
structures indicated that the nitro substituent exerted a
more powerful electronic effect on thiol reactivity with
aromatic ITCs than other compounds. It can be
concluded that inhibition of mycelial growth of R.
solani depended mainly on the hydrophobicity of the
ITCs and electronic nature of the substituents.
a
Table 3. EC50 values of ITCs against R. solani and
E. Carotovora
EC50 , µg/mL
ITCs
log Pb
R. solani E. carotovora
Phenyl
3.20 62.49dc
3.28 80.79e
3.58 13.55b
24.05a,b
20.01a,b
32.36c
13.18a
18.25a
18.32a
19.98a
Antibacterial activity of ITCs against E.
carotovora. The effect of five concentrations of each
ITC on growth-inhibition activity of E. carotovora are
presented in Table 4. p-Methoxyphenyl ITC displayed
the lowest activity against E. carotovora, percentage
inhibition was only 68.08% at 50.0 µg/mL. p-Nitro-
phenyl ITC demonstrated the highest activity against
E. carotovora (20.23 and 89.91% at the concentration
of 5.0 and 50.0 µg/mL, respectively). At the highest
concentration, all tested compounds exhibited
significant antibacterial activity and their percentage
inhibition ranged from 68.08 to 98.81%.
p-Fluorophenyl
p-Methoxyphenyl
p-Nitrophenyl
3.62
3.91
3.92
5.63a
30.39c
33.23c
p-Chlorophenyl
p-Methylphenyl
p-Ethylphenyl
4.43 35.51d
a
EC50 for ITCs causing 50% inhibition of mycelial growth or the
number of bacteria. b Hydrophobicity. c Mean values followed by
same letters within the same column were not significantly
different according to the LSD test (P < 0.05).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 6 2018

p-AROMATIC ISOTHIOCYANATES
1255
Table 4. Antibacterial activity of ITCs against E. carotovora by ITCs
p-Methylphenyl p- Methoxyphenyl p-Ethylphenyl p-Fluorophenyl p-Chlorophenyl p-Nitrophenyl
Phenyl
15.0 17.41aa 10.0 24.97a
20.0 26.39b 20.0 67.07b
25.0 53.31c 50.0 73.53b
30.0 54.77c 80.0 84.68c
50.0 98.81d 100.0 92.83c
10.0
15.0
25.0
30.0
50.0
14.37a
23.67b
36.94c
46.50d
68.08e
5.0
13.25a 1.0
36.13b 5.0
10.12a
14.27a
5.0
12.32a 5.0 20.23a
10.0
20.0
25.0
50.0
10.0 14.97a 10.0 22.93a
15.0 52.21b 15.0 40.38b
20.0 67.20c 25.0 73.68c
50.0 81.04d 50.0 89.91d
48.07c 10.0 28.30b
59.31d 25.0 50.83c
72.61e 50.0 79.49d
a Mean values followed by same letters within the same column were not significantly different according to the LSD test (P < 0.05).
EC50 values determined for reduction of E.
carotovora growth are presented in Table 3. The order
of ITCs antibacterial activity was p-nitrophenyl > p-
chlorophenyl > p-methylphenyl > p-ethylphenyl > p-
fluorophenyl > phenyl > p-methoxyphenyl. Due to
electron-donating nature of the methoxy group reaction
activity of ITC with the cellular thiols was the lowest.
EXPERIMENTAL
The reagent grade chemicals were purchased from
Sigma. HPLC grade methanol was supplied from J.T.
Baker and ultrapure water from a Milli-Q system
(Millipore, Billerica, MA, USA). The fungus R. solani
and bacteria E. carotovora were supplied from the
Laboratory of Seed Pathology and Fungicide
Pharmacology at China Agricultural University.
Hydrophobicity of the substituents favored the
antibacteria activity of ITCs against E. carotovora, and
suggested that it might be more beneficial for the
transport of ITCs to the target sites. Activity of ITCs
containing the nitro group against E. carotovora was
more pronounced than that of other compounds, which
was most likely due to its electron-withdrawing nature.
It was also beneficial for setting off the Michael
addition reaction with the cellular thiols than the
electron-donating substituent. Thus, the electronic
effects influenced upon the antibacteria activity of
ITCs against E. carotovora.
Synthesis of isothiocyanates. Synthetic approach
to ITCs followed the developed earlier method [28].
Characterization of isothiocyanates. HPLC was
carried out for methanol solutions of the compounds
using a SPD-20Avp UV detector at 225 nm. NMR
spectra were measured on a Varian Unity Inova 300
MHz spectrometers using TMS or the solvent (CHCl3)
as an internal reference. IR spectra were recorded for
KBr pellets on a Jasco FT-IR 5300 spectrophotometer.
Mass spectra (70 eV electron impact [EI]) were
measured on a JEOL JMS-AX500 mass spectrometer.
Elemental analyses was carried out with a LECO-183
CHNS analyzer.
Possibly the sulfur containing fungicides act as
hydrogen acceptors in metabolic systems and disturbed
the normal hydrogenation and dehydrogenation
reactions in cells [27]. Activity of ITCs against R.
solani and E. carotovora was not exactly in
accordance with the change of electronic effects and
hydrophobicity of ITCs. Probably the activity could be
entirely related to the electronic effects and
hydrophobicity of ITCs, but also be related to the
differences in the steric factors and differences in
biochemistry and physiology of the fungi and bacteria.
For this reason, more studies should be carried out on
the possible influence of these factors on the
antimicrobial activity of ITCs.
Evaluation of isothiocyanate derivatives against
R. solani. Antifungal activity of ITCs against R. solani
was tested by the growth rate method. ITCs were
dissolved in DMSO. Appropriate concentrations (µg/mL)
of ITCs were determined by preliminary tests. The
blank flat and the flat with solvent were used as the
controls. After rejuvenation, fungus cake of R. solani
(diameter 5 mm) was inoculated in the toxic flat and
cultured at 24–28°C for 2–3 days. The percentage of
relative inhibition of ITCs against fungus was calculated
by comparing the colony diameter with the control.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 6 2018

1256
TANG et al.
Evaluation of isothiocyanate derivatives against
REFERENCES
E. carotovora. The synthesized compounds were
tested for their antibacterial activity against
E. carotovora using the turbidimetric method. An aliquot
(0.1 mL) of the bacterial suspension (109 CFU/mL)
was added into a conical flask (35 mL) containing
10 mL of lysogeny broth (LB), which contained ITCs at
different concentrations (µg/mL) dissolved in DMSO.
The amount of DMSO in both control and assay was
below 0.1% (v/v). The mixtures were cultivated in a
shaker at 30°C for 12 h. After cultivation, the turbidity
of the bacteria solution was determined by using an
Agilent 8453 UV-Vis spectrophotometer. A sample
(1 mL) was taken from each conical flask, and optical
density (OD) value was measured at the wave length
of 600 nm. The relation of OD value with the
predetermined concentration of bacteria was used for
determining the actual concentrations of bacteria.
Inhibition rates of ITCs against bacteria were cal-
culated by comparing OD values with controls.
1. Lalancette, N., Furman, L.A., and White, J.F., Crop
Prot., 2013, vol. 43, p. 7. doi 10.1016/j.cropro.2012.08.006
2. Belakhov, V.V. and Garabadzhiu, A.V., Russ. J. Gen.
Chem., 2014, vol. 84, no. 13, p. 2664. doi 10.1134/
S1070363214130271
3. Belakhov, V.V. and Garabadzhiu, A.V., Russ. J. Gen.
Chem., 2016, vol. 86, no. 13, p. 3002. doi 10.1134/
S1070363216130120
4. Perelló, A., Lampugnani, G., Abramoff, C., Slusarenko, A.,
and Bello, G.D., Int. J. Pest Manage., 2016, vol. 63,
no. 2, p. 157. doi 10.1080/09670874.2016.1252478
5. Smolinska, U., Morra, M.J., Knudsen G.R., and James, R.L.,
Plant Dis., 2007, vol. 87, no. 4, p. 407. doi 10.1094/
pdis.2003.87.4.407
6. Deng, Q., Zinoviadou, K.G., Galanakis, C.M., Orlien, V.,
Grimi, N., Vorobiev, E., Lebovka N., and Barba, F.J.,
Food Eng. Rev., 2015, vol. 7, no. 3, p. 357. doi 10.1007/
s12393-015-9122-2
7. Dufour, V., Stahl M., and Baysse, C., Microbiology,
2015, vol. 161, no. Pt 2, p. 229. doi 10.1099/
mic.0.082362-0
8. Ugolini, L., Martini, C., Lazzeri, L., D’Avino, L., and
Mari, M., Postharvest Biol. Tec., 2014, vol. 90, p. 34.
doi 10.1016/j.postharvbio.2013.12.002
Data analysis. The half maximal effective con-
centration (EC50) values were calculated by the linear
regression of the probit % of inhibition of mycelial
growth or the number of bacteria as a function of the
log of inhibitor concentrations. All data were subjected
to one-way ANOVA using SPSS 17.0 statistical
analysis software (SPSS, Chicago, IL, USA.). The
confidence limits used in this study were based on 95%
(P < 0.05).
9. Ntalli, N. and Caboni, P., Phytochem. Rev., 2017,
vol. 16, no. 5, p. 827. doi 10.1007/s11101-017-9491-7
10. Mochida, K. and Ogawa, T., J. Sci. Food Agr., 2010,
vol. 88, no. 10, p. 1704. doi 10.1002/jsfa.3268
11. Main, M., Mccaffrey J.P., and Morra, M.J., J. Appl.
Entomol., 2015, vol. 138, no. 9, p. 701. doi 10.1111/
jen.12128
CONCLUSIONS
12. Bangarwa, S.K. and Norsworthy, J.K., Crop Prot.,
2015, vol. 74, p. 145. doi 10.1016/j.cropro.2015.04.012
13. Pilyugin, V.S., Sapozhnikov, Y.E., and Sapozhnikova, N.A.,
A series of aromatic ITCs were prepared by
reacting p-aromatic amines with carbon disulphide and
further treating with molecular iodine to yield
corresponding isothiocyanate derivatives. Structure-
activity relationships for the newly synthesized com-
pounds against plant pathogenic fungi and bacteria
were evaluated. The results indicated that p-nitro-
phenyl ITC was the most effective in inhibiting
R. solani and E. carotovora. The present study
revealed that some of the compounds exhibited
promising antimicrobial activities and could be used as
an acceptable alternative to the traditional synthetic
fungicides in controlling R. solani and E. carotovora.
Russ. J. Gen. Chem., 2004, vol. 74, no. 5, p. 738.
14. Ko, M.O., Kim, M.B., and Lim, S.B., J. Microbiol.
Biotechnol., 2016, vol. 26, no. 12, p. 2036. doi 10.4014/
jmb.1606.06008
15. Milelli, A., Fimognari, C., Ticchi, N., Neviani, P.,
Minarini A., and Tumiatti, V., Mini Rev. Med. Chem.,
2014, vol. 14, no. 12, p. 963. doi 10.2174/
1389557514666141106131909
16. Li, D., Shu, Y., Li, P., Zhang, W., Ni H., and Cao, Y.,
Med. Chem. Res., 2012, vol. 22, no. 7, p. 3119. doi
10.1007/s00044-012-0323-4
17. Hansch, C., Gao, H., and Hoekman, D., A Generalized
Approach to Comparative QSAR, Devillers. J., Ed.,
Washington, DC: Taylor and Francis, 1998, p. 285.
ACKNOWLEDGMENTS
This work was supported by the Key Projects in the
National Science and Technology Pillar Program of
China (2014BAC14B00).
18. Schultz, T.W. and Comeaux, J.L., B. Environ. Contam.
Tox., 1996, vol. 56, no. 4, p. 638. doi 10.1007/
s001289900093
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 6 2018

p-AROMATIC ISOTHIOCYANATES
1257
19. Mays, J.R., Weller Roska, R.L., Sarfaraz, S., Mukhtar, H.,
and Rajski, S.R., Chembiochem., 2008, vol. 9, no. 5,
p. 729. doi 10.1002/cbic.200700586
24. Etzenhouser, B., Hansch, C., Kapur, S., and Selassie, C.D.,
Bioorg. Med. Chem., 2001, vol. 9, no. 1, p. 199. doi
10.1016/S0968-0896(00)00238-8
25. Kuroda, K., Caputo, G.A., and DeGrado, W.F., Chem.
Eur. J., 2009, vol. 15, no. 5, p. 1123. doi 10.1002/
chem.200801523
20. Tajima, H., Nakamoto, Y., and Taketo, A., Biosci.
Biotech. Bioch., 2007, vol. 71, no. 4, p. 1094. doi
10.1271/bbb.70001
26. Screnci, D., Mckeage, M.J., Galettis, P., Hambley, T.W.,
Palmer, B.D., and Baguley, B.C., Brit. J. Cancer, 2000,
vol. 82, no. 4, p. 996. doi 10.1054/bjoc.1999.1026
27. Saksena, N.K., Folia Microbiol., 1985, vol. 30, no. 4,
p. 359. doi 10.1007/BF02927591
21. Parmeter, J., Rhizoctonia Solani, Biology and
Pathology, Univ. of California Press, 1970.
22. Ogoshi, A., Annual Rev. phytopathol., 1987, vol. 25,
no. 1, p. 125. doi 10.1146/annurev.py.25.090187.001013
23. Dong, Y.-H., Xu, J.-L., Li, X.-Z, and Zhang, L.-H.,
P. Natl. Acad. Sci. USA., 2000, vol. 97, no. 7, p. 3526.
doi 10.1073/pnas.060023897
28. Nath, J., Ghosh, H., Yella, R., and Patel, B.K., Eur. J.
Org. Chem., 2009, vol. 2009, no. 12, p. 1849. doi
10.1002/ejoc.200801270
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 6 2018