Direct and facile synthesis of acyl isothiocyanates from carboxylic acids using trichloroisocyanuric acid/triphenylphosphine system

Article abstract of DOI:10.5562/cca2381

A mild, efficient, and practical method for one-step synthesis of alkanoyl and aroyl isothiocyanates from carboxylic acids using a safe and inexpensive mixed reagent, trichloroisocyanuric acid/triphenyl-phosphine is described at room temperature. Availability of the reagents and easy workup of the reaction make this method attractive for organic chemists.

Full text of DOI:10.5562/cca2381

CROATICA CHEMICA ACTA
CCACAA, ISSN 0011-1643, e-lSSN 1334-417X
RQATICA
CT
HEMICA
Croat. Chem. Acta 87 (3) (2014) 201-206.
http://dx.doi.org/10.5562/cca2381
Original Scientific Article
Direct and Facile Synthesis of Acyl Isothiocyanates from Carboxylic
Acids Using Trichloroisocyanuric Acid/Triphenylphosphine System
Najmeh Entezari, Batool Akhlaghinia,* and Hamed Rouhi-Saadabad
Department of Chemistry, Faculty ofSciences, Ferdowsi University ofMashhad, Mashhad 9177948974, Iran
RECEIVED NOVEMBER 7,2013; REVISED JUNE 3, 2014; ACCEPTED AUGUST 27, 2014
Abstract. A mild, efficient, and practical method for one-step synthesis of alkanoyl and aroyl isothiocyanates
from carboxylic acids using a safe and inexpensive mixed reagent, trichloroisocyanuric acid/triphenyl-
phosphine is described at room temperature. Availability of the reagents and easy workup of the reaction
make this method attractive for organic chemists.
Keywords: acyl isothiocyanates, carboxylic acids, trichloroisocyanuric acid (TCCA), triphenylphosphine
(TPP), potassium thiocyanate
INTRODUCTION
azides from carboxylic acids and sulfonic acids under
mild and neutral reaction conditions by using the above
mentioned mixed reagents.19-21 Herein we wish to report
a simplified, rapid and one-step method for the conver-
sion of carboxylic acids to acyl isothiocyanates in the
presence of TPP/TCCA as a mild, efficient and inex-
pensive reagent system at room temperature.
Acyl isothiocyanates have found wide application in the
synthesis of various acyclic and heterocyclic compounds,
including those possessing biological activityA3
The methods of preparation of isothiocyanates are
limited.2 many methods have been described for the
preparation of acyl isothiocyanates.4 14which are main-
ly based on the reaction of acyl halides with thiocyanate
ion.2'6 Acyl halides are not always easy to access or
store. As acyl halides are highly sensitive to moisture
and require care in handling, these methods need to
anhydrous conditions and long reaction time.6 The reac-
tion of carbonimidoyl dichloride with metal thiocyanate
is also another reported method of preparation of acyl
isothiocyanates, but the starting material is not easily
available and the yield of the reaction is too low.15
There are few reports on the direct conversion of car-
boxylic acids to acyl isothiocyanates using acid activa-
tors such as Ph3P(SCN)2 (Ref. 16) and PO(NCS)3 (Ref.
17). Preparation of the reagents in these methods suffers
from difficult procedures and the reactions take long
time. Conversion of trialkylsilyl carboxylates to acyl
isothiocyanates was also reported by using Ph3P(SCN)2
(Ref. 18). This methodology cannot be considered as a
direct preparation of acyl isothiocyanates and also needs
initial preparation of reagents.
EXPERIMENTAL
General
The products were purified by column chromatography.
The purity determinations of the products were accom-
plished by TLC on silica gel polygram STL G/UV 254
plates. The melting points of products were determined
with an Electrothermal Type 9100 melting point appa-
ratus. The FT-IR spectra were recorded on an Avatar
370 FT-IR Therma Nicolet spectrometer. The NMR
spectra were provided on Brucker Avance 100 and 400
MHz instruments in CDC13 and DMSO. Mass spectra
were recorded with a CH7A Varianmat Bremem in-
strument at 70 eV; in m /z (rel %). Elemental analyses
were performed using an Elementar, Vario EL III and
Thermofinnigan Flash EA 1112 Series instrument. Most
of the products were known compounds and character-
ized by the IR and comparison of their melting points
with authentic samples. The structure of unknown prod-
ucts and some selected known products was further
confirmed by lH NMR, 13C NMR spectroscopy, mass
spectrometry and elemental analysis.
By considering the activity of trichloroisocyanuric
acid (TCCA) and /V-chlorobenzotriazole (NCBT) to-
wards triphenylphosphine, recently we reported direct
preparation of acyl azides, esters, thioesters and sulfonyl
* Author to whom correspondence should be addressed. (E-mail: akhlaghinia@um.ac.ir)

202
N. Entezari et al., Direct Synthesis ofAcyl Isothiocyanatesfrom Carboxylic Acids
Preparation of Benzoyl Isothiocyanate from Benzoic
Acid
1012, 861, 840, 738, 666, 532; MS m/z: 197 (M+, 2.5 %);
138 (M+-NCS, 100 %); 110 (M+-CONCS, 92.5 %); 75
(Ph, 95 %).
To a cold solution of triphenylphosphine (0.262 g, 1 mmol)
in toluene (3 mL), trichloroisocyanuric acid (0.069 g,
0.3 mmol) was added with continuous stirring. Benzoic
acid (0.097g, 0.8 mmol) was added and stirring was
continued for 15 min. Potassium thiocyanate (0.193 g,
2 mmol) was added and the temperature was raised up
to room temperature. Stirring was continued for 40 min
at room temperature. The progress of the reaction was
followed by TLC. Upon completion of the reaction,
the concentrated residue passed through a short silica-
gel column using w-hexane / ethyl acetate mixture (vol.
ratio: 60:1) as the eluent. Benzoyl isothiocyanate was
obtained with 95 % yield after removing the solvent
under reduced pressure.
4-Bromobenzoyl Isothiocyanate (Table 2, entry 7)
Solid; m.p. 53-55 °C (Ref. 26) 54-55 °C; IR (KBr)
W c n T 1: 3088, 2197, 2039, 1985 (N=C=S), 1687
(C=0), 1587, 1482, 1397, 1269, 1172, 1100, 1066,
1010, 860, 837, 734, 665, 510, 459; 'H NMR (400
MHz, CDC13) <S/ppm: 7.67 (d, 2H, J = 8.8 Hz, ArH),
7.94 (d, 2H, J = 8.8 Hz, ArH); l3C NMR (100 MHz,
CDC13) (5/ppm: 161.4 (C=0), 149.1 (N=C=S), 132.4,
131.8, 130.7, 129.8, 129.7; MS m/z\ 243 (M++2,
25 %); 241 (M4, 25 %); 183 (M+-NCS, 100 %); 155
(M+-CONCS, 85 %).
4-Methylbenzoyl Isothiocyanate (Table 2, entry 8)
Oil; IR27 (neat) iW c n T 1: 3043, 2986, 2913, 2847,
1974 (N=C=S), 1931, 1696 (C=0), 1607, 1511, 1446,
1405, 1256, 1175, 1082, 861,785, 747, 677, 597.
Benzoyl Isothiocyanate (Table 2, entry1)
Oil; IR22 (neat) omax/cm“': 2964, 2932, 2876, 1978
(N=C=S), 1694 (C=0), 1597, 1451, 1253, 1239, 1175,
1083, 1067, 855,693,670, 648.
3,5-Dimethylbenzoyl Isothiocyanate (Table 2, entry 9)
Oil; IR6 (neat) omax/cm“': 3015, 2925, 2864, 1973
(N=C=S), 1697 (C=0), 1606, 1453, 1379, 1301, 1182,
1164, 1100, 937, 865, 762, 735, 669, 547, 449;1HNMR
(400 MHz, CDC13) <$/ppm: 2.41 (s, 6H, 2CH3), 7.30 (d,
1H, J=10 Hz, ArH), 7.69 (s, 2H, ArH); 13C NMR (100
MHz, CDC13) 61ppm: 161.9 (C=0), 147.40 (N=C=S),
138.8, 138.3, 136.9, 136.2, 133.7, 130.7, 128.3, 126.2,
125.2,21.3,21.2.
4-Nitrobenzoyl Isothiocyanate (Table 2, entry2)
Solid; m.p. 90-92 °C (Ref. 13) 92-93 °C; IR (KBr)
umax/cm-1: 3268, 3096, 3072, 3039, 1993 (N=C=S),
1956, 1690 (C=0), 1601, 1523, 1346, 1321, 1270, 1103,
874, 839, 709, 669, 510; MS m/z: 206 (M+, 5 %); 149
(M+-NCS, 72.5 %); 121 (M+-CONCS, 7.5 %); 75 (Ph,
95 %); Anal. Calcd. mass fractions of elements, w/%, for
C8H4N20 3S (Mr = 208.19) are: C 46.15, H 1.94, N 13.46,
S 15.40; Found: C 46.36, H 1.66, N 14.08, S 16.05.
4-Methoxybenzoyl isothiocyanate (Table 2, entry 10)
Oil; IR 4(neat) Omax/c m ': 2961, 2932, 2839, 2160, 1973
(N=C=S), 1930, 1690 (C=0), 1603, 1577, 1506, 1423,
1330, 1250, 1164, 1085, 1023, 863, 785, 750, 681, 599.
3- Nitrobenzoyl Isothiocyanate (Table 2, entry 3)
Solid; m.p. 94-95 °C (Ref. 23) 95-96 °C; IR (KBr)
umax/cm~': 3370, 3244, 3092, 3080, 2929, 2855, 1991
(N=C=S), 1723, 1684 (C=0), 1613, 1537, 1525, 1351,
1290, 1265, 1127, 927, 820, 709, 690; MS m/z: 206
(M+, 15 %); 149 (M+-NCS, 100 %); 121 (M^-CONCS,
25 %); 75 (Ph, 80 %); Anal. Calcd. mass fractions
of elements, w/%, for CgH4N20 3S (Mr = 208.19) are:
C 46.15, H 1.94, N 13.46, S 15.40; Found: C 46.28,
H 1.62, N 13.40, S 15.55.
4-(Isothiocyanatocarbonyl) phenyl acetate (Table 2,
entry 11)
Oil; IR(neat) tW c n T 1: 2956, 2916, 2848, 1981
(N=C=S), 1936, 1774 (C=0), 1703, 1598, 1503, 1417,
1370, 1249, 1198, 1161, 1017, 910, 882, 850, 681, 645,
592; 'H NMR (400 MHz, DMSO-d6) <S/ppm: 2.26 (s,
3H, Me), 7.22 (d, 2H, J= 8.4 Hz, ArH), 7.95 (d, 2H, J =
8.4 Hz, ArH); l3C NMR (100 MHz, DMSO-d6) <$/ppm:
161.9 (0-C=0), 161.4 (N-C=0), 148.2 (N=C=S), 133.2,
132.4, 132.2, 129.9, 22.3; MS m/z: 221 (M4, 5 %); 163
(M+-NCS, 8 %); 104 (PhCO, 100 %); Anal. Calcd. mass
fractions of elements, w/%, for CioH7N 03S (Mr =
221.23) are: C 54.29, H 3.19, N 6.33, S 14.49; Found:
C 54.08, H 3.29, N 6.48, S 14.92.
3,4-Dichlorobenzoyl Isothiocyanate (Table 2, entry 4)
Oil; IR24 (neat) tW c n T 1: 3362, 3166, 3084, 3060,
2018, 1955 (N=C=S), 1693 (C=0), 1658, 1583, 1458,
1383, 1266, 1232, 1106, 1030, 898, 837, 764, 734, 706,
681,547.
2-Chlorobenzoyl Isothiocyanate (Table 2, entry 5)
Oil; IR4 (neat) bmax/cirf': 3076, 1981 (N=C=S), 1948,
1790 (C=0), 1728, 1691, 1590, 1473, 1439, 1319, 1203,
1132, 1077, 932, 997, 775, 742, 620,477.
4-Acetamidobenzoyl Isothiocyanate (Table 2, entry 12)
Oil; IR 28 (neat) vmJ c n f': 3460, 3264, 3182, 3096,
2953, 2921, 2851, 1989 (N=C=S), 1697 (C=0), 1594,
1536,1413, 1315, 1253, 1170, 1021,955,869, 751,677.
4- Chlorobenzoyl Isothiocyanate (Table 2, entry 6)
Solid; m.p. 45-47 °C (Ref. 25) 46^17 °C; IR (KBr)
tw /cn rf1: 3088, 2961, 2925, 2851, 1988 (N=C=S),
1927, 1692 (C=0), 1590, 1485, 1400, 1255, 1171, 1090,
Cinnamoyl Isothiocyanate (Table 2, entry 13)
Solid; m.p. 41-43 °C (Ref. 27) 40-43 °C; IR (KBr)
tw /c n T 1: 3059, 3022, 2018, 1972 (N=C=S), 1678
Croat. Chem. Acta 87 (2014) 201.

N. Entezari et al., Direct Synthesis ofAcyl Isothiocyanatesfrom Carboxylic Acids
203
(C=0), 1624, 1449, 1263, 1229, 1200, 764, 657; 'H NMR
(100 MHz, CDC13) <5/ppm: 6.5 (d, IH, J = 20 Hz,
PhCH=CHCO), 7.31-7.65 (m, 5H, ArH), 7.8 (d, 1H, J=
20 Hz, PhCH=CHCO); MS m/z: 189 (M+, 5 %); 130
(M’-NCS, 100 %); 102 (M+-CONCS, 92 %); 77 (Ph,
87.5 %).
21.1; MS m/z: 264 (M++4, 5 %); 262 (M++2, 10 %),
260 (M+, 18 %); 174 (M+-CONCS, 10 %) 147 (PhCl2,
100 %). 91 (PhO, 98 %); Anal. Calcd. mass fractions of
elements, w/%, for C9HsC12N 02S (Mr = 262.11) are:
C 41.24, H 1.92, N 5.34, S 12.23; Found: C 41.38,
H 1.81, N 5.43, S 12.34.
(E)-3-(3-Nitrophenyl) Acryloyl Isothiocyanate (Table 2,
entry 14)
Stearoyl Isothiocyanate (Table 2, entry 20)
Oil; IR17 (neat) tw /c n f 1: 3053, 2926, 2854, 2684,
2304, 1974 (N=C=S), 1731 (C=0), 1466, 1264, 1106,
894, 746, 705.
Solid; m.p. 118-119 °C (Ref. 29) 116—119 °C; IR(KBr)
Umax/cm 1: 3080, 3035, 2022, 1974 (N=C=S), 1672
(C=0), 1634, 1613, 1536, 1525, 1474, 1442, 1353,
1264, 1245, 1204, 980, 874, 824, 808, 737, 656, 592;
'H NMR (400 MHz, CDC13) <5/ppm: 6.65 (d, 1H, J = 16
Hz, PhCH=CHCO), 7.67 (t, IH, J = 8 Hz, ArH), 7.83
(d, IH, J = 16, PhCH=CHCO), 7.90 (d, IH, J = 7.6 Hz,
ArH), 8.33 (dd, 1H, J = 8.4 Hz, J = 0.8 Hz, ArH), 8.45
(s, 1H, ArH); 13C NMR (100 MHz, CDC13) <5/ppm:
160.8 (0=0), 145.9 (N=C=S), 135.1, 134.1, 130.3,
125.7, 123.2; MS m/z: 233 (M+, 3 %); 175 (M+-NCS, 77
%); 148 (M+-CONCS, 40 %); 102 (PhCH=CH, 85 %).
RESULTS AND DISCUSSION
In this article we report a more simplified one-step me-
thod for the conversion of carboxylic acids to acyl
isothiocyanates (Scheme 1).
ci
Oy^Y0
c r Y ' c i
PPh3/
&
(E)-3-(4-Chlorophenyl) Acryloyl Isothiocyanate (Table 2,
entry 15)
RCOzH + KSCN ---------------------------------
toluene, 0°C- rt
- RCONCS
Solid; m.p. 118—119 °C (Ref. 30) 116-119 °C; IR (KBr)
»max/cm-1: 3060, 3031, 2032, 1981(N=C=S), 1677
(C=0), 1623, 1589, 1495, 1406, 1262, 1244, 1203,
1090, 991, 821, 694, 632,493; MS m/z: 179 (M+-C=S);
165 (M+-NCS, 92.5 %), 137 (M+-CONCS, 22.5 %),
111 (PhCl, 12.5 %); Anal. Calcd. mass fractions of
elements, w/%, for Ci0H6C1NOS (Mr = 223.68) are:
C 53.70, H 2.70, N 6.26, S 14.34; Found: C 53.65,
H 2.95, N 6.25, S 14.29.
R = C6H5, 4-N02C6H4, 3-N02C6H4, 3,4-CI2C6H3, 2-CIC6H4i 4-CIC6H4, 4-BrC6H4l
4-CH3C6H4, 3,5-(CH3)2C6H3i 4-CH3OC6H4, CH3C0NHC6H4, C6H5CH=CH,
3-N02C6H4CH=CH, 4-CIC6H4CH=CH, C6H5CH2i (C6H5)2CH, 4-CH3OC6H4CH2l
CH3(CH2),5CH2
Scheme 1.
The optimization of the reaction conditions was
carried out for the direct preparation of benzoyl isothio-
cyanate from benzoic acid in the presence of TPP/
TCCA system at room temperature in different solvents
and by using various molar ratios of TPP/TCCA/
RC02H/KSCN in order to achieve the maximum chem-
ical yield at the lowest reaction time.
2-Phenylacetyl Isothiocyanate (Table 2, entry 16)
Oil; IR31 (neat) omax/cn f': 3358, 3182, 3064, 3031,
2925, 2859, 1966 (N=C=S), 1716 (0=0), 1646, 1499,
1217, 1104, 1025,713,694, 522.
The representative results are shown in Table 1.
There is not any tendency between benzoic acid and
thiocyanate ion to react in the absence of TCCA and
TPP (Table 1, entries 1-3). Benzoic acid was converted
to benzoyl isothiocyanate completely by applying
1/1/1/1 molar ratio of TPP/TCCA/RC02H/KSCN in
CH3CN (Table 1, entry 4). Increasing the molar ratio of
KSCN reduces the reaction time considerably (Table 1,
entries 5-7). The lower reaction time was obtained
when the reaction was carried out by using 1/1/0.8/2.5
molar ratio of TPP/TCCA/RC02H/KSCN (Table 1,
entries 8). Surprisingly, there is no any difference be-
tween the rate of reaction in CH3CN and CH2C12 by
applying the same reaction conditions (Table 1, com-
pare entry 8 and 9). Because of economic consideration
CH2C12 was chosen for further experiments. In CH2C12,
increasing the molar ratio of KSCN has not any influ-
ence on the reaction time (Tablel, entry 10). As one
equivalent of TCCA (contains three N-Cl bonds) can
react with 3 equivalents of TPP, using the lower ratios
2, 2-Diphenylacetyl Isothiocyanate (Table 2, entry 17)
Oil; IR6 (neat) 5 ^ /c m '1: 3088, 3060, 3031, 1966
(N=C=S), 1721 (C=0), 1495, 1453, 1180, 1121, 984,
792, 742,698,617.
2-(4-Methoxyphenyl) Acetyl Isothiocyanate (Table 2,
entry 18)
Oil; IR6(neat) vmJ c x n ' : 3031, 2956, 2931, 2839, 1979
(N=C=S), 1731 (0=0), 1612, 1513, 1463, 1301, 1250,
1178, 1118, 1033,959,816, 784, 522.
2-(2,4-Dichlorophenoxy) Ethanoyl Isothiocyanate (Table 2,
entry 19)
Oil; IR(neat) tw /c n f 1: 3072, 2978, 2892, 1956
(N=C=S), 1731 (0=0), 1589, 1477, 1311, 1234, 1090,
910, 796, 718, 641; *H NMR (400 MHz, CDC13)
<S/ppm: 2.35 (s, 2H, CH2), 8.15-8.17 (m, 3H, ArH); ,3C
NMR (100 MHz, CDCI3) <5/ppm: 162.5 (0=0), 154.1
(N=C=S), 136.4, 131.8, 131.2, 128.5, 121.5, 115.2,
Croat. Chem. Acta 87 (2014) 201.

N. Entezari et al, Direct Synthesis ofAcyl Isothiocyanatesfrom Carboxylic Acids
204
tion of aromatic carboxylic acids bearing electron-
donating substituents, with TPP/TCCA/KSCN system
was completed in longer reaction time (50-90 min) than
the above mentioned acids (e . g . compare entries 2-7
with 8-12). This novel direct isothiocyanation method
can be applied efficiently for the conversion of cinnamic
acid, substituted cinnamic acids and aliphatic carboxylic
acids to the corresponding acyl isothiocyanates (Table
2, entries 13-20). The isothiocyanation of aliphatic
carboxylic acids was completed in longer reaction time
than the aromatic carboxylic acids. According to the
results obtained from Table 2, we can conclude that
electronic effects of substituents on aromatic rings
have an essential influence on the reaction rate of
isothiocyanation.
The results of Table 2, demonstrate that TPP/
TCCA/KSCN system was found to be compatible with
different functional groups and isothiocyanation pro-
ceeded smoothly with carboxylic acids bearing electron
withdrawing as well as electron donating substituents.
Also, carboxylic acids with sensitive functional groups
such as alkyl, ether, amide and ester wherein the previ-
ously described protocols would not work, can be con-
verted efficiently to corresponding acyl isothiocyanates
(Table 2, entries 8, 9, 10, 11, 12, 18, 19, 20).
of TCCA has not any effect on the reaction rate
(Table 1, entries 11-12). Replacement of KSCN by
NH4SCN in optimized reaction conditions produces
benzoyl isothiocyanate in longer reaction time (Table 1,
entry 13). The optimized molar ratio of TPP/TCCA/
RC02H/KSCN (1/0.3/0.8/2.5) was examined in other
solvents such as THF, CHC13, 1,4-dioxane, acetone,
toluene and hexane (Table 1, entries 14-19). Best result
was obtained when the optimized reaction conditions
were applied in toluene (Table 1, entry 14), but in other
solvents the desired product was produced in longer
reaction time. Complete conversion of benzoic acid was
obtained in 40 min when the isothiocyanation reaction
was examined in toluene by using 1/0.3/0.8/2 molar
ratio of TPP/TCCA/RC02H/KSCN (Table 1, entry 20).
By using the optimized reaction conditions (1/0.3/
0.8/2 molar ratio of TPP/TCCA/RC02H/KSCN in tolu-
ene) different structurally acyl isothiocyanates were
obtained from different carboxylic acids (aromatic and
aliphatic) at room temperature in high yields (80-95 %).
The representative data are shown in Table 2. Electron-
withdrawing substituents on aromatic rings accelerate
the reactions of aromatic carboxylic acids with TPP/
TCCA/KSCN system (Table 2, entries 2-7). The reac-
Table 1. Conversion of benzoic acid to benzoyl isothiocyanate
by using TPP/TCCA/KSCN system under different reaction
conditions
In our experiments, the completion of the reaction
was confirmed by the disappearance of the carboxylic
acid on TLC followed by the disappearance of OH
stretching frequency at 3400-2400 cm-1 in FTIR spec-
tra. Also absorption bands at 2150-1800 and 1780-1620
cm-1 due to N=C=S and carbonyl group of acyl isothio-
cyanate in FTIR spectra confirmed product formation.
In l3C NMR a signal at 162.5-160.8 and 154.1-145.9
ppm is assigned to the quaternary carbonyl and -N=C=S
carbon.
Acyl isothiocyanates (Table 2) are pale yellow oil
or crystalline substances. They were characterized by IR
spectroscopy and comparison of their melting points
with the known compounds. The structures of selected
products were further confirmed by 'H, 1'C NMR spec-
troscopy and mass spectrometry.
Molar Ratio
Conversion
TPP/TCCA/ Time/h
RCO,H/KSCN
Solvent
Entry
%
5
0
CHjCN
c h 3c n
CHj CN
CH3CN
CHj CN
c h 3c n
c h 3c n
c h 3c n
0/0/1/1
1
2
0
5
l/O /l/l
0
5
18
O /l/l/l
3
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
70
4
l / l / l / l
1/1/1/1.5
12
5
4
1/1/1/2
6
1/1/1/2.5
2
7
1/1/0.8/2.5
1/1/0.8/2.5
1/1/0.8/3
55 min
55 min
55 min
55 min
55 min
2
8
9
c h 2c i2
c h 2c i2
c h 2c i2
c h 2c i2
c h 2c i2
toluene
THF
The proposed mechanism of isothiocyanation of
carboxylic acid by using TPP/TCCA/KSCN system was
shown in Scheme 2.
10
11
12
13(a)
14
15
16
17
18
19
20
1/0.5/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2.5
1/0.3/0.8/2
The initial nucleophilic attack of TPP at the halo-
gen of TCCA affords the halogen-phosphonium salt (I).
The reaction of I with carboxylic acid yields II and
[l,3,5]triazine-2,4,6-triol (III), which is in equilibrium
with [l,3,5]triazinane-2,4,6-trione (IV; Scheme 2). A
rapid reaction of II with potassium thiocyanate yields
triphenylphosphine oxide and the corresponding acyl
isothiocyanate (at room temperature).
40 min
6
7
CHClj
1.5
1,4-dioxane
acetone
hexane
1.5
24
On the basis of the results obtained from Table 2
and proposed mechanism in Scheme 2, II was formed in
the rate determining step of the thiocyanation reaction.
40 min
100
toluene
(a)KSCN was replaced by NH4SCN.
Croat. Chem. Acta 87 (2014) 201.

N. Entezari etal., Direct Synthesis ofAcyl Isothiocyanatesfrom Carboxylic Acids
205
©
©
PPh3CI
PPh3Cl
Table 2. Synthesis of different structurally acyl isothiocyana-
Cl
tes by using TPP/TCCA/RC02H/KSCN system.
V r °
c r NY N'ci
0
0
©
PPh3C!
3RCOOH
OH
Scheme 2.
Formation of II was accelerated with electron-with-
drawing substituents on the aromatic rings (e.g. com-
pare entries 1 with 2). In the other words, electron-
withdrawing substituents increase the activity of car-
boxyl functional groups towards nucleophiles, which
leads to an easier formation of II. Benzoic acid is con-
verted to benzoyl isothiocyanate more slowly than
p-nitro benzoic acid and faster than /»-methyl benzoic
acid and p-methoxy benzoic acid respectively.
o
o
o
o
90
80
CONCLUSION
We have demonstrated a facile, new, inexpensive, and
convenient procedure for one-pot conversion of aliphat-
ic and aromatic carboxylic acids to their corresponding
alkanoyl and aroyl isothiocyanates under neutral condi-
tion. The excellent yields, short reaction time, and mild
reaction conditions make this procedure a useful and
attractive alternative to the currently available methods
of preparation of acyl isothiocyanates. In contrast to the
reported methods the present protocol avoids the use of
toxic and corrosive reagents. All reagents in the present
method (TPP, TCCA and KSCN) are highly stable and
commercially available.
Acknowledgements. The authors gratefully acknowledge the
partial support of this study by Ferdowsi University of Mash-
had Research Council (Grant no. p/3/24168).
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