HUGERSHOFF REACTION OF N-1- OR N-2-NAPHTHOYL-N'-MONOSUBSTITUTED AND N',N'-DISUBSTITUTED THIOUREA DERIVATIVES

Article abstract of DOI:10.1135/cccc19942663

Hugershoff reaction of N-1- or N-2-naphthoyl-N'-monosubstituted and N',N'-disubstituted thiourea derivatives, prepared by the reaction of 1-naphthoyl or 2-naphthoyl isothiocyanate with primary or secondary amines, was studied.Depending on substituents the

Full text of DOI:10.1135/cccc19942663

Hugershoff Reaction
2663
HUGERSHOFF REACTION OF N-1- OR N-2-NAPHTHOYL-N′-MONO-
SUBSTITUTED AND N′,N′-DISUBSTITUTED THIOUREA DERIVATIVES
Milan DZURILLA*, Peter KUTSCHY, Jan IMRICH and Stanislav BRTOS
Department of Organic Chemistry,
P. J. Safarik University, 041 67 Kosice, The Slovak Republic
Received September 1, 1994
Accepted November 16, 1994
Dedicated to Professor Milan Kratochvil on the occasion of his 70th birthday.
Hugershoff reaction of N-1- or N-2-naphthoyl-N′-monosubstituted and N′,N′-disubstituted thiourea
derivatives, prepared by the reaction of 1-naphthoyl or 2-naphthoyl isothiocyanate with primary or
secondary amines, was studied. Depending on substituents the corresponding urea or benzothiazole
derivatives were obtained as reaction products. Their structure was determined on the basis of infrared,
1H and 13C NMR and mass spectra.
In our previous papers we have studied the Hugershoff reaction1 i. e. oxidation of
thiourea derivatives with bromine in chloroform. Thioureas prepared from α,β-unsatu-
rated acyl isothiocyanates afforded in the dependence on the substituents of thiourea
grouping thiazolines or benzothiazoles2–4. In the case of O-alkyl-N-(3-phenylprope-
noyl)monothiocarbamates the sole reaction product was 5-benzylidene-1,3-thiazo-
lidine-2,4-dione5.
We were interested in the reaction products of Hugershoff reaction of thioureas pre-
pared from 1-naphthoyl or 2-naphthoyl isothiocyanate and primary and secondary
amines (Table I). It was found that by the action of bromine as an oxidation agent in
chloroform the different products are formed in the dependence on the nature of N′-sub-
stituents (Scheme 1).
The Hugershoff reaction of thioureas with N′-alkyl substituents (IIIa, IIIb, IVa – IVf)
and N′-aryl substituents which have the ortho-position not activated for an electrophilic
substitution (IIIc – IIIg, IIIi – IIIo, IVg – IVk, and IVm – IVs) resulted in the oxidation
to corresponding urea derivatives Va – Vn and VIa – VIr (Table II). The exchange of
sulfur to oxygen can be explained by hydrolysis of transiently formed sulfenyl bro-
* The author to whom correspondence should be addressed.
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Dzurilla, Kutschy, Imrich, Brtos:
mide2 during the work-up of the reaction mixture because the same urea derivatives
were obtained even when the reaction was carried out in anhydrous media. Similar
oxidation of thiourea to urea derivatives was previously observed in the study of the
Hugershoff reaction of N-phenyl-N′-(2-phenyl-4-thiazolylmethyl)thiourea6 and N-phenyl-
N′-(4-pentinoyl)thiourea7. In the case of N-(3-methoxyphenyl) derivatives IIIh and IVl
as well as N′-methyl-N′-phenyl derivatives IIIp and IVt which have the ortho-position
of the phenyl ring activated for an electrophilic reaction2,3 the intermediate sulfenyl
bromide undergoes intramolecular electrophilic substitution with the formation of
benzothiazole derivatives VIIa, VIIb, VIIIa, and VIIIb.
All of investigated thiourea derivatives III and IV reacted with the formation of either
urea or benzothiazole derivatives. Simultaneous formation of both types of products
was not observed. The structure of prepared thioureas III and IV was confirmed by
elemental analysis and spectral data (Table I).
The infrared spectra of obtained ureas exhibit two absorption bands of carbonyl vi-
brations corresponding to the transformation of thiocarbonyl to carbonyl group. In 13C
NMR spectra of ureas Va, Vb, VIa, and VIb there are present the signals of carbon
SCHEME 1
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atoms of C=O groups instead of C=S carbon atoms present in starting compounds. The
structure of urea derivatives was also confirmed by mass spectra of compounds VIa and
VIb.
1
Benzothiazole derivatives VII and VIII were identified on the basis of their IR, H
and 13C NMR and mass spectroscopy. Compared to ureas products VII and VIII exhibit
in the infrared spectra only one absorption band of carbonyl group. The mass spectra of
compounds VIIb and VIIIb are in agreement with the structure of benzothiazolines
(Scheme 2).
In the case of derivatives VIIa and VIIIa there are two possibilities of ring-closure
with the formation of product having methoxy group in position 5 or 7. The structure
1
of obtained product was determined by H NMR spectroscopy. In the spectra of com-
pounds VIIa and VIIIa the signal of H-4 was split into doublet-doublet due to interac-
tion with H-2 and H-5. H-5 and H-2 exhibited doublet signals owing to interaction with
proton H-4. These data indicate the presence of two vicinal and one isolated proton,
which corresponds to the structure with methoxy group in position 5 of benzothiazole
ring.
SCHEME 2
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EXPERIMENTAL
The infrared absorption spectra were recorded on an IR-75 spectrometer (Zeiss, Jena) in chloroform
(compounds II, IIIa – IIIp, IVa – IVt) or in KBr pellets (compounds I, Va – Vn, VIa – VIr, VIIa,
1
VIIb, VIIIa, VIIIb); the wavenumbers are given in cm−1. H and 13C NMR spectra were measured on
Tesla BS 487 (80 MHz for 1H) and Tesla BS 567 (25.15 MHz for 13C) spectrometers in deuterio-
chloroform (compounds I, II, IIIa, IIIb, IIIh, IVa – IVf, IVh, Va, Vb, VIa, VIb, VId) or in
hexadeuteriodimethyl sulfoxide (compounds VIc, VIe, VIf, VIIa, VIIb, VIIIa, VIIIb) with tetramethyl-
silane as internal standard. Chemical shifts are given in ppm (δ-scale), coupling constants (J) in Hz.
The mass spectra of compounds IVa, IVb, VIa, VIb, VIIa, and VIIb were recorded on a JMS 100D
spectrometer (Jeol) at ionization energy 70 eV. The reaction course was monitored by thin-layer
chromatography (TLC) on Silufol plates (Kavalier, The Czech Republic).
1-Naphthoyl Isothiocyanate (I)
A solution of potassium thiocyanate (2.43 g, 25 mmol) in acetone (40 ml) was added to a solution of
1-naphthoyl chloride (4.77 g, 25 mmol) in acetone (20 ml). After stirring for 10 min, benzene (80 ml)
was added and the precipitate of potassium chloride was filtered off. The solvent was evaporated and
the residue was crystallized from hexane. Yield 68%, m.p. 30 – 32 °C. For C12H7NOS (213.3) cal-
culated: 67.57% C, 3.31% H, 6.57% N; found: 67.74% C, 3.42% H, 6.71% N. IR spectrum: 1 697
(C=O); 1 969 (N=C=S). 13C NMR spectrum: 124.37, 125.57, 126.13, 126.91, 128.82, 129.19, 131.54,
133.71, 132.89, and 136.28 (C10H7); 147.89 s (NCS); 161.52 s (CO).
2-Naphthoyl Isothiocyanate (II)
Title compound was prepared from potassium thiocyanate (2.43 g, 25 mmol) and 2-naphthoyl
chloride (4.77 g, 25 mmol) according to the above-described procedure. Yield 85%, m.p. 68 – 69 °C.
For C12H7NOS (213.3) calculated: 67.57% C, 3.31% H, 6.57% N; found: 67.68% C, 3.48% H,
6.69% N. IR spectrum: 1 680 (C=O); 1 950 (N=C=S). 13C NMR spectrum: 124.75, 127.21, 127.85,
127.99, 128.89, 129.49, 129.71, 132.25, 133.03, and 136.39 (C10H7); 147.97 s (NCS); 161.63 s (CO).
General Procedure for Preparation of N-Naphthoyl-N′-monosubstituted IIIa – IIIp
and N,N′-Disubstituted Thioureas IVa – IVt
The corresponding amine (5 mmol) was added dropwise with stirring to a solution of 1- or 2-naphthoyl
isothiocyanate (1.07 g, 5 mmol) in cyclohexane (20 ml; preparation of compounds IIIa, IIIb, IVa – IVf)
or benzene (15 ml; preparation of compounds IIIc – IIIp, IVg – IVt). The precipitate separated within 1 h
was filtered with suction, dried and crystallized from ethanol. Yields, melting points, analytical data and
IR spectra are given in Table I.
General Procedure for Preparation of N-Naphthoyl-N′-monosubstituted Va – Vn
and N,N′-Disubstituted Ureas VIa – VIr
To a stirred solution of substituted thiourea (3 mmol) in chloroform (15 ml) bromine (155 µl, 3 mmol) was
added dropwise. The stirring was continued 1 h until starting compound completely reacted (moni-
tored by TLC). The solvent was evaporated and the residue crystallized from ethanol. Yields, melting
points, analytical data and IR spectra are given in Table II.
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General Procedure for Preparation of Naphtalene-1- or 2-Carboxylic Acid
(Substituted-3H-benzothiazol-2-ylidene)amides VIIa, VIIb, VIIIa, and VIIIb
To a stirred solution of thiourea IIIh, IIIp, IVl, or IVt (2.5 mmol) in chloroform (12.5 ml) bromine
(130 µl, 2.5 mmol) was added dropwise and stirring was continued for 1 h. The precipitate was fil-
tered with suction, dried and crystallized from an appropriate solvent.
Naphthalene-1-carboxylic acid (5-methoxy-3H-benzothiazol-2-ylidene)amide (VIIa); yield 92%, m.p.
228 – 230 °C (acetone). For C19H14N2O2S (334.4) calculated: 68.24% C, 4.22% H, 8.37% N; found:
68.32% C, 4.38% H, 8.56% N. IR spectrum: 3 490 (N−H); 1 672 (C=O); 1 535 (C=N). 1H NMR
spectrum: 3.87 s, 3 H (CH3O); 7.06 dd, 1 H, J(2,4) = 2.4, J(4,5) = 8.8 (H-4); 7.42 d, 1 H, J(2,4) =
2.4 (H-2); 7.82 d, 1 H, J(4,5) = 8.8 (H-5); 8.07 m, 7 H (C10H7); 9.29 s, 1 H (NH). 13C NMR spectrum:
55.41 (C-1); 103.97 (C-2); 112.89 (C-4); 122.08 (C-5); 123.12 (C-6); 149.47 (C-7); 158.66 (C-3);
159.48 (C-8); 167.58 (C-9); 124.80, 126.44, 127.11, 127.37, 127.91, 128.42, 129.69, 131.03, 131.52
and 133.09 (C10H7).
Naphthalene-1-carboxylic acid (3-methyl-3H-benzothiazol-2-ylidene)amide (VIIb); yield 90%, m.p.
199 – 201 °C (acetone). For C19H14N2OS (318.4) calculated: 71.67% C, 4.43% H, 8.80% N; found:
1
71.79% C, 4.58% H, 8.96% N. IR spectrum: 1 670 (C=O); 1 525 (C=N). H NMR spectrum: 4.05 s,
3 H (CH3); 7.68 m, 9 H (3 H of C6H4 and 6 H of C10H7); 8.51 dd, 1 H (1 H of C6H4); 9.13 t, 1 H
(1 H of C10H7). 13C NMR spectrum: 32.03 q (CH3); 111.70, 122.26, 123.46, 124.28, 125.21, 125.73,
126.63, 127.79, 128.95, 130.62, 131.26, 133.20, 133.31, 136.71 (C10H7 and C6H4); 165.97 s (CO);
175.27 s (NCS). Mass spectrum, m/z (%): 318 (M+, 88), 197 (67), 191 (37), 155 (100), 127 (96), 80
(59).
Naphthalene-2-carboxylic acid (5-methoxy-3H-benzothiazol-2-ylidene)amide (VIIIa); yield 85%,
m.p. 226 – 227 °C (ethanol). For C19H14N2O2S (334.4) calculated: 68.24% C, 4.22% H, 8.37% N;
1
found: 68.47% C, 4.39% H, 8.51% N. IR spectrum: 3 460 (N−H); 1 670 (C=O); 1 545 (C=N). H NMR
spectrum: 3.86 s, 3 H (CH3O); 7.00 dd, 1 H, J(2,4) = 2.4; J(4,5) = 8.7 (H-4); 7.35 d, 1 H, J(2,4) =
2.4 (H-2); 7.93 d, 1 H, J(4,5) = 8.7 (H-5); 7.68 and 8.08 m, 7 H (C10H7); 8.85 s, 1 H (NH). 13C NMR
spectrum: 55.45 (C-1); 103.71 (C-2); 112.71 (C-4); 122.07 (C-5); 124.24 (C-6); 149.06 (C-7); 158.66
(C-3); 160.26 (C-8); 165.97 (C-9); 123.04, 126.89, 127.59, 128.13, 128.35, 128.56, 129.20, 129.39,
131.89 and 134.69 (C10H7).
Naphthalene-2-carboxylic acid (3-methyl-3H-benzothiazol-2-ylidene)amide (VIIIb); yield 83%, m.p.
165 – 167 °C (acetone). For C19H14N2OS (318.4) calculated: 71.67% C, 4.43% H, 8.80% N; found:
1
71.82% C, 4.54% H, 8.89% N. IR spectrum: 1 680 (C=O); 1 545 (C=N). H NMR spectrum: 4.05 s,
3 H (CH3); 7.65 m, 9 H (C6H4 and 5 H of C10H7); 8.38 dd, 1 H and 8.88 s, 1 H (2 × 1 H of C10H7).
Mass spectrum, m/z (%): 318 (M+, 26), 191 (26), 155 (16), 127 (96), 82 (100), 80 (96).
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