Facile replacement of the halogen atom in 4-amino-1-chloronaphthalen-2-ols by S- and N-centered nucleophiles

Full text of DOI:10.1134/S1070428007070263

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 7, pp. 1092–1095. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © A.V. Didenko, V.V. Labeish, A.V. Trukhin, M.L. Petrov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 7,
pp. 1097–1100.
SHORT
COMMUNICATIONS
Facile Replacement of the Halogen Atom in 4-Amino-1-chloro-
naphthalen-2-ols by S- and N-Centered Nucleophiles
A. V. Didenkoa, V. V. Labeishb, A. V. Trukhinc, and M. L. Petrova
a St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: dav@lti-gti.ru
b VEKTON Ltd., St. Petersburg, Russia
c St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
Received December 2, 2005; revised October 18, 2006
DOI: 10.1134/S1070428007070263
Reactions of halogen derivatives with thiols and
amines underlie known methods of synthesis of sul-
fides and substituted amines. Aromatic halogen deriva-
tives having electron-withdrawing groups react under
standard conditions of such processes. Reactions of
sulfides and amines with aryl halides having electron-
donor substituents require severe conditions: elevated
temperature, high pressure, and the presence of strong
bases [1–11]. In most cases, sulfides are obtained using
such catalysts as copper [1–5] and nickel compounds
[6]. Some reactions of thiols and their salts with aryl
halides are catalyzed by palladium complexes [7–9].
Thiols and various disulfides are used as sulfur-con-
taining nucleophiles [2, 10, 11]. Sodium sulfide gives
rise to symmetric diaryl sulfides [3, 12].
tures when equimolar amounts of 1-chloronaphthalen-
2-ol and various potassium arenethiolates were heated
in different solvents in a wide temperature range. The
reactivity of the halogen atom was considerably en-
hanced via introduction of an electron-donor substit-
uent into the 4-position of 1-chloronaphthalen-2-ol. By
heating 4-amino-1-chloronaphthalen-2-ols Ia and Ib
with substituted benzenethiols IIa–IIc and some het-
erocyclic thiols IId–IIh in DMF at 70–80°C in the
presence of potassium hydroxide we obtained a series
of arylsulfanyl- and hetarylsulfanyl-substituted naph-
thols IIIa–IIIh.
Likewise, the reactions of 1-chloro-4-morpholino-
naphthalen-2-ol (Ia) with excess secondary amine IVa
and IVb at 200–240°C gave 1,4-diaminonaphthalen-2-
ols Va and Vb, respectively. Alkyl ethers derived from
4-amino-1-chloronaphthalen-2-ols failed to react with
thiols under analogous conditions. Therefore, we pre-
sumed that unusually facile replacement of chlorine in
We examined nucleophilic substitution of the halo-
gen atom in 1-chloronaphthalen-2-ol by aromatic and
heterocyclic thiols and secondary amines. However, no
expected sulfides were detected in the reaction mix-
SR1
OH
Cl
NR2R3
OH
OH
R1SH (IIa–IIh)
KOH
R2R3NH (IVa, IVb)
N
X
N
X
N
O
IIIa–IIIh
Ia, Ib
Va, Vb
I, X = O (a), NMe (b); II, III, R1 = Ph (a), 4-ClC6H4 (b), 4-MeC6H4 (c), 1,3-benzothiazol-2-yl (d), 1,3-benzoxazol-2-yl (e),
4-methyl-4H-1,2,4-triazol-3-yl (f), 1-phenyl-1H-tetrazol-5-yl (g), 1H-benzimidazol-2-yl (h); III, X = O (a–f) NMe (g, h); IV, V,
R2R3N = morpholino (a), R2 = Me, R3 = Ph (b).
1092

FACILE REPLACEMENT OF THE HALOGEN ATOM
1093
8.1 d.d and 8.3 d.d (5-H, 8-H), 9.78 s (OH). Mass
spectrum, m/z (Irel, %): 337 (100), 304 (8), 276 (25),
260 (5), 246 (20), 232 (19), 221 (8), 202 (12), 174
(25), 145 (17), 128 (12), 115 (13), 77 (26), 51 (17), 45
(10), 39 (8). Found, %: C 71.64; H 5.99; N 4.30.
C20H19NO2S. Calculated, %: C 71.19; H 5.68; N 4.15.
4-amino-1-chloronaphthalen-2-ols Ia and Ib is related
to their ability to undergo tautomeric keto–enol trans-
formations.
Initial compounds Ia and Ib were synthesized ac-
cording to the procedure described in [13].
1-Chloro-4-morpholinonaphthalen-2-ol (Ia).
Naphthalen-2-ol, 42.6 g (0.295 mol), was dissolved in
300 ml of toluene on heating. The brown solution was
cooled until the dissolved substance began to crystal-
lize, and 44.2 g (0.623 mol) of chlorine was imme-
diately passed through the solution at a rate of 2–3 g×
min–1. The mixture was purged with argon to remove
excess chlorine and liberated hydrogen chloride, and
36.4 g (0.36 mol) of triethylamine and 25.7 g
(0.295 mol) of morpholine were added dropwise in
succession, maintaining the temperature below 15°C.
The mixture was kept for 1.5 h at that temperature, and
triethylamine hydrochloride was filtered off. The
filtrate was washed with water (4×150 ml) and dried
over anhydrous Na2SO4, the solvent was distilled off,
and the residue was recrystallized from petroleum
ether. Yield 45 g (57.8%), mp 164–165°C; published
data [10]: mp 163–165°C. 1H NMR spectrum, δ, ppm:
3.0 t (CH2NCH2), 3.87 t (CH2OCH2), 6.88 s (3-H),
7.25 d.t and 7.5 d.t (6-H, 7-H), 8.0 m (5-H, 8-H),
9.93 s (OH). 13C NMR spectrum, δC, ppm: 150.8,
148.9, 132.3, 126.8, 123.7, 123.4, 122.8, 122.3, 107.9,
66.5, 53.1.
1-(4-Chlorophenylsulfanyl)-4-morpholinonaph-
thalen-2-ol (IIIb) was synthesized in a similar way
from 1.58 g (6 mmol) of compound Ia and 0.94 g
(6 mmol) of 4-chlorobenzenethiol (IIb); the product
was recrystallized from toluene. Yield 1.2 g (50%),
1
mp 123–125°C. H NMR spectrum, δ, ppm: 3.1 t
(CH2NCH2), 3.9 t (CH2OCH2), 7.4 m (3-H, 6-H, 7-H,
2′-H, 3′-H, 5′-H, 6′-H), 8.0 d.d and 8.2 d.d (5-H, 8-H),
9.83 s (OH). 13C NMR spectrum, δC, ppm: 149.7,
131.9, 127.3, 124.6, 123.5, 123.2, 108.5, 107.3, 77.5,
76.9, 76.3, 67.0, 53.3. Mass spectrum, m/z (Irel, %):
371 (100), 310 (30), 280 (25), 260 (10), 232 (22), 211
(13), 186 (16), 174 (40), 154 (7), 145 (30), 139 (43),
128 (20), 115 (23), 102 (15), 86 (7), 69 (10), 57
(15), 45 (16). Found, %: C 64.83; H 5.04; N 3.81.
C20H18ClNO2S. Calculated, %: C 64.60; H 4.88; N 3.77.
1-(4-Methylphenylsulfanyl)-4-morpholinonaph-
thalen-2-ol (IIIc) was synthesized in a similar way
from 1.58 g (6 mmol) of naphthol Ia and 0.74 g
(6 mmol) of 4-methylbenzenethiol (IIc); the product
was recrystallized from methanol. Yield 1.1 g (52%),
1
mp 116–118°C. H NMR spectrum, δ, ppm: 2.2 s
(CH3), 3.1 t (CH2NCH2), 3.9 t (CH2OCH2), 6.9, 7.3 m
(3-H, 6-H, 7-H, 2′-H, 3′-H, 5′-H, 6′-H), 8.0 d.d and
8.2 d.d (5-H, 8-H), 9.83 s (OH). 13C NMR spectrum,
δC, ppm: 158.5, 152.4, 136.7, 134.6, 133.6, 129.1,
127.0, 125.8, 124.8, 123.8, 123.7, 107.2, 102.7, 66.4,
52.9, 20.4. Mass spectrum, m/z (Irel, %): 351 (100), 318
(5), 290 (34), 260 (30), 232 (33), 221 (8), 202 (15),
174 (40), 145 (33), 128 (23), 115 (26), 102 (15), 91
(60), 65 (48), 45 (23), 39 (26). Found, %: C 72.02;
H 6.25; N 4.17. C21H21NO2S. Calculated, %: C 71.77;
H 6.02; N 3.99.
1-Chloro-4-(4-methylpiperazin-1-yl)naphthalen-
2-ol (Ib) was synthesized in a similar way. Yield
68.4 g (59.5%), mp 226–227°C. 1H NMR spectrum, δ,
ppm: 2.33 s (CH3), 2.7 t (CH2NCH2), 3.15 t (CH2N-
CH2), 6.9 s (3-H), 7.25 d.t and 7.45 d.t (6-H, 7-H),
8.0 m (5-H, 8-H), 9.9 s (OH). Mass spectrum, m/z
(Irel, %): 276 (100), 261 (13), 219 (10), 204 (40), 191
(30), 170 (14), 149 (21), 114 (19), 70 (45), 57 (8),
43 (45). Found, %: C 65.55; H 7.18; N 9.48.
C16H21ClN2O. Calculated, %: C 65.63; H 7.23; N 9.57.
4-Morpholino-1-phenylsulfanylnaphthalen-2-ol
(IIIa). Naphthol Ia, 1.58 g (6 mmol), was dissolved in
20 ml of DMF, a solution of 0.66 g (6 mmol) of ben-
zenethiol (IIa) and 0.34 g (6 mmol) of KOH in 10 ml
of methanol was added, and the mixture was heated at
70°C allowing the solvent to escape over a period of
1.5–2 h. The residue was cooled and treated with
150 ml of water, and the precipitate was filtered off,
washed with water, dried, and recrystallized from
methanol. Yield 1.05 g (52%), mp 126–127°C. 1H NMR
spectrum, δ, ppm: 3.1 t (CH2NCH2), 3.9 t (CH2OCH2),
7.15 m (3-H, 6-H, 7-H, 2′-H, 3′-H, 4′-H, 5′-H, 6′-H),
1-(1,3-Benzothiazol-2-ylsulfanyl)-4-morpholino-
naphthalen-2-ol (IIId) was synthesized in a similar
way from 1.58 g (6 mmol) of naphthol Ia and 1 g
(6 mmol) of 1,3-benzothiazole-2-thiol (IId); the prod-
uct was recrystallized from propan-2-ol. Yield 1.7 g
1
(72%), mp 209–210°C. H NMR spectrum, δ, ppm:
3.1 t (CH2NCH2), 3.95 t (CH2OCH2), 6.93 s (3-H),
7.45 m (6-H, 7-H, 4′-H, 5′-H, 6′-H, 7′-H), 8.1 d.d and
8.3 d.d (5-H, 8-H), 9.83 s (OH). 13C NMR spectrum,
δC, ppm: 159.6, 154.2, 136.5, 127.9, 125.9, 124.2,
123.9, 123.7, 122.8, 121.2, 120.9, 107.1, 66.4, 53.0.
Mass spectrum, m/z (Irel, %): 394 (42), 361 (17), 334
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

DIDENKO et al.
1094
(73), 303 (12), 232 (40), 119 (14), 174 (28), 167 (100),
154 (23), 145 (63), 128 (45), 108 (43), 90 (40), 77
(25), 63 (63), 57 (22), 45 (60), 39 (48). Found, %:
C 64.07; H 4.44; N 7.20. C21H18N2O2S2. Calculated,
%: C 63.93; H 4.60; N 7.10.
(15), 147 (30), 128 (32), 118 (42), 98 (20), 91 (33), 77
(44), 70 (100), 56 (26), 43 (95). Found, %: C 63.37;
H 5.88; N 19.26. C23H26N6OS. Calculated, %: C 63.57;
H 6.03; N 19.34.
1-(1H-Benzimidazol-2-ylsulfanyl)-4-(4-methyl-
piperazino)naphthalen-2-ol (IIIh) was synthesized in
a similar way from 1.66 g (6 mmol) of naphthol Ib and
0.9 g (6 mmol) of 1H-benzimidazole-2-thiol (IIh); the
product was recrystallized from DMF. Yield 1.45 g
1-(1,3-Benzoxazol-2-ylsulfanyl)-4-morpholino-
naphthalen-2-ol (IIIe) was synthesized in a similar
way from 1.58 g (6 mmol) of naphthol Ia and 0.91 g
(6 mmol) of 1,3-benzoxazole-2-thiol (IIe); the product
was recrystallized from propan-2-ol. Yield 1.6 g
1
(62%), mp 216–217°C. H NMR spectrum, δ, ppm:
1
(70.5%), mp 226–227°C. H NMR spectrum, δ, ppm:
2.35 s (CH3), 2.65 t (CH2NCH2), 3.15 t (CH2NCH2),
6.9 s (3-H), 7.3 m (6-H, 7-H, 4′-H, 5′-H, 6′-H, 7′-H),
8.05 d.d and 8.3 d.d (5-H, 8-H), 11.8 s (OH). 13C NMR
spectrum, δC, ppm: 158.7, 152.8, 150.1, 136.6, 126.9,
124.4, 123.8, 123.6, 121.9, 120.6, 107.6, 99.3, 54.6,
51.9, 45.5. Mass spectrum, m/z (Irel, %): 390 (60), 330
(75), 286 (30), 259 (25), 245 (15), 231 (20), 184 (15),
170 (32), 150 (55), 128 (26), 115 (38), 70 (65), 57
(22), 43 (100). Found, %: C 67.69; H 6.33; N 13.62.
C23H26N4OS. Calculated, %: C 67.95; H 6.45; N 13.78.
3.1 t (CH2NCH2), 3.91 t (CH2OCH2), 6.92 s (3-H),
7.3 m (6-H, 7-H, 4′-H, 5′-H, 6′-H, 7′-H), 8.1 d.d and
8.3 d.d (5-H, 8-H), 10.4 s (OH). 13C NMR spectrum,
δC, ppm: 159.0, 153.5, 141.7, 136.7, 127.5, 124.2,
124.1, 123.7, 123.6, 122.5, 118.1, 109.8, 107.3, 66.5,
53.0. Mass spectrum, m/z (Irel, %): 378 (43), 318 (100),
287 (12), 260 (15), 232 (57), 185 (24), 174 (33), 145
(55), 128 (35), 115 (40), 91 (30), 63 (47), 45 (32),
39 (40). Found, %: C 66.83; H 4.63; N 7.43.
C21H18N2O3S. Calculated, %: C 66.65; H 4.79; N 7.40.
1,4-Dimorpholinonaphthalen-2-ol (Va). A mix-
ture of 1.5 g (5.7 mmol) of naphthol Ia and 20 ml of
morpholine was heated for 4 h at 200°C in a sealed
tube. After cooling, the mixture was poured into
150 ml of water, and the precipitate was filtered off
and recrystallized from methanol. Yield 1.1 g (62%),
mp 205–206°C. 13C NMR spectrum, δC, ppm: 151.4,
132.6, 126.0, 124.5, 124.4, 123.8, 122.1, 121.9, 105.4,
68.2, 67.0, 53.3, 50.7. Mass spectrum, m/z (Irel, %):
314 (100), 256 (53), 255 (44), 227 (8), 198 (21), 183
(5) 169 (26), 155 (12), 99 (11), 84 (8), 71 (6), 42 (8).
Found, %: C 68.53; H 6.97; N 8.71. C18H22N2O3. Cal-
culated, %: C 68.77; H 7.05; N 8.91.
1-(4-Methyl-4H-1,2,4-triazol-3-ylsulfanyl)-4-
morpholinonaphthalen-2-ol (IIIf) was synthesized in
a similar way from 1.58 g (6 mmol) of naphthol Ia and
0.69 g (6 mmol) of 4-methyl-4H-1,2,4-triazole-3-thiol
(IIf); the product was recrystallized from DMF–iso-
butyl alcohol. Yield 1.2 g (60%), mp 250–253°C.
1H NMR spectrum, δ, ppm: 3.1 t (CH2NCH2), 3.65 s
(CH3), 3.9 t (CH2OCH2), 6.85 s (3-H), 7.3 d.t and
7.5 d.t (6-H, 7-H), 8.0 d.d and 8.5 d.d (5-H, 8-H),
8.35 s (3′-H), 10.2 s (OH). 13C NMR spectrum, δC,
ppm: 157.7, 152.5, 148.5, 145.5, 136.3, 127.0, 124.8,
123.7, 123.6, 122.2, 107.1, 100.5, 66.3, 52.9, 30.1.
Mass spectrum, m/z (Irel, %): 342 (100), 282 (10), 267
(15), 243 (5), 227 (10), 200 (12), 170 (10), 145
(17), 128 (12), 115 (20). Found, %: C 59.94; H 5.61;
N 16.57. C17H18N4O2S. Calculated, %: C 59.63;
H 5.30; N 16.36.
1-Methyl(phenyl)amino-4-morpholinonaphtha-
len-2-ol (Vb). A mixture of 1.5 g (5.7 mmol) of
naphthol Ia and 15 ml of N-methylaniline was heated
for 4 h at 240°C in a sealed tube. The mixture was
subjected to steam distillation to remove excess
N-methylaniline, and the precipitate was filtered off
and recrystallized from methanol. Yield 0.7 g (37%),
4-(4-Methylpiperazin-1-yl)-1-(1-phenyl-1H-
tetrazol-5-ylsulfanyl)naphthalen-2-ol (IIIg) was syn-
thesized in a similar way from 1.66 g (6 mmol) of
naphthol Ib and 1.07 g (6 mmol) of 1-phenyl-1H-
tetrazole-5-thiol (IIg); the product was recrystallized
from ethanol. Yield 1.83 g (73%), mp 211–212°C.
1H NMR spectrum, δ, ppm: 2.35 s (CH3), 2.7 t (CH2N-
CH2), 3.15 t (CH2NCH2), 6.8 s (3-H), 7.25 d.t and
7.4 d.t (6-H, 7-H), 7.65 m (C6H5), 8.0 d.d and 8.1 d.d
(5-H, 8-H), 10.2 s (OH). 13C NMR spectrum, δC, ppm:
158.7, 153.6, 136.2, 133.4, 129.8, 129.3, 127.2, 124.0,
123.8, 122.1, 107.1, 96.5, 54.8, 52.1, 45.6. Mass spec-
trum, m/z (Irel, %): 273 (40), 245 (70), 161 (15), 147
1
mp 128–130°C. H NMR spectrum, δ, ppm: 3.1 t
(CH2NCH2), 3.3 s (CH3), 3.9 t (CH2OCH2), 6.8 s
(3-H), 7.3 m (6-H, 7-H, C6H5), 8.1 d.d and 8.3 d.d
(5-H, 8-H), 9.2 s (OH). 13C NMR spectrum, δC, ppm:
152.1, 149.2, 149.1, 133.2, 128.4, 126.2, 123.8, 123.6,
122.3, 121.9, 120.8, 115.5, 111.6, 108.1, 66.5, 53.1,
38.0. Mass spectrum, m/z (Irel, %): 334 (50), 291 (50),
276 (11), 261 (5), 233 (25), 218 (10), 204 (15), 178
(5), 167 (43), 137 (17), 130 (35), 116 (38), 115 (33),
102 (25), 91 (15), 77 (100), 51 (44), 39 (15). Found,
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FACILE REPLACEMENT OF THE HALOGEN ATOM
1095
3. Rabai, J., Synthesis, 1989, no. 7, p. 523.
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%: C 75.31; H 6.54; N 8.25. C21H22N2O2. Calculated,
%: C 75.42; H 6.63; N 8.38.
The melting point were measured on a Boetius
1
13
melting point apparatus. The H and C NMR spectra
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1
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007