2,5-Disubstituted-1,4-benzoquinone Derivatives
Experimental
387
2-(4-Phenylpiperazin-1-yl)-5-(3-benzoylamino-2,4,5-thiadiazolyl)-
1,4-benzoquinone (4a)
To a mixture of 3 (0.31 g, 1 mmol) and 4-phenyl piperazine (0.08 g,
0.5 mmol), ethanol (15 ml) followed by 5 drops of glacial acetic acid were
added. The mixture was heated under reflux for 0.5 h. The reaction mixture
was filtered while hot, and the precipitate was washed with 5 ml of boiling
ethanol. The brown solid product was dried, and recrystallized from dichlo-
Chemistry
Material and Methods
romethane:ethanol mixture. mp, decomposes before melting;. IR (cm–1
)
Melting points were determined on Gallenkamp melting point apparatus
and are uncorrected. Thin layer chromatography (TLC) was performed on
silica gel plates with fluorescent indicator F-254 (Sigma Chemical Co.). The
infrared (IR) spectra were determined on a Shimadzu spectrophotometer
IR-435 using the KBr disc technique. The proton nuclear magnetic resonance
(1H-NMR) spectra were recorded on a Bruker WP pulse spectrometer, and
the chemical shifts are reported in δ units downfield from the internal
reference tetramethylsilane. The mass spectra (MS) were measured on a
7070-E VG analytical mass spectrometer. The elemental analysis were
provided by the Microanalytical unit (Alexandria University, Egypt). The
analyzed elements were C, H, N.
3120 (NH), 1670 (C=O).– 1H-NMR ([D6] DMSO) δ 2.96-3.96 (m, 8 H,
NCH2 CH2N), 6.84–8.12 (m, 12 H Ar-H and quinone protons), 9.32
(s,1H,NH); MS, m/z (%) 471 (M+,13), 366 (14,M+–benzoyl), 352 (19,M+–C6
H5 CONH), 312 (41,M+–phenylpiperazinyl),291 (10,M+–[phenylpiperaz-
inyl+ benzamide]), 105 (100, benzoyl cation), 77 (45, phenyl cation).
2-[4-(N-2-(Thiazolylaminosulfonyl)phenyl)amino]-5-(3-benzoylamino-
2,4,5-thiadiazolyl-1,4-benzoquinone (4b)
Obtained from 3 (0.31 g, 1 mmol) and N1-2-(thiazolyl) sulfanilamide.
(0.11 g, 0.5 mmol), as in 4a. mp, decomposes before melting.– TLC with
dichloromethane:methanol (9.2:0.8, v/v).– Rf=0.38.– IR (cm–1) 3400, 3120
(NH); 1665,1640 (C=O); 1320, 1135,1090 (SO). 1H-NMR ([D6] DMSO)
δ6.78–8.25 (m,13 H, Ar H and quinone protons), 12.45 (s, 1H, NH), 12.82
(s, 1H,NH).
Synthesis
2,5-Dihydroxybenzoic acid hydrazide was prepared from methyl 2,5-di-
hydroxybenzoate following the procedure reported in the literature[14]
.
Phenylamino-5-(3-benzoylamino-2,4,5-thiadiazolyl)-1,4-benzoquinone (4c)
N1-(2,5-dihydroxybenzoyl)-N4-benzoylthiosemicarbazide (1)
Obtained from 3 (0.31 g, 1 mmol) and aniline (0.047 g, 0.5 mmol), as
described for 4a. mp, decomposes before melting.– TLC with n-hexane:ethyl
acetate:methanol (3.0:1.8:0.2, v/v/v) Rf= 0.42.– IR (cm–1) 3240, 3120 (NH),
1665, 1630 (C=O). 1H-NMR ([D6] DMSO) δ, 6.82–8.16 (m, 12 H, Ar-H and
quinone), 9.25 (s,1H,NH), 12.25 (s,1H,NH); MS, m/z (%) 402 (M+,21),400
(100,M+–2H), 372 (36, M+ –[2H+CO]), 282 (11,M+–[C6H5CONH]), 105 (8,
benzoyl cation), 77 (18,phenyl cation).
A mixture of 2,5-dihydroxybenzoic acid hydrazide (12.60 g, 75 mmol) in
ethanol (75 ml) was heated under reflux for 0.5 h. The reaction mixture was
allowed to cool to room temperature, the precipitate formed was filtered, and
the product was washed with ethanol. The crude product was recrystallized
from ethanol-chloroform mixture to give white pure crystals. Yield: 22.4g
(90%).– Mp 229–231 °C.– TLC with methylene chloride: methanol
(9.0:1.0,v/v).– Rf = 0.62.– IR (cm–1) 3500 (OH),3280,3160 (NH), 1660,
1645, 1635 (C=O).– 1H-NMR [D6]DMSO (deuterated dimethyl sulfoxide),
δ 6.86-8.05(m, 8 H, Ar-H), 7.37 (s,1 H, NH), 8.60 (s,1H,NH 5),9.16 (s,1 H,
NH), 11.70 (s,1 H,OH), 11.85 (s,1H,OH). The NH and OH hydrogens are
deuterium exchangable.– MS, m/z (%) 331 (M+,46), 313 (13,M+–H2O), 168
(44, M+–dihydroxycarbonyl), 137 (73[2,5-dihydroxycarbonyl cation]), 105
(100, benzoyl cation), 77 (67. phenyl cation).Anal. (C15H13N3O4S.0.5H2O).
2-(4-Methylphenylamino)-5-(3-benzoylamino-2,4-5-thiadiazolyl)-
1,4-benzoquinone (4d)
Obtained from 3 (0.31 g, 1 mmol) and methylaniline (0.054 g, 0.5 mmol),
see 4a. mp, decomposes before melting.– TLC with n-hexane:ethyl ace-
tate:methanol (3.0:1.8:0.2, v/v/v).– Rf = 0.39.– IR (cm–1) 3280, 3120 (NH),
1665 and 1630 (C=O).1H-NMR ([D6] DMSO) δ 3.56 (s, 3H, CH3), 6.85–8.17
(m, 11 H, ArH and quinone), 9.05 (s, 1H, NH), 12.65 (s, 1H, NH); MS, m/z
(%) 416 (M+, 14), 388 (11, M+–CO), 105 (100, benzoyl cation),77 (33,
phenyl cation).
2-Benzoylamino-5-(2,5-dihydroxyphenyl)-1,3,4-thiadiazole (2)
To a stirred solution of 1 (9.00 g, 27 mmol) in absolute ethanol (200 ml),
sulfuric acid (24 ml) was carefully added over a period of 15 min. The
reaction mixture was left at room temperature for 20 h and then poured with
stirring to an equal volume of ice-cold water. The precipitate formed was
filtered, washed with water, and recrystallized from methanol: dichlo-
romethane mixture to give a white product. Yield: 2.52 g (89%).– Mp
285–287 °C (dec.).– TLC with methylene chloride: methanol (9.2:0.8, v/v).–
Rf = 0.56.– IR (cm–1)3330 (OH), 3120 (NH), 1665, 1650, 1625 (C = O).–
1H-NMR ([D6] DMSO) δ 6.82–8.19 (m, 8 H, Ar-H), 9.07 (s, 1H, NH), 10.37
(s, 1H, OH), 12.92 (s,1H, OH); MS, m/z (%) 313 (M+,17), 105 (100,benzoyl
cation), 77 (47,phenyl cation). Anal. (C15H11N3O3S).
2-(4-Hydroxyphenylamino)-5-(3-benzoylamino-2,4,5-thiadiazolyl)-
1,4-benzoquinone (4e)
Obtainedfrom3 (0.31 g, 1 mmol) and 4-aminophenol (0.055 g, 0.5 mmol),
cf. 4a. mp, decomposes before melting.– TLC with dichloromethane:metha-
nol (9.4:0.6, v/v).– Rf =0.36.– IR (cm1)3390 (OH), 3180 (NH), 1665–1620
(C = O, C = N).– 1H-NMR ([D6] DMSO) δ 6.67–8.09 (m, 11 H, Ar-H and
quinone protons) 9.53 (s, 1H, NH), 12.56 (s, 1H, NH) 12.89 (s, 1H, NH); MS,
m/z (%). 418 (M+, 4), 105 (100, benzoyl cation), 77 (34, phenyl cation).
2-(4-Bromophenylamino)-5-(3-benzoylamino-2,4,5-thiadiazolyl)-
1,4-benzoquinone (4f)
2-(3-Benzoylamino-2,4,5-thiadiazolyl)-1,4-benzoquinone (3)
Obtained from 3 (0.31 g, 1mmol) and 4-bromoaniline (0.086 g, 0.5 mmol),
cf. 4a. mp, decomposes before melting.– TLC with n-hexane:ethyl ace-
tate:methanol (3.0:1.8:0.2, v/v/v).– Rf = 0.40.– IR (cm–1) 3390 (NH); 1660–
1625 (C=O, C=N).– 1H-NMR ([D6]DMSO) δ 6.73–8.21 (m,11 H, Ar-H and
quinone protons) 9.15 (s, 1H, NH), 12.85 (s, 1H,NH); MS, m/z (%) 481
(M++2, 59), 479 (46, M+), 400 (15,M+ –Br), 105 (100, benzoyl cation), 77
(89, phenyl cation).
To a stirred solution of 2 (3.13 g, 0.01 mol) in dimethylformamide (10 ml),
a 10% solution of ferric chloride (25 ml) was added, portionwise. Stirring
was continued for 15 min, and the reaction mixture was diluted with water
(50 ml), a yellowish-orange precipitate was formed. The precipitate was
filtered, washed with water until it is free from the ferric ion, dried, and
recrystallized from methanol: dichloromethane mixture togivea yellow solid
product. Yield: 1.92 g (95%).– Mp decomposes before melting.– TLC with
methylene chloride:methanol (9.4:0.6, v/v).– Rf = 0.52.– IR (cm–1) 3160
(NH), 1665, 1650 (C=O), 1610(C = N).– 1H-NMR, ([D6]DMSO) δ6.85–8.10
(m, 8 H, Ar-H and benzoquinone protons), 9.50 (s, 1H, NH); MS, m/z (%)
311 (M+, 100), 282 (3,M+–CHO), 196 (3,M+–benzoyl), 149 (6[1,4-benzo-
quinonyl-CH=N=NH cation]), 105 (30, benzoyl cation), 77 (10, phenyl
cation). Anal. (C15H9N3O3S).
2-(4-Nitrophenylamino)-5-(3-benzoylamino-2,4,5-thiadiazolyl)-
1,4-benzoquinone (4g)
Obtained from 3 (0.31g, 1 mmol) and 4-nitroaniline (0.069 g, 0.5 mmol)
cf. 4a. mp, decomposes before melting.– TLC with n-hexane:ethyl ace-
tate:methanol (3.0:1.8:0.2, v/v/v).– Rf = 0.33.– IR (cm–1) 3395 (NH); 1665,
Arch. Pharm. Pharm. Med. Chem. 331, 385–388 (1998)