182 Aldeen et al.
Asian J. Chem.
addition was prevented by occasional cooling in an ice bath.
After all the alkali has been added, the mixture was allowed to
stand in an ice bath for five minutes to ensure complete precipi-
tation of potassium chloride. Appropriate p-substituted ethyl
benzoate (5g, 0.033 mol) was added with thorough shaking
and the mixture was filtered immediately with suction. The
residue in the funnel was washed with a little methyl alcohol.
The filtrate was placed in an Erlenmeyer flask and allowed to
stand at room temperature. Crystals formed within 20 min to
3 h depending upon the amount of super saturation of the solution.
After 48 h, the crystals were filtered, washed with a little absolute
ethyl alcohol and dried in air.
Synthesis of p-substituted benzohydroxamic acid: A
mixture of 3.5 g (0.02 mol) of potassium salt in 16 mL of 1.25 N
acetic acid stirred and heated until a clear solution was obtained.
The solution was allowed to cool to room temperature and
finally cooled in an ice bath. The target compounds precipitated
as crystals, filtered, dried and the purity of the product was
checked using TLC.
Benzohydroxamic acid (E1):White crystals, m.f.: C7H7NO2,
yield: 75 %, m.p. 126 ºC, Clog P: 1.11. IR (KBr, νmax, cm-1): 3292
(-OH str., br), 3055 (Ar-H str.), 1629 (C=O str., s); 1560 and 1409
(arom. C=C str.). 1H NMR: (δ ppm, DMSO-d6): 7.4-7.8 (5H,Ar-
H); 9 br (1H, NH); 11.2 br (1H, -OH). 13C NMR: (δppm, DMSO-
d6): 127.34, 128.83, 131.59, 133.25 (Ar-C); 164.79 (C=O). EI-
MS: m/z (rel. int): 137 [M]+ (5 %); 136 (11 %); 119 (15 %); 108
(10.5 %); 93 (96 %); 92 (21 %); 91 (27 %); 77 (100 %); 66 (20
%); 65 (17 %); 64 (14 %); 51(12.9 %); 48 (46 %); 44 (43 %).
p-Aminobenzohydroxamic acid (E2): Pale brown crystals,
m.f.: C7H8N2O2, yield: 73 %, m.p. 185 ºC, Clog P: 0.30. IR (KBr,
EXPERIMENTAL
All chemicals used were of commercially available reagent
grade and were used without further purification. Melting
points were determined on Electro thermal Karl Kolb (Scientific
technical supplier Germany) and are uncorrected. Precoated
silica gel plates, GUV254, obtained from SDFCL limited (India)
were used for thin layer chromatography (TLC). Spots were
visualized using UV-lamp at 254 nm. Infrared spectra were
recorded as KBr disk using SHIMADZU FT-IR apparatus-
Japan. NMR Spectra were determined in DMSO-d6 and recorded
on Bruker Avance III NMR Spectrophotometer (400 MHz)
at the research center, College of Pharmacy,Ain Shams Univer-
sity, Egypt. Chemical shifts are expressed as δ values (ppm)
relative to tetramethylsilane (TMS) as internal standard.
Mass spectra were done on Single ISQLT Quadrapole-
MS spectrometer at the research center, College of Pharmacy,
Azhar University, Egypt. Mass spectral data were given as m/z
(intensity %). Ethical approval was obtained fromAnimal Ethics
Committee, Department of Pharmacology, Faculty of Pharmacy
Omdurman Islamic University, Khartoum, Sudan.
Synthesis of p-substituted benzoic acids: Two of p-substi-
tuted benzoic acids namely, (methyl and methoxy derivatives)
were prepared by oxidation of their corresponding aldehyde
derivatives. Each sample (0.01 mol) was added to a solution
of 0.02 mol of KMnO4 in 125 mL water at temperature less
then 20 ºC, then 3M of NaOH (1.5 mL) was added and heated
for 15 min at 40 ºC and boiled for 3 min, the solution was filtered
to remove magnesium dioxide, the filtrate was concentrated
to one-fourth volume by heating, then conc. HCl was added
until the media became acidic, further 5mL of HCl were added,
cooled at ice bath, solid products precipitated and filtered. Melting
points were found to be 180 and 183 ºC for p-methyl and
p-methoxy benzoic acid (lit. 181 ºC and 185 ºC, respectively [5].
Synthesis of ethyl p-substituted benzoate: Esters of all
derivatives were synthesized by the standard esterification method
via Fischer esterification (McMurry, 2012) of corresponding
p-substituted benzoic acids. The appropriate p-substituted
benzoic acid (0.1 mol) was refluxed in 100 mL absolute ethanol
and 14 mL conc. sulphuric acid. Completion of the reactions
(2-8 h) was monitored by TLC using hexane:ethyl acetate as
mobile phase. Solvent was evaporated and sodium bicarbonate
solution was added until the solution became neutral, the resulted
solution was subjected to extraction three times each of 20 mL
dichloromethane. The extracts were collected and the solvent
was evaporated, resulted esters were used in the second step
without further purification, (m.p. ethyl p-amino and p-nitro
benzoate were found to be 89 ºC and 58 ºC (lit. 88-90 ºC and
55-59 ºC, respectively [6].
ν
max, cm-1): 3255 (-OH str., br), 3072(Ar-H str.); 1609 (C=O str.,
s); 1478 and 1534 (arom. C=C str.). 1H NMR: (δ ppm, DMSO-
d6): 5.6 br (2H, Ar-NH2); 6.5-7.5 (4H, Ar-H); 8.69 (1H, NH);
10.77 (1H, -OH). 13C NMR: (δppm, DMSO-d6): 113.14, 119.66,
128.82, 152.10 (Ar-C); 165.61 (C=O). EI-MS: m/z (rel. int): 152
[M]+ (16.8 %); 120 (100 %); 92 (38 %); 65 (20 %).
p-Nitrobenzohydroxamic acid (E3): Pale yellow powder,
m.f.: C7H6N2O4, yield: 51 %, m.p. 180 ºC, Clog P: 0.43. IR
(KBr, νmax, cm-1): 3258 (-OH str., br), 3114 (Ar-H str.), 1665
(C=O str., s), 1506 and 1433 (arom. C=C str.), 1515 and 1352
(NO2 str., s). 1H NMR: (δ ppm, DMSO-d6): 7.95-8.5 (4H, Ar-
H); 9.58 (1H, NH); 11.57 (1H, -OH). 13C NMR: (δppm, DMSO-
d6): 124.07, 128.83, 131.09, 135.87(Ar-C); 165.09 (C=O). EI-
MS: m/z (rel. int): 182 [M]+ (12.8 %); 150 (100 %); 138 (21
%), 120 (14.8 %); 108 (15.8 %); 104 (54.5 %); 92 (32.8 %);
76 (32.6 %); 65 (22 %); 50 (14.5 %); 44(22 %); 40 (54 %).
p-Methylbenzohydroxamic acid (E4):White powder, m.f.:
C8H9NO2, yield: 46 %, m.p. 150 ºC, Clog P: 1.59. IR (KBr, νmax
,
cm-1): 3426 (-OH str., br), 3052 (Ar-H str.), 1646 (C=O str., s);
1
Compounds (E1-E6) were prepared using the general
procedure [7] as follows:
1612 and 1417 (arom. C=C str.); 2917 (aliph. C-H str.). H
NMR: (δ ppm, DMSO-d6): 7.2-7.75 (4H, Ar-H), 9.44 (1H,
NH), 10.84 (1H, -OH), 2.3(3H,-CH3). 13C NMR: (δ ppm,
DMSO-d6): 21.41 (-CH3), 127.3, 129.34, 130.48, 141.40 (Ar-
C); 164.5 (C=O). EI-MS: m/z (rel. int): 151 [M]+ (2.6 %);
119.08 (39.6 %); 107 (80 %); 106(100 %); 91(31.7 %); 79
(13 %); 77(18 %); 44 (34 %); 40(94 %).
Synthesis of p-substituted potassium benzohydroxa-
mate: Separate solutions of 4.67 g (0.067 mol) of hydroxyl-
amine hydrochloride in 240 mL of methyl alcohol and of 5.61 g
(0.1 mol) of KOH in 140 mL of methyl alcohol were prepared
at the boiling point of solvent. Both were cooled to 30-40 ºC
and the one containing alkali was added with shaking to hydroxyl-
amine solution; any excessive rise of temperature during the
p-Methoxybenzohydroxamic acid (E5): White powder,
m.f.: C8H9NO3, yield: 71 %, m.p. 159 ºC, Clog P: 0.90. IR (KBr,