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3
(
s, 1H, CH), 6.74 (bs, 1H, NH), 6.94–7.49 (m, 10H, NH, Ar–H), NH, Ar–H), 9.00 (bs, 1H, NH), 10.15 (bs, 2H, 2 OH). C-NMR
8
.33 (s, 1H, Ar–H), 8.85 (s, 1H, Ar–H), 11.0 (bs, 1H, NH), 11.4 (100 MHz, DMSO-d ), d, ppm: 20.0, 21.1 (CH ), 42.4 (C), 49.4
6 3
1
3
(
bs, 1H, OH). C-NMR (100 MHz, CDCl ), d, ppm: 21.2, 22.5 (CH ), 52.0 (CH ), 74.7 (CH), 128.5, 129.0, 129.3, 129.9,
3 2 2
(
1
CH ), 47.1 (C), 52.1 (CH ), 68.9 (CH), 127.3, 127.7, 129.0, 137.2, 139.5, 141.4, 153.6 (C–Ar), 173.8, 174.9 (2 CO). MS
3 2
+
30.2, 131.6, 132.1, 133.9, 136.2, 145.1 (C–Ar), 167.5, 172.3 (2 (MALDI, positive mode, matrix DHB): m/z ¼ 428.0 (M + Na) .
CO). MS (MALDI, positive mode, matrix DHB): m/z ¼ 431.0 (M Found, %: C, 50.21; H, 5.52; N, 24.07. For C17
23 7 5
H N O
+
+
(
Na) . Found, %: C, 61.92; H, 5.64; N, 20.09. For C21
408.5). Calculated, %: C, 61.75; H, 5.92; N, 20.58.
Methyl 3-hydroxy-3-(4-(2-((2-methoxy-2-oxoethyl)amino) dimethylpropanoate (14). To
acetamido)phenyl)-2,2-dimethyl propanoate (9). A mixture of obenzaldehyde (12) (0.7 g, 5.0 mmol) and Zn (6.0 mmol), in
-[4-(2-chloro-acetylamino)-phenyl]-3-hydroxy-2,2-dimethyl- benzene was added methyl 2-bromo-2-methylpropanoate (13)
H
24
N
6
O
3
(405.4). Calculated, %: C, 50.36; H, 5.72; N, 24.18.
Preparation of methyl 3-(4-chlorophenyl)-3-hydroxy-2,2-
solution of 4-chlor-
a
3
propionic acid methyl ester (5) (2.99 g, 10.0 mmol) and (1.0 ml, 5.0 mmol). The reaction mixture was reuxed for 15 h.
glycine methyl ester hydrochloride (2.50 g, 20.0 mmol) was The reaction mixture was cooled, evaporated under reduced
reuxed in pyridine (30 ml) for 10 hours. Aer cooling to pressure and was then puried by ash column chromatog-
room temperature, the solvent was then removed under raphy (petroleum ether–ethyl acetate). 0.96 g, yield 79%, white
ꢀ
1
reduce pressure and the oil formed was extracted with crystals. Mp 62–63 C. H NMR spectrum, (400 MHz, CDCl
3
),
methylene chloride (100 ml), washed with water and dried d, ppm (J, Hz): 1.11 (s, 3H, CH ), 1.14 (s, 3H, CH ), 3.20 (bs, 1H,
3
3
over sodium sulphate, ltered and evaporated in vacuum, OH), 3.73 (s, 3H, OCH ), 4.88 (s, 1H, CH), 7.24 (d, J ¼ 8.4, 2H, Ar–
3
1
3
the product was crystallized from ethyl acetate–petroleum H), 7.29 (d, J ¼ 8.4, 2H, Ar–H); C-NMR (100 MHz, CDCl ),
3
ether to give methyl 3-hydroxy-3-(4-(2-((2-methoxy-2- d, ppm: 18.9, 22.7 (CH ), 47.5 (C), 52.1 (OCH ), 77.8 (CH), 127.8,
3
3
oxoethyl)amino)acetamido)phenyl)-2,2-
128.9, 133.4, 138.3 (C–Ar), 177.9 (CO). MS (MALDI, positive
+
dimethylpropanoate (9). 2.5 g, yield 71%, white powder. Mp mode, matrix DHB): m/z ¼ 265.0 (M + Na) . Found, %: C, 58.92;
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9–81 C. H NMR spectrum, (400 MHz, CDCl
Hz): 1.07 (s, 3H, CH ), 1.13 (s, 3H, CH ), 3.57–3.79 (m, 2H,
CH ), 3.83, 3.86 (2 s, 6H, OCH ),
), 4.21 (d, J ¼ 6.0 Hz, 2H, CH
3 3
), d, ppm (J, H, 6.07. For C12H15ClO (242.7). Calculated, %: C, 59.39; H, 6.23.
3
3
3-(4-Chlorophenyl)-3-hydroxy-2,2-dimethylpropanehydrazide
(15). To a solution of methyl 3-(4-chlorophenyl)-3-hydroxy-2,2-
2
3
2
5
.01 (d, J ¼ 3.0 Hz, 1H, CH), 5.64 (bs, 1H, OH), 6.38 (bs, 1H, dimethylpropanoate (14) (1.93 g, 8.0 mmol) in methanol (50
13
NH), 7.44–7.69 (m, 5H, NH, Ar–H). C-NMR (100 MHz, ml), hydrazine hydrate (3 ml, 48.0 mmol) was added. The reac-
CDCl ), d, ppm: 20.5, 22.06 (CH ), 44.4 (C), 47.0 (CH ), 49.0 tion mixture was reuxed for 8 h, aer cooling to temperature the
3
3
2
(
CH
2
3
), 58.6, 59.0 (2 OCH ), 75.8 (CH), 127.1, 128.7, 129.0, precipitated hydrazide was ltered off, washed with water and
1
29.4, 130.4, 133.9, 136.6 (C–Ar), 160.6, 173.3 (2 CO). MS ethanol followed by recrystallization from aqueous ethanol to
+
(
MALDI, positive mode, matrix DHB): m/z ¼ 375.0 (M + Na) . give 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanehydrazide
ꢀ
1
Found, %: C, 58.11; H, 7.21; N, 8.03. For C17
Calculated, %: C, 57.94; H, 6.87; N, 7.95.
H
24
N
2
O
6
(352.4). (15). 1.7 g, yield 88%, white crystals. Mp 96–98 C. H NMR
spectrum, (400 MHz, CDCl ), d, ppm (J, Hz): 0.90 (s, 3H, CH ),
3
3
Methyl
3-(4-(2-((2-methoxy-2-oxoethyl)amino)acetamido) 1.03 (s, 3H, CH ), 4.17 (bs, 2H, NH ), 4.77 (s, 1H, CH), 5.55 (d, J ¼
3
2
13
phenyl)-2,2-dimethyl-3-(1H-1,2,4-triazol-1-yl)propanoate (10). 3.0 Hz, 1H, OH), 7.25–7.34 (m, 5H, Ar–H + NH). C-NMR (100
Prepared via reaction of 9 with CDI and triazole, aer 48 h MHz, CDCl ), d, ppm: 19.2, 23.0 (CH ), 49.1 (C), 78.2 (CH), 127.7,
3
3
reux, column chromatography (ethyl acetate–petroleum ether) 129.1, 132.6, 136.5, 139.4 (C–Ar), 179.3 (CO). MS (MALDI, positive
1
+
gave this product 10, yield 71%, yellowish oil. H NMR spec- mode, matrix DHB): m/z ¼ 265.0 (M + Na) . Found, %: C, 54.23;
trum, (400 MHz, CDCl ), d, ppm (J, Hz): 1.04 (s, 3H, CH ), 1.19 H, 6.18; N, 11.81. For C11 15ClN (242.7). Calculated, %: C,
s, 3H, CH ), 3.53–3.80 (m, 2H, CH ), 3.83, 3.86 (2 s, 6H, OCH ), 54.44; H, 6.23; N, 11.54.
.25 (d, J ¼ 6.0 Hz, 2H, CH ), 5.37 (s, 1H, CH), 7.19 (bs, 1H, NH),
.47–8.45 (m, 7H, NH, Ar–H). C-NMR (100 MHz, CDCl3),
3
3
H
2 2
O
(
3
2
3
4
7
2
1
3
General procedure for synthesis of 3-(4-chlorophenyl)-N-arylid
ene-2,2-dimethylpropane hydrazide 16a–d.
d, ppm: 20.1, 22.3 (CH ), 45.2 (C), 45.7 (CH ), 50.0 (CH ), 54.8,
3
2
2
56.9 (2 OCH ), 73.3 (CH), 128.5, 129.0, 129.3, 137.2, 139.5, 141.4,
3
1
53.5, 154.9 (C–Ar), 170.5, 172.8 (2 CO). MS (MALDI, positive A mixture of 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropane
+
mode, matrix DHB): m/z ¼ 426 (M + Na) . Found, %: C, 56.34; H, hydrazide (15) (2.1 g, 0.90 mmol) and aldehydes (1.0 mmol)
6.67; N, 17.71. For C19
H
25
N
5
O
5
(403.4). Calculated, %: C, 56.57; were reuxed in ethanol (30 ml) for 6 hours. Aer cooling to
room temperature, the resulting solid was ltered, washed with
H, 6.25; N, 17.36.
N-Hydroxy-3-(4-(2-((2-(hydroxyamino)-2-oxoethyl)amino) ethanol and recrystallized from ethanol.
acetamido)phenyl)-2,2-dimethyl-3-(1H-1,2,4-triazol-1-yl)
3-(4-Chlorophenyl)-N-(4-uorobenzylidene)-3-hydroxy-2,2-
propanamide (11). Prepared via reaction of 10 with hydroxyl dimethyl propanehydrazide (16a). 2.2 g, ield 73%, yellow
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1
amine hydrochloride in alcoholic KOH, aer 4 h, stirred, crystals. Mp 159–161 C. H NMR spectrum, (400 MHz,
ltration and washed by ethanol gave this product 11. Yield DMSO-d ), d, ppm (J, Hz): 1.03 (s, 3H, CH ), 1.09 (s, 3H, CH ),
6
3
3
ꢀ
1
7
4%, white crystals. Mp 154–157 C. H NMR spectrum, (400 4.88 (d, J ¼ 3.0 Hz, 1H, CH), 5.75 (d, J ¼ 3.0 Hz, 1H, OH), 7.33–
13
MHz, DMSO-d
6
), d, ppm (J, Hz): 1.05 (s, 3H, CH
), 3.98 (d, J ¼ 3.0 Hz, 2H, NMR (100 MHz, DMSO-d
), 5.30 (s, 1H, CH), 6.10 (bs, 1H, NH), 7.19–8.05 (m, 8H, 2 76.5 (CH), 116.4, 116.6, 127.8, 129.5, 129.8, 131.0, 131.1,
3
), 1.09 (s, 7.37 (m, 8H, Ar–H), 8.43 (s, 1H, CH), 10.80 (bs, 1H, NH). C-
3
H, CH
3
), 3.51–3.67 (m, 2H, CH
2
6
), d, ppm: 20.7, 22.5 (CH ), 47.3 (C),
3
CH
2
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 13896–13907 | 13905