1
0.26 mmol). H NMR (400 MHz, (acetone-d6) δ 8.62 (d, J = 1.7
2-(hydroxyimino)-3-(4-methoxyphenyl)propanoic
acid
Hz, 1H), 8.01 (d, J = 8.6 Hz, 2H), 7.76 (d, J = 8.6 Hz, 2H), 6.60
(s, 1H); 13C NMR (125 MHz, (acetone-d6) δ 167.49, 145.32,
141.54, 133.02, 132.69, 132.65, 131.03, 120.00, 110.87, 108.92.
HRMS C10H7NO3 [M-H]- Expected: 188.0353, Found: 188.0346.
(14d). Title compound was prepared following general procedure
3. Yield 71% (0.08 g, 0.36 mmol). 1H NMR (400 MHz, MeOD) δ
7.18 (d, J = 8.6 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 3.86 (s, 2H),
3.74 (s, 3H); 13C NMR (125 MHz, MeOD) δ 167.48, 159.71,
153.20, 131.07, 130.09, 114.79, 55.67, 30.16. HRMS C10H11NO4
[M-H]- Expected: 208.0615, Found: 208.0601.
General Procedure 2. 1,4-diacetylpiperazine-2,5-dione27 (0.5
mmol) was dissolved in DMF (1 mL). Triethylamine (0.5 mmol)
was added followed by corresponding aldehyde (0.5 mmol). The
reaction mixture was stirred for 12 hours at room temperature. It
was extracted with DCM, washed with NH4Cl solution. The
organic layer was dried over Na2SO4 and evaporated. Purification
of the residue on silica gel afforded the product (benzylidene)-
piperazine-2,5-dione intermediate. This intermediate (0.1 mmol)
was refluxed in 6N HCl (4.0 ml) for 4 hours. The reaction was
cooled to room temperature, extracted with ether, dried over
Na2SO4 and evaporated to give the crude keto-acid, which was
recrystallized in water to give pure product and judged by proton
NMR to exist as the enol tautomer.
2-(hydroxyimino)-3-(3-methoxyphenyl)propanoic
acid
(14e). Title compound was prepared following general procedure
3. Yield 72% (0.08 g, 0.37 mmol). 1H NMR (400 MHz, MeOD) δ
7.13-7.17 (t, J = 8.1 Hz, 1H), 6.83 (m, 2H), 6.74 (dd, J = 8.3 Hz,
1H), 3.89 (s, 2H), 3.75 (s, 3H); 13C NMR (125 MHz, MeOD) δ
166.87, 161.21, 152.07, 139.41, 130.29, 122.35, 115.73, 112.86,
55.56, 30.95. HRMS C10H11NO4 [M-H]- Expected: 208.0615,
Found: 208.0612.
2-(hydroxyimino)-3-(2-methoxyphenyl)propanoic
acid
(14f). Title compound was prepared following general procedure
3. Yield 56% (0.07 g, 0.33 mmol). 1H NMR (400 MHz, (acetone-
d6) δ 7.17 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 6.93 (d, J
= 8.5 Hz, 1H), 6.83 (t, J = 7.6 Hz, 1H), 3.90 (s, 2H), 3.82 (s, 3H);
13C NMR (125 MHz, (acetone-d6) δ 165.17, 158.28, 151.76,
129.60, 28.34, 125.57, 121.06, 111.32, 55.72, 25.53. HRMS
C10H11NO4 [M-H]- Expected: 208.0615, Found: 208.0607.
2-Hydroxy-3-(o-tolyl)acrylic acid (17c). Procedure 2 was
followed using 2-methylbenzaldehyde. Yield 58% (0.08 g, 0.45
1
mmol). H NMR (400 MHz, (acetone-d6) δ 8.18 (d, J = 8.2 Hz,
1H), 7.85 (s, 1H), 7.11-7.23 (m, 4H), 6.74 (s, 1H), 2.38 (s, 3H);
13C NMR (125 MHz, (acetone-d6) δ 167.10, 141.15, 137.11,
133.96, 130.84, 130.64, 128.34, 126.63, 107.60, 20.13. HRMS
C10H10O3 [M-H]- Expected: 177.0557, Found: 177.0549.
3-(4-chlorophenyl)-2-(hydroxyimino)propanoic acid (14g).
Title compound was prepared following general procedure 3.
1
3-(3-Chlorophenyl)-2-hydroxyacrylic acid (17h). Procedure
Yield 56% (0.06 g, 0.28 mmol). H NMR (400 MHz, DMSO-d6)
2 was followed using 3-chlorobenzaldehyde. Yield 56% (0.12 g,
0.60 mmol). H NMR (400 MHz, (acetone-d6) δ 7.96 (t, J = 1.96
δ 12.34 (br s, 1H), 7.33 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz,
2H), 3.79 (s, 2 H); 13C NMR (125 MHz, MeOD) δ 166.71,
151.68, 136.88, 133.20, 131.63, 129.40, 30. 39. HRMS
C9H8NO3Cl [M-H]- Expected: 212.0120, Found: 212.0102.
1
Hz, 1H), 7.76 (dt, J = 7.8 Hz, 1H), 7.25-7.41 (m, 3H), 6.54 (s,
1H), 4.28 (s, 0.6H), 4.05 (d, J = 6.2 Hz, 0.5H); 13C NMR (125
MHz, (acetone-d6) δ 166.54, 137.85, 134.59, 130.74, 130.67,
129.80, 128.83, 127.99, 109.31. HRMS C9H7O3Cl [M-H]-
Expected: 197.0011, Found: 197.0005.
3-(3-chlorophenyl)-2-(hydroxyimino)propanoic acid (14h).
Title compound was prepared following general procedure 3.
1
Yield 66% (0.15 g, 0.70 mmol). H NMR (400 MHz, DMSO-d6)
4.1.3.2. Hydroxyimine Analogues
δ 7.24-7.34 (m, J = 8.8 Hz, 3H), 7.17 (d, J = 7.3 Hz, 1H), 3.82 (s,
2H); 13C NMR (125 MHz, DMSO-d6) δ 165.16, 139.26, 132.81,
130.14, 128.32, 127.32, 126.14, 29.64. HRMS C9H8O3NCl [M-
H]- Expected: 212.0120, Found: 212.0108.
General Procedure 3. The corresponding keto-acid (0.50
mmol) was dissolved in a solution of NaOH (1.51 mmol) in
water (1 ml). Hydroxylamine hydrochloride (0.76 mmol) was
added to the reaction and stirred overnight at room temperature.
1N HCl was added to the reaction, the precipitated product was
filtered and dried. The crude product was purified using flash
chromatography (silica gel, 5% MeOH/DCM) as necessary.
3-(2-chlorophenyl)-2-(hydroxyimino)propanoic acid (14i).
Title compound was prepared following general procedure 3.
1
Yield 54% (0.02 g, 0.07 mmol). H NMR (400 MHz, DMSO-d6)
δ 7.41-7.44 (m, 1H), 7.21-7.28 (m, 2H), 7.03 (m, 1H), 3.88 (s,
2H); 13C NMR (125 MHz, DMSO-d6) δ 164.97, 149.01, 134.08,
132.83, 129.22, 129.11, 127.96, 127.11, 27.93. HRMS
C9H8O3NCl [M-H]- Expected: 212.0120, Found: 212.0134.
2-(hydroxyimino)-3-p-tolylpropanoic acid (14a). Title
compound was prepared following general procedure 3. Yield
1
55% (0.03 g, 0.16 mmol). H NMR (400 MHz, MeOD) δ 7.05-
7.14 (m, 4H), 3.86 (s, 2H), 2.27 (s, 3H); 13C NMR (125 MHz,
MeOD) δ 166.90, 152.35, 136.96, 134.84, 129.96, 129.89, 30.51,
21.03. HRMS C10H11NO3 [M-H]- Expected: 192.0666, Found:
192.0673.
2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic
acid
(14j). Title compound was prepared following general procedure
3. Yield 91% (0.10 g, 0.51 mmol). 1H NMR (400 MHz, MeOD) δ
7.08 (d, J = 8.5 Hz, 2H), 6.66 (d, J = 8.5 Hz, 2H), 3.80 (s, 2H);
13C NMR (125 MHz, MeOD) δ 166.93, 156.93, 152.63, 131.06,
128.70, 116.13, 30.03. HRMS C9H9NO4 [M-H]- Expected:
194.0459, Found: 194.0459.
2-(hydroxyimino)-3-m-tolylpropanoic acid (14b). Title
compound was prepared following general procedure 3. Yield
1
74% (0.04 g, 0.21 mmol). H NMR (400 MHz, MeOD) δ 7.03-
2-(hydroxyimino)-3-(3-hydroxyphenyl)propanoic
acid
7.13 (m, 3H), 6.98 (d, J = 7.31 Hz, 1H), 3.87 (s, 2H), 2.28 (s,
3H); 13C NMR (125 MHz, MeOD) δ 166.88, 152.22, 139.03,
137.84, 130.61, 129.26, 128.02, 127.02, 30.85, 21.42. HRMS
C10H11NO3 [M-H]- Expected: 192.0666, Found: 192.0656.
(14k). Title compound was prepared following general procedure
1
3. Yield 65% (0.07 g, 0.36 mmol). H NMR (400 MHz, DMSO-
d6) δ 7.04 (t, J = 8.0 Hz, 1H), 6.55-6.62 (m, 3H), 3.72 (s, 2H); 13
C
NMR (125 MHz, DMSO-d6) δ 165.18, 157.22, 137.89, 129.09,
119.24, 115.44, 113.07, 48.52, 29.74. HRMS C9H9NO4 [M-H]-
Expected: 194.0459, Found: 194.0442.
2-(hydroxyimino)-3-o-tolylpropanoic acid (14c). Title
compound was prepared following general procedure 3. Yield
1
92% (0.12 g, 0.62 mmol). H NMR (400 MHz, (acetone-d6) δ
7.01-7.10 (m, 4H), 3.88 (s, 2H), 2.35 (s, 3H); 13C NMR (125
MHz, (acetone-d6) δ 167.77, 153.63, 137.10, 136.37, 130.67,
129.10, 126.82, 126.60, 28.37, 19.93. HRMS C10H11NO3 [M-H]-
Expected: 192.0666, Found: 192.0652.
3-(4-fluorophenyl)-2-(hydroxyimino)propanoic acid (14l).
Title compound was prepared following general procedure 3.
1
Yield 74% (0.08 g, 0.41 mmol). H NMR (400 MHz, DMSO-d6)
δ 7.20-7.24 (m, 2H), 7.10 (t, J = 8.8 Hz, 2H), 3.79 (s, 2H); 13C