An easy transformation of 2-amino-2-(hydroxyimino)acetates to carbamoylformamidoximes

Article abstract of DOI:10.1055/s-2004-837285

Carbamoylformamidoximes 5 are synthesized from 2-amino-2-(hydroxyimino) acetates 3 by reaction with aminomagnesium bromides 4, prepared in situ from amines 2 and ethylmagnesium bromide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2004-837285

PAPER
407
An Easy Transformation of 2-Amino-2-(hydroxyimino)acetates to
Carbamoylformamidoximes
T
ransformation of
e
2-Amino-2
m
-(hydroxyimino)ace
e
tates to Ca
t
r
bamoy
r
lformam
i
idoxim
o
es s N. Nicolaides,*a Konstantinos E. Litinas,a Theodora Papamehael,a Hanna Grzeskowiak,a
Daman R. Gautam,a Konstantina C. Fylaktakidoub
a
Laboratory of Organic Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
Fax +30(231)0997679; E-mail: nicol@chem.auth.gr; E-mail: klitinas@chem.auth.gr
Molecular Biology and Genetics Department, Democritus University of Thrace, Alexandroupolis 68100, Greece
b
Received 19 July 2004; revised 7 October 2004
EtMgBr, R3R4NH (2a–e)
Et3N
EtO2C-C-NR1R2
Abstract: Carbamoylformamidoximes 5 are synthesized from 2-
amino-2-(hydroxyimino)acetates 3 by reaction with aminomagne-
sium bromides 4, prepared in situ from amines 2 and ethylmagne-
sium bromide.
EtO2CC=NOH
R1R2NH
2a–d
[ R3R4NMgBr ]
NOH
3a–d
Cl
1
4a–e
R3
Key words: amides, amines, amidoximes, amidines, organometal-
lic reagents
R1
R2
N
C
O
C N
R4
NOH
5
Amidoximes possess biological interest due to the pres-
ence of a hydroxyimino and an amino function at the same
carbon atom. The possibility of varying the substituents at
their a-carbon and the two N-containing groups enabled
the synthesis of a large number of amidoximes with pro-
nounced biological activity.1 Meanwhile the substituted
carbamoylformamidoximes have a promising synthetic
potential, particularly for heterocyclic chemistry. Our
continuous interest on amidoximes1–3 prompted us to syn-
thesize the title compounds, which are the monoximes of
the corresponding N1,N2-substituted oxalamides. The
symmetrically N1,N2-substituted bis-oximes of the oxala-
mides are known, being easily prepared by treatment of
dichloroglyoxime or cyanogen di-N-oxide with amines.4,5
Recently6 unsymmetrical imidoyl derivatives such as 2-
(arylamino)-2-(arylimino)acetamides have been reported.
2,3,4
c
e
:
a
: R1 = R3 = Ph, R2 = R4 = H;
: R1 = R3 = c-C6H11, R2 = R4 = H;
: R3 = Bn, R4 = H
b
d
: R1 = R3 = 4-MeC6H4, R2 = R4 = H;
: R1 = R3 = Ph, R2 = R4 = Me;
Scheme 1
ature, according to the literature11 afforded the corre-
sponding 2-amino-2-(hydroxyimino)acetates 3a–d in 74–
97% yield (Table 1). Amidoximes 3a–d were then treated
with aminomagnesium bromides 4a–e, prepared in situ
from the appropriate amines 2a–e and ethylmagnesium
bromide in anhydrous diethyl ether, to give the corre-
sponding title amidoximes 5a–j in 41–83% yield
(Table 2). It is important to be noticed that the C=NOH
group remained unchanged during this reaction with the
organometallic reagent present under the applied reaction
conditions;12 may be in the first step a metalation takes
place leading to a magnesium chelate complex and then
the excess of the reagent is capable of substituting the es-
ter function.
First we attempted unsuccessfully the preparation of the
title compounds by treating symmetrical bis-oximes of
oxalamides with one equivalent of nitrous acid in analogy
to the reported transformation of a-hydroxyiminoamid-
oximes to a-hydroxyiminoamides.7 We also tried to syn-
thesize the title compounds 5 via the in situ reaction of the
known (phenylcarbamoyl)formonitrile oxide, PhNH-
COC≡N→O (prepared by thermal decomposition of a-
methoxycarbamoyl-a-nitroacetanilide,8 or from nitro-
methane and phenyl isocyanate9), with aniline. Both at-
tempts failed, due to the high temperature applied in the
first case or the presence of the phenyl isocyanate in the
second case. In this paper we wish to report the facile syn-
thesis of the title compounds 5 by the reaction sequence
depicted in Scheme 1.
To the best of our knowledge no reactions of organome-
tallic compounds and amidoximes have been reported in
the literature, while our conditions enable the transforma-
tion of an ester group in the a-carbon into an amide. The
described method appears to be well suited for both sec-
ondary and tertiary amidoximes 3a–d (R1 = aryl, alkyl;
R2 = H, Me) and aminomagnesium bromides 4a–e. The
observed low yields in some of the reactions studied are
influenced by the stability of the intermediates 4a–e de-
pending on the reaction conditions. Thus, the yield of the
prepared compound 5c in two efforts was 57 and 83%. No
attempt has been made to optimize the yields, which are
based on ester compounds 3a–d. The final isolated prod-
ucts were purified by column chromatography or crystal-
lization.
Treatment of ethyl 2-chloro-2-(hydroxyimino)acetate
(1)10 with triethylamine and amines 2a–d at room temper-
SYNTHESIS 2005, No. 3, pp 0407–0410
x
x
.
x
x
.2
0
0
5
Advanced online publication: 08.12.2004
DOI: 10.1055/s-2004-837285; Art ID: T08604SS
© Georg Thieme Verlag Stuttgart · New York

408
D. N. Nicolaides et al.
PAPER
Table 1 Preparation of 2-Amino-2-(hydroxyimino)acetates 3
Entry
Amine
2
Acetate 3
Yield
(%)
Mp (°C) (solvent)
Lit. Mp (°C)
R1
R2
H
1
2
3
4
2a
2b
2c
2d
3a Ph
77
87
74
75
105–106 (EtOH)
105–10611
3b 4-MeC6H4
3c c-C6H11
3d Ph
H
125–127 (CH2Cl2–hexane)
69–71 (Et2O–hexane)
101–103 (CH2Cl2–hexane)
–
–
–
H
Me
Table 2 Preparation of Carbamoylformamidoximes 5
Entry
Acetate 3 Amine 2
Carbamoylformamidoxime 5
Yield
Mp (°C)
(solvent)
R1
R2
H
R3
H
R4
(%)
62
51
83
83
80
64
49
41
81
47
1
2
3a
3a
3b
3b
3b
3c
3c
3c
3d
3d
2a
2c
2a
2b
2e
2c
2a
2e
2a
2d
5a Ph
Ph
187–189 (hexane–EtOAc)
180–182 (hexane–CH2Cl2)
194–196 (hexane–EtOAc)
189–191 (hexane–EtOAc)
168–170 (hexane-CH2Cl2)
172–174 (hexane–EtOAc)
72–74 (hexane–CH2Cl2)
235–237 (CH2Cl2)
5b Ph
H
H
c-C6H11
Ph
3
5c 4-MeC6H4
5d 4-MeC6H4
5e 4-MeC6H4
5f c-C6H11
5g c-C6H11
5h c-C6H11
5i Ph
H
H
4
H
H
4-MeC6H4
Bn
5
H
H
6
H
H
c-C6H11
Ph
7
H
H
8
H
H
Bn
9
Me
Me
H
Ph
140–142 (hexane–EtOAc)
177–179 (hexane–EtOAc)
10
5j Ph
Me
Ph
Melting points were determined on a Kofler hot-stage apparatus and
are uncorrected. IR spectra were obtained with a Perkin-Elmer 1310
spectrophotometer as Nujol mulls. NMR spectra were recorded on
a Bruker AM 300 (300 MHz, and 75 MHz for 1H and 13C, respec-
tively) using CDCl3 as the solvent and TMS as an internal standard.
J values are reported in Hz. Mass spectra were determined on a VG-
250 spectrometer at 70 eV under Electron Impact (EI) conditions,
or on a Perkin Elmer API 100 Sciex Simple quadrupole under Elec-
trospray Ionization (ESI) conditions. High-resolution mass spectra
(HRMS) were recorded on an Ionspec mass spectrometer under Ma-
trix-Assisted Laser Desorption-Ionization Fourier Transform Mass
Spectrometer (MALDI-FTMS) conditions with 2,5-dihydroxyben-
zoic acid (DHB) as the matrix. Microanalyses were performed on a
Perkin-Elmer 2400-II Element analyzer. Silica gel Nr. 60, Merck
A.G. was used for column chromatography. Compound 1 was pre-
pared by a known procedure.10
Ethyl 2-Anilino-2-(hydroxyimino)acetate (3a)11
1H NMR (CDCl3, 300 MHz): d = 1.22 (t, 3 H, J = 7.6 Hz), 4.26 (q,
2 H, J = 7.6 Hz), 6.93 (d, 2 H, J = 7.6 Hz), 7.03 (br s, 1 H, exchange-
able with D2O), 7.10 (t, 1 H, J = 7.6 Hz), 7.29 (t, 2 H, J = 7.6 Hz),
9.41 (br s, 1 H, exchangeable with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 13.7, 62.35, 121.0, 123.8, 128.8,
139.05, 143.3, 160.7.
MS (EI): m/z (%) = 208 (86), 191 (30), 163 (20), 145 (45), 118 (98),
104 (70), 93 (100), 77 (76).
MALDI-FTMS: m/z calcd for C10H13N2O3 [M + H]: 209.0921;
found: 209.0927.
Ethyl 2-(Hydroxyimino)-2-(4-toluidino)acetate (3b)
IR (Nujol): 3350, 3150, 1715, 1625, 1605 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.22 (t, 3 H, J = 7.6 Hz), 2.26 (s,
3 H), 4.24 (q, 2 H, J = 7.6 Hz), 6.84 (d, 2 H, J = 7.6 Hz), 6.93 (br s
1 H, exchangeable with D2O), 7.08 (d, 2 H, J = 7.6 Hz), 8.62 (br s,
1 H, exchangeable with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 13.8, 20.8, 62.3, 121.5, 129.4,
133.8, 136.5, 143.8, 160.8.
Compounds 3a–d; General Procedure
The amine 2 (10 mmol) was added to a stirred solution of
chloroxime 1 (1.52 g, 10 mmol) in Et2O (75 mL). To this mixture
was added dropwise a solution of Et3N (1.13 g, 1.56 mL, 11 mmol)
in Et2O (30 mL) over 5 min. After stirring at r.t. for 1.5 h, the white
precipitate of Et3N·HCl formed was filtered. The filtrate was con-
centrated, the residue was dissolved in CH2Cl2 (20 mL) and the so-
lution was washed with H2O. The organic layer was dried (Na2SO4)
and concentrated to give the corresponding amidoxime 3 (Table 1).
MS (EI): m/z (%) = 222 (49), 159 (23), 133 (28), 132 (66), 131 (76),
91 (100).
Anal. Calcd for C11H14N2O3: C, 59.45; H, 6.35; N, 12.61. Found: C,
59.72; H, 6.22; N, 12.59.
Synthesis 2005, No. 3, 407–410 © Thieme Stuttgart · New York

PAPER
Transformation of 2-Amino-2-(hydroxyimino)acetates to Carbamoylformamidoximes
409
Ethyl 2-(Cyclohexylamino)-2-(hydroxyimino)acetate (3c)
13C NMR (CDCl3, 75.5 MHz): d = 24.7, 25.4, 32.7, 48.6, 121.7,
123.5, 128.3, 139.1, 142.8, 159.7.
IR (Nujol): 3408, 3365, 3180, 3110, 1724, 1625 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.08–1.40 (m, 5 H), 1.34 (t, 3 H,
J = 7.6 Hz), 1.54–1.64 (m, 1 H), 1.66–1.78 (m, 2 H), 1.91–2.02 (m,
2 H), 3.75–3.88 (m, 1 H), 4.29 (q, 2 H, J = 7.6 Hz), 4.94 (br d, 1 H,
J = 8.9 Hz, exchangeable with D2O), 8.67 (br s, 1 H, exchangeable
with D2O).
MS (EI): m/z (%) = 261 (43), 244 (56), 234 (6), 208 (25), 199 (15),
191 (8), 163 (11), 145 (29), 135 (16), 118 (100).
Anal. Calcd for C14H19N3O2: C, 64.35; H, 7.33; N, 16.08. Found: C,
64.01; H, 7.19; N, 16.06.
13C NMR (CDCl3, 75.5 MHz): d = 13.9, 24.8, 25.4, 35.0, 52.0, 62.0,
144.8, 161.3.
2-(Hydroxyimino)-N-phenyl-2-(4-toluidino)acetamide (5c)
IR (Nujol): 3383, 3290, 3275, 1660, 1622, 1590 cm–1.
MS (EI): m/z (%) = 214 (55), 197 (100), 169 (22), 151 (23), 132
(43), 56 (45), 43 (53).
MALDI-FTMS: m/z calcd for C10H19N2O3 [M + H]+: 215.139;
found: 215.1390.
1H NMR (CDCl3, 300 MHz): d = 2.30 (s, 3 H), 3.05 (br s, 1 H, ex-
changeable with D2O), 6.96 (d, 2 H, J = 8.9 Hz), 7.07 (d, 2 H,
J = 7.6 Hz), 7.13 (t, 1 H, J = 7.6 Hz), 7.31 (t, 2 H, J = 7.6 Hz), 7.48
(br s, 1 H, exchangeable with D2O), 7.56 (d, 2 H, J = 8.9 Hz), 9.05
(br s, 1 H, exchangeable with D2O).
Ethyl 2-(Hydroxyimino)-2-(methylanilino)acetate (3d)
13C NMR (CDCl3, 75.5 MHz): d = 119.8, 122.5, 124.8, 129.0,
129.1, 141.5, 150.0, 150.8, 157.1, 157.8.
IR (Nujol): 3250, 1710, 1625, 1585 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.15 (t, 3 H, J = 7.3 Hz), 3.32 (s,
3 H), 4.18 (q, 2 H, J = 7.3 Hz), 6.83 (d, 2 H, J = 7.3 Hz), 6.97 (t, 1
H, J = 7.3 Hz), 7.27 (t, 2 H, J = 7.3 Hz), 9.20 (br s, 1 H, exchange-
able with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 13.8, 36.3, 62.1, 116.5, 121.7,
129.1, 148.4, 155.5, 168.7.
MS (EI): m/z (%) = 269 (28), 252 (12), 251 (18), 223 (4), 222 (6),
133 (100), 132 (71), 131 (37), 119 (48), 118 (52), 107 (36).
Anal. Calcd for C15H15N3O2: C, 66.90; H, 5.61; N, 15.60. Found: C,
76.06; H, 5.56; N, 15.54.
2-(Hydroxyimino)-N-(4-methylphenyl)-2-(4-toluidino)acet-
amide (5d)
MS (EI): m/z (%) = 222 (47), 206 (48), 205 (53), 178 (67), 160 (46),
150 (23), 133 (64), 132 (63), 118 (80), 107 (100).
IR (Nujol): 3390, 3350, 3305, 1670, 1625, 1605 cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.30 (s, 3 H), 2.31 (s, 3 H), 4.08
(br s, 1 H, exchangeable with D2O), 6.95 (d, 2 H, J = 8.9 Hz), 7.07
(d, 2 H, J = 7.6 Hz), 7.11 (d, 2 H, J = 8.9 Hz), 7.33 (br s, 1 H, ex-
changeable with D2O), 7.45 (d, 2 H, J = 7.6 Hz), 8.84 (br s, 1 H, ex-
changeable with D2O).
Anal. Calcd for C11H14N2O3: C, 59.45; H, 6.35; N, 12.61. Found: C,
59.57; H, 6.25; N, 12.55.
Compounds 5a–j; General Procedure
Ethyl bromide (3.93 g, 2.69 mL, 36 mmol) was added to a stirred
suspension of Mg turnings (0.864 g, 36 mmol) in anhyd Et2O (30
mL) at r.t. under argon. When the reaction was complete (all Mg
had dissolved), a solution of amine 2a–e (36 mmol) in anhyd Et2O
(8 mL) was added followed at once by a solution of the ester 3a–d
(4.5 mmol) in anhyd Et2O (25 mL) under the same conditions. The
reaction mixture was then refluxed for 0.5 h and stirred at r.t. for a
further 2 h. Then it was washed with aq 5% HCl to dissolve the in-
organic salts and the excess of amine. The aqueous layer was ex-
tracted with EtOAc and the combined organic layers were dried
(Na2SO4) and concentrated in a rotary evaporator. The residue was
purified by column chromatography on silica gel (hexane, EtOAc as
eluents) (Table 2).
13C NMR (CDCl3, 75.5 MHz): d = 20.8, 20.9, 119.8, 122.3, 128.9,
129.6, 143.2, 143.4, 150.1, 151.9, 157.1, 157.9.
MS (EI): m/z (%) = 283 (100), 267 (21), 146 (13), 133 (77), 118
(50), 107 (58), 91 (47), 77 (32).
MALDI-FTMS: m/z calcd for C16H18N3O2 [M + H]+: 284.1393.
Found: 284.1400.
N-Benzyl-2-(hydroxyimino)-2-(4-toluidino)acetamide (5e)
IR (Nujol): 3390, 3270, 3170, 1655, 1635, 1605 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.77 (br s, 1 H, exchangeable with
D2O), 2.31 (s, 3 H), 4.51 (d, 2 H, J = 5.9 Hz), 6.88 (d, 2 H, J = 8.9
Hz), 7.06 (d, 2 H, J = 8.9 Hz), 7.08 (br s, 2 H, exchangeable with
D2O), 7.25–7.35 (m, 5 H).
13C NMR (CDCl3, 75.5 MHz): d = 20.8, 43.7, 122.2, 127.7, 127.8,
128.8, 129.0, 136.5, 142.8, 144.3, 156.0, 160.7.
2-Anilino-2-(hydroxyimino)-N-phenylacetamide (5a)
IR (Nujol): 3375, 3300, 3260, 1661, 1622, 1590 cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.40 (br s, 2 H, exchangeable with
D2O), 7.05 (d, 2 H, J = 7.0 Hz), 7.08–7.25 (m, 1 H), 7.30–7.48 (m,
5 H), 7.61 (d, 2 H, J = 8.9 Hz), 8.81 (br s, 1 H, exchangeable with
D2O).
MS (EI): m/z (%) = 283 (77), 267 (30), 266 (89), 222 (21), 196 (6),
159 (11), 146 (15), 133 (85), 132 (89), 118 (94), 106 (100).
Anal. Calcd for C16H17N3O2: C, 67.83; H, 6.05; N, 14.83. Found: C,
67.63; H, 6.16; N, 14.91.
13C NMR (CDCl3, 75.5 MHz): d = 119.8, 122.1, 124.0, 124.8,
128.4, 129.1, 137.0, 142.0, 153.5, 154.1.
MS (EI): m/z (%) = 255 (100), 238 (19), 132 (20), 119 (66), 104
(57), 93 (74), 77 (68).
MALDI-FTMS: m/z calcd for C14H14N3O2 [M + H]+: 256.1086;
N-Cyclohexyl-2-(cyclohexylamino)-2-(hydroxyimino)acet-
amide (5f)
IR (Nujol): 3360, 3320, 3250, 1655, 1615 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.11–1.50 (m, 10 H), 1.59–1.85
(m, 6 H), 1.90–2.09 (m, 4 H), 3.72–3.86 (m, 1 H), 3.95–4.12 (m, 1
H), 5.20 (br d, 1 H, J = 8.85 Hz, exchangeable with D2O), 6.11 (br
s, 1 H, exchangeable with D2O), 6.72 (br d, 1 H, J = 8.0 Hz, ex-
changeable with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 24.7, 24.8, 25.4, 25.5, 48.4, 52.0,
145.4, 160.1.
found: 256.1080.
2-Anilino-N-cyclohexyl-2-(hydroxyimino)acetate (5b)
IR (Nujol): 3390, 3260, 3170, 1650, 1628, 1590 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.12–1.50 (m, 5 H), 1.55–1.86 (m,
3 H), 1.90–2.05 (m, 2 H), 3.72–3.88 (m, 1 H), 6.72 (br d, 1 H, ex-
changeable with D2O), 6.96 (d, 2 H, J = 7.9 Hz), 6.97 (br s, 1 H, ex-
changeable with D2O), 7.05 (t, 1 H, J = 7.9 Hz), 7.16 (br s, 1 H,
exchangeable with D2O), 7.25 (t, 2 H, J = 7.9 Hz).
MS (EI): m/z (%) = 267 (35), 251 (100), 235 (8), 219 (21), 186 (9),
168 (72), 151 (35), 140 (43), 131 (19), 123 (53), 108 (91).
Synthesis 2005, No. 3, 407–410 © Thieme Stuttgart · New York

410
D. N. Nicolaides et al.
PAPER
Anal. Calcd for C14H25N3O2: C, 62.89; H, 9.42; N, 15.72. Found: C,
63.15; H, 9.69; N, 15.65.
Anal. Calcd for C15H15N3O2: C, 66.90; H, 5.61; N, 15.60. Found: C,
66.72; H, 5.57; N, 15.65.
2-(Cyclohexylamino)-2-(hydroxyimino)-N-phenylacetamide
(5g)
2-(Hydroxyimino)-N-methyl-2-(methylanilino)-N-phenylacet-
amide (5j)
IR (Nujol): 3400, 3320, 3280, 1662, 1620, 1580 cm–1.
IR (Nujol): 3240, 1650, 1610, 1580 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.08–1.23 (m, 3 H), 1.24–1.39 (m,
2 H), 1.59 (d, 1 H, J = 12.8 Hz), 1.70 (d, 2 H, J = 12.8 Hz), 2.00 (d,
2 H, J = 8.9 Hz), 4.02–4.13 (m, 1 H), 5.28 (d, 1 H, J = 8.9 Hz, ex-
changeable with D2O), 7.03 (br s, 1 H, exchangeable with D2O),
7.12 (t, 1 H, J = 7.9 Hz), 7.32 (t, 2 H, J = 7.9 Hz), 7.54 (d, 2 H,
J = 7.9 Hz), 8.73 (s, 1 H, exchangeable with D2O).
1H NMR (CDCl3, 300 MHz): d = 2.39 (s, 3 H), 3.08 (s, 3 H), 6.63
(d, 2 H, J = 7.9 Hz), 6.89 (d, 2 H, J = 6.9 Hz), 6.97 (t, 1 H, J = 6.9
Hz), 7.21–7.32 (m, 3 H), 7.39 (t, 2 H, J = 7.9 Hz), 8.35 (br s, 1 H,
exchangeable with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 35.0, 37.9, 117.4, 121.7, 125.8,
127.5, 128.6, 129.3, 142.5, 143.7, 147.9, 159.5.
13C NMR (CDCl3, 75.5 MHz): d = 24.8, 25.5, 35.0, 52.1, 119.8,
124.6, 129.1, 137.1, 144.9, 158.9.
MS (EI): m/z (%) = 283 (86), 266 (85), 190 (9), 159 (40), 146 (100),
134 (91), 132 (91), 118 (48).
MS (EI): m/z (%) = 261 (18), 244 (53), 162 (24), 147 (10), 132 (14),
120 (32), 108 (100).
Anal. Calcd for C16H17N3O2: C, 67.83; H, 6.05; N, 14.83. Found: C,
67.62; 5.96; N, 14.73.
Anal. Calcd for C14H19N3O2: C, 64.35; H, 7.33; N, 16.08. Found: C,
64.75; H, 7.30; N, 15.72.
Acknowledgment
N-Benzyl-2-(cyclohexylamino)-2-(hydroxyimino)acetamide
(5h)
D. R. Gautam thanks State Scholarships Foundation (IKY), Greece,
for financial support and Tribhuvan University, Kathmandu, Nepal,
for granting him the Ph.D. study leave.
IR (Nujol): 3420, 3330, 3180, 1660, 1635, 1605 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.23–1.80 (m, 8 H), 2.02–2.07 (m,
2 H), 4.08–4.22 (m, 1 H), 4.55 (d, 2 H, J = 5.9 Hz), 7.27–7.38 (m, 3
H), 7.42 (d, 2 H, J = 6.9 Hz), 7.78 (br d, 1 H, J = 8.7 Hz, exchange-
able with D2O), 9.89 (br s, 1 H, exchangeable with D2O), 10.27 (br
t, 1 H, J = 5.9 Hz, exchangeable with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 23.8, 24.8, 31.5, 44.8, 52.3,
127.8, 128.5, 128.7, 136.4, 151.5, 154.9.
References
(1) Nicolaides, D. N.; Varella, E. A. The Chemistry of
Amidoximes, In The Chemistry of Acid Derivatives, Vol. 2;
Patai, S., Ed.; Wiley: New York, 1992, 876–966.
(2) Nicolaides, D. N.; Fylaktakidou, K. C.; Litinas, K. E.;
Hadjipavlou-Litina, D. Eur. J. Med. Chem. 1998, 715.
(3) Nicolaides, D. N.; Litinas, K. E.; Vrasidas, I.; Fylaktakidou,
K. C. J. Heterocycl. Chem. 2004, 41, 499.
(4) Coburn, M. D. J. Heterocycl. Chem. 1968, 5, 83.
(5) Grundmann, C. Angew. Chem. 1963, 75, 450.
(6) Langer, P.; Schroeder, R. Eur. J. Org. Chem. 2004, 1025.
(7) Khalilova, S.; Poplavskaya, I. Izv. Akad. Nauk. Kar. SSR,
Ser. Khim. 1988, 74; Chem. Abstr. 1988, 109, 169982b.
(8) Shimizu, T.; Hayashi, Y.; Ito, T.; Teramura, K. Synthesis
1986, 488.
(9) Huisgen, R.; Christl, M. Chem. Ber. 1973, 106, 3291.
(10) Skinner, G. S. J. Am. Chem. Soc. 1924, 46, 731.
(11) Gilchrist, T. L.; Harris, C. J.; King, F. D.; Peek, M. E.; Rees,
C. W. J. Chem. Soc., Perkin Trans. 1 1976, 2161.
(12) Itsuno, S.; Miyazaki, K.; Ito, K. Tetrahedron Lett. 1986, 27,
3033.
MS (EI): m/z (%) = 275 (4), 258 (52), 211 (12), 196 (19), 176 (20),
123 (9), 108 (100).
Anal. Calcd for C15H21N3O2: C, 65.43; H, 7.69; N, 15.26. Found: C,
65.42; H, 7.69; N, 15.27.
2(Hydroxyimino)-2-(methylanilino)-N-phenylacetamide (5i)
IR (Nujol): 3300, 3240, 1655, 1630, 1580 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.32 (s, 3 H), 6.86 (d, 2 H, J = 8.9
Hz), 6.97 (t, 1 H, J = 7.9 Hz), 7.12 (t, 1 H, J = 6.9 Hz), 7.24–7.40
(m, 4 H), 7.55 (d, 2 H, J = 7.9 Hz), 7.94 (br s, 1 H, exchangeable
with D2O), 8.54 (br s, 1 H, exchangeable with D2O).
13C NMR (CDCl3, 75.5 MHz): d = 37.1, 116.5, 119.7, 121.7, 124.7,
129.0, 129.1, 137.2, 145.2, 148.4, 158.3.
MS (EI): m/z (%) = 269 (44), 253 (39), 252 (42), 181 (8), 160 (49),
147 (9), 133 (51), 118 (81).
Synthesis 2005, No. 3, 407–410 © Thieme Stuttgart · New York