2-Acylpyridazin-3-ones: Novel mild and chemoselective acylating agents for amines

Article abstract of DOI:10.1055/s-2002-25760

2-Acyl-4,5-dichloropyridazin-3-ones served as excellent novel N-acylating reagents for amines under neutral conditions in organic solvent. They are convenient, chemoselective and easy to handle stable N-acylating reagents of amines.

Full text of DOI:10.1055/s-2002-25760

PAPER
733
2-Acylpyridazin-3-ones: Novel Mild and Chemoselective Acylating Agents for
Amines
2
-Acylpyridazin-3
o
-one
s
as Che
u
moselective
n
A
cylating
A
g
g
e
nts
f
or
A
m
-
ine
s
Jin Kang, Hyun-A Chung, Jeum-Jong Kim, Yong-Jin Yoon*
Department of Chemistry and Research Institute of Natural Sciences, Gyeongsang National University, Chinju 660-701, Korea
Fax +82(55)7610244; E-mail: yjyoon@nongae.gsnu.ac.kr
Received 7 January 2002; revised 27 February 2002
Table 1 Preparation of 2-Acylpyridazin-3-ones 2
Abstract: 2-Acyl-4,5-dichloropyridazin-3-ones served as excellent
novel N-acylating reagents for amines under neutral conditions in
organic solvent. They are convenient, chemoselective and easy to
handle stable N-acylating reagents of amines.
Entry Acyl Chloride
Reaction
Conditions
Prod-
uct
Yield
(%)a
1
2
3
4
5
6
7
8
acetyl
25 °C, 5 min
25 °C, 5 min
25 °C, 5 min
–10 °C, 10 min
2a
2b
2c
2d
2e
2f
97
99
96
82
84
81
80
99
Key words: 2-acylpyridazin-3-one, chemoselective N-acylation,
pyridazinone
propionyl
hexanoyl
benzoyl
Chemoselective acylation of amino groups is an important
reaction in synthetic operation1 and is often required in or-
ganic synthesis. Common routes to amides mostly involve
the treatment of activated derivatives of carboxylic acids
such as acyl halides, acid anhydrides, or esters, with am-
monia or amines.2 However, these methods have some
problems such as exothermic reaction, formation of
byproducts, complicated conditions3 and low selectivity.
In order to overcome the problems, a variety of reagents
have been developed,4 and continuing efforts are being
made to find an ideally chemoselective and neutral re-
agent. It is reasonably assumed that a reagent bearing a
bulky, electron acceptable leaving group may satisfy such
a requirement.
In accordance with the literature,5 treatment of 2-alkyl-
substituted pyridazin-3-ones with nucleophiles such as
azide, water, K2CO3/H2O and methoxide give the corre-
sponding pyridazin-3-ones with releasing alkyl moieties.
Retro-ene reaction of 2-hydroxymethyl- or 2-acetyloxym-
ethylpyridazin-3-ones by a base also yields the corre-
sponding pyridazin-3-ones.6 Therefore, pyridazin-3-ones
may be regarded as a good electron acceptable leaving
group. Also, sufficient steric bulkiness would be provided
around the acyl carbonyl group in 2-acylpyridazin-3-ones
2. The present study was undertaken as part of our pro-
gram directed toward development of a new N-acylation
reagent. In this paper, we would like to report a simple,
mild and general procedure for the preparation of amides
under neutral conditions using compound 2 as acylating
reagents. 2-Acylpyridazin-3-ones 2 were easily prepared
by the N(2)-acylation of 1 with acyl chlorides in the pres-
ence of triethylamine in dichloromethane in good to ex-
cellent yields (Table 1).
4-methoxybenzoyl –10 °C, 10 min
4-methylbenzoyl
4-chlorobenzoyl
25 °C, 5 min
–22 °C, 30 min
2g
2h
cyclohexylcarbonyl 25 °C, 10 min
a Isolated yield.
with 2 (1 equiv) was examined in dichloromethane or
THF at 18–20 °C with monitoring by TLC. The results are
shown in Table 2. All compounds 2 served as excellent N-
acylation reagents (Scheme 1).
Scheme 1
Table 2 Acylation Reactivity of 2a,c–e,g,h with 4-Methylbenzy-
lamine (3a) in CH2Cl2 or THF
Entry
2
Reaction Conditions
17 °C, 5 min
Amide
Yield (%)a
1
2
3
4
5
6
2a
2c
2d
2e
2g
2h
4
5
6
7
8
9
98
96
96
99
92
94
20 °C, 5 min
22 °C, 10 min
22 °C, 10 min
20 °C, 10 min
20 °C, 10 min
In order to evaluate their N-acyl transfer potentiality, acy-
lation of 4-methylbenzylamine (3a) as a primary amine
Synthesis 2002, No. 6, 29 04 2002. Article Identifier:
1437-210X,E;2002,0,06,0733,0738,ftx,en;F00202SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
a Yield of isolated product. Compound 1 was also recovered quanti-
tatively.

734
Y.-J. Kang et al.
PAPER
Chemoselective acylation of various amines with 2a, 2d for the -branched amine (Table 4, Entries 4 and 5). In a
and 2e was also examined in THF. The results are shown mixture of N-methylamine 3m and N-isopropylamine 3o,
in Table 3. Aniline, amino alcohols and amino acids were acylation occurred only at the amino group of N-methyl-
all chemoselectively acylated, affording the correspond- amine 3m. In all mixtures of a hindered amine and a less-
ing amides in excellent yields (Scheme 2).
hindered amine, N-acylation occurs generally at the less-
hindered amino group. This selectivity may be due to the
steric bulkiness around the acyl carbonyl group in com-
pounds 2.
Scheme 3
In conclusion, our new acylating reagents have several ad-
vantages as follows: (1) they are easily prepared from
commercially available compound 1 in one step under
mild condition, (2) they are stable in air and easy to han-
dle, (3) they show good chemoselectivity for amino group
in bifunctional amines involving OH and CO2H groups
and for a less-hindered amino group in a molecule con-
taining both less-hindered and hindered amino groups,
and (4) compound 1 can be recovered quantitatively for
reuse. We also believe that these novel acylating and
aroylating reagents should be particularly applicable to
solid phase syntheses.
Scheme 2
We also investigated the selectivity in the benzoylation of
a mixture (1:1 equiv) of a hindered amine and a less-hin-
dered amine with 2e (Scheme 3). The results are summa-
rized in Table 4. In a mixture of a primary amine and a
secondary amine, N-acylation of the primary amine is
more favorable than the secondary amine (Table 4, En-
tries 1, 2 and 3). In the case of a mixture of a -branched
amine and a primary or a secondary amine, acyl transfer
of primary and secondary amines is more selective than
Table 3 Acylation of Various Amines with 2a, 2d, 2e in THF
Entry
2
Amine 3
Reaction Conditionsa
0.5 h, rf
Amide
10
Yield (%)b
1
2a
2a
2a
2a
2a
2d
2d
2d
2d
2d
2e
2e
2e
2e
2e
aniline (3b)
95
94
84
94
95
98
97
98
84
94
99
93
72
87
99
2
2-(4-aminophenyl)ethanol (3c)
glycine (3d)
0.2 h, 17 °C
4 h, rf
11
3
12
4
2-aminobenzoic acid (3e)
4-aminophenol (3f)
aniline (3b)
14 h, rf
13
5
0.2 h, 17 °C
4 h, rf
14
6
15
7
2-(4-aminophenyl)ethanol (3c)
glycine (3d)
18 h, 18 °C
24 h, rf
16
8
17
9
2-aminobenzoic acid (3e)
4-aminophenol (3f)
aniline (3b)
34 h, rf
18
10
12 h, 18 °C
3 h, rf
19
11
20
12
2-(4-aminophenyl)ethanol (3c)
glycine (3d)
7 h, 18 °C
42 h, rf
21
13
22
14
5-aminonaphthol (3g)
4-aminophenol (3f)
14 h, rf
23
15
5 h, 18 °C
24
a rf = Reflux.
b Isolated yield. Also, compound 1 was recovered quantitatively.
Synthesis 2002, No. 6, 733–738 ISSN 0039-7881 © Thieme Stuttgart · New York

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2-Acylpyridazin-3-ones as Chemoselective Acylating Agents for Amines
735
ried out on silica gel 60 (70–230 mesh). Melting points were deter-
mined with a Thomas–Hoover capillary apparatus and are
uncorrected. 1H and 13C NMR spectra were obtained on a Bruker FT
NMR-DRX 500 or Varian Inova 500 spectrometer and with chem-
ical shift values reported in units (part per million) relative to an
internal standard (teteramethylsilane). IR spectra were obtained on
a Hitachi 270-50 or Mattson Genesis Series FT-IR spectrophotom-
eter. Elemental analyses were performed with a Perkin-Elmer 240C
apparatus.
Table 4 Competition Reaction of Amines with 2e
Entry Mixture of Amines 3 Benzamide (%)a
Ratiob
R = 4-MeOC6H4
1
2
3
4
5
EtNH2 (3h)
(Et)2NH (3i)
EtNHCOR 25 (85)
(Et)2NCOR 26 (14)
6:1
–
C6H11NH2 (3j)
(C6H11)2NH (3k)
C6H11NHCOR 27 (97)
PhCH2NHCOR 28 (99)
PhCH2NHCOR 28 (75)
2-Acylpyridazin-3-ones 2; General Procedure
PhCH2NH2 (3l)
PhCH2NHMe (3m)
–
To a solution of 1 (0.5 g, 3.03 mmol) and Et3N (0.42–0.84 mL,
3.03–6.06 mmol) in CH2Cl2 (15 mL) was added dropwise the appro-
priate acyl halide (3.33–6.06 mmol), and the mixture was stirred for
5–30 min at –22 °C to 25 °C (Table 1). The mixture was evaporated
under reduced pressure and the product was extracted with Et2O
(100 mL). The Et2O extract was evaporated under reduced pressure,
and the resulting residue was recrystallized from THF/n-hexane
(1:2, v/v) to give 2 (Table 5).
PhCH2NH2 (3l)
PhMeCHNH2 (3n)
PhMeCHNHCOR 29 (21) 3.5:1
PhMeCHNH2 (3n)
PhCH2NHMe (3m)
PhMeCHNHCOR 29 (9)
PhCH2(Me)NCOR 30
1:10
–
(89)
6
PhCH2NHMe (3m)
PhCH2(Me)NCOR 30
N-Acylation of Amines; General Procedure
PhCH2NH(i-Pr) (3o) (98)
To a solution of the corresponding amine 3 (1 equiv) or a mixture
of two amines (1:1 equiv) in anhyd THF or CH2Cl2 (10 mL) was
added the appropriate 2-acylpyridazinones 2 (3 mmol). The mixture
was stirred at a suitable temperature (Tables 2, 3) until 2 had disap-
peared (TLC monitoring). After evaporation of the solvent, the
product was isolated by silica gel column chromatography. Frac-
tions containing the product were combined and evaporated under
reduced pressure to give the corresponding amides (Tables 6– 9).
a Isolated yield. Compound 1 was isolated quantitatively.
b The ratio was determined by 1H NMR (500 MHz) analysis.
Reagents and solvents were used as received from commercial
sources. TLC was performed on silica gel (60 F254 Merck). The
spots were located by UV light. Column chromatography was car-
Table 5 Physical and Spectral Data of 2a–h
b
Producta Mp (°C)
IR (KBr) (cm–1)
1765, 1700 (C=O)
1780, 1695 (C=O)
1H NMR, , J (Hz)b
13C NMR,
2a
2b
109–110
107–109
2.72 (s, 3 H), 7.88 (s, 1 H)
25.8, 136.7, 136.9, 155.5, 170.6
1.26 (t, 3 H, J = 7.3), 3.09 (q, 2 H, J = 7.3),
8.6, 31.4, 136.5, 136.9, 155.5, 174.4
7.87 (s, 1 H)
2c
2d
2e
2f
80–82
84–85
1780, 1690 (C=O)
1750, 1690 (C=O)
1750, 1675 (C=O)
1760, 1675 (C=O)
1760, 1680 (C=O)
1740, 1670
0.87 (t, 3 H, J = 2.2), 1.31 (m, 4 H), 1.63 (t, 2 13.7, 21.8, 23.5, 30.4, 36.6, 135.1,
H, J = 7.3), 2.99 (t, 2 H, J = 7.4), 8.26 (s, 1 H) 136.0, 136.6, 154.7, 174.1
7.50 (t, 2 H, J = 7.7), 7.67 (t, 1 H, J = 7.5), 7.82 129.0, 130.3, 130.9, 135.1, 135.7,
(m, 2 H), 7.89 (s, 1 H)
136.5, 137.5, 155.6, 168.6
184–185
123–125
130–132
79–81
3.88 (s, 3 H), 6.96 (d, 2 H, J = 9.0), 7.79 (d, 2 55.8, 114.5, 122.3, 133.7, 135.6,
H, J = 9.0), 7.88 (s, 1 H) 136.3, 137.4, 155.6, 165.4, 167.6
2.44 (s, 3 H), 7.30 (d, 2 H, J = 8.1), 7.72 (d, 2 21.9, 127.5, 129.8, 131.1, 135.7,
H, J = 8.3), 7.88 (s, 1 H)
136.4, 137.4, 146.7, 155.6, 168.4
2g
2h
7.50 (d, 2 H, J = 8.6), 7.80 (d, 2 H, J = 8.6),
7.96 (s, 1 H)
128.8, 129.4, 132.2, 135.6, 136.8,
137.6, 141.6, 155.5, 167.8
1.25 (m, 1 H), 1.40 (m, 2 H), 1.73 (m, 2 H),
1.90 (m, 2 H), 3.30 (m, 1 H), 8.27 (s, 1 H)
24.7, 25.2, 27.8, 28.2, 43.7, 134.9,
136.3, 136.8, 154.8, 177.2
a Satisfactory elemental analyses obtained: C 0.21, H 0.12, N 0.12.
b Solvent: CDCl3 for 2a–f, CDCl3 + DMSO-d6 for 2g and DMSO-d6 for 2h. All signals of NH hydrogens were exchangeable with D2O.
Synthesis 2002, No. 6, 733–738 ISSN 0039-7881 © Thieme Stuttgart · New York

736
Y.-J. Kang et al.
PAPER
Table 6 Physical and Spectral Data of 4–11
b
Producta Mp (°C)
IR (KBr)
(cm–1)
1H NMR, , J (Hz)b
13C NMR,
4
5
112–113
69–71
3300 (NH), 1640 (C=O)
1.85 (s, 3 H), 2.27 (s, 3 H), 4.19 (d, 2 H,
J = 5.9), 7.12 (m, 4 H), 8.24 (br s, 1 H, NH)
21.0, 22.9, 42.2, 127.6, 129.1,
136.1, 136.9, 169.4
3290 (NH), 1640 (C=O)
0.85 (t, 3 H, J = 7.2), 1.24 (m, 4 H), 1.51 (q, 2 14.2, 21.0, 22.2, 25.4, 31.3, 35.7,
H, J = 7.1), 2.12 (q, 2 H, J = 7.5), 2.27 (s, 3 H), 42.1, 127.5, 129.1, 136.0, 137.1,
4.20 (d, 2 H, J = 5.8), 7.11 (s, 4 H), 8.19 (br s, 172.4
1 H, NH)
6
7
8
9
131–133
155–156
197–198
136–137
3300 (NH),
1645 (C=O)
2.22 (s, 2 H), 4.40 (d, 2 H, J = 6.0), 7.08 (d, 2
21.0, 42.7, 127.5, 127.6, 128.6,
H, J = 7.9), 7.17 (d, 2 H, J = 7.9), 7.42 (t, 2 H, 129.2, 131.5, 134.8, 136.1, 137.0,
J = 7.2, 7.7), 7.47 (t, 1 H, J = 7.3), 7.85 (t, 2 H, 166.5
J = 7.2), 8.95 (br s, 1 H, NH)
3300 (NH),
1645 (C=O)
2.27 (s, 3 H), 3.80 (s, 3 H), 4.42 (d, 2 H,
J = 8.0), 6.69 (m, 2 H), 7.12 (d, 2 H, J = 7.9),
7.19 (d, 2 H, J = 8.0), 7.87 (m, 2 H), 8.82 (t, 1 161.9, 166.0
H, NH, J = 5.9)
21.0, 42.6, 55.7, 113.8, 127.0,
127.5, 129.1, 129.4, 136.0, 137.2,
3300 (NH),
1640 (C=O)
2.27 (s, 3 H), 4.43 (d, 2 H, J = 5.9), 7.13 (d, 2
H, J = 7.8), 7.20 (d, 2 H, J = 7.9), 7.54 (d, 2 H, 129.1, 133.1, 135.7, 135.9, 136.3,
J = 8.5), 7.90 (d, 2 H, J = 8.5), 9.05 (br s, 1 H, 165.0
NH)
20.6, 42.4, 127.2, 128.3, 128.7,
3300 (NH),
1640 (C=O)
1.19 (m, 3 H), 1.37 (q, 2 H, J = 10.3, 11.8), 1.62 21.0, 25.6, 25.8, 29.6, 41.9, 44.4,
(d, 1H, J = 11.2), 1.71 (d, 4 H, J = 10.9), 2.15 127.3, 129.1, 135.9, 137.2, 175.4
(q, 1 H, J = 11.6), 2.27 (s, 3 H), 4.20 (d, 2 H,
J = 5.9), 7.11 (s, 4 H), 8.13 (br s, 1 H, NH)
10
11
111–113b
102–104
3300 (NH),
1670 (C=O)
2.05 (s, 3 H), 7.02 (t, 1 H, J = 7.3), 7.29 (t, 2 H, 14.2, 21.0, 22.2, 25.4, 31.3, 35.7,
J = 8.0), 7.58 (d, 2 H, J = 7.9), 9.92 (br s, 1 H, 42.1, 127.5, 129.1, 136.0, 137.1,
NH)
172.4
3300–2900 (NH + OH),
1680 (C=O)
2.43 (t, 2 H, J = 7.1), 3.34 (t, 2 H, J = 7.1), 4.39 24.3, 38.8, 62.6, 119.3, 134.5,
(br s, 1 H, OH), 6.89 (d, 2 H, J = 8.3), 7.24 (d, 137.6, 168.4
2 H, J = 8.4), 9.61 (br s, 1 H, NH)
a Satisfactory elemental analyses obtained: C 0.19, H 0.18, N 0.16.
b Solvent: CDCl3 for 10 and DMSO-d6 for 4–9 and 11. All signals of NH and OH hydrogens were exchangeable with D2O.
Table 7 Physical and Spectral Data of 12–17
b
Producta Mp (°C)
IR (KBr) (cm–1)
1H NMR, , J (Hz)b
13C NMR,
12
204–205c
3480–3300 (NH + OH),
1730 (C=O)
1.85 (s, 3 H), 3.72 (d, 2 H J = 5.9), 8.13 (s, 1 H, 22.2, 40.5, 169.5, 171.3
OH), 12.58 (br s, NH)
13
257–259
3400–2900 (NH + OH),
1700 (C=O)
2.10 (s, 3 H), 5.08 (br s, 1 H, OH), 7.05 (t, 1 H, 25.0, 118.9, 120.2, 121.7, 131.1,
J = 7.5), 7.43 (t, 1 H, J = 7.4), 8.02 (d, 1 H,
J = 7.8), 8.47 (d, 1 H, J = 8.3), 12.38 (br s, 1 H,
NH)
132.0, 140.7, 168.0, 170.5
14
15
167–169d
159–161e
3350 (OH), 3230 (NH),
1675 (C=O)
1.99 (s, 3 H), 6.69 (q, 2 H, J = 5.1), 7.35 (t, 2 H, 24.1, 115.4, 121.2, 131.4, 153.5,
J = 6.9), 9.12 (s, 1 H, OH), 9.66 (s, 1 H, NH) 167.9
3350 (NH),
1660 (C=O)
7.14 (t, 1 H, J = 7.5), 7.36 (m, 2 H), 7.47 (m, 2 120.3, 124.6, 127.1, 128.8, 129.1,
H), 7.53 (m, 1 H), 7.63 (d, 2 H, J = 7.7), 7.83 (br 131.8, 135.2, 138.1, 165.7
s, 1 H, NH), 7.85 (m, 2 H)
Synthesis 2002, No. 6, 733–738 ISSN 0039-7881 © Thieme Stuttgart · New York

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2-Acylpyridazin-3-ones as Chemoselective Acylating Agents for Amines
737
Table 7 Physical and Spectral Data of 12–17 (continued)
b
Producta Mp (°C)
IR (KBr) (cm–1)
1H NMR, , J (Hz)b
13C NMR,
16
145–146
3340 (NH),
1660 (C=O)
2.50 (m, 2 H), 3.59 (t, 2 H, J = 7.1), 4.60 (br s, 38.4, 62.2, 120.2, 127.5, 128.2,
1 H, OH), 7.19 (d, 2 H, J = 8.4), 7.51 (t, 2 H,
J = 7.1), 7.57 (d, 1 H, J = 6.1), 7.67 (q, 2 H,
J = 5.2), 7.94 (q, 2 H, J = 5.2), 10.15 (s, 1 H,
NH)
131.3, 134.8, 134.9, 137.0, 165.2
17
189–190f
3350 (NH),
3500–2900
(OH),
3.94 (d, 2 H, J = 5.9), 7.48 (t, 2 H, J = 7.2), 7.54 41.2, 127.1, 128.2, 131.3, 133.8,
(m, 1 H), 7.88 (t, 2 H, J = 7.3), 8.79 (t, 1 H, NH, 166.4, 171.2
J = 5.8), OH signal was not detected
1740 (C=O)
1760 (C=O)
a Satisfactory elemental analyses obtained: C 0.19, H 0.11, N 0.13.
b Solvent: CDCl3 for 15 and DMSO-d6 for 12–14,16,17. All NH and OH signals were exchangeable with D2O.
c Lit.7 mp 206 °C.
d Lit.7 mp 170 °C.
e Lit.7 mp 163 °C.
f Lit.7 mp 191.5 °C.
Table 8 Physical and Spectral Data of 18–23
b
Producta
Mp (°C)
173–175
IR (KBr)
(cm–1)
1H NMR, , J (Hz)b
13C NMR,
18
3300–2800
(NH + OH),
1680 (C=O)
3.39 (br s, 1 H), 7.23 (d, 2 H, J = 8.1), 7.63 (q, 116.5, 119.8, 122.9, 126.9, 128.9,
2 H, J = 7.7), 7.66 (t, 2 H, J = 6.9), 7.97 (t, 2 H, 131.2, 132.1, 134.2, 134.5, 141.1,
J = 7.1), 8.08 (t, 1 H, J = 7.9), 8.14 (t, 1 H,
J = 7.8), 12.19 (s, 1 H)
164.6, 169.9
19
20
21
211–212
170–171
150–151
3420 (OH),
3350 (NH),
1660 (C=O)
6.74 (q, 2 H, J = 4.7), 7.52 (m, 5 H), 7.92 (t, 2 115.4, 123.0, 127.7, 128.9, 130.6,
H, J = 7.1), 9.23 (s, 1 H, OH), 9.99 (s, 1 H, NH) 131.7, 134.9, 153.8, 165.9
3350 (NH),
1660 (C=O)
3.69 (s, 3 H), 6.92 (m, 3 H), 7.19 (t, 2 H,
J = 7.9), 7.62 (d, 2 H, J = 7.8), 7.83 (q, 2 H,
J = 7.0), 9.93 (s, 1 H, NH)
55.8, 113.9, 120.7, 123.8, 127.3,
128.9, 129.9, 139.7, 162.2, 165.3
3400 (OH),
3300 (NH),
1650 (C=O)
2.02 (t, 2 H, J = 7.1), 3.59 (m, 2 H), 3.84 (s, 3 38.9, 55.8, 62.6, 113.9, 120.7,
H), 4.63 (t, 1 H, OH, J = 5.2), 7.05 (d, 2 H,
J = 8.8), 7.18 (d, 2 H, J = 8.4), 7.65 (d, 2 H,
J = 8.4), 7.95 (d, 2 H, J = 8.8), 10.01 (br s, 1 H,
NH)
127.4, 129.2, 129.9, 134.9, 137.6,
162.2, 165.1
22
23
158–160
248–249
3360 (NH),
3500–2850
(OH),
3.82 (s, 3 H), 3.91 (d, 2 H, J = 5.7), 7.01 (d, 2 42.0, 56.2, 114.4, 114.7, 127.0,
H, J = 8.7), 7.85 (d, 2 H, J = 8.7), 8.65 (t, 1 H, 130.0, 132.2, 162.6, 166.9, 172.3
NH, J = 5.6), 12.52 (b s, 1 H, OH)
1740, 1620 (C=O)
3500-3150
(NH + OH)
1640 (C=O)
3.85 (s, 3 H), 6.91 (d, 1 H, J = 7.4), 7.08 (d, 2 55.3, 108.1, 113.6, 113.8, 120.2,
H, J = 8.8), 7.32 (t, 1 H, J = 7.8, 8.2), 7.42 (d, 1 123.9, 124.2, 125.3, 126.2, 126.6,
H, J = 8.4), 7.46 (t, 1 H, J = 7.9), 7.55 (d, 1 H, 129.6, 130.8, 133.6, 153.3, 161.8,
J = 7.2), 8.08 (t, 3 H, J = 8.9), 10.16 (br s, 2 H, 165.4
OH + NH)
a Satisfactory elemental analyses obtained: C 0.18, H 016, N 0.18.
b Solvent: DMSO-d6. All signals of NH and OH hydrogens were exchangeable with D2O.
Synthesis 2002, No. 6, 733–738 ISSN 0039-7881 © Thieme Stuttgart · New York

738
Y.-J. Kang et al.
PAPER
Table 9 Physical and Spectral Data of 24–30
b
Producta
Mp (°C)
223–225
IR (KBr) (cm–1) 1H NMR, , J (Hz)b
13C NMR,
24
3400 (OH),
3300 (NH),
1660 (C=O)
3.83 (s, 3 H), 6.73 (d, 2 H, J = 8.8), 7.04 (d, 2 H, 55.3, 113.4, 114.8, 122.2, 127.1, 129.3,
J = 8.7), 7.04 (d, 2 H, J = 8.7), 7.51 (d, 2 H, J = 8.8), 130.7, 153.5, 161.6, 164.3
7.93 (d, 2 H, J = 8.7), 9.19 (s, 1 H, OH), 9.83 (s, 1
H, NH)
25
69–70
3340 (NH),
1640 (C=O)
1.11 (t, 3 H, J = 7.2), 3.27 (m, 2 H), 3.80 (s, 3 H),
6.97 (d, 2 H, J = 8.8), 7.81 (d, 2 H, J = 8.9), 8.27 (s, 161.3, 165.3
14.8, 33.8, 55.2, 113.3, 126.9, 128.8,
1 H, NH)
26
27
oil
1635 (C=O)
1.09 (t, 6 H, J = 6.7), 3.30 (s, 3 H), 6.96 (d, 2 H,
J = 8.7), 7.30 (d, 2 H, J = 8.7)
13.5, 55.1, 113.5, 127.9, 129.3, 159.7,
169.8
163–164
3320 (NH),
1640 (C=O)
1.13 (m, 1 H), 1.28 (4 H), 1.61 (t, 1 H, J = 11.6),
24.9, 25.2, 32.4, 48.0, 48.1, 55.2, 113.2,
1.72 (2 H, J = 4.6), 1.80 (d, 2 H, J = 8.1), 3.74 (t, 1 127.1, 128.9, 161.3, 164.7
H, J = 3.6), 3.80 (s, 3 H), 6.97 (m, 2 H), 7.83 (m, 2
H), 7.99 (d, 1H, NH, J = 7.8)
28
29
131–132
143–144
3290 (NH),
1640 (C=O)
3.81 (s, 3 H), 4.47 (d, 2 H, J = 5.9), 7.00 (m, 2 H), 42.5, 55.2, 113.4, 126.5, 126.6, 127.1,
7.23 (m, 1 H), 7.31 (m, 4 H), 7.88 (m, 2 H), 8.86 (t, 128.1, 128.9, 139.8, 161.5, 165.6
NH, J = 5.8)
3360 (NH),
1650 (C=O)
1.43 (d, 3 H, J = 7.1), 3.80 (s, 3 H), 5.18 (m, 1 H), 22.6, 48.7, 55.7, 113.7, 126.4, 126.9,
6.99 (d, 2 H, J = 8.8), 7.20 (t, 1 H, J = 7.3), 7.31 (t, 127.2, 128.5, 129.6, 145.5, 161.9, 165.4
2 H, J = 7.8), 7.39 (d, 2 H, J = 8.7), 8.62 (d, 1 H,
NH, J = 8.0)
30
oil
1635 (C=O)
2.84 (s, 3 H), 3.67 (s, 3 H), 4.54 (s, 2 H), 6.77 (d, 2 54.2, 54.3, 112.6, 125.4, 125.7, 126.4,
H, J = 7.0), 7.21 (m, 5 H), 7.32 (t, 2 H, J = 7.1)
126.9, 127.4, 127.7, 127.9, 136.0, 159.7
a Satisfactory elemental analyses obtained: C 0.16, H 0.19, N 0.14.
b Solvent: DMSO-d6 for 24–29 and CDCl3 for 30. All signals of NH and OH hydrogens were exchangeable with D2O.
357. (m) Kikugawa, Y.; Mitsui, K.; Sakamoto, T.; Kawase,
Acknowledgements
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This work was supported by grant No. 2000-1-12300-003-2 from
the Basic Research Program of the Korea Science & Engineering
Foundation.
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Synthesis 2002, No. 6, 733–738 ISSN 0039-7881 © Thieme Stuttgart · New York