Preparation of arylpropynamides and their reaction with malonyl acid derivatives

Article abstract of DOI:10.1055/s-0032-1316851

Synthesis of arylpropynamides and their reactions with different malonic acid derivatives is described. Treatment of arylpropynamides with unsubstituted malonyl chloride furnished N-(3-arylprop-2-ynoyl)-6-chloro-4-hydroxy-2-oxo-2H- pyran-3-carboxamides; m

Full text of DOI:10.1055/s-0032-1316851

PAPER
▌803
paper
Preparation of Arylpropynamides and Their Reaction with Malonyl Acid
Derivatives
Preparation of Arylpropynamides
Olga A. Petina,*a Igor P. Yakovlev,b Detlef Geffkena
a
Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, 20146 Hamburg, Germany
E-mail: petina@chemie.uni-hamburg.de
b
St Petersburg State Chemical Pharmaceutical Academy, ul. Professora Popova 14, 197376 St. Petersburg, Russian Federation
Received: 12.11.2012; Accepted after revision: 17.01.2013
(chlorocarbonyl)ketenes, and a disubstituted malonyl
chloride.
Abstract: Synthesis of arylpropynamides and their reactions with
different malonic acid derivatives is described. Treatment of aryl-
propynamides with unsubstituted malonyl chloride furnished N-(3-
arylprop-2-ynoyl)-6-chloro-4-hydroxy-2-oxo-2H-pyran-3-carbox-
amides; monosubstituted malonyl chlorides or their derivatives,
(chlorocarbonyl)ethylketenes, reacted with arylpropynamides to
give 4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-ones; and the
reaction of arylpropynamides with disubstituted malonyl chlorides
furnished open-chain arylpropenamides exclusively.
3-Phenylprop-2-ynamide (1a) was prepared in high yield
according to literature procedures by the reaction of 3-
phenylprop-2-ynoic acid ester with aqueous ammonia so-
lution.9 Following this procedure, the corresponding aryl-
propynamides 1b–e were obtained in good yields by
ammonolysis of the crude arylpropynoic ethyl esters,
which in turn resulted from esterification of the corre-
sponding arylpropynoic acids with ethanol (Table 1).
Key words: amides, heterocycles, cycloaddition, 1,3-oxazines,
malonyl chlorides
Unexpectedly, treatment of 1a–d with unsubstituted mal-
onyl chloride 2 in diethyl ether or tetrahydrofuran under
ice cooling did not deliver 4-hydroxy-2-(phenylethynyl)-
6H-1,3-oxazin-6-ones of type 8 but N-(3-arylprop-2-yno-
yl)-6-chloro-4-hydroxy-2-oxo-2H-pyran-3-carboxamides
5a–d, the formation of which can be explained according
to Scheme 1: elimination of hydrogen chloride from mal-
onyl chloride affords (chlorocarbonyl)ketene 3 that un-
dergoes [4+2] cycloaddition to give 6-chloro-4-hydroxy-
2-oxo-2H-pyran-3-carbonyl chloride 4,10 which subse-
quently reacts with 1a–d to give N-(3-arylprop-2-ynoyl)-
6-chloro-4-hydroxy-2-oxo-2H-pyran-3-carboxamides
5a–d (Table 1, Scheme 1). In the case of 3-(4-nitrophe-
nyl)prop-2-ynamide (1e), reaction with unsubstituted
malonyl chloride did not take place and 1e was recovered
unchanged from the reaction mixture. Presumably the
presence of the highly electron-withdrawing nitro group
decreases amide nucleophilicity and acylation by 6-chlo-
ro-4-hydroxy-2-oxo-2H-pyran-3-carbonyl chloride (4)
does not occur.
In medicinal chemistry the alkyne group deserves partic-
ular interest because of its bioisosteric relationship to an
aromatic system. In addition, the alkyne group can affect
the pharmacological and pharmacokinetic properties of a
drug molecule.1 As an example, the acetylenic pharmaco-
phore has been realized within steroids,2 the antimycotic
Terbinafin,3 the non-nucleoside reverse transcriptase in-
hibitor Evafirenz and its derivatives,4 and the MAO-inhib-
itors Selegeline and Rasagiline.5
Furthermore, naturally occurring (poly)acetylenes were
found to display interesting biological activity.6 In recent
years enediyne antibiotics, characterized by either nine-
and ten-membered rings containing two triple bonds sep-
arated by a double bond, have attracted considerable inter-
est as novel antitumor agents.7
The present work is aimed at the synthesis of novel and
potentially bioactive alkyne-substituted 1,3-oxazines by
the reaction of arylpropynamides 1 with malonyl chlo-
rides or (chlorocarbonyl)ketenes.
Table 1 Synthesis of Arylpropynamides 1 and N-(3-Arylprop-2-
ynoyl)-4-hydroxy-2-oxo-2H-pyran-3-carboxamides 5
Cyclization of carboxamides with malonyl chlorides or
(chlorocarbonyl)ketenes to 4-hydroxy-6H-1,3-oxazin-6-
ones with different substituents at the 2- and 5-positions is
a well-known reaction.8 A single 4-hydroxy-5-phenyl-2-
(phenylethynyl)-6H-1,3-oxazin-6-one (8e) was prepared
by Komarov et al. from 3-phenylprop-2-ynamide and
phenylmalonyl chloride in refluxing 1,2-dichloroethane.8c
R
Amide 1
Yield (%)
Pyran 5
Yield (%)
Ph
1a
1b
1c
1d
1e
92
72
78
76
67
5a
5b
5c
5d
5e
74
54
63
57
–
2-ClC6H4
4-ClC6H4
4-BrC6H4
4-O2NC6H4
Herein we describe the results from our studies directed to
the reaction of arylpropynamides 1 with unsubstituted
malonyl chloride, monosubstituted malonyl chlorides or
Unambiguous structural assignment of 5a was achieved
by X-ray crystal structure analysis, verifying two intramo-
SYNTHESIS 2013, 45, 0803–0809
Advanced online publication: 15.02.2013
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0
3
9
-
7
8
8
1
1
4
3
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DOI: 10.1055/s-0032-1316851; Art ID: SS-2012-N0882-OP
© Georg Thieme Verlag Stuttgart · New York

804
O. A. Petina et al.
PAPER
Table 2 One-Pot Synthesis of 4-Hydroxy-5-phenyl-2-(phenyleth-
ynyl)-6H-1,3-oxazin-6-ones 8a
Cl
O
O
O
Cl
[4+2]
cycloaddition
Cl
Cl
O
O=C=CRCOCl
O
O
O
7a,b
– HCl
O
Cl
O
Cl
OH
O
3
4
2
O
O
Ph
Ph
R
NH2
N
O
1a
RCH(COCl)2
OH
6a–f
8a–f
O
HN
Et2O
–5 to 0 °C
R
O
O
O
Product
R
Yield (%)
4
R
+
– HCl
NH2
Cl
OH
8a
8b
8c
8d
8e
8f
Me
Et
74
70
62
65
87
61
1a–d
5a–d
Scheme 1 Synthesis of N-(3-arylprop-2-ynoyl)-4-hydroxy-2-oxo-
2H-pyran-3-carboxamides 5a–d
i-Pr
Bu
Ph
lecular hydrogen bonds [O1···H1N1 (d = 1.996 Å, angle
138.70) and O4···H3O3 (d = 1.805 Å, angle 138.61), Fig-
ure 1]. Consequently a significant down field shift of the
Bn
1
a Reaction conditions: Et2O, 0–5 °C.
OH proton resonance signal is observed in the H NMR
spectra (e.g., δ = 15.44 for 5a in DMSO-d6).
OH
R2
O
O
O
O
O
N
O
N
R1
R1
R2
R1
R2
H
N
OH
O
A
B
C
Scheme 2 Possible tautomeric forms of 8a–f
The 1H and 13C NMR spectra of the herein described 4-hy-
droxy-2-(phenylethynyl)-6H-1,3-oxazin-6-ones 8a–f, ex-
hibited only signals consistent with the tautomer A, which
in the case of 8d could unambiguously be proven by X-ray
crystal structure analysis (Figure 2).
Figure 1 Molecular structure of compound 5a
Treatment of 3-phenylprop-2-ynamide (1a) with mono-
substituted malonyl chlorides 6a–f or (chlorocarbon-
yl)ethylketenes 7a,b in diethyl ether at 0–5 °C delivered
the 4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-ones
8a–f in 61–87% yield (Table 2).
Theoretically, the heterocycles 8 (R1 = C≡CPh) can adopt
the tautomeric forms A–C (Scheme 2). Mass spectra of
similar 4-hydroxy-6H-1,3-oxazin-6-ones (R1 = aryl;
R2 = H, Me) showed the presence of 4-hydroxy-6-oxa,
dipolar-ionic and dioxo forms mixture in the gas phase.
The presence of a substituent in the para position of the
benzene ring has a strong influence on the tautomeric ra-
tio. The quantum-chemical calculations revealed structure
A as the most favorable 1,3-oxazine tautomer in the gas
phase. Dissolved in tetrahydrofuran and dimethyl sulfox-
ide-d6 these compounds predominantly exist as tautomer
A.11 In the case of 4-hydroxy-6H-1,3-oxazin-6-ones
(R1 = Bn, Me and R2 = Ph) Sheibani et al were able to de-
tect the tautomer B along with the major tautomer A by
NMR spectroscopy.8b
Figure 2 Molecular structure of compound 8d
Synthesis 2013, 45, 803–809
© Georg Thieme Verlag Stuttgart · New York

PAPER
Preparation of Arylpropynamides
805
Prepared 4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6- In conclusion, we have investigated the reaction of aryl-
ones 8a–f have been proved to be unstable in dimethyl propynamides with malonyl chlorides or (chlorocarbon-
sulfoxide solution. The NMR spectra of samples of 8a–f yl)ethylketenes. Depending on the nature of the malonic
that had been kept in dimethyl sulfoxide-d6 solution for 24 acid derivative N-(3-arylprop-2-ynoyl)-6-chloro-4-hy-
hours at ambient temperature showed in addition to the droxy-2-oxo-2H-pyran-3-carboxamides, 4-hydroxy-2-
signals for 1,3-oxazin-6-ones 8a–f, an additional set of (phenylethynyl)-6H-1,3-oxazin-6-ones, or open-chained
signals belonging to hydrolysis products 9a–f (Supporting monoacylated arylpropenamides are formed.
Information, Figures S32–S41). The reactions of similar
4-hydroxy-6H-1,3-oxazin-6-ones with O-nucleophiles
Melting points were determined using a SMP1 apparatus (Stuart
such as water and alcohols were properly investigated by
Yakovlev’s group and led to formation of the correspond-
ing malonamic acids or their esters through the cleavage
of the C6–O bond in the oxazine ring.8c,g,12 In the case of
8e the intermediate 9e underwent spontaneous decarbox-
ylation giving imide 10 as the final product (Scheme 3);
imide 10 was also obtained on treatment of 4-hydroxy-5-
phenyl-2-(phenylethynyl)-6H-1,3-oxazin-6-one (8e) with
boiling water. The signals of isolated imide 10 (Support-
ing Information, Figures S44–S45) are identical to addi-
tional signals in the NMR spectra of 8e that has been kept
in dimethyl sulfoxide-d6 solution (Supporting Informa-
tion, Figures S42–S43). According to these results, it can
be concluded that 1,3-oxazin-6-ones 8a–f are hydrolyzed
by traces of water in dimethyl sulfoxide solution (Scheme
3).
Scientific). Mass spectra were obtained using a Finnigan MAT
311A instrument (EI, 70 eV). Elemental analyses were carried out
with a Heraeus CHN-O-Rapid instrument. IR spectra were recorded
1
using a Varian 800 FT-IR spectrophotometer. H (400 MHz) and
13C NMR (100 MHz) spectra were recorded utilizing a Bruker AV
400 spectrometer using TMS as an internal standard and DMSO-d6,
DMF-d7, CD3CN, or CDCl3 as the solvent. Full and unambiguous
assignment for all NMR signals was achieved by combined applica-
tion of standard NMR techniques such as DEPT 13C NMR, H,H-
COSY, HSQC [1J (13C,1H) = 145 Hz), HMBC (n>1J (13C,1H) = 10
Hz]. For numbering of the compounds synthesized see the Support-
ing Information. In order to achieve a better structural overview for
compounds 9a–f, 12a,b and 13a,b the numbering provided does not
match IUPAC nomenclature.
3-Phenylprop-2-ynamide (1a)
Prepared from ethyl phenylpropynoate (8.71 g, 8.26 mL, 50 mmol)
according to the literature procedure as colorless crystals;9 yield:
6.70 g (92%); mp 100–102 °C.
IR (KBr): 3383 and 3179 (NH2), 2223 (C≡C), 1654 cm–1 (C=O).
O
O
1H NMR (400 MHz, DMSO-d6): δ = 8.18 (s, 1 H, NH2), 7.71 (s, 1
H, NH2), 7.57 (m, 2 H, o-CHAr), 7.51 (m, 1 H, p-CHAr), 7.46 (m, 2
H, m-CHAr).
Ph
O
Ph
O
R = Ph
– CO2
H2O
HN
O
HN
8a–f
R
OH
Ph
13C NMR (100 MHz, DMSO-d6): δ = 153.9 (C=O), 132.0 (o-CHAr),
130.2 (p-CHAr), 129.0 (m-CHAr), 119.9 (i-CAr), 84.2 (C≡C), 82.9
(C≡C).
10
9a–f
Scheme 3 Hydrolytic ring opening of 8 to 9 and decarboxylation of
9e to 10
MS (EI, 70 eV): m/z (%) = 145 (64) [M]+, 129 (100) [M – NH2]+, 75
(13), no other peaks >10%.
Anal. Calcd for C9H7NO: C, 74.47; H, 4.86; N, 9.65. Found: C,
74.59; H, 4.84; N, 9.57.
Interestingly, the reaction of arylpropynamides 1 with di-
substituted malonyl chlorides did not furnish 1,3-oxazines
of type 8, but rather the open-chained arylpropenamides
12, which were found to be unstable and underwent a fac-
ile decarboxylation to deliver compounds 13 (Scheme 4).
3-Arylprop-2-ynamides 1b–e; General Procedure
The corresponding arylpropynoic acid (15 mmol) was heated under
reflux with EtOH (60 mmol) in the presence of H2SO4 for 5 h. Ex-
cess EtOH was removed under reduced pressure and the residue
was washed with H2O and sat. aq NaHCO3. The organic layer was
separated and the aqueous layer was extracted with CHCl3 (3 × 50
mL). The combined organic layers were dried (MgSO4) and con-
centrated under reduced pressure to give ethyl 3-arylprop-2-ynoates
as oily residues, which were subsequently dissolved in 25% aq NH3
(60 mmol) and stirred at r.t. for 24 h. The resulting solid products
1b–d were filtered off and recrystallized.
O
O
Cl
O
O
O
O
Cl
Cl
H2O
R
R
N
Cl
DCE
reflux
NH2
H
1a,c
11
3-(2-Chlorophenyl)prop-2-ynamide (1b)13
Colorless crystals; yield: 1.94 g (72%); mp 121–122 °C (EtOH–
H2O, 1:1).
Cl
O
O
O
Cl
O
O
IR (KBr): 3318 and 3162 (NH2), 2225 (C≡C), 1655 cm–1 (C=O).
R
N
OH
– CO2
R
N
H
1H NMR (400 MHz, DMSO-d6): δ = 8.25 (s, 1 H, NH2), 7.81 (s, 1
H, NH2), 7.69 (m, 1 H, H6′), 7.62 (m, 1 H, H3′), 7.52 (m, 1 H, H4′),
7.43 (m, 1 H, H5′).
H
12a,b
13a,b
13C NMR (100 MHz, DMSO-d6): δ = 153.4 (C=O), 135.1 (C2′),
134.0 (C6′), 131.6 (C4′), 129.5 (C3′), 127.5 (C5′), 119.8 (C1′), 84.5
(C≡C), 79.2 (C≡C).
Scheme 4 Reaction of dimethyl malonyl chloride and arylpropyn-
amides
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 803–809

806
O. A. Petina et al.
PAPER
MS (EI, 70 eV): m/z (%) = 181/179 (13/46) [M]+, 165/163 (34/100)
[M – NH2]+, 136 (10), 99 (16), 75 (13), 74 (15), no other peaks
>10%.
1H NMR (400 MHz, CDCl3): δ = 15.44 (s, 1 H, OH), 11.29 (s, 1 H,
NH), 7.64 (m, 2 H, o-CHAr), 7.51 (m, 1 H, p-CHAr), 7.41 (m, 2 H,
m-CHAr), 6.34 (s, 1 H, H5).
Anal. Calcd for C9H6ClNO: C, 60.19; H, 3.37; Cl, 19.74; N, 7.80.
Found: C, 60.07; H, 3.38; Cl, 19.75; N, 7.87.
13C NMR (100 MHz, CDCl3): δ = 180.3 (C4), 168.5 (C1′), 161.1
(C2), 155.8 (C6), 150.2 (C3′), 133.3 (o-CHAr), 131.2 (p-CHAr),
128.7 (m-CHAr), 119.3 (i-CAr), 103.1 (C5), 91.8 (C5′), 91.2 (C3),
82.8 (C4′).
MS (EI, 70 eV): m/z (%) = 317 (2) [M]+, 282 (16) [M – Cl]+, 281
(85) [M – HCl]+, 130 (10), 129 (100) [PhC≡CCO]+, 128 (86), 127
(75), 126 (12), 75 (14), 69 (41), 54 (10), no other peaks >10%.
3-(4-Chlorophenyl)prop-2-ynamide (1c)14
Colorless crystals; yield: 2.10 g (78%); mp 186–188 °C (MeCN).
IR (KBr): 3399 and 3172 (NH2), 2218 (C≡C), 1656 cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 8.21 (s, 1 H, NH2), 7.75 (s, 1
H, NH2), 7.60 (m, 2 H, o-CHAr), 7.54 (m, 2 H, m-CHAr).
13C NMR (100 MHz, DMSO-d6): δ = 153.7 (C=O), 135.0 (p-Cl-
CAr), 133.8 (o-CHAr), 129.1 (m-CHAr), 118.8 (i-CAr), 85.0 (C≡C),
81.6 (C≡C).
Anal. Calcd for C15H8ClNO5: C, 56.71; H, 2.54; Cl, 11.16; N, 4.41.
Found: C, 56.68; H, 2.54; Cl, 11.44; N, 4.64.
6-Chloro-N-[3-(2-chlorophenyl)prop-2-ynoyl]-4-hydroxy-2-
oxo-2H-pyran-3-carboxamide (5b)
Yellow solid; yield: 0.38 g (54%); mp 143–145 °C (dec) (CH2Cl2).
MS (EI, 70 eV): m/z (%) = 181/179 (17/53) [M]+, 165/163 (32/100)
[M – NH2]+, 99 (15), 75 (13), no other peaks >10%.
IR (KBr): 3221 (OH), 3091 (NH), 2224 (C≡C), 1708 (C=O), 1674
(C=O), 1655 cm–1 (C=O).
Anal. Calcd for C9H6ClNO: C, 60.19; H, 3.37; Cl, 19.74; N, 7.80.
Found: C, 60.29; H, 3.37; Cl, 19.64; N, 7.92.
1H NMR (400 MHz, CDCl3): δ = 15.38 (s, 1 H, OH), 11.38 (s, 1 H,
NH), 7.66 (m, 1 H, H11′), 7.47 (m, 1 H, H8′), 7.42 (m, 1 H, H9′),
7.31 (m, 1 H, H10′), 6.34 (s, 1 H, H5).
13C NMR (100 MHz, CDCl3): δ = 180.3 (C4), 168.4 (C1′), 161.2
(C2), 155.9 (C6), 149.9 (C3′), 137.8 (C7′), 135.0 (C9′), 132.2
(C11′), 129.7 (C8′), 126.8 (C10′), 119.7 (C6′), 103.1 (C5), 91.3
(C5′), 87.7 (C3), 86.7 (C4′).
MS (EI, 70 eV): m/z (%) = 355/353/351 (1/4/6) [M]+, 318/316
(5/22) [M – Cl]+, 317/315 (10/23) [M – HCl]+, 249/247 (4/11),
165/163 (30/100) [2-Cl-C6H4C≡CCO]+, 164/162 (15/18), 161 (26),
99 (15), 69 (27), no other peaks >10%.
3-(4-Bromophenyl)prop-2-ynamide (1d)
Colorless crystals; yield: 2.55 g (76%); mp 202–204 °C (dec)
(MeCN).
IR (KBr): 3386 and 3172 (NH2), 2216 (C≡C), 1655 cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 8.23 (s, 1 H, NH2), 7.75 (s, 1
H, NH2), 7.68 (m, 2 H, o-CHAr), 7.52 (m, 2 H, m-CHAr).
13C NMR (100 MHz, DMSO-d6): δ = 153.6 (C=O), 133.9 (o-CHAr),
132.0 (m-CHAr), 123.7 (p-Br-CAr), 119.1 (i-CAr), 85.1 (C≡C), 81.6
(C≡C).
MS (EI, 70 eV): m/z (%) = 225/223 (64/65) [M]+, 209/207 (95/100)
[M – NH2]+, 128 (21) [M – NH2 – Br]+, 99 (15), 75 (29), 74 (50), no
other peaks >10%.
Anal. Calcd for C15H7Cl2NO5: C, 51.16; H, 2.00; Cl, 20.14; N, 3.98.
Found: C, 51.24; H, 2.10; Cl, 19.60; N, 4.23.
6-Chloro-N-[3-(4-chlorophenyl)prop-2-ynoyl]-4-hydroxy-2-
oxo-2H-pyran-3-carboxamide (5c)
Yellow crystals; yield: 0.44 g (63%); mp 180–182 °C (dec)
(EtOAc).
Anal. Calcd for C9H6BrNO: C, 48.25; H, 2.70; Br, 35.66; N, 6.25.
Found: C, 48.04; H, 2.83; N, 6.24.
3-(4-Nitrophenyl)prop-2-ynamide (1e)
Colorless crystals; yield: 1.91 g (67%); mp 192–194 °C (dec)
(MeCN).
IR (KBr): 3406 and 3155 (NH2), 2220 (C≡C), 1662 cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 8.34 (s, 1 H, NH2), 7.88 (s, 1
H, NH2), 7.30 (m, 2 H, o-CHAr), 7.85 (m, 2 H, m-CHAr).
IR (KBr): 3219 (OH), 3099 (NH), 2226 (C≡C), 1709 (C=O), 1674
(C=O), 1652 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): δ = 15.38 (s, 1 H, OH), 11.30 (s, 1 H,
NH), 7.59 (m, 2 H, o-CHAr), 7.40 (m, 2 H, m-CHAr), 6.35 (s, 1 H,
H5).
1H NMR (400 MHz, DMF-d7): δ = 13.55 (br s, 2 H, OH, NH), 7.93
(m, 2 H, o-CHAr), 7.70 (m, 2 H, m-CHAr), 5.83 (s, 1 H, H5).
13C NMR (100 MHz, DMF-d7): δ = 168.4 (C4), 166.7 (C1′), 159.3
(C2), 153.5 (C6), 151.4 (C3′), 137.7 (p-Cl-CAr), 135.2 (o-CHAr),
129.7 (m-CHAr), 117.4 (i-CAr), 95.8 (C3), 93.5 (C5′), 90.1 (C5), 81.9
(C4′).
MS (EI, 70 eV): m/z (%) = 353/351 (2/4) [M]+, 318/316 (5/15) [M
– Cl]+, 317/315 (20/60) [M – HCl]+, 165/163 (24/100) [4-Cl-
C6H4C≡CCO]+, 164/162 (23/50), 161 (78), 126 (18), 99 (14), 69
(61), 53 (16), no other peaks >10%.
13C NMR (100 MHz, DMSO-d6): δ = 153.2 (C=O), 147.8 (p-NO2-
CAr), 133.3 (o-CHAr), 126.6 (i-CAr), 124.0 (m-CHAr), 87.8 (C≡C),
80.6 (C≡C).
MS (EI, 70 eV): m/z (%) = 190 (84) [M]+, 174 (100) [M – NH2]+,
128 (70) [M – NH2 – NO2]+, 116 (26), 101 (16), 100 (28), 98 (13),
89 (50), 77 (15), 75 (30), 74 (54), 63 (19), 62 (20), 51 (23), 50 (23),
no other peaks >10%.
Anal. Calcd for C9H6N2O3: C, 56.85; H, 3.18; N, 14.73. Found: C,
56.64; H, 3.24; N, 14.59.
Pyran-3-carboxamides 5a–d; General Procedure
A soln of malonyl chloride (2, 0.4 mL, 4.2 mmol) in anhyd Et2O or
THF (10 mL) was added dropwise over a period of 20 min to a sus-
pension of the corresponding 3-arylpropynamide 1a–d (2 mmol) in
Et2O (10 mL) with ice cooling. The mixture was stirred at –5 to 0
°C for 1–2 h and the resulting solid was filtered off and recrystal-
lized.
Anal. Calcd for C15H7Cl2NO5: C, 51.16; H, 2.00; Cl, 20.14; N, 3.98.
Found: C, 51.29; H, 2.07; Cl, 19.73; N, 4.21.
N-[3-(4-Bromophenyl)prop-2-ynoyl]-6-chloro-4-hydroxy-2-
oxo-2H-pyran-3-carboxamide (5d)
Yellow crystals; yield: 0.45 g (57%); mp 268–279 °C (dec).
IR (KBr): 3259 (OH), 3097 (NH), 2230 (C≡C), 1706 (C=O), 1674
(C=O), 1658 cm–1 (C=O).
6-Chloro-4-hydroxy-2-oxo-N-(3-phenylprop-2-ynoyl)-2H-py-
ran-3-carboxamide (5a)15
Yellow crystals; yield: 0.47g (74%); mp 140–143 °C (dec)
(CH2Cl2).
1H NMR (400 MHz, DMF-d7): δ = 13.57 (br s, 1 H, OH), 11.83 (br
s, 1 H, NH), 7.85 (s, 4 H, o-CHAr, m-CHAr), 5.82 (s, 1 H, H5).
13C NMR (100 MHz, DMF-d7): δ = 168.4 (C4), 166.7 (C1′), 159.2
(C2), 153.5 (C6), 151.4 (C3′), 135.2 (o-CHAr), 132.6 (m-Cl-CAr),
IR (KBr): 3250 (OH), 3103 (NH), 2231 (C≡C), 1714 (C=O), 1676
(C=O), 1655 cm–1 (C=O).
Synthesis 2013, 45, 803–809
© Georg Thieme Verlag Stuttgart · New York

PAPER
Preparation of Arylpropynamides
807
126.4 (p-Br-CAr), 117.8 (i-CAr), 95.8 (C3), 93.6 (C5′), 90.2 (C5),
82.0 (C4′).
13C NMR (100 MHz, DMSO-d6): δ = 164.4 (C6), 160.0 (C4), 147.4
(C2), 132.8 (o-CHAr), 131.6 (p-CHAr), 129.2 (m-CHAr), 118.5 (i-
CAr), 101.9 (C5), 91.2 (C2′), 80.6 (C1′), 23.7 (>CH-), 19.5 (CH3).
MS (EI, 70 eV): m/z (%) = 255 (35) [M]+, 240 (54) [M – CH3]+, 172
(11), 130 (10), 129 (100) [PhC≡CCO]+, 128 (20), 75 (11), 69 (16),
no other peaks >10%.
MS (EI, 70 eV): m/z (%) = 397 (1) [M]+, 362/360 (10/10) [M – Cl]+,
363/361 (52/52) [M
–
HCl]+, 209/207 (35/100) [4-Br-
C6H4C≡CCO]+, 208 (29), 206 (30), 205 (60), 126 (24), 100 (13), 69
(36), 53 (10), no other peaks >10%.
Anal. Calcd for C15H7BrClNO5: C, 45.43; H, 1.78; Br, 20.15; Cl,
8.94; N, 3.53. Found: C, 45.34; H, 1.93; Br, 19.85; Cl, 9.30; N, 3.64.
Anal. Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C,
70.38; H, 5.32; N, 5.43.
Monosubstituted Malonyl Chlorides 6a–f; General Procedure
Monosubstituted malonyl chlorides 6a–f were obtained by reflux-
ing the corresponding malonic acid with SOCl2 and subsequent dis-
tillation. In the case of phenyl- 6e and benzylmalonyl chloride 6f the
corresponding (chlorocarbonyl)ethylketenes 7a,b were formed as a
byproduct, which is in accordance with literature reports.16
5-Butyl-4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-one
(8d)15
Yellow crystals; yield: 0.53 g (65%); mp 157–159 °C.
IR (KBr): 2222 (C≡C), 1743 (C=O), 1628 cm–1 (C=N).
1H NMR (400 MHz, DMSO-d6): δ = 12.71 (br s, 1 H, OH), 7.70 (m,
2 H, o-CHAr), 7.61 (m, 1 H, p-CHAr), 7.52 (m, 2 H, m-CHAr), 2.28
(m, 2 H, CH2), 1.42 (m, 2 H, CH2), 1.29 (m, 2 H, CH2), 0.88 (m, 3
H, CH3).
2-(Phenylethynyl)-6H-1,3-oxazin-6-ones 8a–f; General Proce-
dure
The corresponding malonyl chloride [(chlorocarbonyl)ethylketene]
6a–f (7a,b) (3.1 mmol) was added to a stirred soln of 3-phenylprop-
2-ynamide (1a, 0.44 g, 3 mmol) in anhyd Et2O (30 mL) at r.t. The
mixture was cooled in the refrigerator for 12–14 h. During this time
a solid deposited that was filtered off, washed with Et2O, and dried
to deliver pure 8a–f.
13C NMR (100 MHz, DMSO-d6): δ = 164.9 (C6), 161.0 (C4), 147.2
(C2), 132.7 (o-CHAr), 131.5 (p-CHAr), 129.2 (m-CHAr), 118.4 (i-
CAr), 97.3 (C5), 91.2 (C2′), 80.7 (C1′), 29.3 (C2′′), 22.3 (C1′′), 21.9
(C3′′), 13.7 (C4′′).
MS (EI, 70 eV): m/z (%) = 269 (10) [M]+, 226 (18) [M – C3H7]+, 165
(14), 130 (10), 129 (100) [PhC≡CCO]+, 128 (20), no other peaks
>10%.
For an additional portion of product the filtrate was evaporated un-
der reduced pressure at r.t. and the remaining residue was recrystal-
lized (MeCN).
Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C,
70.97; H, 5.46; N, 5.14.
4-Hydroxy-5-methyl-2-(phenylethynyl)-6H-1,3-oxazin-6-one
(8a)
Yellowish crystals; yield: 0.32 g (74%); mp 184–186 °C.
IR (KBr): 2215 (C≡C), 1747 (C=O), 1635 cm–1 (C=N).
1H NMR (400 MHz, DMSO-d6): δ = 12.74 (br s, 1 H, OH), 7.71 (m,
2 H, o-CHAr), 7.61 (m, 1 H, p-CHAr), 7.52 (m, 2 H, m-CHAr), 1.80
(s, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): δ = 164.8 (C6), 161.3 (C4), 146.9
(C2), 132.7 (o-CHAr), 131.5 (p-CHAr), 129.2 (m-CHAr), 118.4 (i-
CAr), 92.8 (C5), 91.2 (C2′), 80.7 (C1′), 8.1 (CH3).
MS (EI, 70 eV): m/z (%) = 227 (14) [M]+, 171 (20), 130 (11), 129
(100) [PhC≡CCO]+, 128 (12), 83 (14), 77 (13) [Ph]+, 75 (29), 74
(14), 70 (12), 63 (11), no other peaks >10%.
4-Hydroxy-5-phenyl-2-(phenylethynyl)-6H-1,3-oxazin-6-one
(8e)8c
Yellow crystals; yield: 0.76 g (87%); mp 187–189 °C.
IR (KBr): 2220 (C≡C), 1747 (C=O), 1620 cm–1 (C=N).
1H NMR (400 MHz, DMSO-d6): δ = 13.18 (br s, 1 H, OH), 7.74 (m,
2 H, o-CHAr), 7.63 (m, 1 H, p-CHAr), 7.54 (m, 2 H, m-CHAr), 7.52
(m, 2 H, H2′′), 7.38 (m, 2 H, H3′′), 7.29 (m, 1 H, H4′′).
13C NMR (100 MHz, DMSO-d6): δ = 164.8 (C6), 160.0 (C4), 147.9
(C2), 132.8 (o-CHAr), 131.7 (p-CHAr), 130.6 (C1′′), 130.0 (C2′′),
129.2 (m-CHAr), 127.6 (C3′′), 127.2 (C4′′), 118.3 (i-CAr), 97.3 (C5),
91.8 (C2′), 80.8 (C1′).
MS (EI, 70 eV): m/z (%) = 289 (35) [M]+, 218 (14), 190 (12), 172
(12), 130 (10), 129 (100) [PhC≡CCO]+, 118 (18), 89 (16), 77 (11)
[Ph]+, 75 (13), 51 (10) [C4H3]+, no other peaks >10%.
Anal. Calcd for C13H9NO3: C, 68.72; H, 3.99; N, 6.16. Found: C,
68.72; H, 4.01; N, 6.26.
Anal. Calcd for C18H11NO3: C, 74.73; H, 3.83; N, 4.84. Found: C,
74.79; H, 4.01; N, 4.75.
5-Ethyl-4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-one (8b)
Yellowish crystals; yield: 0.51 g (70%); mp 177–178 °C.
5-Benzyl-4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-one
(8f)
IR (KBr): 2221 (C≡C), 1744 (C=O), 1633 cm–1 (C=N).
1H NMR (400 MHz, DMSO-d6): δ = 12.77 (br s, 1 H, OH), 7.71 (m,
2 H, o-CHAr), 7.61 (m, 1 H, p-CHAr), 7.53 (m, 2 H, m-CHAr), 2.29
(q, 3JHH = 7.42 Hz, 2 H, CH2), 1.01 (t, 3JHH = 7.42 Hz, 3 H, CH3).
13C NMR (100 MHz, DMSO-d6): δ = 164.6 (C6), 160.8 (C4), 147.2
(C2), 132.7 (o-CHAr), 131.7 (p-CHAr), 129.1 (m-CHAr), 118.4 (i-
CAr), 98.6 (C5), 91.1 (C2′), 80.6 (C1′), 16.1 (CH2), 12.0 (CH3).
Yellow crystals; yield: 0.55 g (61%); mp 179–181 °C.
IR (KBr): 2221 (C≡C), 1746 (C=O), 1627 cm–1 (C=N).
1H NMR (400 MHz, DMSO-d6): δ = 13.03 (br s, 1 H, OH), 7.71 (m,
2 H, o-CHAr), 7.60 (m, 1 H, p-CHAr), 7.52 (m, 2 H, m-CHAr), 7.25
(m, 4 H, H2′′, H3′′), 7.17 (m, 1 H, H4′′), 3.61 (s, 2 H, CH2).
13C NMR (100 MHz, DMSO-d6): δ = 165.4 (C6), 161.0 (C4), 147.7
(C2), 139.3 (C1′′), 132.7 (o-CHAr), 131.6 (p-CHAr), 129.2 (m-CHAr),
128.21 and 128.18 (C2′′ and C3′′), 126.0 (C4′′), 118.4 (i-CAr), 96.5
(C5), 91.5 (C2′), 80.7 (C1′), 28.3 (CH2).
MS (EI, 70 eV): m/z (%) = 302 (55) [M]+, 176 (28), 158 (74), 131
(15), 130 (65), 129 (100) [PhC≡CCO]+, 128 (20), 103 (12), 102
(15), 91 (27) [PhCH2]+, 77 (22) [Ph]+, 75 (13), 51 (12) [C4H3]+, no
other peaks >10%.
MS (EI, 70 eV): m/z (%) = 241 (28) [M]+, 129 (100) [PhC≡CCO]+,
128 (19), 75 (15), 51 (10), no other peaks >10%.
Anal. Calcd for C14H11NO3: C, 69.70; H, 4.60; N, 5.81. Found: C,
69.42; H, 4.53; N, 5.84.
4-Hydroxy-5-isopropyl-2-(phenylethynyl)-6H-1,3-oxazin-6-one
(8c)
Colorless crystals; yield: 0.47 g (62%); mp 202–203 °C.
IR (KBr): 2226 (C≡C), 1744 (C=O), 1627 cm–1 (C=N).
Anal. Calcd for C19H13NO3: C, 75.24; H, 4.32; N, 4.62. Found: C,
75.27; H, 4.32; N, 4.65.
1H NMR (400 MHz, DMSO-d6): δ = 12.76 (br s, 1 H, OH), 7.70 (m,
2 H, o-CHAr), 7.61 (m, 1 H, p-CHAr), 7.52 (m, 2 H, m-CHAr), 3.01
(sept, 3JHH = 7.00 Hz, 1 H, CH), 1.17 (d, 3JHH = 7.00 Hz, 6 H, CH3).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 803–809

808
O. A. Petina et al.
PAPER
3-Oxo-3-[(3-phenylprop-2-ynoyl)amino]propanoic Acids 9a–f;
General Procedure
13C NMR (100 MHz, DMSO-d6): δ = 170.7 (C=O), 151.6 (C1),
134.3 (C1′), 132.6 (o-CHAr), 131.1 (p-CHAr), 129.5 (C3′), 129.0 (m-
CHAr), 128.3 (C2′), 126.8 (C4′), 119.1 (i-CAr), 89.0 (C3), 83.3 (C2),
43.1 (CH2).
MS (EI, 70 eV): m/z (%) = 263 (26) [M]+, 147 (18), 251 (15), 130
(10), 129 (94) [PhC≡CCO]+, 118 (100), 117 (12), 105 (15), 91 (30)
[PhCH2]+, 90 (22), 75 (13), 65 (11), no other peaks >10%.
After keeping a soln of compounds 8a–f in DMSO-d6 for 24 h at r.t.
1
the H and 13C NMR spectra of the 4-hydroxy-2-(phenylethynyl)-
6H-1,3-oxazin-6-ones 8a–f showed new signals of the correspond-
ing hydrolysis products 9a–d,f and 10.
2-Methyl-3-oxo-3-[(3-phenylprop-2-ynoyl)amino]propanoic
Acid (9a)
Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C,
77.49; H, 5.07; N, 5.25.
1H NMR (400 MHz, DMSO-d6): δ = 12.79 (br s, 1 H, OH), 11.62
(s, 1 H, NH), 7.66 (m, 2 H, o-CHAr), 7.58 (m, 1 H, p-CHAr), 7.50 (m,
2 H, m-CHAr), 3.79 (q, 3JHH = 7.15 Hz, 1 H, H2), 1.27 (t, 3JHH = 7.15
Hz, 3 H, CH3).
3-[(3-Chloroprop-2-enoyl)amino]-2,2-dimethyl-3-oxopropano-
ic Acids 12a,b; General Procedure
Dimethylmalonyl chloride (0.36 mL, 3.1 mmol) was added to a
stirred soln of 1a,c (3 mmol) in anhyd DCE (30 mL) at r.t. The mix-
ture was heated at reflux for 3 h and was then allowed to cool to –5
°C. The resulting solid was filtered off and washed with Et2O. Con-
centrating the filtrate under reduced pressure at r.t. gave an addi-
tional portion of 12. Because compounds 12 suffered rapid
decarboxylation to give compounds 13, elemental analysis data
could not be obtained for 12.
13C NMR (100 MHz, DMSO-d6): δ = 171.3 (C1), 170.1 (C3), 151.5
(C5), 132.6 (o-CHAr), 131.1 (p-CHAr), 129.0 (m-CHAr), 119.0 (i-
CAr), 88.9 (C7), 83.2 (C6), 47.2 (C2), 13.1 (CH3).
2-[(3-Phenylprop-2-ynoyl)carbamoyl]butanoic Acid (9b)
1H NMR (400 MHz, DMSO-d6): δ = 12.84 (br s, 1 H, OH), 11.65
(s, 1 H, NH), 7.66 (m, 2 H, o-CHAr), 7.58 (m, 1 H, p-CHAr), 7.50 (m,
2 H, m-CHAr), 3.61 (m, 1 H, H2), 1.80 (m, 2 H, CH2), 0.90 (m, 3 H,
CH3).
13C NMR (100 MHz, DMSO-d6): δ = 170.3 (C1), 169.2 (C3), 151.5
(C5), 132.7 (o-CHAr), 131.2 (p-CHAr), 129.1 (m-CHAr), 119.0 (i-
CAr), 89.0 (C7), 83.1 (C6), 54.2 (C2), 21.4 (CH2), 11.8 (CH3).
3-{[(2Z)-3-Chloro-3-phenylprop-2-enoyl]amino}-2,2-dimethyl-
3-oxopropanoic Acid (12a)
Colorless crystals; yield: 0.67g (76%); mp 120–122 °C.
IR (KBr): 3202 (OH), 3022 (NH), 1767 (C=O), 1719 (C=O), 1670
cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 12.82 (br s, 1 H, OH), 10.80
(s, 1 H, NH), 7.75 (m, 2 H, o-CHAr), 7.52 (m, 3 H, p-CHAr, m-CHAr),
7.25 (s, 1 H, =CH-), 1.37 (s, 6 H, 2 CH3).
13C NMR (100 MHz, DMSO-d6): δ = 174.0 (C1), 172.6 (C3), 163.3
(C5), 140.7 (C7), 136.5 (i-CAr), 130.7 (p-CHAr), 128.8 (m-CHAr),
126.8 (o-CHAr), 120.3 (C6), 51.0 (C2), 22.5 (CH3).
MS (EI, 70 eV): m/z (%) = 253/251 (2/6) [M – CO2]+, 217 (15), 216
(100), 167/165 (18/55) [PhCCl=CHCO]+, 147 (64), 102 (31), 101
(12), 70 (11), no other peaks >10%.
3-Methyl-2-[(3-phenylprop-2-ynoyl)carbamoyl]butanoic Acid
(9c)
1H NMR (400 MHz, DMSO-d6): δ = 12.74 (br s, 1 H, OH), 11.60
(s, 1 H, NH), 7.66 (m, 2 H, o-CHAr), 7.58 (m, 1 H, p-CHAr), 7.51 (m,
2 H, m-CHAr), 3.46 (m, 1 H, H2), 2.28 (m, 1 H, CH), 0.97 (m, 3 H,
CH3).
13C NMR (100 MHz, DMSO-d6): δ = 169.6 (C1), 168.4 (C3), 151.4
(C5), 132.6 (o-CHAr), 131.2 (p-CHAr), 129.0 (m-CHAr), 119.0 (i-
CAr), 89.1 (C7), 83.1 (C6), 59.3 (C2), 28.0 (CH), 20.2 (CH3), 20.0
(CH3).
2-[(3-Phenylprop-2-ynoyl)carbamoyl]hexanoic Acid (9d)
1H NMR (400 MHz, DMSO-d6): δ = 12.82 (br s, 1 H, OH), 11.62
(s, 1 H, NH), 7.66 (m, 2 H, o-CHAr), 7.58 (m, 1 H, p-CHAr), 7.50 (m,
2 H, m-CHAr), 3.67 (m, 1 H, H2), 1.78 (m, 2 H, H1′), 1.28 (m, 4 H,
H2′, H3′), 0.87 (m, 3 H, H4).
13C NMR (100 MHz, DMSO-d6): δ = 170.4 (C1), 169.2 (C3), 151.5
(C5), 132.6 (o-CHAr), 131.2 (p-CHAr), 129.0 (m-CHAr), 119.0 (i-
CAr), 89.0 (C7), 83.1 (C6), 52.7 (C2), 29.1 (C3′), 27.7 (C1′), 21.9
(C2′), 13.7 (C4′).
3-{[(2Z)-3-Chloro-3-(4-chlorophenyl)prop-2-enoyl]amino}-2,2-
dimethyl-3-oxopropanoic Acid (12b)
Colorless crystals; yield: 0.73g (74%); mp 142–143 °C.
IR (KBr): 3239 (OH), 3143 (NH), 1769 (C=O), 1719 (C=O), 1676
cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 12.81 (br s, 1 H, OH), 10.82
(s, 1 H, NH), 7.76 (m, 2 H, o-CHAr), 7.60 (m, 2 H, m-CHAr), 7.28 (s,
1 H, =CH-), 1.37 (s, 6 H, 2 CH3).
13C NMR (100 MHz, DMSO-d6): δ = 174.0 (C1), 172.6 (C3), 163.4
(C5), 138.9 (C7), 135.32 (p-CClAr), 135.27 (i-CAr), 128.9 (m-CHAr),
128.6 (o-CHAr), 121.1 (C6), 51.0 (C2), 22.5 (CH3).
MS (EI, 70 eV): m/z (%) = 285 (1) [M – CO2]+, 252/250 (33/100),
251 (15), 203/201/199 (6/40/62) [4-Cl-C6H4CCl=CHCO]+, 183/181
(25/78), 182 (11), 139 (24), 138/136 (14/44), 101 (12), 75 (14), 70
(28), no other peaks >10%.
2-Benzyl-3-oxo-3-[(3-phenylprop-2-ynoyl)amino]propanoic
Acid (9f)
1H NMR (400 MHz, DMSO-d6): δ = 13.03 (br s, 1 H, OH), 11.62
(s, 1 H, NH), 7.65 (m, 2 H, o-CHAr), 7.59 (m, 1 H, p-CHAr), 7.52 (m,
2 H, m-CHAr), 7.25 (m, 5 H, H2′, H3′, H4′), 4.07 (t, 3JHH = 7.46 Hz,
1 H, H2), 3.12 (d, 3JHH = 7.46 Hz, 2 H, CH2).
13C NMR (100 MHz, DMSO-d6): δ = 169.7 (C1), 168.5 (C3), 151.4
(C5), 138.4 (C1′), 132.6 (o-CHAr), 131.2 (p-CHAr), 129.0 (m-CHAr),
128.7 (C2′), 128.3 (C3′), 126.4 (C4′), 118.9 (i-CAr), 89.1 (C7), 83.0
(C6), 54.4 (C2), 33.6 (CH2).
3-Chloro-N-(2-methylpropanoyl)prop-2-enamides 13a,b; Gen-
eral Procedure
The corresponding compound 12 (0.3 mmol) was heated to its melt-
ing point for 5 min. After cooling, the resulting product was purified
by flash column chromatography (silica gel, n-hexane–EtOAc).
3-Phenyl-N-(phenylacetyl)prop-2-ynamide (10)
A suspension of 4-hydroxy-5-phenyl-2-(phenylethynyl)-6H-1,3-
oxazin-6-one (8e, 0.3 mmol) in H2O (20 mL) was heated under re-
flux for 30 min until the color of 8e turned from yellow to white.
The solid compound 10 was filtered off and recrystallized (toluene)
to give colorless crystals; yield: 71mg (90%); mp 132–134 °C.
(2Z)-3-Chloro-N-(2-methylpropanoyl)-3-phenylprop-2-en-
amide (13a)
Colorless crystals; yield: 0.23g (90%); mp 119–121 °C.
IR (KBr): 3195 (NH), 1723 (C=O), 1678 cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 10.88 (s, 1 H, NH), 7.74 (m, 2
H, o-CHAr), 7.52 (m, 3 H, p-CHAr, m-CHAr), 7.28 (s, 1 H, =CH-),
2.81 (sept, 3JHH = 6.80 Hz, 1 H, H2), 1.08 (d, 3JHH = 6.80 Hz, 6 H, 2
CH3).
IR (KBr): 3219 (NH), 2213 (C≡C), 1705 (C=O), 1683 cm–1 (C=O).
1H NMR (400 MHz, DMSO-d6): δ = 11.60 (s, 1 H, NH), 7.64 (m, 2
H, o-CHAr), 7.56 (m, 1 H, p-CHAr), 7.49 (m, 2 H, m-CHAr), 7.33 (m,
2 H, H3′), 7.27 (m, 3 H, H2′, H4′), 3.82 (s, 2 H, CH2).
Synthesis 2013, 45, 803–809
© Georg Thieme Verlag Stuttgart · New York

PAPER
Preparation of Arylpropynamides
809
13C NMR (100 MHz, DMSO-d6): δ = 177.3 (C3), 163.7 (C5), 140.3
(C7), 136.4 (i-CAr), 130.6 (p-CHAr), 128.8 (m-CHAr), 126.7 (o-
CHAr), 120.5 (C6), 34.6 (C2), 18.6 (CH3).
MS (EI, 70 eV): m/z (%) = 253/251 (1/4) [M]+, 217 (15), 216 (100)
[M – Cl]+, 167/165 (20/59) [PhCCl=CHCO]+, 147 (60), 102 (33),
101 (11), 77 (30) [Ph]+, 76 (32), 75 (32), 74 (16), 71 (16), 70 (41),
69 (13), 63 (14), 51 (22) [C4H3]+, no other peaks >10%.
(6) (a) Schulte, K. E.; Ruecker, G. Prog. Drug Res. 1970, 387.
(b) Jones, E. R. H.; Thaller, V. In The Carbon–Carbon
Triple Bond; Vol. 2; Patai, S., Ed.; John Wiley & Sons:
Chichester, 1978, 621.
(7) Selected papers: (a) Kobayashi, S.; Hori, M.; Wang, G. X.;
Hirama, M. J. Org. Chem. 2006, 71, 636. (b) Nicolaou, K.
C.; Dai, W. M. Angew. Chem., Int. Ed. Engl. 1991, 30, 1387.
(c) Nicolaou, K. C.; Smith, A. L.; Yue, E. Proc. Natl. Acad.
Sci. U.S.A. 1993, 90, 5881. (d) Walker, S.; Landovitz, R.;
Ding, W. D.; Ellestad, G. A.; Kahne, D. Proc. Natl. Acad.
Sci. U.S.A. 1992, 89, 4608.
(8) Selected papers: (a) Sheibani, H.; Saidi, K.; Foroughi, H.
Russ. Chem. Bull. 2008, 57, 2600. (b) Sheibani, H.;
Mosslemin, M. H.; Behzadi, S.; Islami, M. R.; Foroughi, H.;
Saidi, K. ARKIVOC 2005, (xv), 88. (c) Komarov, A. V.;
Yakovlev, I. P.; Zakhs, V. E.; Prep’yalov, A. V. Russ. J.
Gen. Chem. 2005, 75, 770. (d) Komarov, A. V.; Yakovlev, I.
P.; Novikov, D. V.; Semakova, T. L.; Zakhs, V. E. Russ. J.
Gen. Chem. 2003, 73, 1806. (e) Yakovlev, I. P.; Zakhs, V.
E.; Prep’yalov, A. V.; Rebrov, A. G. Zh. Obshch. Khim.
1996, 66, 668; Chem. Abstr. 1996, 125, 275775.
(f) Yakovlev, I. P.; Zakhs, V. E.; Prep’yalov, A. V.; Ivin, B.
A. Zh. Obshch. Khim. 1994, 64, 1825; Chem. Abstr. 1995,
122, 264669. (g) Zakhs, V. E.; Yakovlev, I. P.; Ivin, B. A.
Khim. Geterotsikl. Soedin. 1987, 3, 386; Chem. Abstr. 1988,
108, 5938. (h) Friedrichsen, W.; Kappe, T.; Bottcher, A.
Heterocycles 1982, 19, 1083. (i) Kappe, T.; Golser, W.;
Hariri, M.; Stadlbauer, W. Chem. Ber. 1979, 112, 1585;
Chem. Abstr. 1979, 91, 20424. (j) Ziegler, E.; Meindl, H.
Monatsh. Chem. 1964, 95, 1318; Chem. Abstr. 1965, 62,
9100.
Anal. Calcd for C13H14ClNO2: C, 62.03; H, 5.61; Cl, 14.08; N, 5.56.
Found: C, 61.66; H, 5.59; N, 5.48; Cl, 14.05.
(2Z)-3-Chloro-3-(4-chlorophenyl)-N-(2-methylpropano-
yl)prop-2-enamide (13b)
Colorless crystals; yield: 0.25g (87%); mp 140–142 °C.
IR (KBr): 3200 (NH), 1725 (C=O), 1677 cm–1 (C=O).
1H NMR (400 MHz, CD3CN): δ = 8.92 (s, 1 H, NH), 7.74 (m, 2 H,
o-CHAr), 7.52 (m, 2 H, m-CHAr), 7.20 (s, 1 H, =CH-), 2.79 (sept,
3JHH = 6.80 Hz, 1 H, H2), 1.16 (d, 3JHH = 6.80 Hz, 6 H, 2 CH3).
13C NMR (100 MHz, CD3CN): δ = 176.9 (C3), 163.1 (C5), 140.2
(C7), 135.8 (p-CHAr), 135.4 (i-CAr), 128.6 (m-CHAr), 128.2 (o-
CHAr), 120.0 (C6), 35.1 (C2), 17.7 (CH3).
MS (EI, 70 eV): m/z (%) = 285 (1) [M]+, 252/250 (26/76) [M – Cl]+,
251 (12), 203/201/199 (4/29/45) [4-Cl-C6H4CCl=CHCO]+, 183/181
(19/60), 139 (13), 138/136 (10/33), 101 (9), 75 (10), 70 (20), 62
(43), 45 (100), no other peaks >10%.
Anal. Calcd for C13H13Cl2NO2: C, 54.56; H, 4.58; Cl, 24.78; N,
4.89. Found: C, 54.67; H, 4.57; N, 4.86
Acknowledgment
(9) Struebing, D.; Neumann, H.; Klaus, S.; Huebner, S.; Beller,
M. Tetrahedron 2005, 61, 11333.
(10) (a) Davis, S. J.; Elvidge, J. A. J. Chem. Soc. 1952, 4109.
(b) Elvidge, J. A. J. Chem. Soc. 1962, 2606.
The authors thank Miss Isabelle Nevoigt for her valuable help in the
preparation of the X-ray crystal structures.
Supporting Information for this article is available online at
(11) (a) Stanovnik, B.; Tisler, M.; Katritzky, A. R.; Denisko, O.
V. Adv. Heterocycl. Chem. 2006, 91, 1. (b) Zakhs, V. E.;
Viktorovskii, I. V.; Ivin, B. A. Khim. Geterotsikl. Soedin.
1990, 552; Chem. Abstr. 1990, 113, 211247 . (c) Zakhs, V.
E.; Yakovlev, I. P.; Smorygo, N. A.; Gindin, V. A.; Ivin, B.
A. Khim. Geterotsikl. Soedin. 1987, 386; Chem. Abstr. 1988,
108, 5938.
(12) (a) Komarov, A. V.; Yakovlev, I. P.; Novikov, D. V.; Zakhs,
V. E. Russ. J. Gen. Chem. 2003, 73, 1936. (b) Zakhs, V. E.;
Yakovlev, I. P.; Trety’yakov, A. A.; Ivin, B. A. Zh. Obshch.
Khim. 1992, 62, 1878; Chem. Abstr. 1993, 119, 8212.
(13) (a) Mariella, R. P.; Conway, T. Can. J. Chem. 1965, 43,
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Chem. 1973, 10, 399.
(14) Schmitt, J. FR 1305340, 1962; Chem. Abstr. 1963, 58,
46538.
(15) CCDC 905990 (5a) and CCDC 905991 (8d) contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
are copies of the 1H NMR and 13C NMR spectra.SunpIgpfoi
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