An easy and convenient synthesis of β-lactams via a one-pot staudinger reaction with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride starting from substituted carboxylic acids

Article abstract of DOI:10.2174/1570178611666141201224959

An easy and convenient direct synthesis of 2-azetidinones is described. The [2+2] cycloaddition reaction of imines and carboxylic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) has been employed to synthesize a variety of 2-azetidinones in high yields. The products were easily isolated because the byproducts are highly soluble in water.

Full text of DOI:10.2174/1570178611666141201224959

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Letters in Organic Chemistry, 2015, 12, 44-49
4
4
An Easy and Convenient Synthesis of ꢀ-Lactams via a One-Pot Staudinger
Reaction with 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium
Chloride Starting from Substituted Carboxylic Acids
Maaroof Zarei*
Department of Chemistry, College of Sciences, Hormozgan University, Bandar Abbas 71961, Iran
Received April 12, 2014: Revised August 27, 2014: Accepted October 20, 2014
Abstract: An easy and convenient direct synthesis of 2-azetidinones is described. The [2+2] cycloaddition reaction of
imines and carboxylic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) has
been employed to synthesize a variety of 2-azetidinones in high yields. The products were easily isolated because the by-
products are highly soluble in water.
Keywords: ꢀ-Lactam, 2-Azetidinone, Staudinger reaction, DMTMM, Ketene, Imine.
INTRODUCTION
,3,5-Triazine derivatives have been known for a long
period of time. They have found widespread applications in
the pharmaceutical, textile, plastic, and rubber industries, and
are used as pesticides, dyestuffs, optical bleaches, explo-
sives, and surface active agents [1].
variety of pharmacological activities [9], for example,
Ezetimibe is used clinically due to its cholesterol absorption
inhibitor property [10]. In addition, the 2-azetidinone scaf-
fold is a versatile intermediate in the preparation of many
classes of compounds [11].
1
The Staudinger reaction (ketene-imine cycloaddition) is
undoubtedly the most widely used route to 2-azetidinones
where it can be used for synthesis of several types of 2-
azetidinones [12]. Ketenes are commonly generated by reac-
tion of acyl halides with tertiary amines [13]. Use of acid
halide has some drawbacks such as commercial unavailabil-
ity, handling and safety concerns. Because of the disadvan-
tages, preparation of ketenes from carboxylic acids is very
useful. This method includes treatment of the carboxylic acid
with carboxylic acid activators to generate an activated in-
termediate, which then generates ketenes in situ by treatment
with base [14]. However, harsh conditions, low yield, cost
and difficulty in purification of product are some of the dis-
advantages.
Treatment of
2-chloro-4,6-dimethoxy-1,3,5-triazine
(
CDMT) and N-methylmorpholine (NMM) in THF at room
temperature afforded 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-
methylmorpholinium chloride (DMTMM) as a white precipi-
tate, which was found active for at least one month by stor-
age in a well-capped bottle [2]. It is also commercially avail-
able. Unlike CDMT, DMTMM is not an irritating agent for
eyes and nose [3].
Recently, DMTMM has been applied as a coupling
agent, in amidation, esterification, glycosidation and phos-
phonylation methodology [4]. This coupling reagent is also
useful for preparation of Weinreb amides [5], formyl amides
[
6] and 1,2,4-oxadiazole [7].
In this paper, a method suitable for facile and efficient
synthesis of ꢀ-lactams from carboxylic acids and DMTMM
as the acid activator has been developed.
ꢀ
-Lactams, 2-azetidinones, are very attractive heterocy-
cles present as core structure in many biologically active
compounds, particularly, in most widely used classes of an-
tibiotics [8]. ꢀ-Lactams have been shown to possess a wide
MeO
N
MeO
O
N
rt
N
Cl
+
O
N
Me
N+
N
N
THF
00%
N
1
Cl-
MeO
MeO
CDMT
DMTMM
*
Address correspondence to this author at the Department of Chemistry,
RESULTS AND DISCUSSION
College of Sciences, Hormozgan University, Bandar Abbas 71961, Iran;
Tel: +98 761 766 0063; Fax: +98 761 667 0714;
E-mails: maaroof1357@yahoo.com, and mzarei@hormozgan.ac.ir
Initially, equimolar amounts of aldehydes and amines
were mixed and heated in ethanol 95% to give Schiff bases.
1
875-6255/15 $58.00+.00
© 2015 Bentham Science Publishers

An Easy and Convenient Synthesis of ꢀ-Lactams via a One-Pot Staudinger Reaction
Letters in Organic Chemistry, 2015, Vol. 12, No. 1 45
Table 1. Reaction condition in the synthesis of 2-azetidinone 3a.
OMe
4
'''
2
''
3''
1''
3'''
O
O
3
4
DMTMM
NMM
1''' 2'''
MeO
CH=N
OEt
PhOCH COOH
4''
+
2
N
2
'
1
'
2 1
3
'
4'
1a
2a
3a
OEt
Entry
Solvent
Temp
mmol DMTMM
Isolated Yield (%)
1
2
3
4
5
6
7
8
9
CH
2
Cl
2
rt
rt
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.3
1.5
67
30
56
51
63
42
58
80
89
Toluene
THF
rt
DMF
rt
CHCl
3
rt
CH
CH
CH
CH
2
2
2
2
Cl
2
2
2
2
0 °C
40 °C
rt
Cl
Cl
Cl
rt
The ꢀ-lactam 3a was synthesized by the [2+2] ketene-imine
cycloaddition of 1.0 mmol (4-methoxybenzylidene)-4-
ethoxyaniline 1a and 1.0 mmol phenoxyacetic acid 2a using
4 at 63.7 ppm. Elemental analysis also supported the forma-
tion of 3a.
Using optimized reaction conditions, a series of substi-
tuted 2-azetidinones were prepared. The 2-azetidinones 3a-o
were synthesized by treatment of 1.0 mmol of imines 1, 1.5
mmol of carboxylic acids 2 and 1.5 mmol of DMTMM in the
presence of NMM in dry dichloromethane at room tempera-
ture (Scheme 1, Table 2).
1
2 2
.0 mmol DMTMM in dry CH Cl in the presence of NMM.
For optimizing the experimental conditions, this reaction was
considered as a model reaction. Several dry solvents such as
CH
dia (Table 1). It was noticed that the best yield was found
with CH Cl (Table 1, Entry 1). Also, the effect of tempera-
2 2 3
Cl , toluene, THF, DMF and CHCl were tested as me-
2
2
ture on the reaction was studied. When the reaction was per-
formed at 0 °C (Table 1, Entry 6), decrease of yield was ob-
served and increase in temperature to 40 °C, was not better
than room temperature (Table 1, Entry 7). For optimization
of the amount of the reagent, equimolar amount of phe-
noxyacetic acid relative to DMTMM was used. According to
Table 1, the highest yield was obtained when 1.5 mmol phe-
noxyacetic acid and 1.5 mmol DMTMM were reacted with
To explore the scope and generality of this method, it
was extended to various substituted contain 3-electron-
withdrawing (Table 2, Entry 12,13) and spirocyclic (Table 2,
Entry 14,15) ketenes. Also, the reaction proceeded effi-
ciently with aliphatic substituted imines (Table 2, Entry 5,6).
After simple aqueous workup, 2-azetidinones 3a-k and 3n-o
were purified by crystallization from EtOAc and 2-
azetidinones 3l-m by short column chromatography on silica
gel. Spectral data and elemental analyses were used for char-
acterization of all products. Their stereochemistry was as-
signed by the comparison of the coupling constant H-3 and
H-4 (J3,4> 4.0 Hz) for the cis stereoisomer and (J3,4ꢁ 3.0 Hz)
for the trans stereoisomer [15].
1
.0 mmol of imine 1a (Table 1, entry 9).
After aqueous workup and crystallization from EtOAc, a
pure white solid was obtained. Full characterization of this
compound was accomplished by spectroscopic methods (IR,
1
13
H-, and C-NMR, and elemental analysis). The IR spec-
trum of this compound revealed C=O signal of ꢀ-lactam ring
This reaction is easy and clean because the by-product of
the reaction with DMTMM (2-hydroxy-4,6-dimethoxy-1,3,
5-triazine, HO-MDT) and resulting salts are water soluble
and then they are easily removed by simple aqueous workup.
-
1
1
(
1747 cm ) and no C=N signal. In H-NMR spectrum, two
doublet peaks at 5.21 and 5.41 ppm were observed, which
can be attributed to the H-4 and H-3 of ꢀ-lactam ring, respec-
tively. The cis stereochemistry of ꢀ-lactam 3a was deduced
from the coupling constant of H-3 and H-4, which was cal-
A plausible mechanism for the formation of ꢀ-lactams by
this method is proposed via an activated ester, according to a
reported mechanism for the Staudinger reaction [16].
1
3
culated to be 4.7 Hz. Moreover, the C-NMR spectrum
definitely showed the lactam CO at 162.6, C-3 at 81.2 and C-

4
6
Letters in Organic Chemistry, 2015, Vol. 12, No. 1
Maaroof Zarei
R2
R3
3
4
DMTMM, NMM
CH Cl , rt
1
2
3
R N=CHR
R CH COOH
2
+
2
N 1
2
2
O
R1
1
2
3a-o
Scheme 1.
Table 2. Synthesis of 2-azetidinones 3a-o using DMTMM.
1
2
3
Entry
R
R
R
cis/trans
Product
Isolated Yield (%)
1
2
3
4
5
6
7
8
9
4-EtOC
4-MeC
4-MeOC
4-MeONaphthyl
PhCH
4-MeOC
4-EtC
4-EtOC
6
H
4
4-MeOC
6
H
4
PhO
PhO
PhO
MeO
MeO
cis
cis
3a
3b
3c
3d
3e
3f
89
91
94
86
88
93
88
85
86
81
84
52
69
6
H
4
2-Naphthyl
CH=CHPh
6
H
4
cis
4-MeC
6
H
4
cis
2
4-NO
2
C
6
H
4
cis
6
H
4
CH
2
4-(Me
4-(Me
2
2
N)C
N)C
6
6
H
H
4
4
2,4-Cl
2
C
6
H
3
O
cis
6
H
4
6
4-ClC H
3
O
cis
3g
3h
3i
6
H
4
4-(Me
4-NO
4-ClC
2-Naphthyl
2
CH)C
6
H
4
2-NaphthO
PhS
cis
C
6
H
5
2
C
6
H
4
cis
1
1
1
1
0
1
2
3
4-EtOC
6
H
4
6
H
4
PhthN
trans
trans
trans
cis
3j
6
4-MeC H
4
PhthN
3k
3l
4-MeOC
6
6
H
H
4
4
4-ClC
6
H
4
6
4-MeC H
4 2
SO
4-MeOC
4-MeOC
6
H
4
N
3
3m
OMe
O
1
4
-
3n
79
N
O
OMe
CI
O
1
5
-
3o
73
N
O
OMe
OMe
open capillaries using a Buchi 535 apparatus apparatus and
are uncorrected. FTIR spectra were recorded on a galaxy
series FT-IR 5000 spectrometer in spectroscopic grade KBr
O
N
N
1
13
C
O
pellets for all the powders. H (300 MHz) and C NMR (75
MHz) spectra were recorded in deuterated chloroform on a
Bruker spectrometer. Chemical shifts are reported in ppm (ꢀ)
relative to TMS and coupling constants (J) are reported in
Hz. Microanalyses were performed by the Elemental Ana-
lyzer (Elemental, Vario EL III). The purity determination of
the products and reaction monitoring were accomplished by
TLC on silica gel 254 analytical sheets obtained from Fluka.
3
R H C
N
OMe
2
activated ester
EXPERIMENTAL
General
Chemical materials were purchased from Acros and
Merck in high purity. Melting points were determined in

An Easy and Convenient Synthesis of ꢀ-Lactams via a One-Pot Staudinger Reaction
Letters in Organic Chemistry, 2015, Vol. 12, No. 1 47
Silica gel 60 (Merck, 70-230 mesh) was used for column
130.1 (C3'), 134.6 (C1'), 141.8 (C1"), 154.0 (C4"), 163.1
chromatography. Spectroscopic data for 3a, 3c-d, 3g-h, 3j,
and 3n have been previously reported [14k, 16b, 17].
(CO, ꢀ-lactam). Anal. Calcd for C17
5.16; N, 8.97. Found: C, 65.46; H, 5.29; N, 9.03.
16 2 4
H N O : C, 65.38; H,
1
-(4-Methoxybenzyl)-3-(2,4-dichlorophenoxy)-4-(4-(dime-
General Procedure for the Synthesis of 2-azetidinones
thylamino)phenyl)azetidin-2-one (3f)
To a stirred solution of CDMT (1.5 mmol) in dry CH
15 mL), N-methylmorpholine (NMM) (6.0 mmol) was
added dropwise and allowed to stir for 10 min. To the white
suspension containing DMTMM salt, the Schiff base (1.0
mmol) and the carboxylic acid (1.5 mmol) were added and
the mixture was stirred overnight. The mixture was washed
2
Cl
2
-1
White solid. M.p. 102-104 °C. IR (KBr) cm : 1754 (CO,
(
1
ꢀ
3
(
(
(
(
-lactam); H NMR (CDCl
3
) ꢁ 2.90 (s, 6H, 2Me), 3.55 (s,
-benzyl), 4.86
d, 1H, J = 4.9, C4H), 5.58 (d, 1H, J = 4.9, C3H), 6.84-7.81
H, OMe), 3.84, 4.81 (2d, 2H, J = 14.6, CH
2
13
m, 11H, ArH); C NMR (CDCl
CH ), 55.0 (OMe), 64.6 (C3), 81.9 (C4), 111.4 (C3"), 115.9
C3'), 120.3 (C2'"), 122.5 (C2"), 127.4 (C1"), 128.1 (C6'"),
29.9 (C4'"), 130.3 (C5'"), 133.4 (C2'), 138.6 (C3'"), 140.0
C1'), 144.2 (C4"), 151.1 (C1'"), 157.4 (C4'), 164.2 (CO, ꢀ-
lactam); Anal. Calcd for C25 : C, 63.70; H, 5.13;
N, 5.94. Found: C, 63.79; H, 5.25; N, 5.87.
3
) ꢁ 40.2 (Me-N), 44.8
2
successively with saturated NaHCO
3
(15 mL) and brine (15
mL), dried with Na SO and concentrated in vacuo. 2-
2
4
1
(
Azetidinones 3a-k, 3n-o were purified by crystallization
from EtOAc and 2-azetidinones 3l-m by short column chro-
matography on silica gel.
H
2 2 3
24Cl N O
1
-(4-Ethoxyphenyl)-4-(4-methoxyphenyl)-3-phenoxy-azeti-
4
-(4-(Dimethylamino)phenyl)-1-(4-ethylphenyl)-3-pheno-
din-2-one (3a) [17b]
xyazetidin-2-one (3g) [14k]
White crystalline solid. M.p. 166-168 °C (lit. 168-170
White solid. M.p. 178-180 °C (lit. 177-179 °C). IR (KBr)
-
1
1
°
(
(
C) [17b]. IR (KBr) cm : 1752 (CO, ꢀ-lactam); H NMR
CDCl ) ꢁ 1.28 (t, 3H, J = 7.0, Me), 3.61 (s, 3H, OMe), 3.93
q, 2H, J = 7.0, OCH ), 5.19 (d, 1H, J = 4.6, C4H), 5.45 (d,
H, J = 4.6, C3H), 6.61-7.21 (m, 13H, ArH).
-1
1
3
cm : 1746 (CO, ꢀ-lactam); H NMR (CDCl ) ꢁ 1.35 (t, 3H, J
3
=
5
7
7.0, Me), 2.54 (q, 2H, J = 7.0, CH ), 2.89 (s, 6H, 2Me),
2
2
.30 (d, 1H, J =4.6, C4H), 5.46 (d, 1H, J =4.6, C3H), 6.77-
.36 (m, 13H, ArH).
1
4
-(Naphthalen-2-yl)-3-phenoxy-1-p-tolylazetidin-2-one (3b)
1
-(4-Ethoxyphenyl)-4-(4-isopropylphenyl)-3-(naphthalen-
-
1
White solid. M.p. 186-188 °C IR (KBr) cm : 1744 (CO,
2-yloxy)azetidin-2-one (3h) [17c]
1
ꢀ
3
-lactam); H NMR (CDCl ) ꢁ 2.51 (s, 3H, Me), 5.28 (d, 1H,
White solid. M.p. 185-187 °C (lit. 182-184 °C). IR (KBr)
J =4.7, C4H), 5.47 (d, 1H, J =4.7, C3H), 6.74-7.30 (m, 16H,
-1
1
cm : 1742 (CO, ꢀ-lactam); H NMR (CDCl
J = 7.0, 2Me), 1.35 (t, 3H, J = 7.0, Me), 2.68 (septet, 1H,
CH), 4.00 (q, 2H, J = 7.0, OCH ), 5.34 (d, 1H, J = 4.7,
C4H), 5.50 (d, 1H, J = 4.7, C3H), 6.78-7.80 (m, 15H, ArH).
3
) ꢁ 1.25 (d, 6H,
1
3
ArH); C NMR (CDCl
14.3 (C2'), 119.2 (C2"), 122.4 (C3'), 124.8 (C4"), 126.0
C5'"), 126.4 (C6'"), 126.7 (C4'"), 128.2 (C7'"), 128.4 (C9'"),
28.5 (C2'"), 129.1 (C10'"), 129.4 (C4'), 129.9 (C3"), 130.3
C3'"), 131.4 (C8'"), 134.7 (C1'"), 144.6 (C1'), 157.1 (C1"),
62.3 (CO, ꢀ-lactam); Anal. Calcd for C26 : C, 82.30;
H, 5.58; N, 3.69; Found: C, 82.36; H, 5.65; N, 3.65.
3
) ꢁ 24.7 (Me), 63.7 (C4), 81.4 (C3),
1
(
1
(
2
4
-(4-Nitrophenyl)-1-phenyl-3-(phenylthio)azetidin-2-one
1
H21NO
2
(
3i)
-
1
White solid. M.p. 153-155 °C. IR (KBr) cm : 1750 (CO,
1
1
-(4-Methoxyphenyl)-3-phenoxy-4-styrylazetidin-2-one (3c)
ꢀ-lactam). H NMR (CDCl
4.89 (d, 1H, J = 4.4, C3H), 6.74-8.07 (m, 14H, ArH);
NMR (CDCl ) ꢁ 59.4 (C3), 62.3 (C4), 109.5 (C2'), 118.3
C3'"), 126.0 (C3"), 128.8 (C4'), 129.3 (C1"), 132.7 (C2'"),
3
) ꢁ 4.36 (d, 1H, J = 4.4, C4H),
13
[
17c]
C
3
White solid; m.p. 181–183 °C (lit. 182-184 °C) [17c]. IR
(
1
-
1
1
(
(
KBr) cm : 1749 (CO, ꢀ-lactam); H NMR (CDCl
s, 3H, OMe), 5.17 (dd, 1H, J = 5.0, 8.6, C4H), 5.66 (d, 1H,
3
) ꢁ 3.58
35.1 (C4"), 136.0 (C3'), 139.9 (C2"), 142.5 (C1'), 145.2
(
C1'"), 157.1 (C4'"), 161.7 (CO, ꢀ-lactam); Anal. Calcd for
S: C, 67.00; H, 4.28; N, 7.44. Found: C, 66.90;
H, 4.40; N, 7.39.
J = 5.0, C3H), 6.25 (dd, J = 8.6, 16.0, C5H), 6.76 (d, 1H, J =
1
21 16 2 3
C H N O
6.0, C6H), 6.88-7.93 (m, 14H, ArH).
3
-Methoxy-1-(4-methoxynaphthalen-1-yl)-4-p-tolyl-
2
-(2-(4-Chlorophenyl)-1-(4-ethoxyphenyl)-4-oxoazetidin-3-
azetidin-2-one (3d) [17a]
yl)isoindoline-1,3-dione (3j) [16b]
White solid. M.p. 135-137 °C (lit. 135-137 °C) [17a]. IR
-
1
1
White solid. M.p. 186-188 °C (lit. 185-187 °C) [16b]. IR
(
(
KBr) cm : 1746 (CO, ꢀ-lactam); H NMR (CDCl
3
) ꢁ 2.49
-1
1
(
KBr) cm : 1727, 1757 (CO, phth), 1784 (CO, ꢀ-lactam). H
NMR (CDCl ) ꢁ 1.35 (t, 3H, J = 6.9, Me), 3.98 (q, 2H, J =
.9, OCH ), 5.21 (d, 1H, J = 4.6, C4H), 5.35 (d, 1H, J = 4.6,
s, 3H, Me), 3.38, 3.60 (2s, 6H, 2OMe), 4.85 (d, 1H, J = 4.5,
C4H), 5.24 (d, 1H, J = 4.6, C3H), 6.75-7.81 (m, 10H, ArH).
3
6
2
C3H), 6.74-7.77 (m, 12H, ArH).
1
-Benzyl-3-methoxy-4-(4-nitrophenyl)azetidin-2-one (3e)
-
1
White solid. M.p. 60-62 °C IR (KBr) cm : 1747 (CO, ꢀ-
1
2-(2-(Naphthalen-2-yl)-4-oxo-1-p-tolylazetidin-3-yl)isoin-
doline-1,3-dione (3k)
lactam). H NMR (CDCl
2d, 2H, J = 14.9, CH -benzyl), 4.94 (d, 1H, J = 4.7, C4H),
.41 (d, 1H, J = 4.7, C3H), 6.82-7.95 (m, 9H, ArH);
NMR (CDCl ) ꢁ 45.2 (CH ), 55.8 (OMe), 61.5 (C3), 81.4
C4), 112.9 (C2"), 117.3 (C3"), 121.9 (C4'), 125.0 (C2'),
3
) ꢁ 3.38 (s, 3H, OMe), 3.88, 4.75
(
5
2
1
3
-1
C
White solid. M.p. 240-242 °C IR (KBr) cm : 1735, 1775
1
3
2
(CO, phth), 1791 (CO, ꢀ-lactam); H NMR (CDCl
3
) ꢁ 2.43
(
(s, 3H, Me), 5.36 (d, 1H, J =2.5, C4H), 5.43 (d, 1H, J =2.5,

4
8
Letters in Organic Chemistry, 2015, Vol. 12, No. 1
Maaroof Zarei
1
3
C3H), 6.58-7.83 (m, 15H, ArH); C NMR (CDCl
3
) ꢀ 24.3
materials. The reagents for the preparation of DMTMM are
cheap and economically beneficial.
(
(
(
1
(
Me), 62.3 (C4), 63.2 (C3), 113.8 (C2'), 114.4 (C2'"), 114.7
C10'"), 117.3 (C2"), 120.8 (C5'"), 121.9 (C6'"), 122.3
C4'"), 124.0 (C7'"), 126.6 (C9'"), 129.3 (C4'), 132.7 (C1'"),
35.5 (C3'), 136.2 (C1"), 138.1 (C3"), 142.7 (C8'"), 146.4
C3'"), 155.5 (C1'), 161.2 (CO, phth), 166.2 (CO, ꢁ-lactam);
Anal. Calcd for C28 : C, 77.76; H, 4.66; N, 6.48;
Found: C, 77.85; H, 4.79; N, 6.55.
CONFLICT OF INTEREST
The author confirms that this article content has no con-
flict of interest.
20 2 3
H N O
4
-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-tosylazetidin-2-
ACKNOWLEDGEMENTS
one (3l)
The author gratefully acknowledges Hormozgan Univer-
sity Research Council for the financial support of this study.
-
1
White solid. M.p. 166-168 °C. IR (KBr) cm : 1151, 1327
1
(
SO
2 3
), 1746 (CO, ꢁ-lactam). H NMR (CDCl ) ꢀ 2.11 (s, 3H,
Me), 3.54 (s, 3H, OMe), 4.51 (d, 1H, J = 2.4, C4H), 5.49 (d,
1
3
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(
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H, J = 2.4, C3H), 6.88-7.80 (m, 12H, ArH); C NMR
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14.1 (C3'), 115.9 (C2'), 119.5 (C2'"), 120.3 (C3'"), 122.0
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Pale-yellow solid. M.p. 89-91 °C IR (KBr) cm : 1745
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(
5
5
2s, 6H, 2OMe), 5.10 (d, 1H, J = 5.0, C4H), 5.22 (d, 1H, J =
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C3'), 121.3 (C2"), 125.5 (C2'), 126.2 (C1"), 139.4 (C1'),
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1
(
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1
White solid. M.p. 228-230 °C IR (KBr) cm : 1753 (CO,
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ꢁ
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13
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CONCLUSION
In summary, a novel and efficient method for the direct
synthesis of ꢁ-lactams from carboxylic acids and imines us-
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good to excellent yields of the products, simple workup, and
straightforward synthesis of ꢁ-lactams via available starting
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An Easy and Convenient Synthesis of ꢀ-Lactams via a One-Pot Staudinger Reaction
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1
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