Pyrolysis of azetidinone derivatives: A versatile route towards electron-rich alkenes, C-1 allylation and/or homologation of aldehydes

Article abstract of DOI:10.1039/c4ra01024h

Pyrolysis of β-lactams and β-thiolactams led essentially to stereoselective synthesis of the high energy electron-rich Z-alkenes. Extension of this methodology to the pyrolysis of 3-allyloxy derivatives gave a simple direct route to the synthetically important 4-pentenal. These pyrolytic transformations convert aldehydes to aryloxyalkenes (a protected homologation) and 4-pentenal (a C-1 allylation and homologation). The starting 3-aryloxy and 3-allyloxy-β-lactams were synthesized by the standard Staudinger ketene-imine [2 + 2] cycloaddition. The corresponding β-thiolactams have readily been obtained in good yields by thiation of β-lactams with Lawesson's reagent. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra01024h

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Pyrolysis of azetidinone derivatives: a versatile
route towards electron-rich alkenes, C-1 allylation
and/or homologation of aldehydes†
Cite this: RSC Adv., 2014, 4, 21023
*
Nouf S. Al-Hamdan, Osama M. Habib, Yehia A. Ibrahim, Nouria A. Al-Awadi
and Osman M. E. El-Dusouqui
Pyrolysis of b-lactams and b-thiolactams led essentially to stereoselective synthesis of the high energy
electron-rich Z-alkenes. Extension of this methodology to the pyrolysis of 3-allyloxy derivatives gave a
simple direct route to the synthetically important 4-pentenal. These pyrolytic transformations convert
aldehydes to aryloxyalkenes (a protected homologation) and 4-pentenal (a C-1 allylation and
homologation). The starting 3-aryloxy and 3-allyloxy-b-lactams were synthesized by the standard
Staudinger ketene-imine [2 + 2] cycloaddition. The corresponding b-thiolactams have readily been
obtained in good yields by thiation of b-lactams with Lawesson's reagent.
Received 5th February 2014
Accepted 22nd April 2014
DOI: 10.1039/c4ra01024h
www.rsc.org/advances
reagents for further chemical elaboration. Scheme 2 illustrates
our strategy to utilize such pyrolytic transformation to convert
1. Introduction
aldehydes to aryloxyalkenes (a protected homologation of the
starting aldehyde) and 4-pentenal (a C-1 allylation and
homologation).
The term “b-lactam synthon method” has been introduced in
1997,1 since then azetidin-2-ones have acquired a prominent
place in organic chemistry as synthons for further elaboration.
The constrained azetidinone ring has been employed success-
fully in synthetic methodologies towards all kinds of nitrogen-
containing compounds.2 The Staudinger [2 + 2] ketene–imine
cycloaddition reaction is considered as one of the most
important synthetic approaches to b-lactams (2-azetidinones)
which have important application in pharmaceutical and
synthetic chemistry.1–5 Although the reaction has been discov-
ered a hundred years ago,4 it still attracts recent interest.1–3,5
Pyrolysis of these b-lactams has received little attention and
was shown to give mainly alkenes with no more functional
groups.6–12 The thermal fragmentation of b-lactams occurs by
two different pathways, the rst one gives the starting ketene
and imine (B) and the second pathway (A) gives alkene and
isocyanate which could be trapped with amine to give the cor-
responding urea derivatives, Fischer found that the thermal
fragmentation favours pathway A, while photolysis favours
pathway B (Scheme 1).11
Scheme 1 Routes for fragmentation of b-lactams.
The present work is part of a project directed towards
exploring the pyrolytic behaviour of this important ring system
and its potentiality in producing useful functionalized organic
Chemistry Department, Faculty of science, Kuwait University, P.O. Box 5969, Safat
13060, Kuwait. E-mail: n.alawadi@ku.edu.kw; Fax: +96524816482; Tel:
+96524985537
† Electronic supplementary information (ESI) available: Characterization data for
all new b-lactams and b-thiolactams including 1H NMR and 13C NMR spectra
(Tables 1 and 2) and mass spectra of some representative examples. See DOI:
10.1039/c4ra01024h
Scheme 2 Strategy to convert aldehydes to aryloxyalkenes and 4-
pentenal through b-lactams and thio-b-lactams pyrolysis.
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that the substrate 2a is stable up to 250 ꢂC and start to pyrolyze
at 270 ꢂC to 25% of the corresponding Z-alkene. However, at
temperature lower 300 ꢂC isomerisation of cis-b-lactam 2a to
trans-b-lactam 3a was the main process, while by increasing the
temperature and thermolysis time, ssion of the b-lactam ring
became the major pathway. Complete pyrolysis of 2a occurred
at 350 ꢂC in 20 minutes with the formation of the Z and E alkene
in 37% yield. Increasing the pyrolysis temperature to 400 ꢂC and
reducing the reaction time to 5 minutes increased Z : E ratio
(Table 1).
2. Results and discussion
The starting b-lactams and their corresponding 2-thioxo deriv-
atives needed in our study were synthesized as outlined in
Scheme 3. Thus, the reaction of imines 1a–g with excess phe-
noxyacetyl chloride (2.5 equiv.) in dry DCM (CH2Cl2) in the
presence of triethylamine with exception of 1d gave the corre-
sponding b-lactams as cis isomer 2a–c,e–g respectively. In case
of 1d a mixture of cis and trans b-lactams 2d and 3d were formed
(40 : 60) respectively. The cis stereochemistry of all products 2a–
g was assigned based on the coupling constants between the
protons at C3 and C4, with observed J-values ¼ 4.8 Hz.13 The
trans stereoisomer 3d was unambiguously assigned based on
the coupling constant between the protons at C3 and C4, with
the observed J-value ¼ 1.8 Hz (ref. 13) (see ESI Table 1†).
Moreover, it seemed worthwhile to compare the pyrolytic
reaction of b-lactams 2a–g and the corresponding thio-b-lac-
tams 4a–g. The later were synthesized in 65–73% yields by
reuxing the corresponding b-lactams 2a–g with Lawesson's
reagent (LR) in dry toluene for 3 h (Scheme 3). All products 4a–g
retained the cis stereochemistry as indicated by the coupling
constants between the protons at C3 and C4, with the observed
J-values ¼ 4.4–4.8 Hz.
The b-lactams 2a–g subjected to static pyrolysis at 350 ꢂC and
ꢂ
ash vacuum pyrolysis (FVP) at 600 C. The pyrolytic reaction
mixtures was carefully analyzed with the use of 1H and 13C NMR
ꢂ
spectra, we found that, in STP at 350 C of b-lactams 2a–g in
addition to formation of the corresponding E and Z alkenes,
imines 1a–g were formed in 6–11% yield. The main cleavage
reaction is postulated to involve a retro [2 + 2] cycloreversion
type fragmentation of the b-lactam ring liberating Z-alkene
isomers together with the E isomers in a high diastereomeric
ratio, however, under FVT the Z isomer is the major products in
all cases (Scheme 4, Table 2). This could be explained by the fact
the long residence time in static pyrolysis leads to isomerization
of the Z isomer to the more stable E isomer.
Similar study revealed that the optimum temperature for the
static pyrolysis of the thiolactams 4a–g is 280 ꢂC and 550 ꢂC for
the FVP. At 250 ꢂC (STP) only partial isomerisation took place to
give the corresponding trans-thio-b-lactams 6. Thus STP (at 250
ꢂC, 20 min) of 4a,c,f gave a mixture of 4a,c,f with the corre-
sponding trans isomers 6a (25%), 6c (37%), 6f (40%).
Moreover, the corresponding thiourea derivatives 13a–d (11–
16%) instead of arylisocyanates were detected in all cases.
Unfortunately at higher temperature 280 ꢂC for 15 min charring
took place with formation of poor yield of the corresponding E
and Z alkenes (5–14%). On the other hand, FVP of thio-b-lac-
tams 4a–g at 550 ꢂC gave better yield of the corresponding
alkenes (Scheme 4, Table 2) with higher Z diastereomeric ratio.
The 5 E/Z isomers percent were calculated depending on the
integration of the E isomer proton (Ar2–CH]) at d ¼ 6.3 ppm (J
¼ 12.8 Hz) with the integration of the Z isomer proton (Ar2–
CH]) at d ¼ 5.6 ppm (J ¼ 6.8 Hz), and all products percent are
calculated using DCM method.14
We rst studied the static pyrolysis (sealed-tube pyrolysis) of
2a to optimize the condition for complete reaction for the
desired pyrolysis products. The products of the reaction were
analyzed directly aer the thermolysis using H and 13C NMR
1
spectroscopy. Table 1 shows the main products obtained under
reduced pressure 1 ꢀ 10ꢁ2 Torr and at different pyrolysis
temperatures (250, 270, 290, 300, 320, 350 and 400 ꢂC). It is clear
Our study was then extended to pyrolysis of the 3-allyloxy
analogues of compounds 2 and 4 which are expected to undergo
further Claisen rearrangement for the initially pyrolytically
produced allyloxyalkene. The new 3-allyloxy-1,4-diaryl-2-
Scheme 3 Synthesis of b-lactams 2a–g and thio-b-lactams 4a–g.
Table 1 Products from STP of cis-b-lactam 2a (yield %)
Entry
Temp.(ꢂC)
Time (min)
cis-b-lactam 2a
trans-b-lactam 3a
Z-5a
E-5a
1
2
3
4
5
6
7
250
270
290
300
320
350
400
30
90
15
30
30
20
5
100
40
50
25
8
0
25
20
25
18
0
0
25
15
25
23
20
21
0
0
0
1
13
17
10
0
0
0
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Scheme 4 Products of SVP and FVP of cis b-lactam 2a–g and cis-thio-b-lactams 4a–g.
Table 2 Products of STP and FVP of cis-b-lactams 2a–g and cis-thio-b-lactams 4a–g
STPa
FVPb
Alkene
(E/Z)
Imine
(yield %)
Urea (thiourea)
(yield %)
Alkene
(E/Z)
Imine
(yield %)
Urea (thiourea)
(yield %)
Comp. no.
2a
2b
2c
2d
2e
2f
2g
4a
4b
4c
4d
4e
4f
5a (17/20)
5a (11/16)
5a (9/17)
5a (11/17)
5b (12/19)
5c (9/12)
5d (16/22)
5a (6/10)
5a (5/10)
5a (6/14)
5a (4/12)
5b (6/12)
5c (4/10)
5d (4/13)
1a (10)
1b (8)
1c (7)
1d (11)
1e (8)
1f (6)
1g (11)
1a (8)
1b (10)
1c (6)
1d (8)
1e (8)
1f (7)
7a (24)
7b (20)
7c (20)
7d (16)
7a (18)
7a (14)
7a (24)
13a (4)
13b (0)
13c (4)
13d (6)
13a (4)
13a (0)
13a (4)
5a (6/25)
5a (9/22)
5a (6/23)
5a (7/26)
5b (5/24)
5c (4/25)
5d (7/24)
5a (4/18)
5a (7/20)
5a (3/22)
5a (5/19)
5b (3/21)
5c (4/19)
5d (8/21)
1a (11)
1b (10)
1c (12)
1d (12)
1e (8)
1f (13)
1g (12)
1a (7)
1b (9)
1c (11)
1d (6)
1e (11)
1f (9)
7a (18)
7b (16)
7c (26)
7d (18)
7a (18)
7a (20)
7a (24)
13a (8)
13b (4)
13c (8)
13d (6)
13a (8)
13a (4)
13a (6)
4g
1g (6)
1g (14)
a
STP, 350 ꢂC, 0.01 Torr, 20 min. for b-lactams 2a–g, 280 ꢂC, 0.01 Torr, 15 min for thio-b-lactams 4a–g. b FVP, 600 ꢂC, 0.02 Torr for b-lactams 2a–g,
550 ꢂC, 0.02 Torr; for thio-b-lactams 4a–g.
azetidinone 8a–e were prepared by the reaction of imines 1a–e 13C NMR spectroscopic analysis of the pyrolysate showed the
with allyloxyacetyl chloride in the presence of triethylamine. In formation of urea derivatives 7a–c and imines 1a–c, but the
all cases cis-b-lactams 8a–e were obtained except in case of the methylene protons signal at d 4.3 corresponding to the olenic
imine 1a trans-b-lactams 9a was formed in 4% yield. The cor- ether intermediate 11a15,16 was not detected in the pyrolysate,
responding 3-allyloxy-b-thiolactams 10a–e were obtained by while the spectroscopic properties were identical with those
thiation of 8a–e with Lawesson's reagent (Scheme 5) (see ESI reported for the corresponding 4-pentenal 12a–c (a Claisen
Table 2†).
The optimum temperature for pyrolysis of allyloxy-1,4-diaryl-
2-azetidinone 8a–e is 300 ꢂC (STP) and 600 ꢂC (FVP). The 1H and the 4-pentenals 12a–c together with the other by-products 7a–c,
rearrangement of aldehydes)17,18 (Scheme 6).
FVP of allyloxy-1,4-diaryl-2-azetidinone 8a–d at 600 C gave
ꢂ
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ꢂ
ꢂC, STP), (550 C, FVP). The aldehydes 12a–c and imines 1a–c
have been detected in the pyrolysate in addition to traces of
thiourea derivatives 13a–c (Table 3).
The percent yield of the products in pyrolysate mixture based
on the characteristic protons, aldehydes based on the charac-
teristic aldehyde proton at 9.7 ppm (d, J ¼ 1.6 Hz),17,18 imines
based on the characteristic CH]N proton at 8.4 ppm, and urea
derivatives on the exchangeable NH proton at 8.5–8.8 (ref. 19) or
based on the characteristic MeO proton at 3.8 ppm.
3. Conclusion
The present work offers an interesting application of synthetic
transformation of a new 2-azetidinones into valuable interme-
diates in synthetic chemistry including electron-rich Z-olens
and 4-pentenal derivatives. The latter have important applica-
tions in synthetic chemistry and were prepared recently by multi
step reaction.20,21 Moreover, the reported synthesized aryl vinyl
ethers found applications in the synthesis of biologically active
molecules and natural product analogues,22 and because of its
importance various methods for their synthesis have been
reported.23 Also, the reported pyrolytic transformations convert
aldehydes to aryloxyalkenes (a protected homologation) and 4-
pentenal (a C-1 allylation and homologation).
Scheme 5 Synthesis of b-lactams 8a–e and thio-b-lactams 10a-e.
4. Experimental
4.1 General
All reactions were carried out in oven-dried glassware under N2,
using commercially supplied solvents and reagents unless
otherwise stated. THF and CH2Cl2 were redistilled from Na–
Ph2CO and CaH2 respectively. Column chromatography was
carried out on silica gel using ash techniques (eluants are
given in parentheses). Analytical thin-layer chromatography was
performed on precoated silica gel F254 aluminum plates with
visualization under UV light.
Scheme 6 Products of SVP and FVP of cis-b-lactam 8a–e and thio-b-
lactams 10a–e.
1a–c but with a higher yields of aldehydes 12a–c. On the other
hand, pyrolysis of thio-b-lactams 10a–e gave poor yields in both
STP and FVP even on decreasing the pyrolysis temperature (270
Melting points were obtained using a melting point apparatus
and are uncorrected. IR spectra were recorded on FT-IR
Table 3 Products of SVP and FVP of cis-b-lactams 8a–e and thio-b-lactams 10a–e
STPa
FVPb
Alde. no.
(yield %)
Imine no.
(yield %)
Urea(thiourea) no.
(yield %)
Alde. no.
(yield %)
Imine no.
(yield %)
Urea(thiourea) no.
(yield %)
Comp. no.
8a
8b
8c
8d
12a (26)
12a (20)
12a (22)
12b (21)
12c (24)
12a (18)
12a (15)
12a (18)
12b (16)
12c (15)
1a (18)
1b (12)
1c (25)
1d (17)
1e (12)
1a (20)
1b (19)
1c (19)
1d (22)
1e (13)
7a (18)
7b (24)
7c (17)
7a (21)
7a (9)
13a (3)
13b (2)
13c (4)
13a (0)
13a (2)
12a (31)
12a (28)
12a (26)
12b (27)
12c (27)
12a (22)
12a (18)
12a (21)
12b (21)
12c (23)
1a (15)
1b (14)
1c (19)
1d (22)
1e (18)
1a (20)
1b (18)
1c (16)
1d (19)
1e (17)
7a (14)
7b (16)
7c (15)
7a (15)
7a (13)
13a (5)
13b (3)
13c (3)
13a (4)
13a (2)
8e
10a
10b
10c
10d
10e
a
STP, 300 ꢂC, 0.01 Torr, 15 min. for b-lactams 8a–e, 270 ꢂC, 0.01 Torr, 15 min for thio-b-lactams 10a–e. b FVP, 600 ꢂC, 0.02 Torr for b-lactams 8a–e,
550 ꢂC, 0.02 Torr; for thio-b-lactams 10a–e.
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spectrophotometer as neat thin lms between NaCl plates in the 121.5, 118.4, 115.0, 80.6, 60.8; HR-MS (EI) m/z [M]+ calcd for
case of liquid substances or as KBr pellets in the case of solids,
with adsorptions reported in wavenumbers (cmꢁ1). 1H NMR
C
21H1635ClNO2 349.0870,found 349.0865.
(ꢃ)-cis-3-Phenoxy-4-(p-tolyl)-1-phenyl-2-azetidinone
(2e).26
spectra were recorded at 400 or 600 MHz with chemical shis (d) Colorless crystals, yield 9.7 g (74%), mp 172–173 ꢂC; nmax(KBr)/
quoted in parts per million (ppm) and coupling constants (J) cmꢁ1 3029, 2947, 2856, 1922, 1746, 1598, 1473, 1388, 746, 684;
recorded in hertz (Hz). 13C NMR spectra were recorded at 100 or dH(600 MHz, CDCl3) 7.36 (d, 2H, J 7.8), 7.26–7.23 (m, 4H), 7.15 (t,
150 MHz with chemical shis (d) quoted in ppm. Mass spectral 2H, J 8.4), 7.06 (d, 3H, J 7.8), 6.90 (t, 1H, J 7.2),6.78 (d, 2H, J 7.8),
data were measured with EI positive ion mode. Microanalyses 5.52 (d, 1H, J 4.8), 5.34 (d, 1H, J 4.8), 2.27 (s, 3H); dC(125 MHz,
were performed on LECO CH NS-932 Elemental Analyzer.
CDCl3) 163.4, 157.2, 138.7, 137.1, 129.6, 129.4, 129.3, 128.2,
124.7, 122.3, 117.8, 116.0, 81.4, 62.1, 21.4; HR-MS (EI) m/z [M]+
calcd for C22H19NO2 329.1416, found 329.1410.
4.2 Synthesis of b-lactams 2a–g: general procedure
(ꢃ)-cis-3-Phenoxy-4-(p-methoxyphenyl)-1-phenyl-2-azetidinone
To a stirred cold (0 ꢂC) solution of appropriate imines 1a–g (40 (2f). Colorless crystals, yield 8.4 g (61%), mp 152–155 ꢂC
mmol, 1 equiv.) and triethylamine (25 mmol, 2.5 equiv.) in dry (150 ꢂC);25 nmax(KBr)/cmꢁ1 3041, 2957, 2872, 1758, 1597, 1458,
CH2Cl2 (15 mL) under nitrogen atmosphere was added drop- 1384, 1362, 1251, 895, 754, 690; dH(400 MHz, CDCl3) 7.36 (d, 2H, J
wise with a syringe a solution of phenoxyacetyl chloride (100 7.6), 7.36–7.25 (m, 4H), 7.17 (t, 2H, J 7.6), 7.08 (t, 1H, J 7.6), 6.92 (t,
mmol, 2.5 equiv.) in dry CH2Cl2 (5 mL). The mixture was stirred 1H, J 7.2), 6.80 (m, 4H), 5.53 (d, 1H, J 4.8), 5.35 (d, 1H, J 4.8), 3.75
ꢂ
at 0 C for 30 min, and then le stirring at room temperature (s, 3H); dC(100 MHz, CDCl3) 163.3, 160.0, 157.2, 137.3, 129.6,
overnight. The reaction mixture washed with water, NaHCO3 129.4, 129.3, 124.7, 124.5, 122.3, 117.8, 115.9, 114.1, 81.4, 61.9,
solution and brine. The organic layer was then dried over 55.4; HR-MS (EI) m/z [M]+ calcd for C22H19NO3 345.1365, found
anhydrous Na2SO4 and the solvent was removed in vacuo. The 345.1361.
remaining solid was recrystallized from ethanol to give corre-
(ꢃ)-cis-3-Phenoxy-4-(p-chlorophenyl)-1-phenyl-2-azetidinone
sponding b-lactams 2a–g as colourless solid in 57–74% yield.
(2g).27 Colorless crystals, yield 6.5 g (58%), mp 193–196 ꢂC;
(ꢃ)-cis-3-Phenoxy-1,4-diphenyl-2-azetindione (2a). Colorless nmax(KBr)/cmꢁ1 3047, 1743, 1598, 1490, 1350, 1251, 865, 837,
24
crystals, yield 8.4 g (67%), mp 193–195 ꢂC (194 ꢂC);
n
max
(KBr)/ 744 and 684; dH(400 MHz, CDCl3) 7.26–7.11 (m, 8H), 7.08 (t, 2H,
cmꢁ1 3003, 2916, 1744, 1588, 1558, 1455, 1419, 1210, 749, 701. J 8.0), 7.01 (t, 1H, J 7.6), 6.84 (t, 1H, J 7.2), 6.68 (d, 2H, J 8.0), 5.47
dH(400 MHz, CDCl3) 7.38–7.26 (m, 9H), 7.16 (t, 2H, J 8.4), 7.09 (t, (d, 1H, J 4.8), 5.28 (d, 1H, J 4.8); dC(100 MHz, CDCl3) 163.0,
1H, J 7.2), 6.93 (t, 1H, J 8.0), 6.78 (d, 2H, J 8.0), 5.57 (d, 1H, J 4.8), 156.9, 136.9, 134.8, 131.4, 129.65, 129.60, 129.4, 128.9, 125.0,
5.40 (d, 1H, J 4.8); dC(100 MHz, CDCl3) 163.3, 157.1, 137.1, 132.7, 122.6, 117.7, 115.8, 81.2, 61.5; HR-MS (EI) m/z [M]+ calcd for
129.49, 129.40, 128.9, 128.6, 128.3, 124.8, 122.4, 117.8, 115.9,
81.3, 62.2; HR-MS (EI) m/z [M]+ calcd for C21H17NO2 315.1259,
found 315.1256.
C
21H1635ClNO2 349.0870, found 349.0867.
(ꢃ)-trans-3-Phenoxy-1-(p-chlorophenyl)-4-phenyl-2-azetidinone
(3d). Colorless crystals, yield 5.1 g (45%), mp 149–150 ꢂC;
(ꢃ)-cis-3-Phenoxy-4-phenyl-1-(p-tolyl)-2-azetidione
(2b). nmax(KBr)/cmꢁ1 3050, 1745, 1599, 1490, 1353, 1250, 866, 838, 746,
Colorless crystals, yield 7.9 g (60%), mp 175–177 ꢂC; nmax(KBr)/ 685; dH(600 MHz, CDCl3) 7.39–7.19 (m, 11H), 7.00 (t, 1H, J 7.2),
cmꢁ1 3029, 2947, 2856, 1743, 1598, 1494, 1253, 864, 825, 746, 6.87 (d, 2H, J 7.8), 5.11 (d, 1H, J 1.8), 5.00 (d, 1H, J 1.8); dC(125 MHz,
684; dH(400 MHz, CDCl3) 7.36 (d, 2H, J 8.4), 7.26 (m, 4H), 7.17 (t, CDCl3) 162.7, 157.0, 135.5, 135.2, 129.9, 129.8, 129.6, 129.5, 129.4,
2H, J 8.4), 7.08 (d, 3H, J 7.6), 6.92 (t, 1H, J 7.6), 6.79 (d, 2H, J 8.4), 126.5, 122.5, 118.9, 115.5, 87.6, 64.3; HR-MS (EI) m/z [M]+ calcd for
5.53 (d, 1H, J 4.8), 5.36 (d, 1H, J 4.8), 2.29 (s, 3H); dC(100 MHz, C21H1635ClNO2 349.0870, found 349.0870.
CDCl3) 163.4, 157.2, 138.7, 137.2, 129.6, 129.4, 129.3, 128.2,
124.7, 122.3, 117.8, 116.0, 81.4, 61.1, 21.4; HR-MS (EI) m/z [M]+
calcd for C22H19NO2 329.1416, found 329.1411.
4.3 Synthesis of thio-b-lactams 4a–g: general procedure
(ꢃ)-cis-3-Phenoxy-1-(p-methoxyphenyl)-4-phenyl-2-azetidinone A mixture of appropriate b-lactams 2a–g (4 mmol) and Law-
(2c). Colorless crystals, yield 8.1 g (60%), mp 190–191 ꢂC esson's reagent (1.6 g, 4 mmol) in dry toluene (15 mL) was
(186 ꢂC);25 nmax(KBr)/cmꢁ1 3035, 2956, 2831, 1742, 1588, 1455, reuxed for 3 h. The solvent was then removed in vacuo and the
1441, 882, 750, 696; dH(600 MHz, CDCl3) 7.30–7.25 (m, 7H), 7.14 resulting solid was recrystallised from ethanol to give the cor-
(m, 2H), 6.90 (t, 1H, J 7.6), 6.80–6.76 (m, 4H), 5.55 (d, 1H, J 4.8), responding thio-b-lactams 4a–g in 65–77% yield.
5.35 (d, 1H, J 4.8), 3.74 (s, 3H); dC(125 MHz, CDCl3) 162.2, 157.1,
(ꢃ)-cis-3-Phenoxy-1,4-diphenyazetidin-2-thione (4a). Color-
156.7, 132.8, 130.6, 129.4, 128.9, 128.5, 128.3, 122.3, 119.1, 115.9, less crystals, 0.88 g (67%), mp 170–175 ꢂC; nmax(KBr)/cmꢁ1 3026,
114.6, 81.4, 62.3, 55.6; HR-MS (EI) m/z [M]+ calcd for C22H19NO3 3006, 2927, 1589, 1494, 1427, 1228, 1205, 1074, 765, 746, 686;
345.1365, found 345.1362.
dH(400 MHz, CDCl3) 7.92 (d, 2H, J 8.4), 7.36–7.13 (m, 10H), 6.93
(ꢃ)-cis-3-Phenoxy-1-(p-chlorophenyl)-4-phenyl-2-azetidinone (t, 1H, J 6.7), 6.78 (d, 2H, J 8.0), 5.89 (d, 1H, J 4.8), 5.35 (d, 1H, J
(2d). Colorless crystals, yield 3.4 g (30%), mp 272–273 ꢂC; 4.8); dC(100 MHz, CDCl3) 195.2, 157.2, 138.0, 132.0, 129.4, 129.2,
nmax(KBr)/cmꢁ1 3048, 1745, 1598, 1492, 1350, 1251, 866, 837, 128.7, 128.3, 126.6, 122.5, 118.5, 116.3, 79.5, 70.4; HR-MS (EI) m/
746, 684; dH(400 MHz, DMSO-d6) 7.39–7.32 (m, 6H), 7.27 (m, z [M]+ calcd for C21H17NOS 331.1031, found 331.1028.
3H), 7.18 (t, 2H, J 7.2), 6.91 (t, 1H, J 7.2), 6.80 (d, 2H, J 7.8), 5.78
(ꢃ)-cis-3-Phenoxy-1-(p-tolyl)-4-phenylazetidin-2-thione (4b).
(d, 1H, J 4.0), 5.70 (d, 1H, J 4.0); dC(100 MHz, DMSO-d6) 162.6, Colorless crystals, 0.95 g (69%), 157–159 ꢂC; nmax(KBr)/cmꢁ1
156.2, 135.2, 132.5, 129.1, 128.8, 128.7, 127.9, 127.7, 127.6, 2916, 2831, 2360, 1579, 1404, 1346, 1207, 750, 688; dH(400 MHz,
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CDCl3) 7.92 (d, 2H, J 8.4), 7.32 (t, 2H J 8.4), 7.26–7.14 (m, 5H), CH2Cl2 (15 mL) under nitrogen atmosphere was added drop-
7.07 (d, 2H J 8.0), 6.92 (t, 1H J 7.6), 6.81 (d, 2H J 8.0), 5.86 (d, 1H, J wise with a syringe a solution of allyloxyacetyl chloride (25
4.4), 5.32 (d, 1H, J 4.4), 2.28 (s, 3H); dC(100 MHz, CDCl3) 195.3, mmol, 2.5 equiv.) in dry CH2Cl2 (5 mL). The mixture was stirred
ꢂ
157.3, 139.1, 138.0, 129.45, 129.41, 129.2, 128.9, 128.2, 126.6, at 0 C for 30 min, and then le stirring at room temperature
122.4, 118.6, 116.3, 79.7, 70.5, 21.4; HR-MS (EI) m/z [M]+ calcd overnight. The reaction mixture was washed with water,
for C22H19NOS 345.1187, found 345.1181.
NaHCO3 solution and brine. The organic layer was then dried
(ꢃ)-cis-3-Phenoxy-1-(p-methoxyphenyl)-4-phenylazetidin-2- over anhydrous Na2SO4 and the solvent was removed in vacuo.
ꢂ
thione (4c). Colorless crystals, 1.03 g (71%), mp 148–150 C; The remaining solid was recrystallized from ethanol to give
nmax(KBr)/cmꢁ1 3031, 2954, 2923, 2835, 1585, 1446, 1438, corresponding b-lactams 8a–e as colourless solid in 69–84%
1259, 1176, 1101, 850, 748, 723, 684; dH(400 MHz, CDCl3) 7.88 yield.
(d, 2H, J 8.0), 7.35–7.26 (m, 5H), 7.14 (t, 2H, J 7.2), 6.92 (t, 1H, J
(ꢃ)-cis-3-Allyloxy-1,4-diphenyl-2-azetidinone (8a). Colorless
7.2), 6.84 (d, 2H, J 7.4), 6.79 (d, 2H, J 8.0), 5.84 (d, 1H, J 4.4), crystals, yield 2.10 g (75%), mp 131–133 ꢂC; nmax(KBr)/cmꢁ1
5.35 (d, 1H, J 4.4), 3.77 (s, 3H); dC(100 MHz, CDCl3) 193.3, 3036, 2910, 2857, 1741, 1595, 1497, 1389, 1184, 1132, 926, 752;
157.9, 157.2, 132.0, 131.5, 129.3, 129.2, 128.6, 128.3, 122.4, dH(400 MHz, CDCl3) 7.42–7.23 (m, 7H), 7.26 (t, 2H, J 7.6), 7.05 (t,
120.2, 116.2, 114.3, 79.5, 70.6, 55.6; HR-MS (EI) m/z [M]+ calcd 1H, J 7.6), 5.57 (m, 1H), 5.19 (d, 1H, J 4.8, H-4), 5.08 (dd, 1H, J
for C22H19NO2S 361.1136, found 361.1133.
8.8, 1.2), 5.00 (dd, 1H, J 18.2, 1.2), 4.96 (d, 1H, J 4.8, H-3), 3.89
(ꢃ)-cis-3-Phenoxy-1-(p-chlorophenyl)-4-phenyl-2-azetidin-2- (dd, 1H, J 12.4, 5.6), 3.74 (dd, 1H, J 12.4, 5.6); dC(100 MHz,
ꢂ
thione (4d). Colorless crystals, 1.12 g (77%), mp 217–218 C; CDCl3) 164.6, 137.2, 133.6, 133.3, 129.2, 128.7, 128.6, 128.2,
nmax(KBr)/cmꢁ1 3030, 2927, 1582, 1494, 1427, 1230, 1200, 1077, 124.5, 118.2, 117.6, 82.7, 71.6, 62.1; HR-MS (EI) m/z [M]+ calcd
765, 750, 686; dH(600 MHz, DMSO-d6) 7.93 (d, 2H, J 7.8), 7.49 for C18H17NO2 279.1259, found 279.1253; anal. calcd: C 77.40, H
(d, 2H, J 7.8),7.31–7.16 (m, 7H) 6.90 (t, 1H, J 7.8), 6.80 (d, 2H, J 6.13, N 5.01. Found C 77.20, H 6.08, N 4.90.
7.8), 6.36 (d, 1H, J 4.2), 5.64 (d, 1H, J 4.2); dC(125 MHz, DMSO-
(ꢃ)-trans-3-Allyloxy-1,4-diphenyl-2-azetidinone (9a). Color-
d6) 195.2, 156.3, 136.0, 131.8130.1, 129.3, 129.2, 128.7, 128.3, less crystals, yield 0.2 g (4%), mp 94–96 ꢂC; nmax(KBr)/cmꢁ1
125.3, 121.9, 119.8, 115.2, 78.8, 69.5; HR-MS (EI) m/z [M]+ calcd 3035, 2910, 2857, 1740, 1595, 1497, 1390, 1184, 1133, 926, 752;
for C21H1635ClNOS 365.0641, found 365.0635.
dH(400 MHz, CDCl3) 7.41–7.24 (m, 9H), 7.07 (t, 1H, J 7.8), 5.95
(ꢃ)-cis-3-Phenoxy-4-(p-tolyl)-1-phenyl-2-azetidin-2-thione (4e). (m, 1H), 5.32 (dd, 1H, J 15.6, 1.6), 5.23 (dd, 1H, J 10.4, 1.2), 4.95
Colorless crystals, 0.89 g (65%), 152–153 ꢂC; nmax(KBr)/cmꢁ1 (d, 1H, J 2.4, H-4), 4.45 (d, 1H, J 2.4, H-3), 4.30 (dd, 1H, J 12.4,
2916, 2831, 2360, 2343, 1589, 1404, 1346, 1207, 750, 688; dH(600 5.6), 4.24 (dd, 1H, J 12.4, 5.6); HR-MS (EI) m/z [M]+ calcd for
MHz, CDCl3) 7.90 (d, 2H, J 7.8), 7.28 (t, 2H, J 7.8), 7.20 (d, 2H, J
C18H17NO2 279.1259, found 279.1254; anal. calcd: C 77.40, H
7.4), 7.15 (m, 3H), 7.03 (d, 2H, J 7.8), 6.88 (t, 1H, J 7.8), 6.79 (d, 2H, 6.13, N 5.01. Found C 77.18, H 6.09, N 4.93.
J 7.8), 5.83 (d, 1H, J 4.2), 5.28 (d, 1H, J 4.2), 2.25 (s, 3H); dC(125
(ꢃ)-cis-3-Allyloxy-1-(p-methoxyphenyl)-4-phenyl-2-azetidinone
MHz, CDCl3) 195.2, 157.3, 139.0, 138.0, 129.38, 129.36, 129.1, (8b). Colorless crystals, yield 2.60 g (84%), mp 120–121 ꢂC;
128.8, 128.2, 126.5, 122.4, 118.5, 116.3, 79.6, 70.4, 21.3; HR-MS nmax(KBr)/cmꢁ1 3036, 2977, 2837, 1741, 1595, 1690, 1514, 1243,
(EI) m/z [M]+ calcd for C22H19NOS 345.1187, found 345.1184.
1185, 1115, 993, 829, 694; dH(400 MHz, CDCl3) 7.39–7.28 (m, 7H),
(ꢃ)-cis-3-Phenoxy-4-(p-methoxyphenyl)-1-phenyl-2-azetidin-2- 6.80–6.78 (m, 2H) 5.59 (m, 1H), 5.17 (d, 1H, J 4.8, H-4), 5.08 (dd,
thione (4f). Colorless crystals, 1.05 g (73%), mp 148–150 ꢂC; 1H, J 8.8, 1.2), 5.04 (dd, 1H, J 18.2, 1.2), 4.97 (d, 1H, J 4.8, H-3),
nmax(KBr)/cmꢁ1 3030, 2953, 2923, 2835, 1586, 1446, 1438, 1259, 3.89 (dd, 1H, J 12.2, 5.6), 3.76 (dd, 1H, J 12.2, 5.6), 3.73 (s, 3H,
1176, 1101, 851, 750, 725, 683; dH(600 MHz, CDCl3) 7.93 (d, 2H, J OCH3); dC(100 MHz, CDCl3) 164.0, 156.5, 133.7, 133.4, 130.8,
8.0), 7.34–7.14 (m, 7H), 6.92 (t, 1H, J 7.6), 6.81 (t, 4H, J 7.6), 5.85 128.7, 128.6, 128.3, 118.9, 118.1, 114.5, 82.9, 71.6, 62.2, 55.6; HR-
(d, 1H, J 4.4), 5.30 (d, 1H, J 4.4), 3.73 (s, 3H); dC(125 MHz, CDCl3) MS (EI) m/z [M]+ calcd for C19H19NO3 309.1365, found 309.1359;
195.1, 160.2, 157.2, 137.9, 129.6, 129.3, 129.1, 126.5, 123.7, anal. calcd: C 73.77, H 6.19, N 4.53. Found C 73.49, H 6.00, N
122.3, 118.6, 116.2, 114.0, 79.6, 70.1, 55.3; HR-MS (EI) m/z [M]+ 4.34.
calcd for C22H19NO2S 361.1136, found 361.1130.
(ꢃ)-cis-3-Allyloxy-1-(p-chlorophenyl)-4-phenyl-2-azetidinone
(ꢃ)-cis-3-Phenoxy-4-(p-chlorophenyl)-1-phenyl-2-azetidin-2-
(8c). Colorless crystals, yield 2.15 g (69%), mp 98–100 ꢂC;
thione (4g). Colorless crystals, 1.05 g (72%), mp 166–167 ꢂC; nmax(KBr)/cmꢁ1 3065, 3037, 2961, 2903, 2857, 1741, 1595, 1496,
nmax(KBr)/cmꢁ1 3033, 2927, 1587, 1494, 1425, 1230, 1212, 1077, 1385, 1176, 1131, 839, 814; dH(400 MHz, CDCl3) 7.37–7.18 (m,
765, 749, 686; dH(400 MHz, CDCl3) 7.90 (d, 2H, J 8.4), 7.35–7.15 9H), 5.55 (m, 1H), 5.17 (d, 1H, J 4.8, H-4), 5.07 (dd, 1H, J 9.6,
(m, 9H), 6.94 (t, 1H, J 7.6), 6.80 (d, 2H, J 8.0), 5.87 (d, 1H, J 4.8), 1.2), 5.03 (dd, 1H, J 18.4, 1.2), 4.97 (d, 1H, J 4.8, H-3), 3.88 (dd,
5.33 (d, 1H, J 4.8); dC(100 MHz, CDCl3) 195.0, 157.0, 137.7, 135.1, 1H, J 12.4, 5.6), 3.74 (dd, 1H, J 12.4, 5.6); dC(100 MHz, CDCl3)
130.6, 129.6, 129.5, 129.3, 128.9, 126.8, 122.6, 118.4, 116.1, 79.3, 164.5, 135.8, 133.3, 133.1, 129.6, 129.3, 129.0, 128.8, 128.2,
69.6; HR-MS (EI) m/z [M]+ calcd for C21H1635ClNOS 365.0641, 118.9, 118.4, 83.0, 71.8, 62.3; HR-MS (EI) m/z [M]+ calcd for
found 365.0635.
C18H16ClNO2 313.0870, found 313.0864; anal. calcd: C 68.90, H
5.14, N 4.46. Found C 68.71, H 5.08, N 4.32.
(ꢃ)-cis-3-Allyloxy-4-(p-methoxyphenyl)-1-phenyl-2-azetidinone
4.4 Synthesis of b-lactams 8a–e: general procedure
(8d). Colorless crystals, yield 2.55 g (82%), mp 90–91 ꢂC;
To a stirred cold (0 ꢂC) solution of appropriate imines 1a–e (10 nmax(KBr)/cmꢁ1 3037, 2960, 2898, 1749, 1615, 1510, 1393, 1247,
mmol, 1 equiv.) and triethylamine (25 mmol, 2.5 equiv.) in dry 1176, 1131, 833, 752; dH(400 MHz, CDCl3) 7.33 (d, 4H, J 6.8), 7.24
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(t, 2H, J 7.2), 7.05 (t, 1H, J 7.2), 6.89 (d, 2H, J 6.8), 5.59 (m, 1H), 3.84 (dd, 1H, J 12.8, 5.6); dC(100 MHz, CDCl3) 197.6, 136.5, 133.3,
5.14 (d, 1H, J 4.8, H-4), 5.11 (dd, 1H, J 8.8, 1.2), 5.07 (dd, 1H, J 132.3, 131.2, 129.2, 129.1, 128.8, 128.2, 119.7, 118.2, 80.7, 71.3,
18.2, 1.2), 4.92 (d, 1H, J 4.8, H-3), 3.89 (dd, 1H, J 12.4, 5.6), 3.80 (s, 70.5; HR-MS (EI) m/z [M]+ calcd for C18H1635ClNOS 329.0641,
3H, OCH3), 3.76 (dd, 1H, J 12.4, 5.6); dC(100 MHz, CDCl3) 164.7, found 329.0633; anal. calcd: C 65.45, H 4.89, N 4.25, S 9.72. Found
160.0, 137.3, 133.5, 129.5, 129.2, 125.4, 124.4, 118.2, 117.7, 114.1, C 65.19, H 4.69, N 4.11, S 9.62.
82.7, 71.7, 61.7, 55.4; HR-MS (EI) m/z [M]+ calcd for C19H19NO3
309.1365, found 309.1359; anal. calcd: C 73.77, H 6.19, N 4.53. thione (10d). Colorless crystals, yield 0.47 g (72%), mp 90–
Found C 73.40, H 6.05, N 4.54.
91 ꢂC; nmax(KBr)/cmꢁ1 3066, 3032, 2955, 2836, 1594, 1517,
(ꢃ)-cis-3-Allyloxy-4-(p-methoxyphenyl)-1-phenylazetidin-2-
(ꢃ)-cis-3-Allyloxy-4-(p-chlorophenyl)-1-phenyl-2-azetidinone 1449, 1267, 1175, 1062, 979, 699; dH(400 MHz, CDCl3) 7.88 (d,
(8e). Colorless crystals, yield 2.19 g (70%), mp 109–110 ꢂC; 2H, J 8.8), 7.32–7.26 (m, 4H), 7.15 (t, 1H, J 7.2), 6.88 (d, 2H, J
nmax(KBr)/cmꢁ1 3062, 3030, 2983, 2905, 1756, 1597, 1497, 8.8), 5.67 (d, 1H, J 4.4, H-4),5.63 (m, 1H), 5.14–5.07 (m, 2H),
1387, 1125, 1087, 929, 750, 685; dH(400 MHz, CDCl3) 7.37–7.23 4.65 (d, 1H, J 4.4, H-3), 4.04 (dd, 1H, J 12.8, 5.6), 3.88 (dd, 1H, J
(m, 8H), 7.07 (t, 1H, J 7.8), 5.60 (m, 1H), 5.17 (d, 1H, J 4.8,H-4), 12.8, 5.6), 3.79 (s, 3H, OCH3); dC(100 MHz, CDCl3) 197.5,
5.08 (dd, 1H, J 9.6, 1.2), 5.06 (dd, 1H, J 18.4, 1.2), 4.95 (d, 1H, 160.2, 138.1, 133.5, 129.7, 129.0, 126.3, 124.5, 118.6, 118.1,
J 4.8, H-3), 3.93 (dd, 1H, J 12.4, 5.6), 3.78 (dd, 1H, J 12.4, 5.6); 114.2, 80.6, 71.3, 70.1, 55.4; HR-MS (EI) m/z [M]+ calcd for
dC(100 MHz, CDCl3) 164.5, 137.0, 134.7, 133.2, 132.3, 129.6,
129.3, 129.0, 124.7, 118.4, 117.5, 82.7, 71.9, 61.4; HR-MS H 5.88, N 4.30, S 9.85. Found C 69.89, H 5.58, N 4.23, S 9.69.
(EI) m/z [M]+ calcd for C18H1635ClNO2 313.0870, found
(ꢃ)-cis-3-Allyloxy-4-(p-chlorophenyl)-1-phenylazetidin-2-thione
313.0863; anal. calcd: C 68.90, H 5.14, N 4.46. Found C 68.69, (10e). Colorless crystals, yield 0.45 g (68%), mp 58–59 ꢂC;
C19H19NO2S 325.1136, found 325.1132; anal. calcd: C 70.12,
H 5.04, N 4.38.
nmax(KBr)/cmꢁ1 3069, 3047, 2923, 2857, 1595, 1494, 1426, 1266,
1164, 934, 834; dH(400 MHz, CDCl3) 7.83 (d, 2H, J 8.8), 7.36–7.26
(m, 6H), 7.18 (t, 1H, J 7.2), 5.69 (d, 1H, J 4.4,H-4), 5.60 (m, 1H),
5.14–5.09 (m, 2H), 4.67 (d, 1H, J 4.4, H-3), 4.09 (dd, 1H, J 12.8, 5.6),
4.5 Synthesis of thio-b-lactams 10a–e: general procedure
A mixture of appropriate b-lactams 1a–e (2 mmol) and Law- 3.89 (dd, 1H, J 12.8, 5.6); dC(100 MHz, CDCl3) 197.5, 137.8, 135.0,
esson's reagent (0.8 g, 2 mmol, 2 equiv.) in dry toluene (15 mL) 133.3, 131.5, 129.7, 129.1, 129.0, 126.5, 118.4, 118.3, 80.4, 71.5,
was reuxed for 3 h. Then the solvent evaporated at reduced 69.6; HR-MS (EI) m/z [M]+ calcd for C18H1635ClNOS 329.0641,
pressure. Finally, the resulting solid was recrystallised in found 329.0636; anal. calcd: C 65.45, H 4.89, N 4.25, S 9.72. Found
ethanol to give thio-b-lactams 10a–e in 65–76% yield.
C 65.21, H 4.76, N 4.14, S 9.53.
(ꢃ)-cis-3-Allyloxy-1,4-diphenylazetidin-2-thione (10a). Color-
less crystals, yield 0.40 g (70%), mp 70–72 C; nmax(KBr)/cmꢁ1
3067, 3036, 2981, 2920, 1586, 1495, 1497, 1389, 1184, 1132, 926,
ꢂ
4.6 Pyrolysis product
752; dH(400 MHz, CDCl3) 7.88 (d, 2H, J 8.0), 7.40-7.26 (m, 7H),
(A) Flash vacuum pyrolysis. The apparatus used was
7.17 (t, 1H, J 7.8), 5.71 (d, 1H, J 4.4, H-4),5.58 (m, 1H), 5.10–5.05 similar to the one which has been described in our recent
(m, 2H), 4.68 (d, 1H, J 4.4, H-3), 4.05 (dd, 1H, J 12.8, 5.6), 3.85 publications.28–30 The sample of the substrate was volatilized
¨
(dd, 1H, J 12.8, 5.6); dC(100 MHz, CDCl3) 197.5, 138.1, 133.5, from a tube in a Buchi Kugelrohr oven through a 30 ꢀ 2.5 cm
132.8, 129.1, 128.7, 128.3, 126.4, 118.5, 118.1, 80.6, 71.3, 70.4; horizontal fused quartz tube. This was heated externally by a
HR-MS (EI) m/z [M]+ calcd for C18H17NOS 295.1031, found Carbolite Eurotherm tube furnace MTF-12/38A to a temperature
295.1024; anal. calcd: C 73.19, H 5.80, N 4.74, S 10.85. Found C of 550 or 600 ꢂC, the temperature being monitored by Pt/Pt-13%
72.89, H 5.57, N 4.61, S 10.64.
Rh thermocouple situated at the center of the furnace. The
(ꢃ)-cis-3-Allyloxy-1-(p-methoxyphenyl)-4-phenylazetidin-2- products were collected in a U-shaped trap cooled in liquid
thione (10b). Colorless crystals, yield 0.49 g (76%), mp 93–94 ꢂC; nitrogen. The whole system was maintained at a pressure of
nmax(KBr)/cmꢁ1 3066, 3031, 2955, 2836, 1597, 1510, 1449, 1267, 10ꢁ2 Torr by an Edwards Model E2M5 high capacity rotary oil
1175, 1062, 830, 699; dH(400 MHz, CDCl3) 7.83 (d, 2H, J 7.6), pump, the pressure being measured by a Pirani gauge situated
7.37–7.33 (m, 5H), 6.78 (d, 2H, J 7.2), 5.67 (d, 1H, J 4.4, H-4), 5.56 between the cold trap and pump. Under these conditions the
(m, 1H), 5.07–5.03 (m, 2H), 4.68(d, 1H, J 4.4, H-3), 4.00 (dd, 1H, J contact time in the hot zone was estimated to be ca. 10 ms. The
12.8, 5.6), 3.83 (dd, 1H, J 12.8, 5.6), 3.73 (s, 3H, OCH3); dC(100 different fractions of the product collected in the U-shaped trap
MHz, CDCl3) 195.5, 157.6, 133.4, 132.7, 131.6, 129.0, 128.7, were analyzed by 1H, 13C NMR, IR and LC-MS. Relative and
128.3, 120.1, 118.0, 114.1, 80.6, 71.2, 70.5, 55.5; HR-MS (EI) m/z percent yields were determined from NMR.
[M]+ calcd for C19H19NO2S 325.1136, found 325.1132; anal.
(B) Static pyrolysis. A sample of the substrate (1 mmol), was
calcd: C 70.12, H 5.88, N 4.30, S 9.85. Found C 69.97, H 5.52, N introduced in the reaction tube (1.5 ꢀ 12 cm Pyrex), cooled in
4.21, S 9.70.
liquid nitrogen, sealed under vacuum (0.01 Torr) and placed in
ꢂ
(ꢃ)-cis-3-Allyloxy-1-(p-chlorophenyl)-4-phenylazetidin-2-thione the pyrolyzer for 15 minutes at 320 and 270 C, a temperature
(10c). Colorless crystals, yield 0.42 g (65%), mp 34–35 ꢂC; that is required for complete pyrolysis of the substrate. The
nmax(KBr)/cmꢁ1 3067, 3031, 2981, 2903, 2864, 1576, 1493, 1399, static sealed-tube (STP) pyrolysis was conducted in a custom-
1266, 1166, 989, 827; dH(400 MHz, CDCl3) 7.83 (d, 2H, J 7.6), 7.36 made Chemical Data System (CDS) pyrolyser consisting of an
(m, 5H), 7.22 (d, 2H, J 8.8), 5.69 (d, 1H, J 4.4, H-4), 5.57 (m, 1H), aluminum block with a groove to accommodate the Pyrex
5.09–5.05 (m, 2H), 4.69 (d, 1H, J 4.4, H-3), 4.03 (dd, 1H, J 12.8, 5.6), sealed-tube reactor, and tted with a platinum-resistance
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1,3-Bis-(p-chlorophenyl)urea (7d).19 Colorless solid, mp 297–
thermometer and thermocouple connected to a Comark
microprocessor thermometer. The block temperature was
controlled by a Eurothem 093 precision temperature regulator.
Aluminum was chosen for its low temperature gradient and
resistance to elevated temperatures.
All the identied products in the STP and FVP gave satis-
factory NMR (1H, 13C) and MS., compounds (E/Z) 5a–d,31–35 yield
3–25%; compounds 7, 13a–d,19,36,37 yield 0–24%; compounds
12a–c,17,18 yield 12–31%.
(E)-2-Phenyl-1-phenoxyethene (5a).31 Colorless oil, dH(400
MHz, CDCl3) 7.38–7.21 (m, 9H), 7.09 (d, 2H, J 8.0), 6.35 (d, 1H, J
12.4); dC(100 MHz, CDCl3) 157.1, 143.4, 135.1, 129.7, 128.7,
126.7, 125.6, 123.2, 116.9, 113.6; HR-MS (EI) m/z [M]+ calcd for
299 ꢂC (301 C):19 dH(400 MHz, DMSO-d6): 8.85 (s, 2H), 7.41 (d,
ꢂ
4H, J 8.6), 7.34 (d, 4H, J 8.6); dC(100 MHz, DMSO-d6): 157.3,
143.6, 133.3, 130.5, 125.3; HR-MS (EI) m/z [M]+ calcd for
C
13H1035Cl2N2O 280.0170, found 280.0167.
1,3-Diphenylthiourea (13a).36 Colorless solid, mp 150–151 C
ꢂ
(154 ꢂC): dH(400 MHz, CDCl3): 8.30 (s, 2H), 7.41–7.27 (m, 10H);
dC(100 MHz, CDCl3): 180.1, 137.6, 129.5, 127.1, 125.5; HR-MS
(EI) m/z [M]+ calcd for C13H12N2S 228.0721, found 228.0718.
1,3-Bis-(p-tolyl)thiourea (13b).36 Colorless solid, mp 178–180
ꢂC (179 ꢂC): dH(400 MHz, DMSO-d6): 9.56 (s, 2H), 7.34–7.14 (m,
8H), 2.31 (s, 6H); dC(100 MHz, DMSO-d6): 181.2, 137.6, 134.3,
130.7, 125.8, 21.9; HR-MS (EI) m/z [M]+ calcd for C15H16N2S
256.1034, found 256.1031.
C
14H12O 196.0888, found 196.0882.
(Z)-2-Phenyl-1-phenoxyethene (5a).34 Colorless oil, dH(400
1,3-Bis-(p-methoxyphenyl)thiourea (13c).37 Colorless solid, mp
ꢂ
ꢂ
MHz, CDCl3) 7.40–7.10 (m, 10H), 6.63 (d, 1H, J 6.6), 5.64 (d, 1H, J
6.6); dC(100 MHz, CDCl3) 157.7, 142.1, 135.4, 130.2, 129.1, 128.7,
127.1, 123.8, 117.4, 110.9; HR-MS (EI) m/z [M]+ calcd for
184–185 C (200 C): dH(400 MHz, DMSO-d6): 9.54 (s, 2H), 7.31
(d, 4H, J 8.8), 6.85 (d, 4H, J 8.8), 3.72 (s, 6H); dC(100 MHz, DMSO-
d6): 185.7, 162.6, 137.0, 131.9, 119.0, 60.2; HR-MS (EI) m/z [M]+
calcd for C15H16N2O2S 288.0932, found 288.0928.
C
14H12O 196.0888, found 196.0885.
(E)-2-p-Tolyl-1-phenoxyethene (5b).31 Colorless oil, dH(400
1,3-Bis-(p-chlorophenyl)thiourea (13d).36 Colorless solid, mp
167–169 ꢂC (172 ꢂC): dH(400 MHz, CDCl3): 7.92 (s, 2H), 7.41–7.32
(m, 8H); dC(100 MHz, CDCl3): 180.2, 135.6, 132.3, 129.5, 125.9;
HR-MS (EI) m/z [M]+ calcd for C13H1035Cl2N2S 295.9942, found
295.9940.
2-Phenylpent-4-enal (12a).17,18 Colorless oil, dH(400 MHz,
CDCl3) 9.69 (d, 1H, J 1.6), 7.41–7.18 (m, 5H), 5.70 (m, 1H), 5.07–
4.99 (m, 2H), 3.61 (t, 1H, J 7.2), 2.84 (q, 1H, J 6.8), 2.50 (q, 1H, J
6.8); dC(100 MHz, CDCl3) 201.8, 136.6, 135.7, 129.0, 128.8, 127.6,
117.1, 58.7, 33.9; HR-MS (EI) m/z [M]+ calcd for C11H12O
160.0888, found. 160.0885.
MHz, CDCl3) 7.41–7.06 (m, 10H), 6.40 (d, 1H, J 12.4), 2.34 (s,
3H); dC(100 MHz, CDCl3) 157.0, 142.3, 135.8, 132.0, 128.7, 128.6,
125.7, 123.3, 116.8, 113.6, 21.1; HR-MS (EI) m/z [M]+ calcd for
C
15H14O 210.1045, found. 210.1040.
(E)-2-(p-Methoxyphenyl)-1-phenoxyethene (5c).35 Pale yellow oil,
dH(400 MHz, CDCl3) 7.61–7.34 (m, 6H), 7.13 (m, 2H), 6.89 (d,
2H, J 8.4), 6.45 (d, 1H, J 12.4), 3.93 (s, 3H); dC(100 MHz, CDCl3)
156.0, 156.4, 133.0, 132.7, 129.3, 128.7, 123.6, 118.4, 114.8,
113.9, 55.4; HR-MS (EI) m/z [M]+ calcd for C15H14O2 226.0994,
found 226.0990.
(Z)-2-(p-Methoxyphenyl)-1-phenoxyethene (5c).33 Pale yellow oil:
dH(400 MHz, CDCl3) 7.61–7.34 (m, 5H), 7.12 (m, 2H), 6.87 (d,
2H, J 8.4), 6.48 (d, 1H, J 6.8), 5.50 (d, 1H, J 6.8), 3.91 (s, 3H);
dC(100 MHz, CDCl3) 156.9, 156.2, 133.1, 132.7, 129.2, 128.7,
123.7, 118.3, 114.8, 113.6, 55.4; HR-MS (EI) m/z [M]+ calcd for
2-p-Methoxyphenylpent-4-enal (12b).17 Pale yellow oil, dH(400
MHz, CDCl3) 9.62 (d, 1H, J 1.6), 7.14 (m, 2H), 6.88 (m, 2H), 5.71
(m, 1H), 5.03 (m, 2H), 3.78 (s, 3H), 3.56 (m, 1H), 2.85 (m, 1H),
2.46 (m, 1H); dC(100 MHz, CDCl3) 200.2, 159.1, 135.3, 129.9,
127.5, 117.1, 114.4, 57.7, 55.3, 33.9; HR-MS (EI) m/z [M]+ calcd
for C12H14O2 190.0994, found. 190.0988.
2-p-Chlorophenylpent-4-enal (12c).18 Colorless oil, dH(400
MHz, CDCl3) 9.60 (d, 1H, J 1.6), 7.31–7.18 (m, 4H), 5.71 (m, 1H),
5.00 (m, 2H), 3.62 (m, 1H), 2.84 (m, 1H), 2.49 (m, 1H); dC(100
MHz, CDCl3) 200.1, 134.7, 134.5, 134.0, 130.8, 129.6, 118.1, 58.5,
34.5; HR-MS (EI) m/z [M]+ calcd for C11H1135ClO 194.0498,
found. 194.0491.
C
15H14O2 226.0994, found 226.0991.
(E)-2-(p-Chlorophenyl)-1-phenoxyethene (5d).32 Colorless oil,
dH(400 MHz, CDCl3): 7.36 (t, 2H, J 8.0), 7.26–7.10 (m, 6H), 7.03
(d, 2H, J 8.0), 6.32 (d, 1H, J 12.4); dC(100 MHz, CDCl3): 157.1,
144.0, 133.5, 132.0, 129.9, 128.8, 126.6, 123.1, 117.1, 112.0; HR-
MS (EI) m/z [M]+ calcd for C14H1135ClO 230.0498, found
230.0498.
1,3-Diphenylurea (7a).19 Colorless solid, mp 241–242 C (240
ꢂ
ꢂC):19 dH(400 MHz, DMSO-d6): 8.70 (s, 2H), 7.51–7.22 (m, 8H),
7.00–6.89 (m, 2H); dC(100 MHz, DMSO-d6): 152.3, 139.6, 128.3,
121.9, 118.0; HR-MS (EI) m/z [M]+ calcd for C13H12N2O 212.0950,
found 212.0950.
Acknowledgements
Support from the University of Kuwait, received through
Research Grant no. SC 02/11, The Faculty of Graduate Studies
for supporting the M. Sc. Student Nouf Al-Hamdan and facilities
of GF-S (grant no. GS01/01, GS02/01, GS01/03, GS01/05) are
gratefully acknowledged.
1,3-Bis-(p-tolyl)urea (7b).19 Colorless solid, mp 262–264 ꢂC
(268 C):19 dH(400 MHz, DMSO-d6): 8.56 (s, 2H), 7.33 (d, 4H, J
ꢂ
8.0), 7.05 (d, 4H, J 8.0), 2.24 (s, 6H); dC(100 MHz, DMSO-d6):
157.3, 142.6, 135.3, 134.9, 123.0, 24.9; HR-MS (EI) m/z [M]+ calcd
for C15H16N2O 240.1263, found 240.1260.
References
1,3-Bis-(p-methoxyphenyl)urea (7c).19 Colorless solid, mp 241–
242 ꢂC (242 C):19 dH(400 MHz, DMSO-d6): 8.65 (s, 2H), 7.43 (d,
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21030 | RSC Adv., 2014, 4, 21023–21031
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