The synthesis of aryl halomethylated unsaturated iminolactones

Article abstract of DOI:10.3184/174751911X13099687368563

Halomethylated iminolactones have been synthesised from alkyl isocyanides, acetylene dicarboxylic acid esters and halogenated acetophenones in solvent free microwave assisted multi-component reactions.

Full text of DOI:10.3184/174751911X13099687368563

412 RESEARCH PAPER
JULY, 412–415
JOURNAL OF CHEMICAL RESEARCH 2011
The synthesis of aryl halomethylated unsaturated iminolactones
Afsaneh Zonouzia*, Hossein Rahmanib, Mojtaba Biniaza, Zakieh Izakiana and Seik Weng Ngc
aSchool of Chemistry, University College of Science, University ofTehran, Tehran, Iran
bInstitute of ChemicalTechnologies, Iranian Research Organisation for Science andTechnology (IROST), Tehran, Iran
cDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
Halomethylated iminolactones have been synthesised from alkyl isocyanides, acetylene dicarboxylic acid esters and
halogenated acetophenones in solvent free microwave assisted multi-component reactions.
Keywords: one-pot, solvent-free reaction, microwave irradiation, halomethylated iminolactone
The presence of perfluoroalkyl groups in organic molecules
leads to the dramatic modification of their physico-chemical
properties and biological activities. It may significantly
improve metabolic stability and is a powerful tool of modern
drug design and drug discovery.1 Iminolactones are an impor-
tant class of heterocyclic compounds which can be converted
to other heterocyclic compounds or hydrolysed with aqueous
hydrochloric acid to produce butenolides (furan-2(5H-ones)).
They are an important class of natural products with biological
activities used in medicine and agriculture.2 Various synthetic
methods have been used to prepare iminolactone derivatives.
The synthesis of iminolactones from aldehydes and diketones
has been established.2–6 Nair and coworkers reported in 2000
the one-pot reaction of diketones, dimethyl acetylenedicarbox-
ylate and cyclohexylisocyanide using hot benzene.7 All of
the previous methods used benzene and methylene chloride as
solvents.2–8
We have already reported multi-component procedures
for the synthesis of some heterocyclic compounds.9–14 We now
report a one-pot, solvent-free and multi-component reaction
of acetophenone derivatives 1, acetylenic esters 2 and alkyl
isocyanides 3 to afford the halomethylated iminolactones 4 in
fairly high yields. Microwave irradiation improved the yields
and shortened the reaction times (Scheme 1, Table 1).
Scheme 1
In 2008, Shaabani and coworkers reacted 2-bromo-1-
(4-bromophenyl) ethanol, isocyanides and acetylenic esters in
CH2Cl26 to give four derivatives of iminolactons after 12 hours.
In our work, we have used solvent free microwave assisted
reaction using some different reactants to produce the new imi-
nolactons 4a–p in short times (4–7 minutes) and higher yields.
For comparison purposes we also performed the reaction using
Table 1 Times and yields in the synthesis of halomethylated iminolactones 4 using heat or microwave irradiation
Compd
R
R1
R2
Time/h (∆)
Yield/% (∆)
Time/min (MW)
Yield/% (MW)
4a
4b
4c
4d
CF3
CF3
CF3
CF3
Me
Et
Me
Et
Cyclohexyl
Cyclohexyl
t-Bu
10
12
12
12
85
80
75
70
4
5
5
6
98
97
95
95
t-Bu
4e
4f
CF3
CF3
Me
Et
11
12
80
78
5
5
97
96
4g
4h
4i
CH2Cl
CH2C
CH2Cl
CH2Cl
CH2Cl
Me
Et
Me
Et
Me
t-Bu
20
24
18
20
20
65
62
75
70
65
6
7
5
6
6
87
85
95
93
87
t-Bu
Cyclohexyl
Cyclohexyl
4j
4k
4l
CH2Br
CH2Br
CH2Br
CH2Br
CH2Br
Me
Et
Me
Et
Me
t-Bu
18
24
18
24
20
65
60
76
68
64
6
7
5
6
7
85
83
95
92
90
4m
4n
4o
4p
t-Bu
Cyclohexyl
Cyclohexyl
* Correspondent. E-mail: zonouzi @khayam.ut.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2011 413
We have already reported the X-ray structure analysis of 4n
which confirmed unambiguously its highly functionalised
structure.15 Structures 4 were assigned on the basis of their
1
elemental analysis, IR, H, 13C, 19F NMR and mass spectral
data. The mass spectra of compounds 4 displayed molecular
ion peaks at appropriate m/z values. Initial fragmentation
1
involved the loss of R1OH and R2N. H NMR and 13C NMR
spectra of 4a–p displayed resonances in agreement with their
structures; the partial assignments of these resonances are
given in the experimental section. The IR spectra of com-
pounds 4 showed two sharp absorptions for C=O and a medium
absorption for C=N. There were also three or four sharp C–O
absorptions for compounds 4a–p (see Experimental).
In conclusion, we have developed a simple and efficient
procedure for the synthesis of some new stable highly
functionalised halomethylated iminolactones with potential
biological activities.
Experimental
Chemicals and solvents were obtained from Merck (Germany) and
Fluka (Switzerland) and were used without further purification.
Microwave assisted reactions were carried out in the microwave oven
(ETHOS 1600, Milestone) with a power of 600W specially designed
for organic synthesis. Column chromatography was performed on
silica gel (0.015–0.04 mm, mesh-size) and TLC on precoated plastic
sheets (25 DCUV-254) respectively. Melting points were measured
on Barnstead Electrothermal melting point apparatus and were not
corrected. Elemental analysis for C, H and N were performed using a
Thermo Finnigan Flash EA1112 instrument. IR spectra were mea-
Fig. 1 X-ray crystal structure of 4a.
conventional heating (oil bath). We kept the quantities of
the reactant exactly the same as in the microwave promoted
reaction and performed the solvent-free reaction in a 50 mL
three-necked flask with a thermometer. The reaction mixtures
were heated at 100 °C and the reaction was kept for 10–24 h.
Moderate yields (62–85%) of the final products were obtained.
Clearly, the microwave irradiation has shortened the reaction
time and improved the yield (Table 1). This multi-component
reaction can be carried out in hot p-xylene with lower yields.
For example the product 4g was obtained in refluxing p-xylene
(b.p. 138 °C) after 7 days in less than 20% yield.
sured on a Bruker EQUINOX 55 spectrometer as ATR. 1H NMR, 13
C
NMR and 19F NMR spectra were determined in CDCl3 on a Bruker
500 MHzspectrometer and chemical shifts were expressed in ppm
downfield from tetramethylsilane. Mass spectra were recorded on a
Finnigan-MAT 8430 spectrometer at an ionisation potential of 70 ev.
General procedure
Conventional heating: Acetophenone derivatives 1 (2 mmol) were
added at 5 °C to a magnetically stirred mixture of alkyl isocyanide 3
(2 mmol) and acetylenic esters 2 (2 mmol) in a 50 mL three-necked
flask with a thermometer, and the reaction mixture was stirred for
10 min and heated at 100 °C for 10–24 h. The precipitated products
were washed and recrystallised from methanol as colourless crystals.
Microwave assisted reaction: Magnetically stirred mixture of alkyl-
isocyanide (2 mmol), acetylenic esters (2 mmol) and acetophenone
derivatives (2 mmol) was stirred for 10 min and then was placed in
an open glass container. Microwave irradiation in a microwave
oven at 100 °C for 4–7 min gave the solid products. The white to
yellow crystals of 4 were purified by washing and recrystallisation in
methanol.
The highly functionalised iminolactones 4 which are pro-
duced in this reaction are stable and were not converted to the
other products. For example, they were unchanged by heating
with aqueous inorganic acids, probably as a result of steric
hindrance by the substituents.
Crystals of 4a were obtained from a mixture of methanol
and acetone. The X-ray crystal structure of 4a has been reported
to confirm its highly functionalised structure (Fig. 1).
A possible mechanism is illustrated in Scheme 2. Addition
of alkyl isocyanide to the acetylenic esters generates the 1:1
adduct 5. Nuleophilic attack of this adduct on the acetophe-
none derivatives, followed by another attack of negative
oxygen to the carbon of the nitrile part of adduct 5 afforded the
products 4 (Scheme 2).
Dimethyl 5-(cyclohexylimino)-2-(trifluoromethyl)-2,5-dihydro-2-
phenylfuran-3,4-dicarboxylate (4a): White crystals, m.p. 70–71 °C;
IR; νmax 3043, 2932, 2756 (C–H), 1740, 1737 (C=O), 1693 (C=N),
1
1302, 1274 (C–F), 1149, 1090, 1020 (C–O) cm−1; H NMR, δ 1.21–
1.26, 1.30–1.37, 1.40–1.47, 1.60–1.63, 1.75–1.81 (5m, 10H, CH2 of
cyclohexyl), 3.72 (m, 1H, CH of cyclohexyl), 3.76, 3.92 (2s, 6H, CH3
of CO2Me), 7.43–7.44, 7.49–7.54 (2m, 5H, Ph protons); 13C NMR,
δ 26.07, 33.53, 33.76 (13CH2 of cyclohexyl), 53.40, 53.60 (2CH3 of
CO2Me), 57.45 (13CH of cyclohexyl), 129.14 (13CF3), 122.15, 124.42,
126.70, 126.91, 127.03, 130.31, 132.16, 139.18, 141.36 (alkene and
Ph carbons), 152.67 (13C=N-cyclohexyl), 160.64, 161.71 (213C=O of
2CO2Me); 19F NMR, δ –73.62 (s, CF3); Ms (EI, 70ev): m/z 425 (M+),
393 (M+–CH3OH), 296 (M+-C6H11N, CH3OH), Anal. Calcd for
C21H22F3NO5; C, 59.29; H, 5.21; N, 3.29. Found: C, 59.27; H, 5.20; N,
3.30%. Crystallographic data for the structure of compound 4a have
been deposited with the Cambridge Crystallographic Data Center
as supplementary publication No. CCDC 731528. These data can be
obtained free of charge via www.ccdc.com.ac.uk/data_request/cif
Diethyl 5-(cyclohexylimino)-2-(trifluoromethyl)-2,5-dihydro-2-
phenylfuran-3, 4-dicarboxylate (4b): White crystals, m.p. 69–70 °C;
IR; νmax 3068, 2997, 2856 (C–H), 1735, 1721 (C=O), 1693 (C=N),
1
1342, 1288 (C–F), 1228, 1193, 1118 (C–O) cm−1; H NMR, δ 1.24–
1.27, 1.39–1.41 (2t, 6H, CH3 of CO2Et), 1.3–1.37, 1.46–1.55, 1.64–
1.67, 1.79–1.86 (4m, 10H, CH2 of cyclohexyl), 3.78, 3.83 (m, 1H, CH
Scheme 2

414 JOURNAL OF CHEMICAL RESEARCH 2011
of cyclohexyl), 4.23–4.27, 4.41–4.45 (2q, 4H, J = 7.14 Hz, CH2
of CO2Et); 7.47–7.48, 7.60–7.62 (2m, 5H, Ph protons), 13C NMR,
δ 14.06, 14.40 (213CH3 of CO2Et), 24.95, 26.12, 33.54, 33.76 (13CH2
of cyclohexyl), 57.24 (13CH of cyclohexyl), 62.68, 62.83 (213CH2
of CO2Et), 129.01 (13CF3) 122.21, 124.49, 127.00, 130.21, 132.37,
139.15, 141.18 (alkene and Ph carbons), 152.77 (13C=N-cyclohexyl),
160.23, 161.30 (213C=O of 2CO2Et); 19F NMR, δ –73.63 (s, CF3); Ms
(EI, 70ev): m/z 453 (M+), 407 (M+-C2H5OH), 310 (M+–C2H5OH,
C6H11N), Anal. Calcd for C23H26F3NO5; C, 60.92; H, 5.78; N, 3.09.
Found: C, 60.90; H, 5.78; N, 3.10%.
2CO2Me), 55.37 (13CMe3), 91.77 (13C–CH2Cl), 126.20, 129.26,
129.52, 137.22, 139.56, 141.64 (alkene and Ph carbons), 152.66
(13C=N-t-Bu), 161.57, 162.78 (13C=O of 2CO2Me) ppm; MS: m/z
(fragment) 379, 381 (M+, M++2), 347.379 (M+, M++2- CH3OH), 308,
310 (M+, M++2- CH3OH, C4H9N); Anal. Calcd for C19H22ClNO5:
C, 60.08; H, 5.84; N, 3.69. Found: C, 60.10; H, 5.82; N, 3.71.
Diethyl 5-(tert-butylimino)-2-(chloromethyl)-2,5-dihydro-2-
phenylfuran-3,4-dicarboxylate (4h): Light yellow crystals, m.p. 70–
71°C. IR υmax: 3010, 2985 (C–H), 1750, 1723 (C=O), 1680 (C=N),
1280, 1251, 1211, 1039 (C–O), 745, 707 (C–Cl) cm−1; 1H NMR
δ 1.30–1.34, 1.39–1.42 (2t, 6H, 2CH3 of CO2Et), 1.49 (s, 9H, t-Bu),
4.29–4.31, 4.67–4.69 (2H, d. of d., J = 199.53 Hz, J = 11.80 Hz, CH2
of CH2Cl), 4.52–4.58 (2m, 2H, CH2 of CO2Et), 7.40–7.51 (3m, 5H, Ph
protons) ppm; 13C NMR δ 14.92, 15.11 (2CH3 of CO2Et), 29.98 (CH3
of CO2t-Bu), 48.58 (13CH2 of CH2Cl), 6.71 (13CMe3), 61.48, 61.99
(213CH2 of CO2Et), 92.07 (13C–CH2Cl), 126.21, 129.28, 129.53,
137.35, 139.15, 142.61 (alkene and Ph carbons), 159.09 (13C=N-
cyclohexyl), 162.17, 163.21 (13C=O of 2CO2Et) ppm; MS: m/z (frag-
ment) 407, 409 (M+, M++2), 361, 363 (M+, M++2- C2H5OH), 290, 292
(M+, M++2- C2H5OH, C4H9N);Anal. Calcd for C21H26ClNO5: C, 61.84;
H, 6.42; N, 3.43. Found: C, 61.83; H, 6.44; N, 3.46%.
Dimethyl 2-(chloromethyl)-5-(cyclohexylimino)-2,5-dihydro-2-
phenylfuran-3, 4-dicarboxylate (4i): Light yellow crystals, m.p. 70–
71°C. IR υmax: 3084, 2935 (C–H), 1753, 1724 (C=O), 1683 (C=N),
1290, 1253, 1205, 1082 (C–O), 792, 736 (C–Cl) cm−1; 1H NMR
δ 1.27–1.48, 1.78–1.88 (4m, 10H, CH2 of cyclohexyl), 3.74–3.76 (m,
1H, CH of cyclohexyl), 3.80, 3.94 (2s, 6H, 2CH3 of CO2Me), 4.22–
4.25, 4.66–4.69 (2H, CH2 of CH2Cl, d. of d., J = 201.21 Hz, J = 11.64
Hz), 7.38–7.46 (2m, 5H, Ph protons,) ppm; 13C NMR δ 25.24, 25.26,
26.19, 33.40, 33.93 (13CH2 of cyclohexyl), 48.43 (13CH2 of CH2Cl),
57.26 (13CH of cyclohexyl), 91.05 (13C–CH2Cl), 126.12, 129.33,
129.62, 137.10, 138.18, 142.73 (alkene and Ph carbons), 154.75
(13C=N-cyclohexyl), 161.57, 162.56 (13C=O of 2CO2Me) ppm; MS:
m/z (fragment) 405, 407 (M+, M++2), 373, 375 (M+–CH3OH), 276,
778 (M+–CH3OH, C6H11N); Anal. Calc. for C21H24ClNO5: C, 62.14; H,
5.95; N, 3.45. Found: C, 62.13; H, 5.94; N, 3.46%.
Diethyl 2-(chloromethyl)-5-(cyclohexylimino)-2,5-dihydro-2-
phenylfuran-3, 4-dicarboxylate (4j): Light yellow crystals, m.p. 72–
73°C. IR υmax: 3017, 2982 (C–H), 1749, 1720 (C=O) 1681 (C=N),
1284, 1251, 1199, 1082 (C–O), 771, 734, 702 (C–Cl) cm−1; 1H NMR
δ 1.28–1.37, 1.38–1.41 (2t, 6H, 2CH3 of CO2Et), 1.37–1.91 (4m, 10H,
CH2 of cyclohexyl), 3.76–3.80 (m, 1H, CH of cyclohexyl), 4.27–4.29,
4.66–4.68 (2H, CH2 of CH2Cl, d. of d., J = 199.14 Hz, J = 11.68 Hz),
4.31–4.31 (2m, 2H, CH2 of CO2Et), 4.40–4.44 (q, 2H, J = 7.05 Hz,
CH2 of CO2Et), 7.39–7.49 (2m, 5H, Ph protons) ppm; 13C NMR δ
14.20, 14.48 (2CH3 of CO2Et), 25.17, 26.24, 33.42, 33.94 (CH2 of
cyclohegxyl), 48.52 (CH2 of CH2Cl), 57.06 (CH of cyclohegxyl),
62.44, 62.56 (2CH2 of CO2Et), 90.99 (13C–CH2Cl), 126.20, 129.24,
129.50, 137.30, 138.17, 142.50 (alkene and Ph carbons), 154.76
(13C=N-cyclohegxyl), 161.23, 162.17 (13C=O of 2CO2Et) ppm; MS:
m/z (fragment) 434 (M+), 388 (M+-C2H5OH), 291 (M+-C2H5OH,
C6H11N); Anal. Calcd for C23H28ClNO5: C, 63.66; H, 6.50; N, 3.23.
Found: C, 63.65; H, 6.48; N, 3.25%.
Dimethyl 5-(tert-butylimino)-2-(trifluoromethyl)-2,5-dihydro-2-
phenylfuran-3, 4-dicarboxylate (4c): White crystals, m.p. 72–73 °C;
IR; νmax 3011, 2961, 2879 (C–H), 1739, 1720 (C=O), 1685 (C=N),
1
1301, 1274 (C–F), 1173, 1149, 1039, 1009 (C–O) cm−1; H NMR,
δ 1.41 (1s, 9H, t-Bu protons), 3.80, 3.96 (2s, 6H, 2CH3 of CO2Me),
7.46–7.47, 7.60–7.61 (2m, 5H, Ph protons); 13C NMR, δ 30.03 (13CH3
of t-Bu), 53.43, 53.65 (213CH3 of CO2Me), 55.93 (13CMe3), 121.93,
123.51, 127.34, 130.97, 132.04, 139.52, 140.18 (alkene and Ph
carbons), 129.04 (13CF3), 151.76 (13C=N-cyclohexyl), 160.97, 162.85
(213C=O of 2CO2Me); 19F NMR, δ –73.69 (s, CF3); Ms (EI, 70ev): m/z
399 (M+), 367 (M+–CH3OH), 296 (M+–CH3OH, t-BuN), Anal. Calcd
for C19H20F3NO5; C, 57.14; H, 5.05; N, 3.51. Found: C, 57.13; H, 5.06;
N, 3.53%.
Diethyl 5-(tert-butylimino)-2-(trifluoromethyl)-2,5-dihydro-2-
phenylfuran-3, 4-dicarboxylate (4d): White crystals, m.p. 74–75 °C;
IR; νmax 3062, 2955, 2939 (C–H), 1737, 1713 (C=O), 1693 (C=N),
1
1371, 1340, 1280 (C–F), 1191, 1165, 1014 (C–O) cm−1; H NMR,
δ 1.24–1.26, 1.27–1.29 (2t, 6H, CH3 of CO2Et), 1.41 (s, 9H, t-Bu),
4.22–4.27, 4.40–4.44 (2q, 4H, J = 7.01 Hz, CH2 of CO2Et), 7.46–7.61
(2m, 5H, Ph protons); 13C NMR, δ 14.06, 14.43 (213CH3 of CO2Et),
29.98 (13CH3 of t-Bu), 55.83 (13C of t-Bu), 62.63, 62.73 (213CH2
of CO2Et), 128.99 (13CF3), 122.28, 124.56, 127.03, 130.11, 132.48,
139.87, 140.79 (alkene and Ph carbons), 150.69 (13C=t-Bu), 160.22,
161.59 (213C=O of 2CO2Et); 19F NMR, δ –73.60 (s, CF3); Ms (EI,
70ev): m/z 427 (M+), 381 (M+-C2H5OH), 310 (M+-C2H5OH, t-BuN),
Anal. Calcd for C21H24F3NO5; C, 59.01; H, 5.66; N, 3.28. Found:
C, 59.02; H, 5.65; N, 3.30%.
Dimethyl 5-(2,4-trimethylpenan-2-ylimino)-2-(trifluoromethyl)-
2,5-dihydro-2-phenylfuran-3,4- dicarboxylate (4e): White crystals,
m.p. 76–77 °C; IR; νmax 3062, 2953, 2966 (C–H), 1739, 1725 (C=O),
1
1697 (C=N), 1284, 1227 (C–F), 1220, 1108, 1028 (C–O) cm−1; H
NMR, δ 1.038 (s, 9H, t-Bu protons), 1.44–1.46 (2s, 6H, 2CH3), 1.69,
1.71 (2s, 2H, CH2 protons), 3.80, 3.93 (2s, 6H, 2CH3 of CO2Me),
7.46–7.47, 7.61–7.63 (2m, 5H, Ph protons); 13C NMR, δ 29.93, 30.04
(13CH3 of alkyl group), 32.03 (13CH3 of t-Bu), 32.34 (13C of t-Bu),
53.35, 53.53 (13CH3 of CO2Me), 55.80 (13CH2), 59.44 ((CH3)213C–N),
129.04 (13CF3), 122.23, 124.51, 127.03, 130.17, 132.45, 139.25,
141.48 (alkene and Ph carbons), 149.38 (13C=N-alkyl), 160.64, 162.12
(213C=O of CO2Me); 19F NMR, δ –73.62 (s, CF3); Ms (EI, 70ev): m/z
455 (M+), 423 (M+–CH3OH), 296 (M+–CH3OH, C8H17N), Anal. Calcd
for C23H28F3NO5; C, 60.65; H, 6.20; N, 3.80. Found: C, 60.63; H, 6.20;
N, 3.10%.
Diethyl 5-(2,4,4-trimethylpentan-2-ylimino-2-(trifluoromethyl)-
2,5-dihydro-2-phenylfuran-3,4-dicarboxylate (4f): White crystals,
m.p. 72–73 °C; IR; νmax 3159, 2954, 2931 (C–H), 1735, 1713 (C=O),
Dimethyl 5-(2,4,4-trimethylpentan-2-ylimino)-2-(chloromethyl)-
2,5-dihydro-2-phenylfuran-3,4-dicarboxylate (4k): Light yellow crys-
tals, m.p. 73–74°C. IR υmax: 3060, 2982 (C–H), 1748, 1726 (C=O),
1
1697 (C=N), 1294, 1253 (C–F), 1217, 1188, 1018 (C–O) cm−1; H
1
NMR, δ 1.037 (s, 9H, t-Bu), 1.24–1.27, 1.38–1.41 (2t, 6H, CH3 of
CO2Et), 1.44, 1.45 (2s, 6H, 2CH3), 1.69– 1.71 (2s, 2H, CH2), 4.22–
4.26, 4.37–4.41 (2q, 4H, J = 7.11 Hz, CH2 of CO2Et), 7.45–7.47,
7.62–7.64 (2m, 5H, Ph protons); 13C NMR, δ 14.06, 14.45 (213CH3 of
CO2Et) 30.04, 30.13 (13CH3, 13CH2 of alkyl group), 32.05 (13CH3 of
t-Bu), 32.32 (13C of t-Bu), 55.78 (13CH2), 59.36 ((CH3)213C–N), 62.59,
62.68 (213CH2 of CO2Et), 128.95 (13CF3), 122.29, 124.57, 127.12,
130.08, 132.64, 139.25, 141.48 (alkene and Ph carbons), 149.38
(13C=N-alkyl), 160.64, 162.12 (213C=O of CO2Et); 19F NMR, δ –73.63
(s, CF3); Ms (EI, 70ev): m/z 483 (M+), 437 (M+-C2H5OH), 310 (M+-
C2H5OH, C8H 17N), Anal. Calcd for C25H32F3NO5; C, 62.10; H, 6.67;
N, 2.90. Found: C, 62.10; H, 6.70; N, 2.91%.
1679 (C=N), 1239, 1217, 1028 (C–O), 746, 709 (C–Cl) cm−1; H
NMR δ 1.04 (s, 9H, t-Bu), 1.43, 1.45 (2s, 6H, 2CH3), 2.89 (s, 2H,
CH2), 3.81, 3.94 (2s, 6H, 2CH3 of CO2Me), 4.57–4.59, 4.62–4.64 (2H,
d. of d., J = 199.76 Hz, J = 11.17 Hz, CH2 of CH2Cl), 7.39–7.51 (3m,
5H, Ph protons) ppm; 13C NMR δ 29.94, 30.14 (13CH3 of alkyl group),
31.14 (13CH2 of alkyl group), 32.01 (13CH3 of t-Bu), 35.39 (13C of
t-Bu), 51.15, 51.78 (213CH3 of CO2Me), 55.80 (13CH2–Cl), 59.44
((CH3)3 13C–N), 92.50 (13C–CH2Cl), 123.17, 124.51, 126.35, 129.17,
132.54, 139.94, 142.48 (alkene and Ph carbons), 154.09 (13C=N-
alkyl), 162.69, 163.25 (13C=O of 2CO2Me) ppm; MS: m/z (fragment)
477, 479 (M+, M++2), 431, 433 (M+, M++2-C2H5OH), 334, 336 (M+,
M++2-C2H5OH, C6H11N); Anal. Calcd for C23H28BrNO5: C, 57.75;
H, 5.90; N, 2.93. Found: C, 57.75; H, 5.87; N, 2.94%.
Dimethyl 5-(tert-butylimino)-2-(chloromethyl)-2,5-dihydro-2-
phenylfuran-3,4-dicarboxylate (4g): Light yellow crystals, m.p. 69–
70°C. IR υmax: 3019, 2958 (C–H), 1751, 1748, 1719 (C=O), 1682
Dimethyl 5-(tert-butylimino)-2-(bromomethyl)-2,5-dihydro-2-
phenylfuran-3,4-dicarboxylate (4l): Yellow crystals, m.p. 77–78 °C.
IR υmax: 3058, 2990 (C–H), 1756, 1723 (C=O), 1680 (C=N), 1290,
1
(C=N), 1298, 1255, 1213, 1045 (C–O), 738, 694 (C–Cl) cm−1; H
1
NMR δ 1.42 (s, 9H, t-Bu), 3.81, 3.94 (2s, 6H, 2CH3 of CO2Me), 4.25–
4.27, 4.67–4.69 (2H, CH2 of CH2Cl, d. of d., J = 201.71 Hz, J = 11.74
Hz), 7.39–7.40, 7.41–7.49 (2m, 5H, Ph protons) ppm; 13C NMR
δ 30.02 (CH3 of t-Bu), 48.54 (13CH2 of CH2Cl), 53.24, 53.33 (CH3 of
1238, 1219 (C–O), 789, 740(C–Br) cm−1; H NMR δ 1.45 (s, 9H,
t-Bu), 3.87, 3.99 (2s, 6H, 2CH3 of CO2Me), 4.33–4.35, 4.53–4.55 (2H,
d. of d., J = 200.12 Hz, J =11.01 Hz, CH2 of CH2Br), 7.36–7.40 (2m,
5H, Ph protons) ppm; 13C NMR δ 30.16 (CH3 of t-Bu), 37.29 (13CH2

JOURNAL OF CHEMICAL RESEARCH 2011 415
of CH2Br), 50.46(13CMe3), 52.26, 52.68 (213CH3 of CO2Me), 91.03
(13CH2–Br), 126.24, 129.29, 129.51, 137.63, 138.86, 143.52 (alkene
and Ph carbons), 155.70 (13C=N-t-Bu), 162.15, 163.28 (13C=O of
2CO2Me) ppm; MS: m/z (fragment) 423, 425 (M+, M++2), 391, 393
(M+, M++2–CH3OH), 320, 322 (M+, M++2–CH3OH, C4H9N); Anal.
Calcd for C19H22BrNO5: C, 53.79; H, 5.23; N, 3.30. Found: C, 53.81;
H, 5.26; N, 3.33%.
for C23H28BrNO5: C, 57.75; H, 5.90; N, 2.93. Found: C, 57.75; H,
5.87; N, 2.94%.
Dimethyl 5-(2,4,4-trimethylpentan-2-ylimino)-2-(bromomethyl)-
2,5-dihydro-2-phenylfuran-3,4-dicarboxylate (4p): Yellow crystals,
m.p. 75–76 °C. IR υmax: 3062, 2975 (C–H), 1745, 1727 (C=O), 1680
1
(C=N), 1260, 1249, 1225 (C–O), 785, 738 (C–Br) cm−1; H NMR
δ 1.05 (s, 9H, t-Bu), 1.45, 1.47 (2s, 6H, 2CH3), 2.89 (s, 2H, CH2), 3.79,
3.95 (2s, 6H, 2CH3 of CO2Me), 4.35–4.37, 4.42–4.44 (2H, d. of d.,
J = 201.70 Hz, J = 11.48 Hz, CH2 of CH2Cl), 7.46–7.54 (3m, 5H, Ph
protons) ppm; 13C NMR δ 28.85, 29.70 (13CH3 of alkyl group), 31.35
(13CH2 of alkyl group), 31.91 (13CH3 of t-Bu), 36.86 (13C of t-Bu),
50.61, 51.57 (213CH3 of CO2Me), 53.16 (13CH2–Cl), 59.46 ((CH3)2
13C–N), 90.08 (13C–CH2Br), 124.19, 125.85, 126.16, 129.09, 132.47,
139.43, 141.62 (alkene and Ph carbons), 154.16 (13C=N-alkyl),
162.71, 163.30 (13C=O of 2CO2Me) ppm; MS: m/z (fragment) 479,
481 (M+, M++2), 447, 449 (M+, M++2–CH3OH), (M+, M++2-C2H5OH,
C8H17N); Anal. Calcd for C23H30BrNO5: C, 57.50; H, 6.29; N, 2.92.
Found: C, 57.51; H, 6.27; N, 2.93%.
Diethyl 5-(tert-butylimin-o)-2-(bromomethyl)-2,5-dihydro-2-
phenylfuran-3,4-dicarboxylate (4m): Yellow crystals, m.p. 79–80 °C.
IR υmax: 3049, 2993 (C–H), 1753, 1718 (C=O), 1681 (C=N), 1287,
1245, 1209 (C–O), 781, 739 (C–Br) cm−1; 1H NMR δ 1.29–1.33, 1.37–
1.41 (2t, 6H, 2CH3 of CO2Et), 1.48 (s, 9H, t-Bu), 4.30–4.32, 4.50–4.52
(2H, d. of d., J = 199 08 Hz, J = 11.05 Hz, CH2 of CH2Br), 7.32–7.37
(3m, 5H, Ph protons) ppm; 13C NMR δ 15.03, 15.98 (213CH3 of
CO2Et), 30.14 (CH3 of t-Bu), 38.90 (13CH2 of CH2Br), 53.09 (13CMe3),
60.19, 60.95 (2 13CH2 of CO2Et), 91.72 (13C–CH2-Br), 126.01, 128.93,
129.60, 137.51, 139.57, 142.12 (alkene and Ph carbons), 157.11
(13C=N-t-Bt), 161.83, 162.64 (13C=O of 2CO2Me) ppm; MS: m/z
(fragment) 451, 453 (M+, M++2), 405, 407 (M+, M++2–CH3OH), 334,
336 (M+, M++2–CH3OH, C4H9N); Anal. Calcd for C21H26BrNO5:
C, 55.76; H, 5.79; N, 3.10. Found: C, 55.78; H, 5.77; N, 3.12%.
Dimethyl 2-(bromomethyl)-5-(cyclohexylimino)-2,5-dihydro-2-
phenylfuran-3, 4-dicarboxylate (4n): Yellow crystals, m.p. 74–75 °C.
IR υmax: 3032, 2944 (C–H), 1758, 1726 (C=O), 1684 (C=C), 1292,
1236, 1205, 1083 (C–O), 792, 736, 698 (C–Br) cm−1; 1H NMR δ 1.27–
1.91 (5m, 10H, CH2 of cyclohexyl), 3.74–3.76 (m, 1H, CH of cyclo-
hexyl), 3.81, 3.94 (2s, 6H, 2CH3 of CO2Me), 4.12–4.14, 4.56–4.58
(2H, CH2 of CH2Br, d. of d., J = 201.62 Hz, J = 11.59 Hz), 7.37–7.47
(2m, 5H, Ph protons) ppm; 13C NMR δ 25.23, 25.27, 26.18, 33.36,
33.95 (CH2 of cyclohexyl), 24.88, 37.23 (13CH2 of CH2Br), 53.32,
53.47 (13CH3 of 2CO2Me), 57.30 (13CH of cyclohexyl), 90.31 (13C–
CH2Br), 126.18, 129.33, 129.59, 137.24, 137.95, 143.39 (alkene and
Ph carbons), 154.66 (13C=N-cyclohexyl), 161.52, 162.56 (13C=O of
2CO2Me) ppm; MS: m/z (fragment) 449, 451 (M+, M++2), 417, 419
(M+, M++2–CH3OH), 320, 322 (M+, M++2–CH3OH, C6H11N); Anal.
Calcd for C21H24BrNO5: C, 56.01; H, 5.37; N, 3.11. Found: C, 56.00;
H, 5.38; N, 3.13%.
The support of this study by the Research Council at the
University of Tehran is gratefully acknowledged.
Received 20 April 2011; accepted 5 July 2011
Paper 1100669 doi: 10.3184/174751911X13099687368563
Published online: 5 August 2011
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