Reactivity of various α-halo ketones in one-pot synthesis of γ-iminolactones

Article abstract of DOI:10.1080/00397911.2011.571806

(Chemical Equation Presented) The highly reactive 1:1 intermediate generated in the reaction of tert-butyl isocyanide and dialkyl acetylenedicarboxylate is trapped by a-halo ketones to produce halogenated iminolactones as the sole product in good yields.

Full text of DOI:10.1080/00397911.2011.571806

This article was downloaded by: [University of Sydney]
On: 10 April 2013, At: 09:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Reactivity of Various α-Halo Ketones in
One-Pot Synthesis of γ-Iminolactones
Sakineh Asghari a & Ahmad Khabbazi Habibi a
a Department of Organic Chemistry, Faculty of Chemistry, University
of Mazandaran, Babolsar, Iran
Accepted author version posted online: 02 Jan 2012.Version of
record first published: 29 May 2012.
To cite this article: Sakineh Asghari & Ahmad Khabbazi Habibi (2012): Reactivity of Various α-Halo
Ketones in One-Pot Synthesis of γ-Iminolactones, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 42:19, 2894-2906
To link to this article: http://dx.doi.org/10.1080/00397911.2011.571806
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 42: 2894–2906, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.571806
REACTIVITY OF VARIOUS a-HALO KETONES IN
ONE-POT SYNTHESIS OF c-IMINOLACTONES
Sakineh Asghari and Ahmad Khabbazi Habibi
Department of Organic Chemistry, Faculty of Chemistry,
University of Mazandaran, Babolsar, Iran
GRAPHICAL ABSTRACT
Abstract The highly reactive 1:1 intermediate generated in the reaction of tert-butyl isocya-
nide and dialkyl acetylenedicarboxylate is trapped by a-halo ketones to produce haloge-
nated iminolactones as the sole product in good yields.
Keywords a-Bromo ketones; a-chloro ketones; acetylenic esters; halogenated c-imino-
lactones; tert-butyl isocyanide
INTRODUCTION
The importance of isocyanides in the synthesis of heterocyclic compounds is
evident by the diversity of available products. They are known to form zwitterionic
intermediates during reactions with acetylenic esters in which the third component
can be added to the system to produce the new heterocyclic target molecules that
have been reported by several groups.[1–9] Iminolactones have been the subject of
interest because of their use as antibacterial agents, aldosterone inhibitors, and pre-
cursors for preparation of a wide spectrum of the natural compounds.[10a] For
example, iminolactones can be hydrolyzed to corresponding butenolides[10b–e] with
various pharmacological activities.[10f,g] The most widely used approach to imino-
lactone synthesis is isocyanide-based reactions.[4,5,7,8,11–13] The reactive 1:1 inter-
mediate generated in the reaction of isocyanide and acetylenic ester is trapped by
an electron-deficient ketone such as isatin,[5a,7b] 1,2-diketone,[5,12c] a-ketoester,[4e,7a]
and di(2-pyridyl) ketone.[12a]
Received January 3, 2011.
Address correspondence to Sakineh Asghari, Department of Organic Chemistry, Faculty of
Chemistry, University of Mazandaran, Babolsar 47416-95447, Iran. E-mail: s.asghari@umz.ac.ir
2894

REACTIVITY OF a-HALO KETONES
2895
Recently Shaabani et al. reported the synthesis of the c-iminolactones through
a three-component condensation using 2-bromo-1-(4-bromophenyl)ethanone, and a
mechanism was also proposed by the authors.[8b] Although the supposition mech-
anism seems to be reasonable, utilization of different a-haloketones could alter the
mechanism, especially those a-halo ketones containing electron-withdrawing groups,
which enhance the acidity strength of Ha of the halo ketones and virtually bring it
into the reaction with zwitterionic intermediate that is generated in the reaction of
tert-butyl isocyanide and dialkyl acetylenedicarboxylate. Thus, to investigate the
generalization of the mechanism, a series of a-halo ketone derivatives with a variety
of electronic properties were prepared and their reactivities toward a three-
component condensation were studied.
Herein, we report the reaction of tert-butyl isocyanide with dialkyl acetylene-
dicarboxylate 1 in the presence of a-haloketone derivatives 2 that leads to the halo-
genated c-iminolactones 3a–v as the sole product in good yields (Scheme 1).
Initially the reaction of tert-butyl isocyanide and dialkyl acetylenedicarboxy-
late with acetophenone was examined at room temperature. The reaction was very
slow and yielded an unidentified mixture without formation of any iminolactone.
When phenacylchloride was used under similar reaction conditions, compound 3e
was obtained as the sole product in good yield after only 3 h. This implies the effects
of the halogens at the a-position of the carbonyl group, which probably enhance the
electrophilicity of the carbonyl carbon atom. Based on this interesting preliminary
result, the reaction of isocyanide and dialkyl acetylenedicarboxylate with various
a-halo ketones was examined and the obtained results are tabulated in Table 1.
As is clear from the table, the a-chloro and a-bromo ketones reacted smoothly
and chemoselectively with tert-butyl isocyanide and acetylenic esters to give the cor-
responding iminolactones in good yields. The a-chloro ketones were more reactive
than the a-bromo analogous (entries 3j and 3m). The a,a-dichloro ketone reacted
faster and afforded the expected products in excellent yield (compare 3c and 3d with
3a and 3b or 3k and 3l with 3i and 3j, respectively). Moreover, the aryl substituted a-
halo ketones afforded the expected iminolactones similarly in good yields under the
reaction conditions (entries 3o–3r). An interesting feature of this procedure is that all
the reactions chemoselectively afforded the desired iminolactone derivatives and no
ketenimine or 4H-pyran derivative was observed.
On the basis of the established chemistry of isocyanide,[14–16] it is reasonable
to assume that the initial event is the Michael addition of tert-butyl isocyanide to
Scheme 1. Synthesis of compound 3.

2896
S. ASGHARI AND A. K. HABIBI
Table 1. Reactions of tert-butyl isocyanide with dialkyl acetylenedicarboxylates in the presence of a-halo
ketone
3
R
Z
X
Y
Yield (%)
Time (h)
a
b
c
d
e
f
CH3
C2H5
CH3
CH3
CH3
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
80
77
95
92
70
65
40
36
70
70
90
92
60
58
80
75
70
68
50
48
60
55
3
3
2
2
3
3
5
5
3
3
1
1
4
4
3
3
4
4
4
5
5
5
H
CH3
CH3
Cl
Cl
H
C2H5
CH3
CH2Cl
CH2Cl
CH3
C2H5
CH3
H
g
h
i
CH3
CH3
H
C2H5
CH3
CH3
C6H5
j
C2H5
CH3
C6H5
C6H5
H
k
l
Cl
Cl
H
C2H5
CH3
C6H5
C6H5
C6H5
m
n
o
p
q
r
C2H5
CH3
H
O2N-C6H5
O2N-C6H5
Cl-C6H5
Cl-C6H5
CF3
H
C2H5
CH3
H
H
C2H5
CH3
H
s
H
t
C2H5
CH3
C2H5
CF3
CH2Br
CH2Br
H
u
v
H
H
dialkyl acetylenedicarboxylate to form the zwitterionic intermediate 4. The inter-
mediate 4 either can attack the carbonyl group of a-halo ketone that leads to the
dipolar species 5, which cyclizes subsequently to form the iminolactone derivative
3 (route a in Scheme 2), or can be protonated by a-halo ketone as a CH acid to give
positively charged ion 6. Reaction of the enolate anion of the a-halo ketone with 6
forms the ketenimine 7, which can isomerize to produce the enol tautomer 8 under
the reaction conditions. An intramolecular attack of the enole 8 to the sp-hybridized
carbon atom of the ketenimine moiety and a subsequent proton transfer can form
4H-pyran derivative 9 (route b in Scheme 2). As is clear from the results in
Table 1, the reactions did not give any ketenimine or 4H-pyran derivatives. This is
probably a result of the inductive effects of the a-halogenes in the a-halo ketones,
which make the carbonyl group more electrophile. The a-hydrogenes in a-halo
ketones are not acidic enough to protonate the zwitterion 4 through route b in
Scheme 2 to afford ketenimine or 4H-pyran derivatives, as was observed for the
b-diketones.[4b,6b,6c,17]
The structures of 3a–v were deduced from their 1H and 13C NMR and infrared
(IR) spectra as well as elemental analyses. The mass spectra of these compounds dis-
played molecular ion peaks at the appropriate m=z values (Mþ and Mþ þ 2). The 1H
NMR spectrum of 3a in CDCl3 displayed a singlet at d ¼ 1.24 ppm for the tert-butyl
group, another singlet at d ¼ 1.61 ppm for the methyl group, and two singlets at
d ¼ 3.79 ppm and 3.86 ppm for two methoxy groups. The methylene protons of the
CH2Cl moiety are diastereotopic and showed a characteristic AB quartet system
at d ¼ 3.81 and 3.96 ppm (2JHH ¼ 11.2–11.6 Hz). The 13C NMR spectrum of 3a

REACTIVITY OF a-HALO KETONES
2897
Scheme 2. Proposed mechanism for the formation of compound 3 and 4H-pyran derivatives 9.
displayed 12 sharp lines in agreement with the proposed structure. The partial
assignment of these resonances is given in the experimental section. The mass spec-
trum of 3a exhibited molecular ion peaks at m=z 318 (Mþ þ 1) (63) and 320 (Mþ þ 3)
(23) due to the existence of the isotopes of the chlorine atom (35Cl and 37Cl). The 1H
and 13C NMR spectra of 3b–v were similar to those of 3a except those the

2898
S. ASGHARI AND A. K. HABIBI
substituents in positions 2, 3, and 4, which showed characteristic resonances in
appropriate regions of the spectrum.
It can be concluded that a series of a-halo ketones were prepared under neutral
conditions without the use of a catalyst, and their reactivities in a three-component
condensation of tert-butyl isocyanide and dialkyl acetylenedicarboxylates with a-
halo ketones were investigated. The prepared halogenated c-iminolactone reveals
that although two different routes are possible for this type of the reaction, the sole
and high-yielding products confirm the generalization of the mechanism using a var-
iety of a-halo ketones with different electronic properties. The simplicity of the
present procedure also makes it an interesting alternative to the other approaches.
EXPERIMENTAL
Dialkyl acetylenedicarboxylates, tert-butyl isocyanide, chloroacetone, 1,1-dichlor-
oacetone, 1,3-dichloroacetone, 3-chloro-2-butanone, 1-chloro-acetophenone, 1,1-
dichloroacetophenone, 1,3-dibromoacetone, 2-bromo-acetophenone, 2-bromo-4-
nitroacetophenone, 2-bromo-4-chloroacetophenone, and 1,1,1-trifluoroacetone were
purchased from Fluka and Merck and used without further purification. Melting points
were measured on an Electrothermal 9100 apparatus. NMR spectra were recorded with
1
a Bruker DRX-400 Avance instrument (400.1 MHz for H, 100.6MHz for 13C, and
376.5MHz for 19F) with CDCl3 as solvent. Chemical shifts are given in parts per million
(ppm, d) relative to tetramethylsilane (TMS), and coupling constants (J) are reported in
hertz (Hz). IR spectra were recorded on a Fourier transform (FT–IR) Bruker vector 22
spectrometer. Mass spectra were recorded on a Finnigan-Matt 8430 mass spectrometer
operating at an ionization potential of 70 eV. Elemental analyses were performed using a
Heraeus CHN-O Rapid analyzer.
General Procedure for the Preparation of Compound 3
tert-butyl isocyanide (0.24 ml, 2.0 mmol) was added to a stirred solution of dia-
lkyl acetylenedicarboxylate (2.0 mmol) and a-halo ketone derivatives (2.0 mmol) in
10 ml of dry dichloromethane at room temperature. The mixture was allowed to stir
for 1–5 h. The solvent was removed under reduced pressure. The powder products
3e–g, 3i–s, 3u, and 3v were isolated and purified by recrystallization in ethanol from
the mixture of the reactions. The oil products 3a–d, 3h, and 3t were purified by silica
gel (Merck silica gel, 230–400 mesh) column chromatography using hexane–ethyl
acetate (4:1) as eluent. The solvent was removed under reduced pressure, and the
products 3a–d, 3h, and 3t were obtained as yellow oils.
Dimethyl
5-(tert-butylimino)-2-(chloromethyl)-2-methyl-2,5-dihydro-
furan-3,4-dicarboxylate (3a). Yellow oil, yield 80%. IR (KBr) (vmax=cmꢀ1): 1750
and 1729 (C O), 1686 (C N), 1616 (C C) cmꢀ1. H NMR (400.1 MHz, CDCl3):
1
=
=
=
d ¼ 1.24 (9H, s, CMe3), 1.61 (3H, s, CH3), 3.79 and 3.86 (6H, 2 s, 2OCH3), 3.88
2
(2H, AB system, JAB ¼ 11.6 Hz, DtAB ¼ 60 Hz, CH2Cl) ppm. 13C NMR
(100.6 MHz, CDCl3): d ¼ 22.3 (CH3), 29.3 (CMe3), 48.6 (CH2Cl2), 52.8 and 52.9
=
(2OCH3), 54.6 (NCMe3), 88.8 (C), 139.9 (C), 140.9 (C),þ152.5 (C N), 160.9 and
þ
=
162.6 (2C O). MS: m=z (%) ¼ 318 (M þ 1, 63), 320 (M þ 3, 23), 302 (100), 304

REACTIVITY OF a-HALO KETONES
2899
(34), 262 (9), 264 (3), 246 (3), 244 (9), 213 (9), 57 (24). Anal. calcd. for C14H20ClNO5
(317.77): C, 52.92; H, 6.34; N, 4.41%. Found: C, 53.03; H, 6.36; N, 4.42%.
Diethyl 5-(tert-butylimino)-2-(chloromethyl)-2-methyl-2,5-dihydrofuran-
3,4-dicarboxylate (3b). Yellow oil, yield 77%. IR (KBr) (vmax=cmꢀ1): 1741 and
ꢀ1
=
=
=
1719 (C O), 1686 (C N), 1614 (C C) cm
.
1H NMR (400.1 MHz, CDCl3):
d ¼ 1.20 (9H, s, CMe3), 1.22 (3H, t, 3JHH ¼ 7.2 Hz, CH3), 1.27 (3H, t, 3JHH ¼ 7.2 Hz,
2
CH3) 1.56 (3H, s, CH3), 3.84 (2H, AB system, JHH ¼ 11.6 Hz, DtAB ¼ 56 Hz,
3
3
CH2Cl), 4.19 (2H, q, JHH ¼ 7.2 Hz, OCH2), 4.27 (2H, q, JHH ¼ 7.2 Hz, OCH2).
13C NMR (100.6 MHz, CDCl3): d ¼ 13.8 (CH3), 14.0 (CH3), 22.3 (CH3), 29.3
(CMe3), 48.6 (CH2Cl), 54.4 (NCMe3), 61.7 and 61.8 (2CH2), 88.7 (C), 139.7 (C),
þ
=
=
145.6 (C), 152.5 (C N), 160.4 and 162.1 (2C O). MS: m=z (%) ¼ 346 (M þ 1,
81), 348 (Mþ þ 3, 28), 330 (100), 332 (34), 290 (19), 292 (6), 244 (10), 246 (3), 199
(9), 201 (3), 65 (5) 57 (20). Anal. calcd. for C16H24ClNO5 (345.83): C, 55.57; H,
7.00; N, 4.05%. Found: C, 55.68; H, 7.02; N, 4.06%.
Dimethyl 5-(tert-butylimino)-2-(dichloromethyl)-2-methyl-2,5-dihydrofuran-
3,4-dicarboxylate (3c). Yellow powder, mp 50–53 ꢁC, yield 95%. IR ꢀ(K1 Br) (vmax
=
cmꢀ1): 1752 and 1725 (C O), 1687 (C N), 1655 (C C) cm
.
1HNMR
=
=
=
(400.1 MHz, CDCl3): d ¼ 1.34 (9H, s, CMe3), 1.77 (3H, s, CH3), 3.85 and 3.92
(6H, 2 s, 2OCH3), 6.23 (1H, s, CHCl2). 13C NMR (100.6 MHz, CDCl3): d ¼ 22.0
(CH3), 29.3 (CMe3), 53.0 and 53.1 (2OCH3), 55.2 (NCMe3), 74.7 (CHCl2), 91.1
=
=
(C), 139.6 (C), 140.9 (C), 151.9 (C N), 160.8 and 162.2 (2C O). MS: m=z
(%) ¼ 352 (Mþ þ 1, 29), 354 (Mþ þ 3, 19), 356 (Mþ þ 5, 3), 336 (100), 338 (70),
340 (12), 296 (8), 298 (6), 300 (1), 253 (20), 181 (8), 57 (34). Anal. calcd. for
C14H19Cl2NO5 (352.22): C, 47.74; H, 5.44; N, 3.98%. Found: C, 47.84; H, 5.45;
N, 3.99%.
Diethyl 5-(tert-butylimino)-2-(dichloromethyl)-2-methyl-2,5-dihydrofuran-
3,4-dicarboxylate (3d). Yellow viscous oil, yield 92%. IR (KBr) (vmax=cmꢀ1): 1752
1
and 1729 (C O), 1693 (C N), 1654 (C C) cmꢀ1. H NMR (400.1 MHz, CDCl3):
d ¼ 1.28 (3H, t, 3JHH ¼ 7.2 Hz, CH3), 1.30 (9H, s, CMe3), 1.33 (3H, t, 3JHH ¼ 7.2 Hz
CH3), 1.73 (3H, s, CH3), 4.25 (2H, q, 3JHH ¼ 7.2 HZ, OCH2), 4.33 (2H, q, 3JHH ¼ 7.2
HZ, OCH2), 6.21 (1H, s, CHCl2). 13C NMR (100.6 MHz, CDCl3): d ¼ 13.8 (CH3),
14.0 (CH3), 22.0 (CH3), 29.3 (CMe3), 55.0 (NCMe3), 62.1 and 62.2 (2OCH2), 74.8
=
=
=
=
=
(CHCl2), 91.0 (C), 139.5 (C) 140.6 (C), 152.0 (C N), 160.4 and 161.7 (2C O).
MS: m=z (%) ¼ 380 (Mþ þ 1, 37), 382 (Mþ þ 3, 26), 384 (Mþ þ 5, 4), 364 (100),
366 (68), 368 (12), 324 (18), 326 (12), 328 (2), 281 (10), 57 (23). Anal. calcd. for
C16H23Cl2NO5 (380.27): C, 50.54; H, 6.10; N, 3.68%. Found: C, 50.64; H, 6.11;
N, 3.69%.
Dimethyl 5-(tert-butylimino)-2,2-bis(chloromethyl)-2,5-dihydrofuran-
3,4-dicarboxylate (3e). White powder, mp 130–132 ꢁC, yield 70%. IR (KBr)
ꢀ1
(vmax=cmꢀ1): 1750 and 1734 (C O), 1686 (C N), 1660 (C C) cm
.
1H NMR
=
=
=
(400.1 MHz, CDCl3): d ¼ 1.33 (9H, s, CMe3), 3.86 and 3.93 (6H, 2 s, 2OCH3), 4.00
2
(4H, AB system, JHH ¼ 11.6 Hz, DtAB ¼ 11.12 Hz, 2CH2Cl). 13C NMR
(100.6 MHz, CDCl3): d ¼ 29.4 (CMe3), 45.8 (CH2Cl), 53.0 and 53.1 (2OCH3), 55.2
=
=
(NCMe3), 89.9 (C), 137.4 (C) 142.0 (C), 151.7 (C N), 160.8 and 162.1 (2C O).
MS: m=z (%) ¼ 352 (Mþ þ 1, 27), 354 (Mþ þ 3, 18), 356 (Mþ þ 5, 3), 336 (100),

2900
S. ASGHARI AND A. K. HABIBI
338 (67), 340 (11), 296 (9), 298 (6), 300 (1), 257 (8), 57 (20). Anal. calcd. for
C14H19Cl2NO5 (350.22): C, 47.74; H, 5.44; N, 3.98%. Found: C, 47.85; H, 5.46;
N, 3.99%.
Diethyl 5-(tert-butylimino)-2,2-bis(chloromethyl)-2,5-dihydrofuran-3,4-
dicarboxylate (3f). White powder, mp 78–79 ꢁC, yield 65%. IR (KBr) (vmax=cmꢀ1):
ꢀ1
=
=
=
1740 and 1729 (C O), 1686 (C N), 1660 (C C) cm
.
1H NMR (400.1 MHz,
CDCl3): d ¼ 1.33 (9H, s, CMe3), 1.34 (3H, t, 3JHH ¼ 7.2 Hz, CH3), 1.38 (3H, t, 3JHH
¼
2
7.2 Hz, CH3), 4.01 (4H, AB quartet system, JHH ¼ 11.6 Hz, DtAB ¼ 20.0 Hz,
3
3
2CH2Cl), 4.30 (2H, q, JHH ¼ 7.2 Hz, OCH2), 4.40 (2H, q, JHH ¼ 7.2 Hz, OCH2).
13C NMR (100.6 MHz, CDCl3): d ¼ 13.8 (CH3), 14.1 (CH3), 29.4 (CMe3), 45.9
(CH2Cl), 55.1 (NCMe3), 62.2 and 62.3 (2OCH2), 89.8 (C), 137.3 (C) 141.9 (C),
þ
=
=
151.8 (C N), 160.4 and 161.8 (2C O). MS: m=z (%) ¼ 380 (M þ 1, 9), 382
(Mþ þ 3, 6), 384 (Mþ þ 5, 1), 364 (100), 366 (67), 368 (11), 280 (5), 233 (9), 235
(6), 237 (1), 57 (29). Anal. calcd. for C16H23Cl2NO5 (380.27): C, 50.54; H, 6.15; N,
3.68%. Found: C, 50.64; H, 6.12; N, 3.69%.
Dimethyl 5-(tert-butylimino)-2-(1-chloroethyl)-2-methyl-2,5-dihydrofuran-
3,4-dicarboxylate (3g). Yellow powder, mp 35–38 ꢁC, yield 40%. IR (KBr) (vmax
=
ꢀ1
cmꢀ1): 1751 and 1728 (C O), 1682 (C N), 1655 (C C) cm
.
1H NMR
=
=
=
3
(400.1 MHz, CDCl3): d ¼ 1.33 (9H, s, CMe3), 1.39 (3H, d, JHH ¼ 6.8 Hz, CH3),
3
1.74 (3H. s, CH3), 3.84 and 3.91 (6H, 2 s, 2 OCH3), 4.54 (1H, q, JHH ¼ 6.8 Hz,
CHCl). 13C NMR (100.6 MHz, CDCl3): d ¼ 19.6 (CH3), 23.0 (CH3), 29.3 (CMe3),
52.9 and 60.5 (2OCH3), 54.9 (NCMe3), 59.8 (CHCl), 91.4 (C), 138.6 (C), 143.1(C),
þ
=
=
152.6 (C N), 161.2 and 162.4 (2C O). MS: m=z (%) ¼ 332 (M þ 1, 37), 334
(Mþ þ 3, 12), 316 (100), 318 (33), 276 (8), 278(3), 222 (13), 57 (20). Anal. calcd.
for C15H22Cl2NO5 (331.80): C, 54.30; H, 6.68; N, 4.22%. Found: C, 54.41; H,
6.69; N, 4.23%.
Diethyl
5-(tert-butylimino)-2-(1-chloroethyl)-2-methyl-2,5-dihydrofuran-
3,4-dicarboxylate (3h). Yellow oil, yield 36%. IR (KBr) (vmax=cmꢀ1): 1740 and
1721(C O), 1682 (C N), 1651 (C C) cmꢀ1. H NMR (400.1 MHz,CDCl3): d ¼
1
=
=
=
3
3
1.32 (3H, t, JHH ¼ 7.2 Hz, CH3), 1.33 (9H, s, CMe3),1.36 (3H, t, JHH ¼ 7.2 Hz,
3
3
CH3), 1.38 (3H, d, JHH ¼ 6.80 Hz, CH3),1.74 (3H, s, CH3), 4.28 (2H, q, JHH
¼
7.2 Hz, OCH2), 4.37 (2H, q,3JHH ¼ 7.2 Hz, OCH2), 4.55 (1H, q, JHH ¼ 6.8 Hz,
CHCl). 13C NMR (100.6 MHz, CDCl3): d ¼ 13.9 (CH3), 14.1 (CH3), 19.6 (CH3),
22.0 (CH3), 29.3 (CMe3), 54.7 (NCMe3), 60.6 (CHCl), 62.0 and 62.1 (2OCH2),
3
=
=
91.3 (C), 138.5 (C), 142.8 (C), 152.7 (C N), 160.8 and 162.0 (2C O). MS: m=z
(%) ¼ 360 (Mþ þ 1, 44), 362 (Mþ þ 3, 15), 344 (100), 346 (33), 304 (8), 306 (3), 236
(8), 57 (17). Anal. calcd. for C17H26ClNO5 (359.85): C, 56.74; H, 7.28; N, 3.89%.
Found: C, 56.85; H, 7.30; N, 3.90%.
Dimethyl 5-(tert-butylimino)-2-(chloromethyl)-2-phenyl-2,5-dihydrofuran-
3,4-dicarboxylate (3i). White powder, mp ¼ 110–112 ꢁC, yield 70%. IR (KBr)
1
(nmax=cmꢀ1): 1747 and 1731 (C O), 1683 (C N), 1661 and 1439 (C C) cmꢀ1. H
=
=
=
NMR (400.13 MHz, CDCl3): d ¼ 1.40 (9H, s, CMe3), 3.79 and 3.92 (6H, 2 s,
2
2
2OCH3), 4.23 (1H, d, JHH ¼ 11.6 Hz, CH), 4.66 (1H, d, JHH ¼ 11.6 Hz, CH),
7.37–7.47 (5H, m, C6H5). 13C NMR (100.6 MHz, CDCl3): d ¼ 29.6 (CMe3), 48.1
(CH2Cl), 52.9 and 53.0 (2OMe), 55.0 (NCMe3), 91.4 (C), 125.8 128.8, 129.0 and

REACTIVITY OF a-HALO KETONES
2901
=
136.8 (aromatic carbons), 139.1 and 14þ1.2 (olefinic carbons), 152.2 (C N), 161.2 and
þ
=
162.4 (2C O). MS: m=z (%) ¼ 380 (M þ 1, 3), 382 (M þ 3, 1), 394(100), 366 (30),
332 (34), 334 (12), 275 (10), 277 (3), 238(9), 105 (40), 57 (29). Anal. calcd. for
C19H22ClNO5 (379.74): C, 60.08; H, 5.84; N, 3.69%. Found: C, 59.92; H, 5.80; N,
3.65%.
Diethyl 5-(tert-butylimino)-2-(chloromethyl)-2-phenyl-2,5-dihydrofuran-
3,4-dicarboxylate (3j). White powder, mp ¼ 58–60 ꢁC, yield 70%. IR (KBr) (nmax
=
1
cmꢀ1): 1742 and 1726 (C O), 1688 (C N), 1666 and 1455 (C C) cmꢀ1. H NMR
=
=
=
3
3
(400.13 MHz, CDCl3): d ¼ 1.27 (3H, JHH ¼ 7.2 Hz, CH3), 1.37 (3H, JHH ¼ 7.2 Hz,
2
CH3), 1.40 (9H, s, CMe3), 4.16–4.31 (2H, m, OCH2), 4.24 (1H, d, JHH ¼ 11.6 Hz,
2
CH), 4.35–4.41 (2H, m, OCH2), 4.63 (1H, d, JHH ¼ 11.6 Hz, CH), 7.35–7.48 (5H,
m, C6H5). 13C NMR (100.6 MHz, CDCl3): d ¼ 13.8 and 14.1 (2CH3), 29.6
(CMe3), 48.2 (CH2Cl), 54.9 (NCMe3), 62.0 and 62.1 (2OCH2), 91.3(C), 125.9,
128.8, 129.0, and 137.0 (aromatic carbons), 139.0 and 141.0 (olefinic carbons),
þ
=
=
152.4 (C N), 160.8 and 162.0 (2C O). MS: m=z (%) ¼ 408 (M þ 1, 10), 410
(Mþ þ 3, 3), 392 (100), 394 (38), 346 (20), 348 (7), 306 (10), 308 (3), 238 (14), 155
(10), 105 (41), 57 (47). Anal. calcd. for C21H26ClNO5 (407.79): C, 61.84; H, 6.42;
N, 3.43%. Found: C, 61.78; H, 6.38; N, 3.40%.
Dimethyl 5-(tert-butylimino)-2-(dichloromethyl)-2-phenyl-2,5-dihydro-
furan-3,4-dicarboxylate (3k). White powder, mp 140–142 ꢁC, yield 90ꢀ%1. IR
(KBr) (vmax=cmꢀ1): 1761 and 1729 (C O), 1686 (C N), 1644 (C C) cm
.
1H
=
=
=
NMR (400.1 MHz, CDCl3): d ¼ 1.49 (9H, s, CMe3), 3.81 and 3.90 (6H, 2 s,
2OCH3), 6.96 (1H, s, CHCl2), 7.40–7.42 (3H, m, 2H meta and H para), 7.50–7.53
(2H, m, 2H meta). 13C NMR (100.6 MHz, CDCl3): d ¼ 29.6 (CMe3), 53.0 and
53.1 (2OCH3), 55.5 (NCMe3), 74.3 (CHCl2), 94.1 (C), 125.8, 128.9, 129.2, and
=
135.7 (aromatic carbons), 138.0þ(C), 141.8 (C), 151.6 (C N), 161.2 and 161.9
þ
þ
=
(2C O). MS: m=z (%) ¼ 414 (M þ 1, 9), 416 (M þ 3, 6), 418 (M þ 5, 1), 398
(100), 400 (67), 402 (11), 315 (36), 283 (32), 242 (9), 77 (33), 57 (33). Anal. calcd.
for C19H21Cl2NO5 (414.29): C, 51.09; H, 5.11; N, 3.38%. Found: C, 51.19; H,
5.13; N, 3.39%.
Diethyl
5-(tert-butylimino)-2-(dichloromethyl)-2-phenyl-2,5-dihydro-
furan-3,4-dicarboylate (3l). White powder, mp 115–117 ꢁC, yield 92ꢀ%1. IR (KBr)
(vmax=cmꢀ1): 1755 and 1724 (C O), 1692 (C N), 1649 (C C) cm
.
1HNMR
=
=
=
3
(400.1 MHz, CDCl3): d ¼ 1.27 (3H, t, JHH ¼ 7.2 Hz, CH3), 1.36 (3H, t,
3JHH ¼ 7.2 Hz, CH3), 1.49 (9H, s, CMe3), 4.19–4.38 (2H, m, 2OCH2), 7.38–7.44
(3H, m, 2H ortho and H para), 7.52–7.54 (2H, m, 2H meta). 13C NMR
(100.6 MHz, CDCl3): d ¼ 13.7 (CH3), 14.1 (CH3), 29.6 (CMe3), 55.3 (NCMe3),
62.2 and 62.4 (2O CH2), 74.4 (CHCl2), 94.1 (C), 125.8, 128.8, 129.11, and 135.9
=
=
(aromatic carbons), 138.0 (C), 141.5 (C), 151.7 (C N), 160.8 and 161.5 (2C O).
MS: m=z (%) ¼ 441 (Mþ þ 1, 18), 443 (Mþ þ 3, 12), 445 (Mþ þ 5, 2), 426 (100),
428 (66), 430 (11), 343 (30), 297 (20), 77 (9), 57 (28). Anal. calcd. for C21H25Cl2NO5
(442.34): C, 57.02; H, 5.70; N, 3.17%. Found: C, 57.13; H, 5.72; N, 3.18%.
Dimethyl
2-(bromomethyl)-5-(tert-butylimino)-2-phenyl-2,5-dihydro-
furan-3,4-dicarboxylate (3m). White powder, mp ¼ 100–102 ꢁC, yield 92%. IR
(KBr) (nmax=cmꢀ1): 1740 (C O), 1687 (C N), 1656 (C C) cm
.
1H NMR
ꢀ1
=
=
=

2902
S. ASGHARI AND A. K. HABIBI
(400.13 MHz, CDCl3): d ¼ 1.40 (9H, s, CMe3), 3.79 and 3.92 (6H, 2 s, 2OCH3), 4.14
2
2
(1H, d, JHH ¼ 11.2 Hz, CH), 4.54 (1H, d, JHH ¼ 11.2 Hz, CH), 7.36–7.48 (5H, m,
C6H5). 13C NMR (100.6 MHz, CDCl3): d ¼ 29.6 (CMe3), 36.8 (CH2Br), 52.9 and
53.0 (2 OMe), 55.0 (NCMe3), 90.7 (C), 125.9 128.8, 129.1 and 136.9 (aromatic car-
=
=
bons), 138.9 and 141.9 (olefinic carbons), 152.2 (C N), 161.1 and 162.4 (2C O).
MS: m=z (%) ¼ 423 (Mþ, 3), 425 (Mþ þ 2, 3), 408 (100), 410 (100), 376 (34), 378
(Mþ þ 2, 34), 351 (Mþ þ 1, 4), 353 (4), 272 (3), 238 (10), 213 (7), 105 (18), 77 (11),
57 (13). Anal. calcd. for C19H22BrNO5 (424.29): C, 53.79; H, 5.23; N, 3.30%. Found:
C, 53.73; H, 5.19; N, 3.27%.
Diethyl 2-(bromomethyl)-5-(tert-butylimino)-2-phenyl-2,5-dihydrofuran-
3,4-dicarboxylate (3n). White powder, mp ¼ 73–75 ꢁC, yield 90%. IR (KBr)
(nmax=cmꢀ1): 1735 (C O), 1677 (C N), 1614 (C C) cmꢀ1
.
1H NMR
=
=
=
3
3
(400.13 MHz, CDCl3): d ¼ 1.27 (3H, JHH ¼ 7.2 Hz, CH3), 1.37 (3H, JHH ¼ 7.2 Hz,
2
CH3), 1.41 (9H, s, CMe3), 4.15 (1H, d, JHH ¼ 11.2 Hz,CH3), 4.18–4.32 (2H, m,
3
2
OCH2), 4.38 (2H, q, JHH ¼ 7.2 Hz,OCH2), 4.52, (1H, d, JHH ¼ 11.2 Hz, CH),
7.36–7.50 (5H, m, C6H5). 13C NMR (100.6 MHz, CDCl3): d ¼ 13.8 and 14.1
(2CH3), 29.6 (CMe3), 35.9 (CH2Br), 54.9 (NCMe3), 62.0 and 62.1 (2OCH2), 90.6
(C), 125.9, 128.8, 129.0, and 137.2 (aromatic carbons), 138.8 and 141.6þ(olefinic car-
=
=
bons), 152.2 (C N), 160.8 and 162.0 (2C O). MS: m=z (%) ¼ 452 (M þ 1, 3), 454
(Mþ þ 3, 3), 436 (90), 438 (90), 396 (100), 398 (100), 350 (98), 352 (98), 294 (50),
296 (50), 277 (52), 279 (52), 238 (23), 225 (17), 209 (10), 211 (10), 199 (13), 181
(11), 158 (13), 105 (38), 77 (21), 57 (38). Anal. calcd. for C21H26BrNO5 (452.34):
C, 55.76; H, 5.79; N, 3.10%. Found: C, 55.71; H, 5.74; N, 3.07%.
Dimethyl
2-(bromomethyl)-5-(tert-butylimino)-2-(4-nitrophenyl)-2,5-
dihydrofuran–3,4-dicarboxylate (3o). White powder, mp ¼ 105–107 ꢁC, yield
80%. IR (KBr) (nmax=cmꢀ1): 1746 and 1724 (C O), 1693 (C N), 1656 (C C) cm
.
ꢀ1
=
=
=
1H NMR (400.13 MHz, CDCl3): d ¼ 1.41 (9H, s, CMe3), 2.81 and3.92 (6H, 2 s,
2
2
2OCH3), d ¼ 4.17 (1H, d, JHH ¼ 11.2Hz, CH), 4.46 (1H, d, JHH ¼ 11.2 Hz, CH),
3
3
7.69 (2H, d, JHH ¼ 8.8 Hz, 2CH),8.26 (2H, d, JHH ¼ 8.8 Hz, 2CH). 13C NMR
(100.6 MHz, CDCl3):d ¼ 29.6 (CMe3), 35.9 (CH2Br), 53.1 and 53.2 (2OCH3), 55.3
(NCMe3), 90.1 (C), 123.9, 127.3, 140.7 and 143.8 (aromatic carbons), 139.6 and
=
=
148.1 (olefinic carbons), 151.1 (C N), 160.8 and 162.0 (2C O). MS: m=z (%) ¼ 469
(Mþ þ 1, 2), 471 (Mþ þ 3, 2), 453 (100), 455 (100), 421 (12), 423 (12), 396 (4), 398
(4), 368 (5), 370 (5), 317 (8), 283 (12), 215 (6), 150 (13), 104 (7), 84 (20), 57 (50). Anal.
calcd. for C19H21BrN2O7 (469.28): C, 48.63; H, 4.51; N, 5.97%. Found: C,48.69; H,
4.48; N, 5.95%.
Diethyl
2-(bromomethyl)-5-(tert-butylimino)-2-(4-nitrophenyl)-2,5-
dihydrofuran-3,4-dicarboxylate (3p). Yellow powder, mp ¼ 68–70 ꢁC, yield 75%.
IR (KBr) (nmax=cmꢀ1): 1735 and 1698 (C O), 1698 (C N), 1660 (C C) cmꢀ1. H
1
=
=
=
3
NMR (400.13 MHz, CDCl3): d ¼ 1.27 (3H, t, JHH ¼ 7.2 Hz, CH3), 1.37(3H, t,
3JHH ¼ 7.2 Hz, CH3), 1.40 (9H, s, CMe3), 4.19 (1H, d, JHH ¼ 11.2 Hz, CH),
2
2
4.22–4.30 (2H, m, OCH2), 4.35–4.39 (2H, m,OCH2), 4.42 (1H, d, JHH ¼ 11.2 Hz,
CH), 7.70 (2H, d, JHH ¼ 8.8 Hz, 2CH), 8.25 (2H, JHH ¼ 8.8 Hz, 2CH). 13C NMR
(100.6 MHz, CDCl3): d ¼ 13.8 and 14.1 (2CH3), 29.6 (CMe3), 36.0 (CH2Br), 55.2
(NCMe3), 62.3 and 62.4 (2 OCH2), 90.0 (C), 123.8, 127.3, 140.4 and 144.0 (aromatic
3
3

REACTIVITY OF a-HALO KETONES
2903
=
=
carbons), 139.5 and 148.1 (olefinic carbons), 151.2 (C N), 160.5 and 161.6 (2C O).
MS: m=z (%) ¼ 497 (Mþ þ 1, 13), 499 (Mþ þ 3, 13), 481 (100), 483 (100), 441 (7), 443
(7), 395 (3), 397 (3), 363 (5), 365 (5), 352 (7), 354 (7), 283 (24), 272 (7), 243 (6), 225
(11), 150 (24), 104 (9), 84 (13), 57 (49). Anal. calcd. for C21H25BrN2O7 (497.34): C,
50.72; H, 5.07; N, 5.63%. Found: C, 50.68; H, 5.04; N, 5.59%.
Dimethyl 2-(bromomethyl)-5-(tert-butylimino)-2-(4-chlorophenyl)-2,5-
dihydrofuran-3,4-dicarboxylate (3q). White powder, mp ¼ 73–75 ꢁC, yield 70%.
1
IR (KBr) (nmax=cmꢀ1): 1747 and 1720 (C O), 1690 (C N), 1660 (C C) cmꢀ1. H
=
=
=
NMR(400.13 MHz, CDCl3): d ¼ 1.39 (9H, s, CMe3), 3.79 and 3.92 (6H, 2 s,
2
2
2OCH3), 4.11 (1H, d, JHH ¼ 11.2 Hz, CH), 4.47 (1H, d, JHH ¼ 11.2 Hz, CH), 7.36
(2H, d, JHH ¼ 8.8 Hz, 2CH), 7.41 (2H, d,3JHH ¼ 8.8 Hz, 2CH). 13C NMR
3
(100.6 MHz, CDCl3): d ¼ 29.6(CMe3), 36.4 (CH2Br), 53.0 and 53.1 (2OCH3), 55.1
(NCMe3),90.2 (C), 127.4, 129.0, 135.2 and 135.4 (aromatic carbons), 139.0 and
=
=
141.4 (olefinic carbons), 151.8 (C N), 161.0 and 162.2 (2C O). MS: m=z
(%) ¼ 457 (Mþ, 3), 459 (Mþ þ 2, 4), 461 (Mþ þ 4,1), 442 (74), 444 (100), 446 (24),
410 (43), 412 (60), 414 (15), 385 (3), 387 (4), 389 (1), 357 (6), 359 (8), 361 (2), 327
(5), 272 (16), 247 (9), 249 (3), 189 (9), 191 (3), 139 (33), 141 (11), 111 (12), 113 (4),
84 (15), 57 (31). Anal. calcd. for C19H21BrClNO5(458.73): C, 49.75; H, 4.61; N,
3.05%. Found: C, 49.70; H, 4.57;N, 3.01%.
Diethyl
2-(bromomethyl)-5-(tert-butylimino)-2-(4-chlorophenyl)-2,5-
dihydrofuran-3,4-dicarboxylate (3r). White powder, mp ¼ 90–92 ꢁC, yield 68%.
IR (KBr) (nma=cmꢀ1):1731 (C O), 1687 (C N), 1650 and 1484 (C C) cmꢀ1. H
1
=
=
=
3
NMR (400.13 MHz, CDCl3): d ¼ 1.27 (3H, t, JHH ¼ 7.2 Hz, CH3), 1.37(3H, t,
3JHH ¼ 7.2 Hz, CH3), 1.39 (9H, s, CMe3), 4.12 (1H, d, JHH ¼ 11.2 Hz, CH),
2
3
4.18–4.29 (2H, m, OCH2), 4.38 (2H, q, JHH ¼ 7.2 Hz, OCH2), 4.44 (1H,
3
3
d,¼ 11.2 Hz, CH), 7.36 (2H, d, JHH ¼ 8.8 Hz, 2CH), 7.42 (2H, d, JHH ¼ 8.8 Hz,
2CH), 13C NMR(100.6 MHz, CDCl3): d ¼ 13.8 and 14.1 (2CH3), 29.6 (CMe3), 36.5
(CH2Br), 55.0 (NCMe3), 62.1 (2OCH2), 90.2 (C), 127.5, 128.9,134.0 and 135.7 (aro-
=
matic carbons), 139.0 and 141.1 þ(olefinic carbons)þ, 151.8 (C N), 160.6 and 161.8
=
(2C O). MS: m=z (%) ¼ 486 (M þ 1, 3), 488 (M þ 3, 4), 490 (1), 470 (78), 472
(100), 474 (27), 424 (30), 426 (38), 428 (10), 339 (9), 341 (12), 343 (3), 261 (16),
263 (6), 189 (11), 191 (4), 139 (30), 141 (10), 111 (9), 113 (3), 84 (16), 57 (51). Anal.
calcd. for C21H25BrClNO5 (486.78): C, 51.81; H, 5.18; N, 2.88%. Found: C, 51.76; H,
5.14; N, 2.85%.
Dimethyl 2-(bromomethyl)-5-(tert-butylimino)-2-(trifluoromethyl)-2,5-
dihydrofuran-3,4-dicarboxylate (3s). White powder, mp ¼ 50–52 ꢁC, yield 50%.
1
IR (KBr) (nmax=cmꢀ1): 1747 (C O), 1698 (C N), 1650 (C C) cmꢀ1. H NMR
=
=
=
(400.13 MHz, CDCl3): d ¼ 1.34 (9H, s, CMe3), 3.88 and 3.94 (6H, 2 s,2OCH3),
4
2
3.91 (1H, d, JHH ¼ 11.2 Hz, CH), 4.33 (1H, d, JHH ¼ 11.2 Hz, CH). 13C NMR
(100.6 MHz, CDCl3): 29.3 (CH2Br), d ¼ 29.4 (CMe3), 53.2 and 53.3 (2OCH3), 55.7
2
1
(NCMe3), 88.2 (q, JFC ¼ 31.9 Hz, CCF3), 121.9 (q, JFC ¼ 287.7 Hz, CF3), 135.1
and143.4 (olefinic carbons), 149.7 (C N), 159.7 and 161.3 (2C O). 19F NMR
(376.50, CDCl3): d ¼ ꢀ75.68. MS: m=z (%) ¼ 416 (Mþ þ 1, 60), 418 (Mþ þ 3, 60),
400 (14), 402 (14), 277 (17), 265 (16), 250 (9), 192 (20), 136 (11), 69 (38), 57 (100).
=
=

2904
S. ASGHARI AND A. K. HABIBI
Anal. calcd. for C14H17 Br F3 NO5 (416.19): C, 40.40; H, 4.76; N, 3.15%. Found: C,
40.34; H, 4.72; N, 3.11%.
Diethyl
dihydrofuran-3,4-dicarboxylate (3t). Yellow oil, yield 48%. IR (KBr) (nmax
2-(bromomethyl)-5-(tert-butylimino)-2-(trifluoromethyl)-2,5-
=
cmꢀ1): 1741 (C O), 1690 (C N), 1655 (C C) cmꢀ11. H NMR (400.13 MHz,
=
=
=
3
CDCl3):d ¼ 1.33 (9H, s, CMe3), 1.34 (3H, t, JHH ¼ 7.2 Hz, CH3), 1.38 (3H,t,
4
3JHH ¼ 7.2 Hz, CH3), 3.90 (1H, d, JHH ¼ 11.2 Hz, CH), 4.29–4.38 (2H, m, OCH2),
2
3
4.34 (1H, d, JHH ¼ 11.2 Hz, CH), 4.41 (2H, q, JHH ¼ 7.2 Hz, OCH2). 13C NMR
(100.6 MHz, CDCl3): d ¼ 13.8 and 14.0 (2CH3), 29.4 (CMe3), 29.6 (CH2Br), 55.6
2
(NCMe3), 62.4 and 62.5 (2OCH2), 88.1 (q, JFC ¼ 31.2 Hz, CCF3), 122.0 (q,
1
=
JFC ¼ 287.7 Hz, CF3), 134.9 and 143.4 (olefinic carbons), 149.8 (C N), 159.3 and
160.9 (2C O). 19F NMR (376.50, CDCl3): d ¼ ꢀ75.64. MS: m=z (%) ¼ 444
=
(Mþ þ 1, 48), 446 (Mþ þ 3, 48), 428 (17),430 (17), 416 (15), 418 (15), 360 (28), 362
(28), 308 (24), 275(27), 219 (22), 192 (52), 136 (24), 84 (30), 69 (44), 57 (100). Anal.
calcd. for C16H21BrF3NO5 (416.19): C, 43.26; H, 4.76; N,3.15%. Found: C, 43.21; H,
4.73; N, 3.13%.
Dimethyl 2,2-bis (bromomethyl)-5-(tert-butylimino)-2,5-dihydrofuran-
3,4-dicarboxylate (3u). White powder, mp ¼ 131–133 ꢁC, yield 60%. IR (KBr)
ꢀ1
(nmax=cmꢀ1): 1739 (C O), 1681 (C N), 1650 and 1448 (C C) cm
.
1HNMR
=
=
=
(400.13 MHz, CDCl3): d ¼ 1.34 (9H, s, CMe3), 3.86 (3H, s,OCH3), 3.90 (4H, s,
2CH2Br), 3.93 (3H, s, OCH3). 13C NMR (100.6 MHz, CDCl3): d ¼ 29.4 (CMe3),
33.8 (2CH2Br), 53.1 and 53.2 (2OCH3), 55.2 (NCMe3), 88.3 (C), 138.5 and 141.6 (ole-
þ
=
=
finic carbons), 151.5 (C N), 160.6 and 162.1 (2C O). MS: m=z (%) ¼ 439 (M , 3), 441
(Mþ þ 2, 6), 443 (Mþ þ 4, 3), 424 (49), 426 (100), 428 (50), 408 (22), 410 (40), 412 (21),
392 (15), 394 (30), 396 (15), 393 (3), 395 (6), 397 (3), 384 (3), 386 (6), 388 (3), 367 (13),
369 (26), 371 (14), 95 (3), 93 (3), 84 (5), 57 (8). Anal. calcd. for C14H19Br2NO5(441.11):
C, 38.12; H, 4.34; N, 3.18%. Found: C, 38.07; H, 4.31; N, 3.16%.
Diethyl 2,2-bis (bromomethyl)-5-(tert-butylimino)-2,5-dihydrofuran-
3,4-dicarboxylate (3v). White powder, mp ¼ 83–85 ꢁC, yield 55%. IR (KBr)
1
(nmax=cmꢀ1): 1735 (C O), 1687 (C N), 1650 and 1466 (C C) cmꢀ1. H NMR
=
=
=
3
(400.13 MHz, CDCl3): d ¼ 1.33 (9H, s, CMe3), 1.34 (3H, t, JHH ¼ 7.2 Hz, CH3),
3
2
1.40 (3H, t, JHH ¼ 7.2 Hz, CH3), 3.91 (4H, AB system, JHH ¼ 11.2 Hz,
3
Dn ¼ 13.1 Hz, 2CH2Br), 4.31 (2H, q, JHH ¼ 7.2 Hz, OCH2), 4.40 (2H, q,
3JHH ¼ 7.2 Hz, OCH2). 13C NMR (100.6 MHz, CDCl3): d ¼ 13.8 and 14.1 (2CH3)
29.4 (CMe3), 34.0 (CH2Br), 55.1 (NCMe3), 62.2 and 62.3 (2OCH2), 88.2 (C), 138.3
=
=
and 141.5 (olefinic carbons), 151.5 (C N), 160.4 and 161.7 (2C O). MS: m=z
(%) ¼ 467 (Mþ, 4), 469 (8), 471 (4), 452 (50),454 (100), 456 (50), 422 (2), 424 (4),
426 (2), 412 (4), 414 (8),416 (4), 346 (2), 348 (2), 321 (8), 323 (15), 325 (8), 84 (15),
57 (36). Anal. calcd. for C16H23Br2NO5 (469.17); C, 40.96; H, 4.94; 2.99; N,
2.98%. Found: C, 40.91; H, 4.91; N, 2.96%.
ACKNOWLEDGMENT
This research was supported by the Research Council of the University of
Mazandaran in Iran.

REACTIVITY OF a-HALO KETONES
2905
REFERENCES
1. Marcaccini, S.; Torroba, T. The use of isocyanides in heterocyclic synthesis: A review.
Org. Prep. Proced. Int. 1993, 25, 141–172.
2. Domling, A. Recent developments in isocyanide-based multicomponent reactions in
applied chemistry. Chem. Rev. 2006, 106, 17–89.
3. Oakes, T. R.; Donovan, D. J. Reactions of isocyanides with activated acetylenes in protic
solvents. J. Org. Chem. 1973, 38, 1319–1325.
4. (a) Nair, V. J.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.; Mahess, J. S.;
Balagopal, L. Strategies for heterocyclic construction via novel multicomponent reactions
based on isocyanides and nucleophilic carbenes. Acc. Chem. Res. 2003, 36, 899–909; (b)
Yavari, I.; Esmaeili, A. A.; Sghari, S.; Bijanzadeh, H. R. A new and efficient one-pot syn-
thesis of trialkyl 6-tert-butylamino-2H-pyran-2-one-3,4,5-tricarboxylates. J. Chem. Res.,
Synop.Synop. 1999, 368–369; (c) Yavari, I.; Adib, M.; Sayahi, M. H. Reaction between
isocyanides and dialkyl acetylenedicarboxylates in the presence of 3-methylcyclopen-
tane-1,2,4-trione: One-pot diastereoselective synthesis of tetrahydrocyclopenta[b]pyran
derivatives. J. Chem. Soc. Perkin Trans. 1 2002, 2343–2346; (d) Yavari, I.; Djahaniani,
H. One-step synthesis of substituted 4,7-bis[alkyl(aryl)imino]-3-oxa-6-thia-1-azaspiro[4.4]-
nona-1,8-dienes. Tetrahedron Lett. 2005, 46, 7491–7493; (e) Yavari, I.; Hossaini, Z.;
Sabbaghan, M. Synthesis of functionalized 5-imino-2,5-dihydro-furans through the reac-
tion of isocyanides with activated acetylenes in the presence of ethyl bromopyruvate. Mol.
Div. 2006, 10, 479–482; (f) Yavari, I.; Sabbaghan, M.; Hossaini, Z. Efficient synthesis of
functionalized 2,5-dihydrofurans and 1,5-dihydro-2H-pyrrol-2-ones by reaction of isocya-
nides with activated acetylenes in the presence of hexachloroacetone. Monatsh. Chem.
2008, 139, 625.
5. (a) Nair, V.; Unni Vinod, A.; Abhilash, N.; Menon, R. S.; Santhi, V.; Luxmi Varma, R.;
Viji, S.; Methew, S.; Srinivas, R. Multicomponent reactions involving zwitterionic inter-
mediates for the construction of heterocyclic systems: One-pot synthesis of aminofurans
and iminolactones. Tetrahedron 2003, 59, 10279–10286; (b) Nair, V.; Menon, R. S.;
Deepthi, A.; Rema Devi, B.; Biju, A. T. One-pot, four-component reaction of isocyanides,
dimethyl acetylenedicarboxylate, and cyclobutene-1,2-diones: A synthesis of novel spiro-
heterocycles. Tetrahedron lett. 2005, 46, 1337–1339.
6. (a) Asghari, S.; Qandalee, M. A facile one-pot synthesis of amino furans using trans-cinnamal-
dehyde in the presence of nucleophilic isocyanides. Acta. Chem. Slov. 2007, 54, 638–641; (b)
Asghari, S.; Zati, M.; Safiri, S. Chemoselective synthesis of dialkyl 2-(tert-butylamino)-6-
methyl-5-trifluoroacetyl-4H-pyran-3,4-dicarboxylates. Russ. Chem. Bull. Int. Ed. 2004, 53,
1763–1764; (c) Baharfar, R.; Hosseinnia, R.; Baghbanian, S. M. A novel approach to the syn-
thesis of highly functionalized thiophenes using isocyanides catalyzed reaction of acetylenic
esters with 3-mercapto-2-butanone. Lett. In-Org. Chem. 2008, 5, 128–132.
7. (a) Esmaeili, A. A.; Zeudegani, H. Three-component reactions involving zwitterionic
intermediates for the construction of heterocyclic systems: One pot synthesis of highly
functionalized c-iminolactones. Tetrahedron 2005, 61, 4031–4034; (b) Esmaili, A. A.;
Darbanian, M. Reaction between alkyl isocyanides and dialkyl acetylenedicarboxylates
in the presence of N-alkyl isatins: Convenient synthesis of c-spiro-iminolactones.
Tetrahedron 2003, 59, 5545–5548.
8. (a) Shaabani, A.; Yavari, I.; Teimouri, M. B.; Bazgir, A.; Bijanzadeh, H. R. New and
efficient synthesis of dialkyl 2-[1-p-nitrophenyl-2-(alkylamino)-2-oxoethyl]malonates.
Tetrahedron 2001, 57, 1375–1378; (b) Shaabani, A.; Soleimani, E.; Sarvary, A. Synthesis
of fully substituted iminolactones via a three-component condensation of isocyanides
and acetylenic esters with 2-bromo-1-(4-bromophenyl)ethanone. Monatsh. Chem. 2008,
139, 629–632.

2906
S. ASGHARI AND A. K. HABIBI
9. (a) Baharfar, R.; Hosseini, J. The reaction between tert-butyl isocyanide and acetylenic
esters in presence of 2-thenoyltrifluoroacetone: A synthesis of highly functionalised 4H-
pyrans. J. Chem. Res. Syncop. 2003, 616–617; (b) Adib, M.; Mohammadi, B.; Bijanzadeh,
H. R. A novel one-pot, three-component synthesis of dialkyl 5-(alkylamino)-1-aryl-1H-
pyrazole-3,4-dicarboxylates. Synlett. 2008, 20, 3180–3182; (c) Adib, M.; Sayahi, M. H.;
Aali Koloogani, S.; Mirzaei, P. Facile one-pot, three-component synthesis of functiona-
lized pyridylfuran-2-amines. Helv. Chim. Acta 2006, 89, 299–303.
10. (a) Oliaruso, M. A.; Wolf, J. F. In Synthesis of Lactones and Lactams; Wiley: New york,
1993; (b) Avetissyan, A.; Karapetyan, L. The synthesis of new 2-iminoderivatives of 2,5-dihy-
drofurans and their chemical transformations. Synth. Commun. 2009, 39, 7–19; (c)
LarchevGque, M.; Debal, A. A convenient synthesis of c-hydroxy and c-keto nitriles. Synth.
Commun. 1980, 10, 49–57; (d) Avetisyan, A. A.; Karapetyan, L. V. Synthesis of new hetero-
cyclic derivatives of 2-imino-2,5-dihydro-furans and some of their chemical transformations.
Chem. Heterocycl. Comp. 2010, 46, 15–19; (e) Avetisyan, A. A.; Karapetyan, L. V. Synthesis
and some chemical transformations of N-cyclohexyl-2-imino-4-methyl-5,5-pentamethylene-
2,5-dihydrofuran-3-carboxamide. Russ. J. Org. Chem. 2009, 45, 1578–1580; (f) Avetissyan,
A. A.; Tokmadjyan, G. G. Biologically active derivatives of 2-buten- and 3-buten-4-olides.
Chem. J. Arm. 1993, 46, 219–236; (g) Avetissyan, A. A.; Tokmadzhyan, G. G. Chemistry
of Db,c-butenolides. Khim. Geter. Soed. 1987, 6, 723–739.
11. (a) Nair, V.; Vinod, A. V.; Somarajan Nair, J.; Sreekanth, A. R. The reaction of cyclo-
hexyl isocyanide and dimethyl acetylenedicarboxylate with o- and p-quinones: A novel
synthesis of iminolactones. Tetrahedron Lett. 2000, 41, 6675–6679; (b) Shaabani, A.;
Rezayan, A. H.; Ghasemi, S.; Sarvary, A. A mild and efficient method for the synthesis
of 2,5-dihydro-5-imino-2-methylfuran-3,4-dicarboxylates via an isocyanide-based multi-
component reaction. Tetrahedron Lett. 2009, 50, 1456–1458.
12. (a) Hazeri, N.; Maghsoodlou, M. T.; Habibi-Khorassani, S. M.; Marandi, G.;
Khandan-Barani, K.; Ziyaadini, M.; Aminkhani, A. Synthesis of novel 2-pyridyl-substituted
2,5-dihydro-2-imino- and 2-amino-furan derivatives via a three-component condensation of
alkyl isocyanides and acetylenic esters with di-(2-pyridyl)ketone or 2-pyridinecarboxalde-
hyde. Arkivoc 2007, 1, 173–179; (b) Maghsoodlou, M. T.; Habibikhorassani, S. M.; Marandi,
G. Synthesis of 3-hydroxy-2H-iminolactones and 3-hydroxy-2H-pyrrol-2-ones from reaction
between isocyanides and methyl 2-acetylacetoacetate. Arkivoc 2008, 14, 282–288; (c)
Khorassani, S. M.; Ziyaadini, M.; Mardani, G.; Khandan-Barani, K.; Bijanzadeh, H. R.
c-Dispiro-iminolactone synthesis by three-component reaction between alkyl isocyanides
and acetylenic esters with a-dicarbonyl compounds. Arkivoc 2007, 13, 34–40.
13. (a) Shaabani, A.; Farrokhzad, F. [1 þ 4]-Cycloaddition of isocyanides with 3-(1-
hydroxyethylidene)pentane-2,4-dione: A convenient synthesis of iminolactones. J. Chem. Res.
Synop. 1997, 344–345; (b) Bayat, M.; Imanieh, H.; Abbasi, H. Chemoselective and regiospecific
synthesis of iminospiro-c-lactones from maleic anhydride or citraconic anhydride and alkyl iso-
cyanides with dialkyl acetylenedicarboxylates. Helv. Chim. Acta 2010, 93, 757–762.
14. Ugi, I. Isonitrile Chemistry; Academic Press: London, 1971.
15. Domling, A.; Ugi, I. Multicomponent reactions with isocyanides. Angew. Chem. Int. Ed.
Eng. 2000, 39, 3168–3210.
16. Walborsky, H. M.; Persiasamy, M. P. In The Chemistry of Functional Groups; S. Patai and
Z. Rappoport (Eds.); Wiley: New York, 1983; chap 2, p. 835.
17. (a) Baharfar, R.; Hosseini, J. The reaction between tert-butyl isocyanide and acetylenic
esters in presence of 2-thenoyltrifluoroacetone: A synthesis of highly functionalised 4H-
pyrans. J. Chem. Res. Synop. 2003, 616–617; (b) Asghari, S.; Qandalee, M., Bijanzadeh,
H. R. Synthesis of polyfunctional ketenimines and 1-azadienes use of tert-butyl isocyanide
and acetylenic esters in the presence of 3-chloropentane-2,4-dione. J. Chem. Res. Synop.
2006, 233–235.