Monobromomalononitrile: An efficient regioselective mono brominating agent towards active methylene compounds and enamines under mild conditions

Article abstract of DOI:10.1039/c3ra46687f

The potential of monobromomalononitrile (MBM) as a convenient source of cationic bromine in organic bromination reaction has been explored. Studies reveal that MBM can be a good substitute for N-bromosuccinimide (NBS) in various respects. Enamines and act

Full text of DOI:10.1039/c3ra46687f

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Monobromomalononitrile: an efficient
regioselective mono brominating agent towards
active methylene compounds and enamines under
mild conditions†
Cite this: RSC Adv., 2014, 4, 10180
*
Sudipta Pathak, Ashis Kundu and Animesh Pramanik
The potential of monobromomalononitrile (MBM) as a convenient source of cationic bromine in organic
bromination reaction has been explored. Studies reveal that MBM can be a good substitute for N-
bromosuccinimide (NBS) in various respects. Enamines and active methylene compounds bearing
aromatic rings are selectively mono brominated on the vinylic and active methylene group respectively
on reaction with MBM. This methodology has the advantages of easy preparation of MBM, shorter
reaction time and high yields of the product formation. Moreover it provides a metal free green
brominating agent which is more convenient for the pharmaceutical industry. Mono bromination
reaction takes place only on active methylene groups even after addition of excess amount of MBM.
Enamines containing electron withdrawing, electron donating and ortho substituted amines react
smoothly affording only the vinylic mono bromo products in good yields without producing any side
products.
Received 14th November 2013
Accepted 30th January 2014
DOI: 10.1039/c3ra46687f
www.rsc.org/advances
Bromination on organic molecules has been a workhorse in the 1,2-dipyridiniumditribromide-ethane (DPTBE),8h Me4NBr3,8a
eld of organic synthesis because of the commercial signi- 1,8-diazabicyclo[5.4.0]undec-7-ene hydrobromide perbromide
cance of intermediate bromoorganics for the construction of (DBUHBr3),8c and phenyltrimethylammonium tribromide8e are
important natural products, as well as in the production of employed for bromination avoiding the direct use of molecular
intermediates for agrochemicals and pharmaceuticals. As for bromine. Another method involves oxidative bromination using
example, a huge number of commercially important products hydrogen bromide and bromide salts as a bromine source
such as herbicides, pesticides, re retardants, and other new where bromine is generated in situ in the reaction mixture upon
important materials have bromo functionality.1 Formation of oxidation of bromide ions.9–13 The mostly employed bromides
C–C bond using cross-coupling reactions can be employed with and oxidants combinations are H2O2–V2O5–Et4NBr,9d oxone/
these bromides. Therefore, the halide compounds have huge HBr,10b oxone (the active component is potassium monop-
impact on Heck,2 Stille–Suzuki3 and Sonogashira4 and other ersulfate, KHSO5)/NaBr,10a H2O2–HBr,9a–c t-BuOOH–HBr,9b,c
hetero coupling reaction via aromatic functionalization Selectuor®/KBr,12 NaBrO3–NaBr,13 CAN/LiBr,11b and cerium(IV)
process.5 The use of elemental bromine is the traditional
method of bromination. Careful control of the temperature
and rate of bromine addition to avoid undesirable side reac-
tions are the main disadvantages for the use of elemental
bromination.6 Moreover, corrosive and toxic nature of
Table 1 Optimization of reaction conditions for bromination of ace-
tylacetone with MBM
Entry
Solvent (10 ml)
Time (h)
Yield (%)
elemental bromine is
a serious drawback for handling
elemental bromine. Therefore, milder brominating agents are
urgently needed for the bromination on organic molecules.7–13
Various solid organic ammonium tribromides like 2,4-diamino-
1
2
3
4
5
6
7
8
CCl4
CHCl3
Hexane
2
2
2
2
2
2
2
2
2
2
2
0.5
__
__
__
__
__
30
32
25
45
49
70
91
Benzene
Toluene
Methanol
Ethanol
H2O
Tetrahydrofuran
Ethyl acetate
Acetonitrile
DMF
1,3-thiazole
hydrotribromide,8b
Bu4NBr3,8d,e
PyHBr3,8e–g
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata-700 009,
India. E-mail: animesh_in2001@yahoo.co.in; Fax: +91-33-2351-9755; Tel: +91-33-
2484-1647
9
10
11
12
† Electronic supplementary information (ESI) available. CCDC 962394 and
962395. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3ra46687f
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ammonium nitrate (CAN)/KBr.11a In all these reactions the use phenols, amines etc.14d,e It can also brominate double bonds to
of binary solvent systems (an organic solvent and water) is 1,2-dibromo compounds; carbonyl compounds to a-bromi-
necessary for satisfactory result. The most signicant drawback nated compounds;14c active methylene compounds to mon- and
of all these methods is the undesirable oxidation of the sensitive di-brominated compounds14f and enamines to vinylic and allylic
functional groups present in the substrates by the oxidizing brominated compounds.14g Though it is a mild brominating
agents.
agent, it gives various side products on bromination of aromatic
With respect to the above mentioned methodologies, N- compounds14d,e and enamines or active methylene group.14c,g So
bromosuccinimide (NBS) is one of the most potent brominating it is a less selective brominating agent. For bromination of
agents due to its stability and safe and easy handling.14 NBS can enamines containing electron rich aromatic ring, the selectivity
brominate efficiently the activated aromatic compounds like of NBS is lost as it may brominate both the active aromatic ring
Table 2 Scope of bromination on active methylene compounds 1 with MBM
Entry
Substrates (1)
Products (2)
Time (min)
30
Yield (%)
91
Melting point/ref. 16
1
137–139/138–140
2
25
94
168–170/168–170
3
4
25
35
93
89
172–176/174–176
130–132/129
5
6
40
30
86
90
195–197/196
115–117/115–118
7
8
25
35
86
93
180–182/182
190–192/192–194
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and enamines, moreover the latter may also give rise to a is applicable to both cyclic as well as acyclic active methylene
mixture of vinylic and allylic brominated compounds. Herein compounds. It is interesting to note that in presence of
we wish to report a general, efficient and highly selective aromatic ring, bromination takes place only on active methy-
brominating agent for mono bromination of active methylene lene group (1d) even aer addition of excess amount of MBM
compounds and enamines under mild reaction condition.
(2.2 equiv.), conrmed by single crystal X-ray diffraction study
Monobromomalononitrile (MBM)15 is reported in the litera- (Fig. 1). Even the presence of excess amount of MBM (2.2
ture for the syntheses of various important compounds where equiv.), cannot produce a,a-dibromo derivatives. The reaction
it participates mainly in addition reaction with carbonyl stops selectively at mono bromo stage. This result establishes
group,15a–c a,b-unsaturated double bond15a–c and isolated double that the reaction of MBM is very specic for the formation of
bond.15d It is also used for synthesis of biologically important mono bromo derivatives of 1,3-dicarbonyl compounds. Acti-
heterocycles.15e In all the cases malononitrile part of MBM is vated compounds like 5-methyl-2H-pyrazole-3-ol (1g) and 4-
added in the products. To the best of our knowledge, the hydroxycoumarin (1h) are also brominated with MBM to
appropriate reaction condition is not explored as yet for MBM produce 4-bromo-5-methyl-2H-pyrazole-3-ol (2g) and 3-bromo-4-
where it may act solely as a brominating agent. Therefore hydroxycoumarin (2h) respectively in high yields within 30 min
initially an optimization study is carried out with a model at room temperature (Table 2, entries 7 and 8).
reaction between acetylacetone and MBM in various non polar
Subsequently we explore the brominating ability of MBM
solvents to examine whether it gives only the brominated with various substituted phenols (phenol, m-cresol, o-cresol, p-
product or the products from the usual addition reaction with cresol, p-methoxyphenol, o-chlorophenol and m-aminophenol),
carbonyl group and O or C-alkylation reaction of enol substrate. anilines (aniline, m-anicidine, o-chloraniline and p-uo-
When the reaction is carried out in non polar solvents like CCl4, rophenol), methylketone carbonyl compounds (acetophenone,
hexane, benzene and toluene employing 1.2 equivalent of MBM p-chloroacetophenone, p-nitroacetophenone and p-methox-
at room temperature, the reaction does not proceed at all (Table yacetophenone), alkenes (styrene) and alkynes (phenyl-
1, entries 1–5). Literature results show that polar solvent is acetylene). But MBM does not react with all these substrates
necessary to carry out the bromination reaction with NBS on
double bond or active methyelene group. Since MBM is chem-
ically analogous to NBS, various polar solvents are chosen for
bromination (Table 1, entries 6–12). When polar protic solvent
methanol is used as a reaction medium, TLC analysis suggests
the formation of only one product along with substantial
amount of unreacted starting material (Table 1, entry 6). The
Scheme 1 Bromination on active methylene group using MBM.
structure of the isolated product (yield ꢀ 30%) is conrmed by
IR, 1H NMR and 13C NMR spectroscopy and elemental analysis,
which establishes the formation of only the mono brominated
product 3-bromopentane-2,4-dione 2a (Table 2, entry 1). This
result incites us to perform the reaction in various polar
solvents of varying polarities. However when the reaction is
carried out in ethanol or water, the yield of the product 2a is
only 32 and 25% respectively indicating the unsuitability of
protic polar solvent for the reaction (Table 1, entries 7 and 8).
Intriguingly, the yield of the product 2a increases substantially
in aprotic polar solvents in presence of 1.2 equivalent of MBM at
room temperature (Table 1, entries 9–11). Moreover when the
polarity of the employed aprotic solvents increases in the order
THF, EtOAc and CH3CN the yield of 2a also increases from 45%
to 70% (Table 1, entries 9–11). Gratifyingly, the maximum yield
Fig. 1 The crystal structure of 2d, the mono brominated product of
acetoacetanilide (1d).
of the product 2a is obtained in aprotic polar solvent DMF,
nearly 91%, employing 1.2 equivalent of MBM at room
temperature (Table 1, entry 12).
Aer having prepared 2a successfully, we decide to explore
the scope and generality of this reaction with various 1,3-
dicarbonyl compounds including 1,3-cyclohexanedione (1b),
5,5-dimethylcyclohexane-1,3-dione (1c), acetoacetanilide (1d),
barbituric acid (1e) and 1,3-indandione (1f) to furnish expected
mono bromo-compound 2 in the optimized reaction conditions
(Scheme 1 and Table 2). The results show that the reactions can
produce the mono brominated products 2a–f in high yields
Scheme 2 Bromination on enamines of 1,3-cyclohexanedione and
within 25–40 min at room temperature (Table 2). This reaction dimedone.
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Table 3 Possibility of bromination on enemines 3 with MBM
Entry
1
Substrate
Product
Time (min)
Yield (%)
Observed/ref. melting point17c (ꢁC)
30
94
128–130
2
3
4
35
37
40
92
91
89
96–98
131–133
122–124
5
6
7
8
40
28
25
25
86
92
91
95
158–160
140–142
176–178
179–181/177–179
9
25
30
94
94
89–91/90–92
10
183–185/186–188
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Table 3 (Contd.)
Entry
Substrate
Product
Time (min)
Yield (%)
90
Observed/ref. melting point17c (ꢁC)
11
36
156–158/158–159
12
13
14
15
39
42
45
30
88
86
85
90
178–180
156–158
146–148
128–130
16
35
92
188–190
even when the reactions are carried out at high temperature room temperature, only the vinylic brominated enamine is
using excess amount of MBM (2.2 equivalent) and allowing a formed in good yield (Scheme 2 and Table 3). Then this simple
prolonged reaction time. It is interesting to note that even procedure has been applied to different enamines of 1,3-cyclo-
activated aromatic ring like m-aminophenol does not produce hexandione and dimedone. As evident from Table 3, several
any brominated product. Since phenoxide ion is more reactive enamines 3 containing electron withdrawing and electron
than phenol, the above reaction has also been carried out in donating amines react smoothly with MBM affording the vinylic
basic medium employing aqueous sodium hydroxide and mono bromo products 4 in good yields without producing any
organic base triethyl amine separately. But in both the cases the side products. The enamines 3f, 3g, 3o and 3p although contain
brominated compounds are not formed. In fact MBM is electronically rich aromatic ring; bromination takes place only
destroyed in aqueous sodium hydroxide solution. The results at the vinylic position. Even in presence of ortho substituted
demonstrate that MBM does not react with aromatic amine as in the case of enamines 3e and 3n, the formation of
compounds even under drastic condition.
vinylic brominated product is not hindered due to the steric
There are several reports of bromination of enamino reason. The structures of all the mono brominated products were
compounds by using Br2/CCl4, NBS/MeOH, BrCN and NBS/ determined by matching the reported melting points and also the
montmorillonite (K-10).17 All these procedures give low to spectroscopic data. Furthermore, the formation of product 4a is
moderate yield of the vinylic brominated enamines aer pro- conrmed by X-ray crystallographic analysis (Fig. 2).
longed reaction time.17a,c Moreover some of these methods have
The formation of brominated compounds 4 from enamines
serious drawbacks of formation of side products like allylic 3 can be explained on the basis of the proposed mechanism
brominated enamines.17a,b But when the enamine of 1,3-cyclo- depicted in Scheme 3.18 At rst, the activated double bond of
hexandione and benzylamine is treated with MBM in DMF at enamine attacks the electropositive bromine of MBM to
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Table
4
Comparative studies with different brominating agents
towards active methylene compounds and enamines
MBMa
NBSa
Substrate
Product
Yield (%)
Product
Yield (%)
1a
1b
1c
1d
1e
1f
1g
1h
3b
3c
3e
3f
3g
3k
3l
3n
3o
3p
2a
2b
2c
2d
2e
2f
2g
2h
4b
4c
4e
4f
4g
4k
4l
4n
4o
4p
91
94
93
89
86
90
86
93
92
91
86
92
91
90
88
85
90
92
2a
91
65
74
53
66
69
75
89
89
90
80
80
73
89
85
75
60
60
2bb
2cb
2db
2eb
2fb
2gb
2h
4b
Fig. 2 The crystal structure of 4a, the mono brominated product of
3a.
4c
4e
4fb
4gb
4k
4l
4n
4ob
4pb
Scheme 3 Plausible mechanism for bromination of enamines 3 by
MBM.
a
Reactions are carried out in DMF medium at room temperature with
b
1.2 equivalent brominating agent with respect to substrate. Mixture
of products obtained.
generate bromo intermediate 5 and malononitrate anion.
Finally malononitrate anion abstracts proton from cationic
intermediate 5 to form mono bromo emino derivatives 4. Since
the reaction passes through an ionic path way, a polar medium
is necessary for the reaction. The poor product formation in
protic polar solvents e.g. methanol, ethanol and water may be
due to the protonation of malononitrate anion from solvents
(Table 1, entries 6–8).
In order to assess the relative efficiency and selectivity of NBS
and MBM in mono bromination of active methylene
compounds and enamines some representative studies have
been carried out under similar reaction conditions (Table 4). In
case of NBS the formation of mixture of products is observed by
TLC and NMR analysis and the results are included in Table 4.
The results clearly demonstrate that NBS is less selective in
bromination producing mixture of brominated products. On
the other hand MBM produces only mono brominated product
without formation of any side products. Therefore MBM is a
superior mono brominating agent towards active methylene
compounds and enamines.19
Experimental section
General information
Starting materials and solvents are purchased from commercial
suppliers and used without further purication. Melting points
are determined in open capillary tubes and are uncorrected. IR
spectra are recorded on a Perkin-Elmer 782 spectrophotometer.
1H (300 MHz) and 13C NMR (75 MHz) spectra are recorded on
Bruker 300 MHz instrument in [D6]DMSO or in CDCl3.
Elemental analyses (C, H and N) are performed using Perkin-
Elmer 240C elemental analyzer. The X-ray diffraction data for
crystallized compounds are collected with MoKa radiation at
296 K using the Bruker APEX-II CCD System. The crystals are
positioned at 50 mm from the CCD. Frames are measured with
a counting time of 5 s. Data analyses are carried out with the
Bruker APEX2 and Bruker SAINT program. The structures are
solved using direct methods with the Shelxs 97 program (Shel-
drick, 2008).
In conclusion, we have successfully developed a set of mild
reaction conditions for MBM where it can act as a selective and
efficient mono brominating agent. The efficacy of the method-
General procedure for the preparation of
monobromomalononitrile (MBM)
ology lies in the bromination of 1,3-dicarbonyl compounds and A solution of malononitrile (3.3 g, 0.05 mol) in water (10 ml) and
enamines containing activated aromatic rings. This method- 2-propanol (10 ml) was cooled in an ice cold water-bath at 20 ꢁC.
ology has the advantages of easy preparation of MBM, shorter Then bromine (8.0 g, 0.05 mol) was added slowly into the
reaction time and high yields of the product formation. The less solution with constant stirring, during which the temperature
reactive MBM can be a very good substitute for relatively more of the reaction mixture will rise and the colour of bromine will
reactive NBS in regioselective mono bromination of 1,3-dicar- disappear immediately. Aer the addition of bromine, the
bonyl compounds and enamines. Moreover the application of reaction mixture was stirred at room temperature for 15 min
ꢁ
this metal free organo brominating agent is environmental and le at 0 C for 10 h. The solid monobromomalononitrile
friendly and can be considered as a green reagent within the was precipitated out from the reaction mixture and ltered off
domain of Green Chemistry principles.
through suction.
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CDCl3) dC 188.2, 156.8, 135.9, 132.5, 129.6, 127.0, 97.3, 50.6,
41.4, 32.8, 27.9.
General procedure for the preparation of 2a–h and 4a–p
The compounds 1a–h or 3a–p (1.0 mmol) were dissolved in
dimethylformamide (5 ml) at room temperature. Then mono-
bromomalononitrile (00.174 g, 1.2 mmol) was added and the
resulting mixture was stirred at room temperature for 25–45
min (as mentioned in Table 2). Then the reaction mixture was
poured into cold water and extracted with ethylacetate. Ethyl-
acetate was removed under reduced pressure to get a gummy
mass which was puried by column chromatography on silica
gel using ethylacetate/hexane to obtain pure 2a–h and 4a–p.
2-Bromo-3-oxo-N-phenylbutyramide (2d): IR (KBr) 3238, 1738
cmꢂ1; 1H NMR (300 MHz, CDCl3) dH 8.44 (br s, 1H), 7.52 (d, J ¼
7.5 Hz, 2H), 7.35 (t, J ¼ 8.4 Hz, 2H), 7.17 (t, J ¼ 6.3 Hz, 1H), 4.88
(s, 1H), 2.48 (s, 3H); 13C NMR (75 MHz, CDCl3) dC 198.1, 161.7,
136.7, 129.1, 125.4, 120.1, 49.5, 27.3.
2-Bromo-3-(4-uorophenylamino)-5,5-dimethylcyclohex-2-
enone (4m): IR (KBr) 3205, 1622 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) dH 7.27–7.14 (m, 4H), 2.42 (s, 2H), 2.23 (s, 2H), 1.04 (s,
6H); 13C NMR (75 MHz, CDCl3) dC 188.1, 163.0, 157.4, 133.3,
128.1, 128.0, 116.6, 116.3, 96.7, 50.7, 41.4, 32.7, 27.9.
2-Bromo-3-(2-bromophenylamino)-5,5-dimethylcyclohex-2-
enone (4n): IR (KBr) 3201, 1615 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) dH 7.69 (d, J ¼ 7.8 Hz, 1H), 7.36 (t, J ¼ 7.5 Hz, 1H), 7.26–
7.21 (m, 2H), 2.44 (s, 2H), 2.31 (s, 2H), 1.05 (s, 6H); 13C NMR (75
MHz, CDCl3) dC 188.3, 156.8, 136.3, 133.5, 128.4, 128.3, 127.9,
121.6, 97.3, 50.7, 41.3, 32.7, 28.0.
2-Bromo-3-(4-methoxyphenylamino)-5,5-dimethylcyclohex-2-
enone (4o): IR (KBr) 3212, 1607 cmꢂ1 1H NMR (300 MHz,
;
CDCl3) dH 7.27 (br s, 1H), 7.08 (d, J ¼ 7.2 Hz, 2H), 6.90 (d, J ¼ 7.2
3-Benzylamino-2-bromocyclohex-2-enone (4a): IR (KBr) 3180,
Hz, 2H), 3.87 (s, 3H), 2.42 (s, 2H), 2.32 (s, 2H), 0.96 (s, 6H); 13
C
1
1570 cmꢂ1; H NMR (300 MHz, CDCl3) dH 7.42–7.24 (m, 5H),
NMR (75 MHz, CDCl3) dC 188.0, 158.7, 158.2, 130.0, 127.9, 114.7,
95.9, 55.5, 50.7, 41.4, 32.5, 28.0.
6.08 (br s, 1H), 4.52 (d, J ¼ 6 Hz, 2H), 2.59–2.48 (m, 4H), 2.00–
1.94 (m, 2H); 13C NMR (75 MHz, CDCl3) dC 187.8, 161.1, 137.0,
129.1, 128.0, 126.7, 96.5, 47.3, 36.7, 26.7, 20.8.
2-Bromo-3-(3-hydroxyphenylamino)-5,5-dimethylcyclohex-2-
enone (4p): IR (KBr) 3330, 3217, 1601 cmꢂ1; 1H NMR (300 MHz,
D6-DMSO) dH 9.65 (br s, 1H), 8.60 (br s, 1H), 7.18 (t, J ¼ 6.6 Hz,
2-Bromo-3-phenylaminocyclohex-2-enone (4b): IR (KBr)
1
3195, 1590 cmꢂ1; H NMR (300 MHz, CDCl3) dH 7.43–7.27 (m,
1H), 6.92–6.60 (m, 3H), 2.43 (s, 2H), 2.29 (s, 2H), 0.93 (s, 6H); 13
C
3H), 7.16 (d, J ¼ 7.5 Hz, 2H), 2.59–2.57 (m, 4H), 196–1.92 (m,
2H); 13C NMR (75 MHz, CDCl3) dC 188.5, 159.4, 137.3, 129.5,
126.9, 125.8, 97.9, 37.2, 28.2, 21.4.
NMR (75 MHz, D6-DMSO) dC 187.2, 158.6, 158.3, 139.6, 130.1,
117.4, 113.8, 113.1, 95.1, 50.8, 42.0, 32.8, 27.7.
2-Bromo-3-(4-chlorophenylamino)-cyclohex-2-enone (4c): IR
(KBr) 3202, 1610 cmꢂ1; 1H NMR (300 MHz, CDCl3) dH 7.39–7.28
(m, 2H), 7.12–7.10 (m, 2H), 2.59–2.47 (m, 4H), 1.99–1.94 (m,
2H); 13C NMR (75 MHz, CDCl3) dC 188.56, 158.81, 135.8, 132.5,
129.5, 126.9, 98.4, 37.0, 28.0, 21.3.
2-Bromo-3-(4-uorophenylamino)-cyclohex-2-enone (4d): IR
(KBr) 3233, 1633 cmꢂ1; 1H NMR (300 MHz, CDCl3) dH 7.30 (d, J ¼
1.8 Hz, 1H), 7.21–7.08 (m, 4H), 2.57–2.48 (m, 4H), 1.99–1.91 (m,
2H); 13C NMR (75 MHz, CDCl3) dC 188.6, 163.0, 159.7, 133.3,
128.2, 128.1, 116.5, 116.2, 97.8, 37.1, 28.1, 21.3.
Acknowledgements
S.P. and A.K. thank CSIR and UGC New Delhi, India, for offering
Senior Research Fellowship respectively. The nancial assis-
tance of CSIR, New Delhi is gratefully acknowledged
[Major Research Project, no. 02(0007)/11/EMR-II]. Crystallog-
raphy was performed at the DST-FIST, India-funded Single
Crystal Diffractometer Facility at the Department of Chemistry,
University of Calcutta.
2-Bromo-3-(4-bromophenylamino)-cyclohex-2-enone (4e): IR
(KBr) 3185, 1590 cmꢂ1; 1H NMR (300 MHz, CDCl3) dH 7.67 (d, J ¼
7.8 Hz, 1H), 7.48–7.16 (m, 3H), 2.60–2.49 (m, 4H), 2.02–1.96 (m,
2H); 13C NMR (75 MHz, CDCl3) dC 188.8, 158.8, 136.2, 133.5,
128.3, 128.3, 127.5, 121.2, 99.1, 37.1, 28.0, 21.4.
2-Bromo-3-(4-methoxyphenylamino)-cyclohex-2-enone (4f):
IR (KBr) 3196, 1601 cmꢂ1; 1H NMR (300 MHz, CDCl3) dH 7.28 (br
s, 1H), 7.10 (d, J ¼ 8.7 Hz, 2H), 6.92 (d, J ¼ 9 Hz, 2H), 3.85 (s, 3H),
2.5 (t, J ¼ 6.3 Hz, 2H), 2.47 (t, J ¼ 6 Hz, 2H), 1.96–1.88 (m, 2H);
13C NMR (75 MHz, CDCl3) dC 188.5, 160.3, 158.7, 129.9, 127.8,
114.6, 97.0, 55.5, 37.1, 28.1, 21.3.
2-Bromo-3-(4-hydroxyphenylamino)-cyclohex-2-enone (4g):
IR (KBr) 3350, 3215, 1575 cmꢂ1; 1H NMR (300 MHz, D6-DMSO)
dH 9.62 (s, 1H), 8.56 (s, 1H), 7.16 (t, J ¼ 7.8 Hz, 1H), 6.68–6.61 (m,
3H), 2.50–2.34 (m, 4H), 1.80–1.78 (m, 2H); 13C NMR (75 MHz,
D6-DMSO) dC 187.6, 160.8, 158.2, 139.6, 130.0, 117.4, 113.8,
113.8, 96.2, 37.4, 29.0, 21.7.
2-Bromo-3-(4-chlorophenylamino)-5,5-dimethylcyclohex-2-
enone (4l): IR (KBr) 3185, 1572 cmꢂ1; 1H NMR (300 MHz, CDCl3)
dH 7.39 (d, J ¼ 8.4 Hz, 2H), 7.28 (br s, 1H), 7.10 (d, J ¼ 8.7 Hz,
2H), 2.43 (s, 2H), 2.38 (s, 2H), 1.04 (s, 6H); 13C NMR (75 MHz,
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