JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39
RESEARCH PAPER 509
SEPTEMBER, 509–514
Diastereoselective and one-pot synthesis of highly substituted cyclohexenones using Claisen–Schmidt condensation and Michael addition Mir Rasul Mousavia,b*, Hadigheh Ghararic, Malek Taher Maghsoodloua, Nourallah Hazeria, Parvaneh Dastorania, Ruben Soria-Martínezd and Santiago García-Grandad Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, PO Box 98135-674 Zahedan, Iran Faculty of Science, Payame Nour University of Khoy, Khoy, Iran c Sina 24 hour Clinic, Marand, Iran d Department of Physical and Analytical Chemistry, University of Oviedo-CINN, Oviedo, Spain a
b
A high efficient and convenient one-pot three-component diastreoselective synthesis of polysubstituted cyclohexenones in excellent yields has been developed through Michael addition and Claisen–Schmidt condensation of aldehydes and acetophenone with 3-oxo-N phenylbutanamide using piperidine as an effective reagent under mild conditions within sort reaction time without using any previous activation. Keywords: highly substituted cyclohexenone, Claisen–Schmidt condensation, Michael addition, diastreoselective, multi-component reaction Increasingly, efforts have been made to synthesise complex molecules in a single operation rapidly and without the isolation of intermediates.1 Multi-component reactions (MCRs) are useful tools for the synthesis of innovative and complex scaffolds according to a convergent approach, providing a molecule that contains fragments derived from all the building blocks employed in the MCR condensation in a single synthetic step. As they can be followed by postcondensation transformations exploiting additional functional groups present in the building blocks which are inert during the MCR step, they are particularly suitable for diversityoriented synthesis.2 The Michael addition reaction is widely recognised as one of the key reactions for carbon–carbon bond formation in organic reactions.3,4 One of the important precursors in Michael reaction is α,β-unsaturated compound such as a chalcone. Chalcones are aromatic ketones that form the central core in a variety of important biological compounds. They are an important class of compounds due to their various properties and applications.5-15 Extended conjugation and a high degree of electrophilicity associated with this moiety play an important role in the activity of this class of compounds.16 The conjugate addition of a stabilised carbanion to α,β-unsaturated carbonyl compounds is one of the fundamental C–C bond-forming reactions in organic synthesis.17-19 Hence, an important feature of chalcones is their ability to act as activated unsaturated systems in conjugated additions of carbanions as a nucleophile in the presence of suitable basic catalysts.20,21 For example, Michael addition of 1,3-dicarbonyl compounds such as acetoacetic esters to chalcone lead to the formation 4,6-diaryl-2-oxo-cyclohex-3ene-1-carboxylate derivatives.22 They are also used as versatile starting materials for the synthesis of a variety of N and O
containing heterocyclic compounds.5,23-27 Cyclohexenone derivatives are well known molecules used for the treatment of inflammation and autoimmune diseases.27 Also, cyclohexenone derivatives and indazoles exhibit a variety of pharmacological properties such as antitumour, tyrosine kinases inhibitor, antipyretic, antiasthametic, antiviral, anti-bacterial, antifungal, anti-cancer and anti-tubercular activity.28-33 Due to their potential therapeutic applications in a wide range of human diseases, we are interested in developing a concise methodology for constructing combinatorial libraries of derivatives of 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamide derivatives. The present study is a continuation of our previous efforts34 that aimed to locate novel synthetic lead compound(s) for development as important synthones and medicinal intermediates. We now report an efficient, convenient and facile method for the condensation of acetoacetanilide (1) with acetophenone (2) and aromatic aldehydes (3) leading to the corresponding 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides (4) promoted by piperidine as a Lewis base (Scheme 1).
Results and discussion We first chose a one-pot three component reaction of acetoacetanilide (1 mmol) and acetophenone (1 mmol) with 4-nitrobenzaldehyde (1 mmol) in the presence of 10 mol% piperidine as a model reaction in ethanol at ambient temperature. Next, the influence of the three experimental parameters (solvent, catalyst load, and temperature) was studied using piperidine as the most efficient catalyst. Hence, different solvents i.e. MeCN, H2O, EtOAc, CH2Cl2 and EtOH were used for the synthesis of cyclohexenones to test for their efficacy (Table 1). As shown in Table 1, variation of the solvents
R O
H N
CH3
O O 1
CHO
EtOH, 50 °C
R 2
O
Piperidine (20 mol%)
3
O 4a-j
Scheme 1 Metal-free synthesis of highly substituted cyclohexenones using piperidine. * Correspondent. E-mail:
[email protected]
N H
510 JOURNAL OF CHEMICAL RESEARCH 2015 had a pronounced effect on reaction rate and yield (entries 2–6). Most notably, when the model reaction was performed in ethanol, a nearly complete conversion was achieved in a shorter time (entry 6). Therefore, EtOH proved to be the best for synthesising the corresponding compounds. After choosing the appropriate solvent, a series of comparative experiments were performed to compare the effectiveness of different amounts of piperidine in the formation of 6-(4-nitrophenyl)2-oxo-N,4-diphenylcyclohex-3-enecarboxamide 4b (entries 6–12). As illustrated in Table 1, the best result was obtained with 20 mol% of piperdine (entry 9). Remarkably, the reaction did not progress even after 48 h in the absence of catalyst (entry 1). Also, the reaction lead to the desired product in moderate yield under solvent-free conditions (Table 1, entry 13). That might have been due to the lack of effective interaction between reactants and the catalyst in the absence of the solvent. Using these simplified reaction conditions, the variation of reaction temperature was evaluated. Hence, the effect of temperature was studied by carrying out the model reaction at
Table 1 Optimisation of conditions for the synthesis of poly substituted cyclohexenone 4b in the presence of different amounts of catalyst and various solvents at room temperature NO2 O
H N O O 1
NO2 3
2
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 a
CHO CH3
Catalyst/mol% 10 10 10 10 10 5 15 20 25 30 40 20
O
Piperidine (mol%) solvent, r.t
O
N H
4b
Solvent EtOH MeCN H2 O EtOAc CH2Cl2 EtOH EtOH EtOH EtOH EtOH EtOH EtOH -
Time/h 48 18 20 18 24 15 20 12 10 14 15 15 20
Yield/%a – 75 45 63 68 82 78 84 88 87 86 85 55
different temperatures (room temperature, 30 ºC, 40 ºC, 50 ºC and 60 ºC) in 5 mL ethanol as the most appropriate medium, and the best results were obtained at 50 ºC, 95% was generated (entry 3, Table 2); the higher temperature did not increase the reaction yield (entry 4, Table 3). Therefore, the shorter reaction time and higher yield were observed at 50 ºC. Therefore, 20 mol% of catalyst, 5 mL of ethanol and 50 ºC were selected as the standard reaction conditions. The optimised conditions were used to construct a variety of 2-oxo-N,4,6triarylcyclohex-3-enecarboxamides (4a–j). Under the optimised reaction conditions, to demonstrate the generality and high potency of this methodology, various substituted aldehydes were reacted with acetoacetanilide and acetophenone which gave excellent yields of the desired polysubstituted cyclohexenones. As shown in Table 3, the electron withdrawing or donating group on the phenyl rings did not affect the reaction. The procedure is very simple: 1 equiv. of aldehyde was mixed with 1 equiv. of acetophenone and 1 equiv. of acetoacetanilide in 5 mL ethanol in a vial equipped and stirred at 50 ºC in the presence of 20 mol% of piperidine for 9–25 h. After completion of the reaction, solid products were washed with ethanol to remove organic impurities. The results are summarised in Table 3. The notable advantages of this method are the easy isolation of products by simple filtration, there is no need for column chromatography nor further purification. All known products were characterised by comparison of the melting points and the analytical data (IR, 1H NMR) with those reported in our previous research.34 The constitution of the synthesised product has been characterised by using elemental analysis, IR spectroscopy and 1 H and 13C NMR spectroscopy and further supported by mass spectroscopy. For example, the IR spectra of 4i revealed that a sharp absorption band at 3298 cm-1 was due to NH while two sharp strong absorption bands were noticed at approximately 1666 and 1649 cm-1 and were assigned to the carbonyl groups. The 1H and 13C NMR, and mass spectra substantiated the results of the IR analysis. The mass spectrum of 4i displayed molecular ion peak (M+) at m/z = 367, which consistent with the suggested structure. The 1H NMR spectrum of compound 4i, exhibited two doublets of doublets at 3.04 ppm (J = 18.0, 4.8 Hz) and 3.13 ppm (J = 18.0, 11.2 Hz) for methylene protons of cyclohexenone ring (H-5, H’-5) respectively. One of the methine protons of
Table 3 Synthesis of 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides using piperidine R
Pure isolated produc yield. H N
Table 2 Synthesis of 6-(4-nitrophenyl)-2-oxo-N,4-diphenylcyclohex-3enecarboxamide 4b in ethanol at different temperatures.a O
H N
CH3
O O 1
2
Entry 1 2 3 4
CHO
NO2 3
T/°C 30 40 50 60
1
O
Piperidine (20 mol%) EtOH, T °C
O
Entry 1 2 3 4 5 6 7 8 9 10
N H
4b
Time/h 15 10 9 9
Yield/%b 88 91 95 93
All the reactions were carried out using acetoacetanilide (1 mmol), acetophenone (1 mmol) and 4-nitro benzaldehyd (1 mmol) in the presence of 20 mol% piperidine in EtOH (5 mL) at different temperatures. b Pure isolated product yield.
CH3
O O
NO2
a
a b
CHO
O
Product 4a 4b 4c 4d 4e 4f 4g 4h 4i 4j
EtOH, 50 °C
R 2
R 4-OMe 4-NO2 2-Cl 3-NO2 2-Br 3-Cl 4-CN 2,6-Cl2 H 4-Br
O
Piperidine (20 mol%)
3
Time/h 20 9 20 15 10 25 25 15 12 9
Pure isolated product yield. New compounds synthesised in this work.
O 4a-i
Yield/%a 94 95 96 92 93 95 90 89 97 95
M.p./°C 218–220 203–204 223–225 202–204 219–221 189–191 224–226 186–188 256–258 220–222
Lit. m.p./°Cref. 217–219 34 202–204 34 224–226 34 200–222 34 220–202 34 187–189 34 224–226 34 188–190 34 Newb Newb
N H
JOURNAL OF CHEMICAL RESEARCH 2015 511 cyclohexenone ring (H-6) was observed as a triplet of doublets at δ 3.83 ppm (J = 12.8, and 4.8 Hz) and another methine proton (H-1) appeared as a doublet at δ 3.98 ppm (J = 13.2 Hz). The vinyl proton (H-3) was observed as a doublet at 6.58 ppm (J = 1.2 Hz). The aromatic protons resonance observed as triplets and multiplets at δ 7.00–7.73 ppm. The NH proton was observed at δ 10.04 ppm as a singlet, which indicated intramolecular hydrogen bond formation with the vicinal carbonyl group on cyclohexenone ring. The 13C NMR spectrum of compound 4i showed 19 distinct resonances consistent with the cyclohexenone structure. According to the structure of 4i, it should contain 25 carbons in a 13C NMR spectrum. However, due to the same carbons of (C-3, C-5), (C-2, C-6) and C-4 in the aromatic rings in the structure of 4i, on the 13C NMR spectrum, one peak is observed for each of the pairs. In 13C NMR spectrum of this compound, the C-6 carbon was observed at δ 36.0 ppm and C-5 was exhibited at δ 43.4 ppm. The C-1, C-3 and C-4 carbons were observed at δ 59.9, 127.3 and 159.4 ppm, respectively. The aromatic carbons were exhibited at δ 119.4–142.6 ppm. Also, the carbon from the carbonyl of the amide group was evident at δ 167.8 ppm. In addition, the carbon of carbonyl of conjugated double bond C=C system (C-2), was observed at 195.9 ppm. Furthermore, the structure of the cyclohexenone 4 was further confirmed by single X-ray crystallography. The cyclohexenone molecule crystallised as the monohydrate in monoclinic group with a P21/c space group, the asymmetric unit is shown in Fig. 1 (selected bond length, bond angles and torsion angles for compound 4e are contained in CCDC no. 1416411; these data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif ). The bond lengths and angles in the molecule are within normal ranges, the molecular conformation can be described using three dihedral angles between aromatic rings. In the crystal, the dihedral angles between the least-square planes through the Cg1 (C1–C6) and Cg2 (C20–C25) are 112.95º (2), and the distance between them is 6.26(1) Å. Between Cg1 and Cg3 (C13–C18) is 109.34 º (4) and the distance between centroids is 7.36(6) Å. The dihedral angle between Cg2 and Cg3 is 90.09º (3) and the distance between them is 11.096(4) Å.
Fig. 1 ORTEP representation, drawn at 50% probability level of the X-ray structure of cyclohexenone 4e.
The average distance C=C in the centroids are 1.381 Å, 1.380 Å and 1.381 Å for Cg1, Cg2 and Cg3 respectively. The carbonyl groups present in the molecule have 1.216(1) Å and 1.221(3) Å for C9–O2, and C19–O1 respectively, which is very close to a formal C=O bond length (1.21 Å). The difference in the distance of C–N bond length of C19–N1 due to the conjugation, is an amide so there is a nitrogen atom in Å to the carbonyl group which, with this lone pair of electrons, may form a resonant structure. The bond C19–N1 is 1.345(3) Å, this value is intermediate between a single (1.47 Å) and double (1.28 Å) bond. In the crystal packing the water molecule is involved in strong O–H···O intermolecular hydrogen bonds (Fig. 2). The values obtained in the X-ray experiment are described in Table 4. Based on the observations, the obtained results and the previous report34 on the catalytic synthesis of polyfunctionalised cyclohexenone derivatives, we propose a mechanism of Claisen– Schmidt condensation and Michael addition as depicted below (Scheme 2). This reaction may proceed via Claisen–Schmidt condensation for the formation of chalcones after the loss of a water molecule. This condensation for the synthesis of chalcones is very attractive since it specifically generates the trans (E)isomer that in this form is stable.35 Therefore, in this research, the reaction of acetophenone 2 with different arylaldehydes 3 in the presence of catalytic amount of 20 mol% piperidine afforded the desired chalcone 5 after the loss of a water molecule. Subsequently, Michael addition of chalcone with acetoacetanilide 1 in the presence of piperidine followed by internal Claisen condensation give 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides 4 by the loss of a water molecule.
Table 4 Hydrogen bonds for cyclohexenone 4e D–H···A N1–H1···O3a O3–H3A···O2b O3–H3B···O1c
d(D–H)(Å) 0.86(1) 0.85 0.85(2)
d(A···H) (Å) 2.04(3) 2.00(1) 1.96(1)
d(D···A)* (Å) 2.897(3) 2.828(4) 2.880(1)
Symmetry code a x , –1+y, z; b1–x ,1–y,z; c x , y, z
Fig. 2 Hydrogen bonds present in the packing.
D–H···A(º) 175(2) 166(3) 172(1)
512 JOURNAL OF CHEMICAL RESEARCH 2015
HH H N O O 1 O
Piperidine -H
CHO R
6
O
Michel addition O 7
O
Claisen-Schmidt Piperidine
3
R
O O
+
CH3 2
H N
R 5 (Chalcone)
-H2O
N H
-H+
Piperidine
R
O
R O O
O
Claisen-Schmidt
N H
-H2O
4 (Cyclohexenone)
O
O
N H
8
Scheme 2 Suggested mechanism for the formation of cyclohexenone derivatives 4.
In summary, we have demonstrated that the one-pot, threecomponent reaction between acetoacetanilide (1), acetophenone (2) and aromatic aldehydes (3) in the presence of piperidine provides a simple, mild, efficient and transition metal-free method for the preparation of 2-oxo-N,4,6-triarylcyclohex-3enecarboxamides of potential synthetic and pharmacological interest. The products were formed in good yields on mixing the readily available substrates in ethanol as the solvent. Fairly high yields of the products, the ready availability of the starting materials, the simplicity of the reaction, mild conditions and no need for column chromatography are the main advantages of this method. Also the protocol does not need complex nor expensive catalysis.
Experimental Melting points and IR spectra of all compounds were obtained on an Electrothermal 9100 apparatus and a JASCO FT/IR-460 plus spectrometer, respectively. 1H and 13C NMR spectra of compounds were recorded on a Bruker DRX-400 Avance instrument with DMSO or CDCl3 as the solvent with TMS as the internal standard at 400 and 100 MHz respectively. Elemental analyses for C, H, and N for the new compounds were performed using a Heraeus CHN-O-Rapid analyser. The mass spectra for the new compounds were recorded on an Agilent Technology (HP) mass spectrometer, operating at an ionisation potential of 70 eV. All reagents were purchased from Merck (Darmstadt, Germany), Acros (Geel, Belgium) and Fluka (Buchs, Switzerland), and used without further purification. Synthesis of 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides; general procedure A mixture of arylaldehyde (1 mmol), acetophenone (1 mmol), and piperidine (20 mol%) was stirred in EtOH (98%, 5 mL ) at room temperature for 10 min, and then acetoacetanilide (1 mmol) was added. The resulting mixture was stirred at 50 °C for the appropriate time as indicated in Table 3. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was chilled to room temperature. The products were precipitated from the reaction mixtures, filtered off and washed EtOH (3×2 mL) to give pure product. The pure products were characterised by conventional spectroscopic methods.
(1S,6 R) - 6 - (4-Nitrophenyl) -2- oxo-N,4- diphenylcyclohex-3enecarboxamide (4b): Pale yellow solid; yield 95%; m.p. 203–204 ºC. 1 H NMR (400 MHz, CDCl3): 3.05 (dd, J = 18.0, 8.4 Hz, 1H, H-5), 3.33 (dd, J = 18.0, 4.8 Hz, 1H, H’-5), 3.76 (d, J = 9.2 Hz, 1H, H-1), 4.27 (m, 1H, H-6), 6.58 (s, 1H, H-3), 7.09 (t, J = 7.2 Hz, 1H, ArH), 7.27 (t, J = 8.0 Hz, 2H, ArH), 7.39–7.48 (m, 5H, ArH), 7.49–7.55 (m, 4H, ArH), 8.16(d, J = 8.4 Hz, 2H, ArH), 8.32 (s, 1H, NH). (1S,6 R) - 6 - (3-Nitrophenyl) -2- oxo-N,4- diphenylcyclohex-3enecarboxamide (4d): Pale yellow solid; yield 92%; m.p. 202–204 ºC. 1 H NMR (400 MHz, CDCl3): 3.08 (dd, J = 8.4, 18.0 Hz, 1H, H-5), 3.38 (dd, J = 18.2, 4.8 Hz, 1H, H’-5), 3.76 (d, J = 8.8 Hz, 1H, H-1), 4.32 (dd, J = 13.1, 8.8 Hz, 1H, H-6), 6.63 (s, 1H, H-3), 7.10 (t, J = 7.6 Hz, 1H, ArH), 7.28 (dd, J = 9.2, 5.2 Hz, 2H, ArH), 7.45 (d, J = 2.4 Hz, 2H, ArH), 7.48 (d, J = 7.2 Hz, 3H, ArH), 7.52 (d, J = 8.0 Hz, 1H, ArH), 7.57 (t, J = 6.4 Hz, 2H, ArH), 7.69 (d, J = 7.6 Hz, 1H, ArH), 8.13 (d, J = 8.4 Hz, 1H, ArH), 8.19(s, 1H, ArH), 8.25 (s, 1H, NH). (1S,6R) - 6- (3-Chlorophenyl) -2-oxo-N,4-diphenylcyclohex-3enecarboxamide (4f): White solid; yield 95%; m.p. 189–191 ºC. 1 H NMR (400 MHz, DMSO): 3.06 (dd, J = 18.0, 4.4 Hz, 1H, H-5), 3.17 (m, 1H, H’-5), 3.86 (td, J = 12.8, 4.4 Hz, 1H, H-6), 3.97 (d, J = 13.2 Hz, 1H, H-1), 6.58 (d, J = 2.0 Hz, 1H, H-3), 7.01 (t, J = 7.2 Hz, 1H, ArH), 7.24 (d, J = 8.4 Hz, 2H, ArH), 7.27 (t, J = 2.0 Hz, 1H, ArH), 7.34 (t, J = 8.0 Hz, 1H, ArH), 7.40 (d, J = 8.0 Hz, 1H, ArH), 7.44–7.47 (m, 5H, ArH), 7.55 (s, 1H, ArH), 7.74 (dd, J = 7.2, 2.4 Hz, 2H, ArH), 10.08 (s, 1H, NH). (1S,6R) -6- (2,6-Dichlorophenyl) -2-oxo-N,4-diphenylcyclohex3-enecarboxamide (4h): White solid; yield 89%; m.p. 186–188 ºC. 1 H NMR (400 MHz, CDCl3): 2.98 (dd, J = 18.0, 4.8 Hz, 1H, H-5), 3.60 (ddd, J = 18.8, 12.0, 2.4 Hz, 1H, H’-5), 4.78 (d, J = 13.2 Hz, 1H, H-1), 5.01 (td, J = 12.4, 4.8 Hz, 1H, H-6), 6.64 (d, J = 2.4 Hz, 1H, H-3), 7.05 (t, J = 7.2 Hz, 1H, ArH), 7.15 (t, J = 8.0 Hz, 1H, ArH), 7.25 (t, J = 8.0 Hz, 2H, ArH), 7.30 (d, J = 8.0 Hz, 1H, ArH), 7.41 (dd, J = 8.0, 1.2 Hz, 1H, ArH), 7.44 (d, J = 3.2 Hz, 2H, ArH), 7.46–7.49 (m, 3H, ArH), 7.59–7.61 (m, 2H, ArH), 8.21 (s, 1H, NH). (1S,6R)-2-Oxo-N,4,6-triphenylcyclohex-3-enecarboxamide (4i): Pale yellow; yield 97%; m.p. 256–258 ºC; IR (KBr) (νmax/cm-1): 3415, 3298, 1666, 1649, 1602, 1551, 1495, 1445, 1370, 1245, 1175, 759, 701, 692, 503; 1H NMR (400 MHz, CDCl3): 3.04 (dd, J = 18.0, 4.8 Hz, 1H, H-5), 3.13 (dd, J = 18.0, 11.2 Hz, 1H, H’-5), 3.83 (td, J = 12.8, 4.8 Hz, 1H, H-6), 3.98 (d, J = 13.2 Hz, 1H, H-1), 6.58 (d, J = 1.2 Hz, 1H, H-3), 7.00 (t, J = 7.2 Hz, 1H, ArH), 7.18–7.25 (m, 3H, ArH), 7.31 (t, J = 7.2
JOURNAL OF CHEMICAL RESEARCH 2015 513 Hz, 2H, ArH), 7.43–7.48 (m, 7H, ArH), 7.73 (t, J = 2.8 Hz, 2H, ArH), 10.04 (s, 1H, NH); 13C NMR (100 MHz, CDCl3): δ 36.0, 43.4, 59.9, 119.4, 120.6, 123.7, 123.9, 126.9, 127.3, 128.0, 128.8, 129.3, 130.9, 137.9, 139.2, 142.6, 159.4, 167.8, 195.9; MS (EI, 70 eV) m/z (%): 367 (M+, 27), 320 (6), 273 (3), 247 (100), 202 (7), 179 (1), 157 (19), 131 (29), 93 (32), 65 (9), 43 (5). Anal. calcd for C25H21NO2: C, 81.72; H, 5.76; N, 3.81; found: C, 81.80; H, 5.83; N, 3.88%. (1S,6R) - 6- (4-Bromophenyl) -2-oxo-N,4-diphenylcyclohex-3enecarboxamide (4j): White solid; yield 95%; m.p. 220–222 ºC; IR (KBr) (νmax/cm-1): 3271, 3141, 1682, 1661, 1604, 1547, 1488, 1445, 1363, 1278, 1261, 1010, 822, 758, 691, 507; 1H NMR (400 MHz, DMSO): 3.01–3.18 (m, 2H, H-5), 3.84 (td, J = 12.8, 4.8 Hz, 1H, H-6), 3.97 (d, J = 13.2 Hz, 1H, H-1), 6.58 (s, 1H, H-3), 7.03 (t, J = 7.6 Hz, 1H, ArH), 7.25 (t, J = 7.6 Hz, 2H, ArH), 7.41 (d, J = 8.4 Hz, 2H, ArH), 7.46 (d, J = 5.6 Hz, 5H, ArH), 7.51 (d, J = 8.4 Hz, 2H, ArH), 7.73 (d, J = 7.6 Hz, 2H, ArH), 10.08 (s, 1H, NH); 13C NMR (100 MHz, DMSO): δ 35.6, 42.9, 59.8, 119.5, 120.3, 123.8, 123.9, 126.9, 129.1, 129.3, 130.3, 130.9, 131.7, 137.8, 139.1, 142.0, 159.3, 167.6, 195.6; MS (EI, 70 eV) m/z (%): 445 ((M-1) +, 19), 403 (3), 353 (4), 327 (94), 298 (3), 273 (5), 246 (40), 209 (26), 183 (14), 157 (55), 115 (2), 93 (100), 65 (18), 43 (3); Anal. calcd for C25H20BrNO2: C, 67.27; H, 4.52; N, 3.14; found: C, 67.36; H, 4.63; N, 3.19%. X-ray determination single crystal The diffraction data from selected single crystal of cyclohexenone 4e was collected at 100 K on Oxford Diffraction Xcalibur Gemini S diffractometer equipped with CuKα radiation (λ= 1.5418 Å). The data were processed with CrysAlis software an empirical absorption correction using spherical harmonics, were implemented in SCALE3 ABSPACK scaling algorithm.36 The crystallographic data, the data collection parameters, and the refinement parameters for each structure are summarised in Table 5.
Table 5 The crystallographic data, the data collection parameters, and the refinement parameters for each structure of 4e Empirical formula C25H20 BrNO2·H2O Formula weight 464.34 Temperature/K 297 Wavelength CuKα(1.5418 Å) Crystal system Monoclinic Space group P21/c Lattice constants a/Å 10.7168(3) b/Å 7.2261(3) c/Å 27.9360(8) 90 α/º 96.626(3) β/º 90 γ/º Volume/ų 2148.93(12) Z 4 Absorption coefficient 2.819 F(000) 952 Crystal size 0.021 x 0.031 x 0.079 3.185–70.708 θ range for data collection Index ranges –12 ≤ h ≤ 10, –8≤ k ≤ 8, –34 ≤ l ≤ 33 Reflections collected 4069 Independent reflections 2972 [Rint=0.0535 ] Completeness/% 98.7 Data/restrains/parameters 4069/0/274 Good of fit on F² 1.052 Final R indices [I>2 theta (I)] R1= 0.0536; wR2= 0.1356 R indices (all data) R1= 0.0751; wR2 = 0.1527 Largest diff. peak and hole 0.850 and –0.510
Crystal structures were solved by direct methods using Sir2011,37 and refined by full-matrix least-squares calculations against F2 using SHELXL.38 All non-hydrogen atoms were refined with anisotropic displacement parameters. All the hydrogen atoms were localised experimentally through Fourier map differences. The figures were produced using MERCURY.39 The software used for the preparation of the materials for publication were Olex2,40 PLATON 41 and PARST.42
We gratefully acknowledge the funding support from the Research Council of the University of Sistan and Baluchestan. This work was partially supported by ERDF funding and the Spanish Ministerio de Economía y Competitividad, MAT2013– 40950-R. Received 1 July 2015; accepted 3 August 2015 Paper 1503458 doi: 10.3184/174751915X14396601175593 Published online: 1 September 2015
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