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One-Pot Multicomponent CondensationReaction of Aldehydes with CyclicKetonesPing Wu a , Xi-Mei Cai b , Qi-Fang Wang b & Chao-Guo Yan ba Yangzhou Polytechnic University, Yangzhou, Chinab College of Chemistry and Chemical Engineering, YangzhouUniversity, Yangzhou, China

Version of record first published: 25 Feb 2011

To cite this article: Ping Wu, Xi-Mei Cai, Qi-Fang Wang & Chao-Guo Yan (2011): One-PotMulticomponent Condensation Reaction of Aldehydes with Cyclic Ketones, Synthetic Communications:An International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:6, 841-850

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ONE-POT MULTICOMPONENT CONDENSATIONREACTION OF ALDEHYDES WITH CYCLIC KETONES

Ping Wu,1 Xi-Mei Cai,2 Qi-Fang Wang,2 and Chao-Guo Yan21Yangzhou Polytechnic University, Yangzhou, China2College of Chemistry and Chemical Engineering, Yangzhou University,Yangzhou, China

GRAPHICAL ABSTRACT

Abstract Under microwave irradiation, the one-pot multicomponent condensation reaction

of three molar aromatic aldehydes with two molar cyclic ketones having free a,a0-methylene

ethylene positions such as cyclopentanone or cyclohexanone in the presence of ammonium

acetate and acetic acid afforded dicyclocalkenopyridines with two a-arylidene groups in

good yields. In similar reaction conditions, 1-tetralone, which has only one a-methylene

position, results in 10-aryl-2,3:5,6-dibenzoacridines.

Keywords Acridine; aldol condensation; aromatic aldehyde; cyclic ketone; microwave

irradiation; pyridine

INTRODUCTION

The pyridyl heterocyclic core is a widespread subunit in numerous naturalproducts and pharmaceuticals. These facts consequently generate interest in develop-ing a new efficient synthetic procedure of pyridines.[1–4] Polysubstituted pyridineshave been synthesized using various methods and procedures, and two methods havedistinct advantages over other procedures. One is the two-step Krohnke synthesis[5–9]

via condensation of pyridinium salts with a,b-unsaturated ketones in the presence ofa mixture of ammonium acetate and acetic acid. The second method is Hantzsch-type synthesis via cyclocondensation of aromatic aldehyde, acetophenone, and a

Received March 19, 2008.

Address correspondence to Chao-Guo Yan, College of Chemistry and Chemical Engineering,

Yangzhou University, Yangzhou, China. E-mail: cgyan@yzu.edu.cn

Synthetic Communications1, 41: 841–850, 2011

Copyright # Taylor & Francis Group, LLC

ISSN: 0039-7911 print=1532-2432 online

DOI: 10.1080/00397911003706990

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nitrogen derivative such as ammonium acetate or urea.[10] The key step of thisreaction is Michael addition of the second molecule of acetophenone to a,b-unsatu-rated ketones formed in situ from the aldol condensation of aromatic aldehyde withacetophenone to form 1,5-diketone. Recently, several improved procedures havebeen developed for this method, including solvent-free reaction conditions,[11,12]

reaction in aqueous media,[13] a one-pot procedure under microwaveirradiation,[14,15] and direct heating of a,b-unsaturated ketones and ammonium acet-ate in the presence of a catalytic amount of acetic acid.[16] In continuation of ourefforts to develop new, facile, and efficient synthetic methods for polysubstitutedpyridines, herein we report the interesting results of microwave-assisted one-potreactions of aromatic aldehydes with cyclic ketones.

RESULTS AND DISCUSSION

When a mixture of cyclopentanone 1a, aromatic aldehydes 2a–f, ammoniumacetate, and acetic acid was heated under microwave irradiation, Hantzsch-type syn-thesis of pyridine occurred with the formation of dicyclopenta[b,e]pyridines. Afterworkup, in our experiments the main products were dicyclopenta[b,e]pyridines withtwo additional a-arylidene groups. Then an optimized molar ratio of aromatic alde-hydes (3mol) and cyclopenanone (2mol) was used in the same reactions. Com-pounds 3a–e were prepared in 65–78% yields. Cyclohexanone 1b reacted similarlyto give dicyclohexa[b,e]pyridine (sym-ocathydroacridine) with two additional benzy-lidene groups 3f–j (Scheme 1).

The dibenzylidene derivatives of dicyclocalkenopyridines have been preparedby several methods in the literature. One is conventionally heating the mixture ofaldehyde, cyclic ketone, and ammonium acetate.[17] The second is heating dicy-cloalkenopyridines with aromatic aldehyde in acetic anydride.[18] The third is lettingcyclic ketone react with formaldedyde to form bis (2-oxocycloalkyl)methane, whichin turn is heated with ammonium acetate.[19] The structures of the dicycloalkeno-pyridine derivatives 3a–j were characterized by infrared (IR), 1H NMR, and 13CNMR, as well as mass spectroscopy. It should be mentioned that the reaction undermicrowave irradiation is very clean, and very few by-products have been detected.

Scheme 1. One-pot synthesis of dicycloalkenopyridines 3a–j.

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Therefore, the workup procedure involves only a simple filtration of the precipitatefollowed by crystallization with alcohol. In all instances, the products can beobtained in a high purity, with very good 1H and 13C NMR results. Their struc-tures were further confirmed by x-ray crystal analysis of the representative com-pound 3g (Fig. 1). In the molecule of 3g, the p-chlorophenyl group in the4-position of the pyridine ring is torsioned from the plane of the pyridine ring.Each fused cyclohexene ring is in screw-boat conformation attached to a p-chlorol-benzylidene group.

The formation of 3a–j is very interesting and involves three molecules of aro-matic aldehydes and two molecules of ketones as well as one molecule of ammonia.The reaction mechanism of Hantzsch-type synthesis of pyridine via cyclocondensa-tion of aromatic aldehyde with acetophenone and a nitrogen source has long beenestablished,[20–23] which includes several steps: aldol condensation of aromatic alde-hyde with acetophenone to give a,b-unsaturated ketones, Michael addition of thesecond molecule of acetophenone to a,b-unsaturated ketones to form 1,5-diketone,which in turn cyclizes with a nitrogen source to form a hydropyridine ring. Thiskind of mechanism also should apply to the formation of dicycloalkenopyridines.

Figure 1. Molecular structure of 3g. Hydrogen atoms are omitted for clarity.

Scheme 2. One-pot synthesis of dicycloalkenopyridines 4a–e.

ONE-POT MULTICOMPONENT CONDENSATION 843

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According to this mechanism, the 2-substituted cyclic ketone, which has onemethylene group, would produce the normal bicyclic fused pyridines in the reactions.In fact, when 1-tetralone 1c is heated with aromatic aldehydes in the presenceof NH4OAc=HOAc under microwave irradiation, the normal 10-aryl-2,3–5,6-dibenzotetrahydroacridines 4a–e are formed in excellent yields (Scheme 2), whichhas been reported recently.[14] X-ray crystal structure of 4c (Fig. 2) further confirmsthe proposed structures.

EXPERIMENTAL

Material and Apparatus

Melting points were taken on a hot-plate microscope apparatus. IR spectrawere obtained on a Bruker Tensor 27 spectrometer (KBr disc). 1H NMR spectrawere recorded with a Bruker AV-600 spectrometer with CDCl3 as solvent and tetra-methylsilane (TMS) as internal standard. High-performance liquid chromatography=mass spectra (HPLC=MS) were measured on a Fennigan LCQ Deca XP MAXinstrument. Microwave heating was conducted with a Lingjiang LMMC-201 micro-wave reactor (Nanjing, Chnia). Aromatic aldehydes, cyclic ketones, and otherreagents are commercial reagents and were used as received. Solvents were purifiedby standard techniques. The reaction process was monitored by thin-layerchromatography (TLC).

Figure 2. Molecular structure of the compound 4c. Hydrogen atoms are omitted for clarity.

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General Procedure for the Preparation of 3a–j

To a 50-mL flask, Aromatic aldehyde (3.0mmol), cyclic ketone (2.0mmol),ammonium acetate (3.0 g), and acetic aid (2.0mL) were added. The mixture wasput in the microwave and heated for about 2–4min (520W). After cooling, the reac-tion mixture was diluted with 50mL of water, and the resulting precipitate was col-lected with filtration. The crude product was recrystallizated with ethanol to givethe pure solid sample for analysis with IR, HPLC=MS, and 1H NMR and 13CNMR specotroscopy.

Selected Data for 3a–j

Compound 3a. Yield 65%, mp 230.6 �C. 1H NMR (600MHz, CDCl3) d 7.33(s, 2H, PhH), 7.62 (d, 4H, J¼ 7.8Hz, PhH), 7.50 (t, 2H, J¼ 7.8Hz, PhH), 7.44–7.39(m, 2H, PhH), 7.29–7.27 (m, 3H, PhH, CH¼), 3.20 (s, 4H, 2CH2), 3.00 (s, 4H,2CH2).

13C NMR (600MHz, CDCl3) d 160.9, 143.7, 141.6, 138.0, 138.0, 136.8,

Table 1. Crystal data of the compounds 3g and 4c

Parameter 3g 4c

Empirical formula C34H27Cl6N C27H20ClN

Formula weight 662.27 393.89

Temperature (K) 273 (2) 273 (2)

Wavelength (A) 0.71073 0.71073

Crystal system, space group Monoclinic, P2 (1)=n Triclinic, P-1

Unit cell dimensions

a (A) 11.8330 (14) 8.8056 (13)

b (A) 11.2754 (14) 10.4493 (15)

c (A) 23.607 (3) 11.9107 (17)

a (�) 90 79.633 (2)

b (�) 91.556 (2) 76.310 (2)

c (�) 90 69.007 (2)

Volume (A3) 3148.5 (7) 988.6 (2)

Z, calculated density (g cm�3) 4, 1.397 2, 1.323

Absorption coefficient (mm�1) 0.571 0.206

F (0 0 0) 1360 412

Crystal size (mm) 0.30� 0.30� 0.20 0.40� 0.30� 0.30

h range for data collection (�) 2.50–25.00 2.10 to 25.00

Limiting indices �14� h� 12,�12� k� 13,

�28� l� 28

�10�h� 8, �12�k� 12,

�14� l� 13

Reflections collected=unique 15923=5539 [R (int)¼ 0.0374] 5159=3426 [R (int)¼ 0.0173]

Completeness (%) 99.9 98.4

Absorption correction non Semi-empirical from equivalents

Max. and min. transmission 0.8943 and 0.8473 0.9407 and 0.9220

Refinement method Full-matrix least-squares on F2 Full-matrix least-squares on F2

Data=restraints=parameters 5539=0=370 3426=0=262

Goodness of fit on F2 1.060 1.079

Final R indices [I> 2rI] R1¼ 0.0911, wR2¼ 0.2588 R1¼ 0.0442, wR2¼ 0.1075

R indices (all data) R1¼ 0.1339, wR2¼ 0.1339 R1¼ 0.0637, wR2¼ 0.1188

Largest difference peak

and hole (e A�3)

1.266 and �1.103 0.151 and �0.236

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136.8, 129.1, 128.6, 128.4, 128.1, 128.0, 126.7, 122.0, 29.4, 27.7. IR (KBr) t 2913 (w),2375 (w), 1632 (m), 1493 (m), 1444 (m), 1377 (vs), 1239 (m), 1193 (m), 1077 (w), 816(w), 761 (m) cm�1. MS (m=z): 411.80.

Compound 3b. Yield 74%, mp 235.6–236.6 �C. 1H NMR (600MHz, CDCl3) d7.67 (s, 2H, ArH), 7.43 (d, 4H, J¼ 7.8Hz, ArH), 7.27–7.24 (m, 4H, ArH, CH¼),7.20–7.19 (d, 4H, ArH, CH¼), 3.12 (s, 4H, 2CH2), 2.95–2.93 (m, 4H, 2CH2), 2.41 (s,3H, CH3), 2.37 (s, 6H, CH3).

13C NMR (600MHz, CDCl3) d 135.3, 131.5, 130.7,129.3, 129.2, 128.6, 128.5, 128.1, 128.0, 127.8, 127.7, 126.5, 120.0, 28.4, 26.7. IR (KBr)t 3012 (w), 2915 (m), 1632 (m), 1571 (w), 1509 (s), 1453 (w), 1382 (vs), 1294 (w), 1238(m), 1179 (w), 1123 (w), 1029 (w), 896 (w), 808 (m), 720 (w) cm�1. MS (m=z): 553.67.

Compound 3c. Yield 78%, mp >250 �C. 1H NMR (600MHz, CDCl3) d7.56(s, 1H, ArH), 7.43 (d, 3H, J¼ 8.4Hz, ArH), 7.39 (d, 2H, J¼ 7.8Hz, ArH), 7.29 (d,4H, J¼ 7.2Hz, ArH), 7.23 (d, 2H, J¼ 7.2Hz, CH¼), 7.19 (s, 2H, ArH), 3.06 (d,J¼ 7.2Hz, 4H, 2CH2), 2.89 (d, J¼ 7.2Hz, 4H, 2CH2);

13C NMR (600MHz, CDCl3)d 136.1, 135.6, 134.7, 133.5, 131.8, 130.9, 129.5, 129.3, 128.7, 128.7, 128.3, 128.2,128.1, 128.0, 127.9, 126.7, 123.9, 120.4, 120.3, 28.5, 26.9. IR (KBr) t 2912 (w),2841 (w), 1631 (w), 1537 (w), 1491 (s), 1457 (w), 1357 (m), 1265 (w), 1239 (m),1130 (w), 1090 (s), 1011 (w), 825 (w), 797 (m), 703 (w) cm�1. MS (m=z): 513.60.

Compound 3d. Yield 70%, mp 186.8 �C. 1H NMR (600MHz, CDCl3) d 7.65(s, 2H, ArH), 7.55 (d, 3H, J¼ 8.4Hz, ArH), 7.33 (d, 2H, J¼ 8.4Hz, CH¼), 7.28 (s,1H, ArH), 7.01 (d, 3H, J¼ 8.4Hz, ArH), 6.96 (d, 3H, J¼ 8.4Hz, ArH), 3.88, 3.86 (s,s, 9H, 3OCH3), 3.14 (s, 4H, 2CH2), 2.99–2.97 (t, J¼ 7.2Hz, 4H, 2CH2);

13C NMR(600MHz, CDCl3) d139.4, 131.2, 131.0, 130.4, 130.3, 130.0, 129.4, 127.4, 114.3,114.09, 114.0, 113.9, 55.3, 29.3, 27.8; IR (KBr) t 2923 (w), 2836 (w), 1605 (m),1511 (s), 1453 (w), 1383 (w), 1293 (w), 1248 (vs), 1176 (m), 1125 (m), 1031 (w),814 (w) cm�1. MS (m=z): 501.80.

Compound 3e. Yield 69%, mp >250 �C. 1H NMR (600MHz, CDCl3) d 9.28(s, 1H, OH), 9.21 (s, 2H, OH), 7.45 (s, 2H, ArH), 7.15 (s, 2H, ArH), 7.05–7.04 (m,3H, ArH), 6.90 (s, 2H, ArH), 6.84 (d, 2H, J¼ 8.4Hz, CH¼), 3.84–3.81 (m, 9H,3OCH3), 3.08 (s, 4H, 2CH2), 2.99 (s, 4H, 2CH2).

13C NMR (600MHz, CDCl3) d161.2, 148.5, 148.4, 147.3, 146.8, 144.1, 139.6, 136.7, 130.1, 128.6, 122.8, 122.0,121.9, 116.6, 116.5, 113.9, 113.4, 57.0, 56.8, 56.5, 40.5, 40.4, 40.21, 40.1, 39.9, 29.7,28.3, 19.3. IR (KBr) t 2932 (w), 1598 (w), 1513 (vs), 1457 (w), 1382 (m), 1271 (s),1208 (m), 1123 (m), 1030 (w), 810 (w) cm�1. MS (m=z): 549.67.

Compound 3f. Yield 71%, mp 158.9–159.6 �C. 1H NMR (600MHz, CDCl3) d8.36 (s, 2H, PhH), 7.62 (d, 6H, J¼ 6.6Hz, PhH), 7.54–7.52 (m, 5H, PhH), 7.41 (d,2H, J¼ 7.2Hz, PhH), 7.29 (d, 2H, J¼ 7.2Hz, CH¼), 3.03 (s, 4H, CH2), 2.60 (s,4H, CH2), 1.89 (s, 4H, CH2). IR (KBr) t 3052 (w), 3020 (w), 2935 (m), 2858 (w),1596 (w), 1544 (m), 1492 (m), 1442 (m), 1384 (vs), 1265 (w), 1183 (w), 1032 (w),918 (w), 967 (w), 867 (w),753 (m), 694 (s), 616 (w). 13C NMR (600MHz, CDCl3)d 149.9, 149.5, 138.5, 138.4, 136.4, 129.7, 129.4, 128.7, 128.3, 128.1, 127.4, 126.6,126.5, 28.2, 27.9, 23.1. MS (m=z): 440.27.

Compound 3g. Yield 70%, mp 195.6–196.8 �C. 1H NMR (600MHz, CDCl3)d 8.02 (s, 2H, ArH), 7.38 (d, 2H, J¼ 7.8Hz, ArH), 7.30–7.28 (m, 8H, ArH, ¼CH),

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6.99 (d, 2H, J¼ 7.8Hz, ArH), 2.74 (s, 4H, CH2), 2.35 (s, 4H, CH2), 1.67 (s, 4H,CH2).

13C NMR (600MHz, CDCl3) d 149.7, 148.5, 136.7, 136.6, 133.6, 132.4,130.9, 129.7, 129.6, 129.2, 129.1, 128.3, 128.1, 125.7, 125.6, 28.1, 27.8, 22.9. IR(KBr) t 2932 (w), 1630 (m), 1489 (w), 1385 (s), 1091 (w), 1019 (w), 834 (w), 582(w) cm�1. MS (m=z): 541.73.

Compound 3h. Yield 67%, mp 226.5–228.5 �C. 1H NMR (600MHz, CDCl3)d 7.94 (s, 2H, ArH), 7.24 (d, 4H, J¼ 8.4Hz, ArH, CH¼), 6.88 (d, 2H, J¼ 8.4Hz,ArH), 6.82 (d, 2H, J¼ 9.0Hz, ArH), 6.75 (d, 4H, J¼ 9.0Hz, ArH), 3.69–3.66 (d,9H, 3OCH3), 2.68 (t, 4H, J¼ 6.6Hz, 2CH2), 2.27 (t, 4H, J¼ 6.0Hz, 2CH2), 1.55(t, 4H, J¼ 6.0Hz, 2CH2).

13C NMR (600MHz, CDCl3) d 158.8, 158.3, 150.0,135.0, 131.0, 129.5, 129.4, 126.0, 114.1, 113.5, 55.3, 28.2, 28.0, 23.1. IR (KBr) t2932 (w), 1605 (m), 1507 (s), 1458 (w), 1385 (m), 1248 (vs), 1174 (m), 1029 (m),839 (m) cm�1. MS (m=z): 529.73.

Compound 3i. Yield 75%, mp 226.4–228.0 �C. 1H NMR (600MHz, CDCl3) d7.95 (s, 2H, ArH), 7.05 (d, 2H, J¼ 9.0Hz, CH¼), 6.68 (d, 1H, J¼ 7.8Hz, ArH), 6.37(s, 2H, ArH), 6.30 (s, 4H, ArH), 3.67–3.64 (m, 15H, OCH3), 3.50 (s, 3H, OCH3),2.61–2.50 (m, 4H, CH2), 2.27–2.14 (m, 4H, CH2), 1.52 (s, 4H, CH2). IR (KBr) t2935 (w), 2835 (w), 1608 (s), 1502 (m), 1459 (m), 1385 (w), 1293 (m), 1259 (m),1209 (s), 1159 (s), 1038 (m), 925 (w), 836 (w), 582 (w). 13C NMR (600MHz, CDCl3)d 160.5, 159.8, 159.0, 157.2, 149.9, 145.9, 135.6, 131.0, 130.1, 129.9, 121.5, 120.7,120.0, 104.6, 103.7, 98.8, 98.3, 55.5, 55.4, 28.1, 27.7, 23.0. MS (m=z): 619.53.

Compound 3j. Yield 72%, mp > 250 �C. 1H NMR (600MHz, CDCl3) d 8.00(s, 2H, ArH), 7.62 (d, 4H, J¼ 8.4Hz, ArH), 6.90–6.89 (m, 2H, CH¼), 6.70 (d, 2H,J¼ 9.0Hz, ArH), 6.65 (d, 4H, J¼ 8.4Hz, ArH), 2.91 (s, 7H, CH3), 2.88–2.83 (m,11H, CH3), 2.80–2.78 (m, 4H, CH2), 2.37 (t, 4H, J¼ 6.0Hz, CH2), 1.61 (t, 4H,J¼ 6.0Hz, CH2). IR (KBr) t 2927 (w), 1608 (s), 1519 (vs), 1478 (w), 1443 (w),1384 (m), 1353 (m), 1223 (w), 1188 (w), 1160 (w), 946 (w), 823 (m), 763 (w), 553(w). 13C NMR (600MHz, CDCl3) d 149.6, 148.8, 148.6, 148.4, 132.9, 130.2,128.6, 128.5, 126.3, 125.8, 125.7, 111.6, 111.5, 111.4, 40.0, 39.8, 27.6, 22.6. MS(m=z): 568.93.

General Procedure for the Preparation of 4a–e

Aromatic aldehyde (1.0mmol), 1-tetralone (2.0mmol), ammonium acetate(3.0 g), and acetic acid (2.0mL) was added to a 50-mL flask. The mixture was putinto a microwave and heated for about 2–4min (520W). After cooling, the reactionmixture was diluted with 50mL of water, and the resulting precipitate was collectedby filtration. The crude product was recrystallized with ethanol to give the pure solidsample.

Selected Data for 4a–e

Compound 4a. Yield 68%, mp 164–165 �C. 1H NMR (600MHz, CDCl3) d8.45 (d, 2H, J¼ 7.8Hz, ArH), 7.36 (t, 2H, J¼ 7.2Hz, ArH), 7.31–7.26 (m, 3H,ArH), 7.21–7.18 (m, 3H, ArH), 7.08–7.07 (m, 3H, ArH), 2.75–2.68 (m, 4H,

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2CH2), 2.53–2.50 (m, 4H, 2CH2).13C NMR (600MHz, CDCl3) d 147.8, 145.1, 139.7,

138.3, 135.7, 135.5, 135.4, 133.0, 127.9, 127.3, 126.4, 126.3, 126.3, 126.3, 126.2, 126.0,125.7, 125.5, 125.3, 125.1, 124.7, 124.6, 124.1, 123.6, 123.4, 123.0, 25.8, 25.2, 23.5. IR(KBr) t 3029 (w), 2943 (w), 2835 (w), 1631 (w), 1547 (m), 1489 (w), 1434 (w), 1387(s), 1225 (m), 1167 (w), 1031 (w), 945 (w), 807 (w), 762 (s) cm�1. MS (m=z): 359.60.

Compound 4b. Yield 79%, mp 165.2–166.7 �C. 1H NMR (600MHz, CDCl3)d 8.42 (d, 1H, J¼ 7.2Hz, ArH), 7.97 (d, 1H, J¼ 8.4Hz, ArH), 7.70 (s, 1H, ArH),7.31 (t, 1H, J¼ 7.2Hz, ArH), 7.24 (t, 1H, J¼ 7.2Hz, ArH), 7.14 (d, 2H, J¼ 7.2Hz,Hz, ArH), 7.06 (d, 3H, J¼ 7.2Hz, ArH), 6.92 (d, 1H, J¼ 7.8Hz, ArH), 2.96 (t, 2H,J¼ 6.0Hz, CH2), 2.76 (t, 2H, J¼ 6.6Hz, CH2), 2.65 (t, 2H, J¼ 7.2Hz, CH2), 2.56 (t,2H, J¼ 7.8Hz, CH2), 2.49 (t, 2H, J¼ 7.8Hz, CH2), 2.24 (s, 3H, CH3).

13C NMR(600MHz, CDCl3) d 187.9, 150.0, 143.2, 138.8, 137.8, 137.3, 136.8, 135.5, 134.9,134.8, 133.6, 133.2, 133.1, 130.0, 129.3, 129.2, 128.9, 128.7, 128.6, 128.2, 128.1,127.4, 127.0, 125.3, 28.9, 28.2, 27.3, 25.8, 21.4, 21.3. IR (KBr) t 3033 (w), 2949(w), 2839 (w), 1660 (m), 1587 (s), 1506 (w), 1444 (w), 1387 (m), 1293 (m), 1222(m), 1181 (w), 1126 (w), 1027 (w), 877 (m), 736 (s) cm�1. MS (m=z): 373.67.

Compound 4c. Yield 75%, mp 200.0–201.8 �C. 1H NMR (600MHz, CDCl3)d 8.49 (d, 2H, J¼ 7.8Hz, ArH), 7.40 (d, 2H, J¼ 8.4Hz, ArH), 7.34 (t, 2H,J¼ 7.2Hz, ArH), 7.25 (t, 2H, J¼ 7.2Hz, ArH), 7.13 (d, 2H, J¼ 7.2Hz, ArH),7.08 (d, 2H, J¼ 8.4Hz, ArH), 2.76 (t, 4H, J¼ 7.2Hz, 2CH2), 2.56 (t, 4H, J¼ 7.8Hz,Hz, 2CH2).

13C NMR (600MHz, CDCl3) d 150.2, 146.2, 137.7, 136.3, 135.2, 133.7,131.0, 130.1, 128.9, 128.8, 128.6, 128.2, 127.6, 127.5, 127.1, 127.0, 125.3, 63.7, 28.1,25.8. IR (KBr) t 3035 (w), 2926 (w), 1597 (w), 1545 (m), 1488 (m), 1386 (vs), 1225(w), 1168 (w), 1088 (m), 1014 (w), 944 (w), 833 (m), 735 (s) cm�1. MS (m=z): 393.87.

Compound 4d. Yield 71%, mp 187.9–188.6 �C. 1H NMR (600MHz, CDCl3)d 8.62 (d, 2H, J¼ 7.8Hz, ArH), 7.44 (t, 2H, J¼ 7.8Hz, ArH), 7.34 (t, 2H, J¼ 7.2Hz,ArH), 7.23 (d, 2H, J¼ 7.2Hz, ArH), 7.15 (d, 2H, J¼ 8.4Hz, ArH), 7.05 (d, 2H,J¼ 8.4Hz, ArH), 3.91 (s, 3H, OCH3), 2.87–2.85 (m, 4H, 2CH2), 2.72–2.69 (m,4H, 2CH2).

13C NMR (600MHz, CDCl3) d 159.1, 150.1, 147.3, 137.8, 135.5,130.0, 129.9, 129.2, 128.6, 127.4, 127.0, 125.3, 114.0, 55.3, 28.2, 25.9. IR (KBr) t3033 (w), 2919 (w), 2833 (w), 1608 (m), 1548 (w), 1510 (s), 1427 (w), 386 (s), 1291(m), 1241 (s), 1173 (m), 1033 (w), 838 (m), 806 (w), 735 (m), 660 (w), 515 (w) cm�1.MS (m=z): 389.53.

Compound 4e. Yield 64%, mp > 250 �C. 1H NMR (600MHz, CDCl3) d 9.28(s, 1H, OH), 8.57 (d, 2H, J¼ 7.8Hz, ArH), 7.40 (t, 2H, J¼ 7.2Hz, ArH), 7.31 (t, 2H,J¼ 7.2Hz, ArH), 7.21 (d, 2H, J¼ 7.2Hz, ArH), 7.04 (d, 2H, J¼ 8.4Hz, ArH),6.72–6.68 (m, 2H, ArH), 3.89 (s, 3H, OCH3), 2.84 (t, 4H, J¼ 7.2Hz, CH2), 2.70(t, 4H, J¼ 7.2Hz, CH2).

13C NMR (600MHz, CDCl3) d 150.1, 147.4, 146.7,145.1, 137.8, 135.4, 129.8, 129.1, 128.6, 127.4, 127.0, 125.3, 121.7, 114.6, 111.2,56.1, 28.2, 25.8. IR (KBr) t 3444 (w), 2926 (w), 2836 (w), 2345 (w), 1604 (w), 1543(w), 1512 (s), 1464 (w), 1416 (w), 1387 (m), 1266 (m), 1238 (w), 1193 (m), 1120(w), 1021 (w), 750 (m) cm�1. MS (m=z): 405.53.

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Supporting Information

Crystallographic data (CCDC-628460 for 3g, CCDC-618867 for 4c) have beendeposited at the Cambridge Crystallographic Database Centre.

ACKNOWLEDGMENTS

This work was financially supported by the National Natural Science Foun-dation of China (Grant No. 20672091), China. We are grateful to Ms. Min Shaofor assistance with measuring the x-ray single-crystal structures.

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