Mild and efficient syntheses of 1-aryl-3,4-dihydroisoquinolines and 1-aryl-3,4-dihydro-β-carbolines via regiospecific β-eliminations of the corresponding N-tosyl-1,2,3,4-tetrahydroisoquinolines and N-tosyl-1,2,3,4-tetrahydro-β-carbolines

Article abstract of DOI:10.1080/00397911.2011.568659

(Chemical Equation Presented) Treatment of N-tosyl-1-aryl-1,2,3,4- tetrahydro-isoquinolines or N-tosyl-1-aryl-1, 2,3,4-tetrahydro-β-carbolines with a strong base such as NaOH or KOH at 70 °C in dimethylsulfoxide (DMSO) produced 1-aryl-3,4-dihydroisoquinolines or 1-aryl-3,4-dihydro-β- carbolines in good yields via mild and regiospecific β-eliminations. A dramatic solvent effect was observed, DMSO was crucial for the reactions. The temperature is also crucial for the reactions and should be kept between 60 and 80 °C. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2011.568659

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Mild and Efficient Syntheses of 1-
Aryl-3,4-dihydroisoquinolines and
1-Aryl-3,4-dihydro-β-carbolines
via Regiospecific β-Eliminations of
the Corresponding N-Tosyl-1,2,3,4-
tetrahydroisoquinolines and N-
Tosyl-1,2,3,4-tetrahydro-β-carbolines
Jing Dong a , Xiao-Xin Shi a , Jing Xing a & Jing-Jing Yan a
a Department of Pharmaceutical Engineering, School of Pharmacy,
East China University of Science and Technology, Shanghai, China
Accepted author version posted online: 17 Nov 2011.Version of
record first published: 29 May 2012.
To cite this article: Jing Dong, Xiao-Xin Shi, Jing Xing & Jing-Jing Yan (2012): Mild and Efficient
Syntheses of 1-Aryl-3,4-dihydroisoquinolines and 1-Aryl-3,4-dihydro-β-carbolines via Regiospecific
β-Eliminations of the Corresponding N-Tosyl-1,2,3,4-tetrahydroisoquinolines and N-Tosyl-1,2,3,4-
tetrahydro-β-carbolines, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:19, 2806-2817
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Synthetic Communications1, 42: 2806–2817, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.568659
MILD AND EFFICIENT SYNTHESES OF
1-ARYL-3,4-DIHYDROISOQUINOLINES AND
1-ARYL-3,4-DIHYDRO-b-CARBOLINES VIA
REGIOSPECIFIC b-ELIMINATIONS OF THE
CORRESPONDING N-TOSYL-1,2,3,4-
TETRAHYDROISOQUINOLINES AND
N-TOSYL-1,2,3,4-TETRAHYDRO-b-CARBOLINES
Jing Dong, Xiao-Xin Shi, Jing Xing, and Jing-Jing Yan
Department of Pharmaceutical Engineering, School of Pharmacy, East China
University of Science and Technology, Shanghai, China
GRAPHICAL ABSTRACT
Abstract Treatment of N-tosyl-1-aryl-1,2,3,4-tetrahydro-isoquinolines or N-tosyl-1-aryl-1,
2,3,4-tetrahydro-b-carbolines with a strong base such as NaOH or KOH at 70 ꢀC in dime-
thylsulfoxide (DMSO) produced 1-aryl-3,4-dihydroisoquinolines or 1-aryl-3,4-dihydro-b-
carbolines in good yields via mild and regiospecific b-eliminations. A dramatic solvent effect
was observed, DMSO was crucial for the reactions. The temperature is also crucial for the
reactions and should be kept between 60 and 80 ꢀC.
Keywords 3,4-Dihydro-b-carboline; 3,4-dihydroisoquinoline; synthesis; 1,2,3,4-tetrahydro-
b-carboline; 1,2,3,4-tetrahydroisoquinoline
INTRODUCTION
1-Substituted 3,4-dihydroisoquinolines (3,4-DHIQs) and 3,4-dihydro-b-
carbolines (3,4-DHBCs) are important compounds because they not only have
exhibited various biological activities[1,2] but also can be reduced to produce
1-substituted 1,2,3,4-tetrahydroisoquinolines (THIQs)[3] and 1,2,3,4-tetrahydro-b-
carbolines (THBCs)[3c–3e,4] or oxidized to afford fully aromatized 1-substituted
isoquinolines[1b,1c,5] and b-carbolines.[6]
1-Substituted 3,4-DHIQs and 3,4-DHBCs normally can be obtained via
Bischler–Napieralski cyclization of N-2-aryl=indolyl ethyl amides[7] or the oxidation
Received December 6, 2010.
Address correspondence to Xiao-Xin Shi, Department of Pharmaceutical Engineering, School of
Pharmacy, East China University of Science and Technology, P.O. Box 363, 130 Mei-Long Road,
Shanghai 200237, China. E-mail: xxshi@ecust.edu.cn
2806

1-ARYL-3,4-DHIQS AND 1-ARYL-3,4-DHBCS
2807
of 1-substituted THIQs and THBCs.[8] However, Bischler–Napieralski cyclization
may suffer from poor yields and use of hazardous,[7b] toxic,[7d] strongly acidic,[7e]
or expensive[7f] reagents, whereas the oxidation of 1-substituted THIQs and THBCs
needs strong oxidants that may lead to overoxidation.[8b,8c] Therefore, mild and
efficient methods for the syntheses of 1-substituted 3,4-DHIQs and 3,4-DHBCs
should be highly desirable. Herein we report a novel method for the syntheses of
1-substituted 3,4-DHIQs and 3,4-DHBCs via regiospecific b-eliminations of the
readily available 1-substituted N-tosyl-THIQs and N-tosyl-THBCs.
RESULTS AND DISCUSSION
1-Substituted N-tosyl-THIQs 1 were directly obtained from N-sulfonyl Pictet–
Spengler reaction[9] of N-2-arylethyl p-toluenesulfonamides with aldehydes. 1-Substi-
tuted N-tosyl-THBCs 2 were obtained in a two-step fashion: Pictet–Spengler reac-
tion of tryptamine hydrochloride with aldehydes[10] first gave 1-substituted
THBCs, which were then transformed into the compound 2 in almost quantitative
yields by exposure to p-toluenesulfonyl chloride in the presence of excess powdered
potassium carbonate and a catalytic amount of pyridine.
With 1-substituted N-tosyl-THIQs 1a–i and N-tosyl-THBCs 2a–j to hand, we
then attempted the conversions of compound 1 into 1-substituted 3,4-DHIQs 3
and compound 2 into 1-substituted 3,4-DHBCs 4 under various conditions. The
results are summarized in Tables 1 and 2, respectively.
As can be seen from Table 1, 1-substituted N-tosyl-THIQs 1a–i were treated
with 3 molar equivalents of NaOH at 70 ꢀC in dimethylsulfoxide (DMSO). b-Elim-
ination[11] of p-toluenesulfinic acid (p-CH3C6H4SO2H) took place rapidly (1.5–2.5 h),
affording 1-substituted 3,4-DHIQs 3a–i in 86–95% yields. DMSO was crucial for the
reaction: when other solvents such as ethanol, isopropanol, octanol, 1,4-dioxane,
and N,N-dimethylformamide were used instead of DMSO, the b-elimination was
sluggish and 3,4-DHIQs were obtained only in poor yields after the reaction mix-
tures were stirred at 70 ꢀC for 12 h. Other bases have also been tried: Strong bases
such as KOH, NaOCH3, and NaOEt also worked well, whereas weak bases such
as Na2CO3, K2CO3, and Na3PO4 could not be used for the reaction.
As can be seen from Table 2, 1-substituted N-tosyl-THBCs 2a–j were treated
with 3 molar equivalents of NaOH at 70 ꢀC in DMSO. b-Elimination also took place
quickly, and 1-substituted 3,4-THBCs 4a–j were obtained in 85–96% yields. A dra-
matic solvent effect was also observed here, and DMSO was found to be the best
solvent for the reaction. Strong bases such as NaOH, KOH, NaOCH3, and NaOEt
were appropriate to the reaction, among which NaOH gave the best yields.
For both b-eliminations, the reaction temperatures should be kept between 60
and 80 ꢀC (70 ꢁ 10 ꢀC); otherwise the reactions would be too slow (<60 ꢀC) or yields
would be diminished by formation of by-products (>80 ꢀC). Moreover, substituents
at the C-1 position were limited to only aryl groups. When substituents were changed
to alkyl groups such as methyl, hexyl, and isopropyl groups, the b-eliminations were
sluggish even at 100 ꢀC. If the reaction temperature was raised up to 125 ꢀC, tandem
b-elimination and aromatization would occur to afford fully aromatized
1-alkyl-isoquinolines or 1-alkyl-b-carbolines as described in our previous article.[12]

2808
J. DONG ET AL.
Table 1. Synthesis of 1-aryl-3,4-DHIQs 3 via highly selective b-elimination of N-tosyl-1-aryl-THIQs 1 by
treatment with 3 molar equivalents of NaOH at 70 ꢀC in DMSO
Entry
N-Tosyl-THIQs 1
Time (h)
3,4-DHIQs 3[lit.]
Yield (%)a
1
2
93
2
3
1.5
1.5
91
95
4
1.5
92
5
6
7
8
9
2
90
89
90
88
86
1.5
2
2.5
2.5
aIsolated yield.

1-ARYL-3,4-DHIQS AND 1-ARYL-3,4-DHBCS
2809
Table 2. Synthesis of 1-aryl-3,4-DHBCs 4 via b-elimination of N-tosyl-1-aryl-THBCs 2 by treatment of 3
molar equivalents of NaOH at 70 ꢀC in DMSO
Entry
N-Tosyl-THBCs 2
Time (h)
3,4-DHBCs 4[lit.]
Yield (%)a
1
0.5
95
2
3
4
R¼OMe 2b
R¼OEt 2c
0.5
1
R¼OMe 4b
R¼OEt 4c
90
85
93
0.5
5
6
7
R¼OMe 2e
R¼OEt 2f
R¼Cl 2 g
0.5
1
R¼OMe 4e
R¼OEt 4f
R¼Cl 4 g
94
90
87
1
8
9
0.5
0.5
91
96
(Continued )

2810
J. DONG ET AL.
Table 2. Continued
Entry
N-Tosyl-THBCs 2
Time (h)
3,4-DHBCs 4[lit.]
Yield (%)a
10
0.5
91
aIsolated yield.
Scheme 1. A plausible mechanism for both b-eliminations from compounds 1 to 3 and from compounds 2
to 4.
A plausible mechanism is proposed in Scheme 1. N-Tosyl-1-aryl-THIQs 1 or
N-tosyl-1-aryl-THBCs 2 first reacts with a strong base to form an anion, A-I or
B-I, which then immediately undergoes b-elimination with Ts– (p-CH3C6H4SOO–)
as a leaving group to afford 1-aryl-3,4-DHIQs 3 or 1-aryl-3,4-DHBCs 4. Regioslec-
tivities of the b-eliminations from compounds 1 to 3 and from compounds 2 to 4 are
actually very high; almost none of 1-aryl-1,4-DHIQs or 1-aryl-1,4-DHBCs could be
detected. It is probably because the protons at the bis-allylic C-1 positions of com-
pounds 1 and 2 are much more acidic than the protons at C-3 positions.
CONCLUSION
A mild and efficient method for the transformations from N-tosyl-1-aryl-
THIQs 1 to 1-aryl-3,4-DHIQs 3 and from N-tosyl-1-aryl-THBCs 2 to 1-aryl-3,4-
DHBCs 4 has been developed. Reaction conditions were optimized, DMSO was
found to be the best solvent, and the most appropriate temperature was around
70 ꢀC. Considering that N-tosyl-1-aryl-THIQs 1 and N-tosyl-1-aryl-THBCs 2 could
be readily prepared via Pictet–Spengler reactions,[9,10] the work described herein
might provide an efficient, mild, and practical approach to the syntheses of 1-aryl-3,
4-DHIQs 3 and 1-aryl-3,4-DHBCs 4.

1-ARYL-3,4-DHIQS AND 1-ARYL-3,4-DHBCS
2811
EXPERIMENTAL
All chemicals were analytically pure and were used as such from commercial
suppliers. 1H NMR spectra were acquired on a Bruker AM-500 instrument. Chemi-
cal shifts were given on the d scale as parts per million (ppm) with tetramethylsilane
(TMS) as the internal standard. Infrared (IR) spectra were recorded on a Nicolet
Magna IR-550 instrument. Mass spectra were recorded on a HP5989A device.
High-performance liquid chromatographic (HPLC) analysis was performed with
an Agilent=HP 1200 series instrument equipped with a variable wavelength detector
(VWD). Column chromatography was performed on silica gel (Qingdao Ocean
Chemical Corp.). 1-Substituted N-tosyl-THIQs 1 were directly obtained from N-sul-
fonyl Pictet–Spengler reaction according to a known procedure.[9] 1-Substituted N-
tosyl-THBCs 2 were obtained via Pictet–Spengler reaction of tryptamine hydro-
chloride with aldehydes[10] and the subsequent N-tosylation of the resulting 1-substi-
tuted THBCs according to our previous report.[12]
Typical Procedure for the Preparation of 1-Aryl-3,4-DHIQs 3 from
N-Tosyl-1-aryl-THIQs 1
A freshly prepared aqueous solution of NaOH (1.20 g, 30.00 mmol) in water
(3 mL) was dropwise added at 70 ꢀC over 5 min to a well-stirred solution of com-
pound 1a (3.93 g, 9.99 mmol) in DMSO (20 mL). After addition was finished, stirring
was continued at 70 ꢀC, and the reaction was traced by thin-layer chromatography
(TLC, EtOAc=hexane ¼ 1:3). When the reaction was complete, the mixture was
immediately cooled down to room temperature. The reaction mixture was diluted
with water (90 mL), and then the aqueous solution was extracted twice with ethyl
acetate (80 mL ꢂ 2). The extracts were combined and dried over anhydrous MgSO4.
Evaporation of the solvent gave a crude oil, which was purified by flash chromato-
graphy (eluent: EtOAc=hexane ¼ 1:4) to afford compound 3a (2.21 g, 9.32 mmol) in
93% yield. Compounds 3b–i were obtained from the same procedure in the yields
indicated in Table 1. HPLC analysis (column: C18 4.6 ꢂ 250 mm; mobile phase:
10% IPA in hexane; wavelength: 230 nm; flow rate: 2.5 mL=min) showed that the
purity of the compounds 3a–i was greater than 99%.
Characterization Data of Compounds 3a–3i
Compound 3a. Mp 212–213 ꢀC (lit.[13] 212–214 ꢀC). 1H NMR (CDCl3)
d ¼ 2.79 (t, J ¼ 7.2 Hz, 2H), 3.81 (t, J ¼ 7.2 Hz, 2H), 3.86 (s, 3H), 6.95 (d, J ¼ 8.6 Hz,
Hz, 2H), 7.22–7.29 (m, 2H), 7.31 (d, J ¼ 7.4 Hz, 1H), 7.38 (t, J ¼ 7.4 Hz, 1H), 7.57 (d,
J ¼ 8.6 Hz, 2H). MS m=z (%) 237 (Mþ, 48), 236 (100), 221 (9), 206 (17), 193 (7), 178
(6), 165 (7), 71 (7), 57 (8). IR (KBr) n ¼ 3065, 2930, 2840, 1610, 1515, 1450, 1250,
1175, 1040, 840, 750 cmꢃ1
.
Compound 3b[7f]. Mp 174–175 ꢀC. 1H NMR (CDCl3) d ¼ 2.72 (t, J ¼ 7.3 Hz,
2H), 3.77 (t, J ¼ 7.3 Hz, 2H), 7.12–7.21 (m, 3H), 7.27–7.38 (m, 4H), 7.48–7.55 (m,
2H). MS m=z (%) 207 (Mþ, 51), 206 (100), 204 (23), 178 (22), 165 (3), 152 (3), 102
(4), 77 (4). IR (KBr) n ¼ 3060, 2930, 2790, 1610, 1560, 1440, 1320, 1310, 1020,
760, 750, 700, 680, 650 cmꢃ1
.

2812
J. DONG ET AL.
Compound 3c[14]. Mp 185–186 ꢀC. 1H NMR (CDCl3) d ¼ 2.74–3.00 (m, 2H),
3.63–4.33 (m, 2H), 6.91 (d, J ¼ 7.6 Hz, 1H), 7.18 (dd, J1 ¼ 7.6 Hz, J2 ¼ 7.5 Hz, 1H),
7.25 (d, J ¼ 6.4 Hz, 1H), 7.33–7.39 (m, 3H), 7.39–7.45 (m, 2H); MS m=z (%) 243
(20), 241 (Mþ, 68), 206 (100), 178 (33), 151 (4), 102 (8), 77 (4). IR (KBr) n ¼ 3020,
2958, 2898, 2848, 1615, 1569, 1471, 1429, 1312, 1059, 1020, 761, 746 cmꢃ1
.
Compound 3d. Mp 205–206 ꢀC (lit.[15] 251–253 ꢀC). 1H NMR (CDCl3)
d ¼ 2.74 (t, J ¼ 7.2 Hz, 2H), 3.72 (s, 3H), 3.84 (t, J ¼ 7.2 Hz, 2H), 6.82 (d, J ¼ 2.4 Hz,
Hz, 1H), 6.95 (dd, J1 ¼ 8.2 Hz, J2 ¼ 2.5 Hz, 1H), 7.20 (d, J ¼ 8.2 Hz, 1H), 7.47–7.39
(m, 3H), 7.53–7.65 (m, 2H). MS m=z (%) 237 (Mþ, 44), 236 (100), 221 (7), 206 (7),
193 (5), 165 (6), 152 (1), 91 (1). IR (KBr) n ¼ 3050, 2940, 2930, 1600, 1570, 1495,
1320, 1275, 1220, 1040, 700 cmꢃ1. Anal. calcd for C16H15NO (%): C, 80.98; H,
6.37; N, 5.90; Found: C, 80.80; H, 6.63; N, 5.80.
1
Compound 3e[16]. Mp 231–232. H NMR (CDCl3) d ¼ 2.73 (t, J ¼ 7.2 Hz,
2H), 3.74 (s, 3H), 3.80 (t, J ¼ 7.2 Hz, 2H), 3.86 (s, 3H), 6.87 (d, J ¼ 2.5 Hz, 1H),
6.93–6.99 (m, 3H), 7.20 (d, J ¼ 8.2 Hz, 1H), 7.60 (d, J ¼ 8.7 Hz, 2H). MS m=z (%)
267 (Mþ, 46), 266 (100), 251 (7), 236 (17), 223 (4), 208 (5), 195 (2), 181 (2), 149
(2), 91 (1). HRMS calcd for C17H17NO2: 267.1259; found: 267.1258. IR (KBr)
n ¼ 3000, 2940, 2830, 1610, 1560, 1510, 1495, 1460, 1300, 1250, 1220, 1165, 1040,
840, 570 cmꢃ1
.
1
Compound 3f. Mp 73–74 ꢀC. H NMR (CDCl3) d ¼ 2.76–2.84 (m, 2H), 3.69
(s, 3H), 3.68–3.76 (m, 1H), 4.00–4.09 (m, 1H), 6.46 (s, 1H), 6.92 (d, J ¼ 8.2 Hz, 1H),
7.18 (d, J ¼ 8.2 Hz, 1H), 7.32–7.39 (m, 2H), 7.39–7.46 (m, 2H). 13C NMR (CDCl3)
d ¼ 166.14, 158.41, 138.18, 132.57, 130.40, 129.93, 129.71, 129.67, 129.30, 128.27,
126.99, 115.82, 113.00, 55.41, 48.22, 25.03. MS m=z (%) 273 (21), 271 (Mþ, 68),
236 (100), 221 (10), 205 (12), 165 (12), 118 (3), 91 (3). HRMS calcd for C16H14ClNO:
271.0764; found: 271.0765. IR (KBr) n ¼ 2939, 2831, 1608, 1577, 1316, 1302, 1279,
1217, 1050, 767, 750 cmꢃ1
.
Compound 3g. Mp 118–119 ꢀC (lit.[17] 120–121 ꢀC). 1H NMR (CDCl3)
d ¼ 2.74 (t, J ¼ 7.3 Hz, 2H), 3.73 (s, 3H), 3.82 (t, J ¼ 7.3 Hz, 2H), 3.95 (s, 3H), 6.79
(d, J ¼ 6.4 Hz, 2H), 7.39–7.48 (m, 3H), 7.57–7.64 (m, 2H). MS m=z (%) 267 (Mþ,
58), 266 (100), 250 (14), 236 (10), 222 (6), 180 (3), 152 (3), 115 (1), 77 (1). IR
(KBr) n ¼ 2925, 1606, 1562, 1515, 1280, 1357, 1210, 1116, 712 cmꢃ1
.
Compound 3h. Mp 169–170 ꢀC (lit.[18] 168–169 ꢀC). 1H NMR (CDCl3)
d ¼ 2.73 (t, J ¼ 7.2 Hz, 2H), 3.76 (s, 3H), 3.79 (t, J ¼ 7.2 Hz, 2H), 3.93 (s, 3H), 3.94
(s, 3H), 3.96 (s, 3H), 6.79 (s, 1H), 6.88 (s, 1H), 6.92 (d, J ¼ 8.3 Hz, 1H), 7.16 (d,
J ¼ 8.3 Hz, 1H), 7.24 (s, 1H). MS m=z (%) 327 (Mþ, 88), 326 (100), 312 (39), 296
(64), 281 (11), 268 (7), 252 (5), 238 (4), 226 (3), 195 (2), 140 (2), 77 (1). IR (KBr)
n ¼ 2941, 2839, 1603, 1563, 1516, 1356, 1280, 1257, 1611, 1132, 1114, 1018, 870,
805 cmꢃ1
.
Compound 3i. Mp 109–110 ꢀC (lit.[18] 110–111 ꢀC). 1H NMR (CDCl3)
d ¼ 2.71 (t, J ¼ 7.4 Hz, 2H), 3.76 (s, 3H), 3.77 (t, J ¼ 7.4 Hz, 2H), 3.95 (s, 3H), 6.02
(s, 2H), 6.78 (s, 1H), 6.85 (s, 1H), 6.86 (d, J ¼ 7.9 Hz, 1H), 7.11 (d, J ¼ 7.9 Hz,
1H), 7.14 (s, 1H). MS m=z (%) 311 (Mþ, 59), 310 (100), 294 (12), 280 (16), 266

1-ARYL-3,4-DHIQS AND 1-ARYL-3,4-DHBCS
2813
(6), 252 (3), 167 (1), 139 (2), 89 (1). IR (KBr) n ¼ 2958, 2829, 1604, 1558, 1512, 1489,
1358, 1278, 1238, 1115, 1034, 924, 864, 800 cmꢃ1
.
Typical Procedure for the Preparation of 1-Aryl-3,4-DHBCs 4 from
N-Tosyl-1-aryl-THBCs 2
A freshly prepared aqueous solution of NaOH (1.20 g, 30.00 mmol) in water
(3 mL) was dropwise added at 70 ꢀC over 5 min to a well-stirred solution of com-
pound 2a (4.03 g, 10.01 mmol) in DMSO (20 mL). After addition was finished, stir-
ring was continued at 70 ꢀC, and the reaction was traced by TLC (EtOAc=
hexane ¼ 1:3). When the reaction was complete, the mixture was immediately cooled
down to room temperature. Water (120 mL) was then slowly added while vigorous
stirring was continued, and a pale yellow solid precipitated. The solid was collected
on a Buchner funnel and rinsed with water. After drying in warm air, the crude pro-
duct could be purified by recrystallization in aqueous isopropanol (i-PrOH=
H2O ¼ 90:10) or by flash chromatography (eluent: EtOAc=CH2Cl2 ¼ 1:5) to afford
compound 4a (2.34 g, 9.50 mmol) in 95% yield. Compounds 4b–j were obtained from
the same procedure in the yields as indicated in Table 2. HPLC analysis (Column:
C18 4.6 ꢂ 250 mm; mobile phase: 5% IPA in dichloromethane; wavelength:
230 nm; flow rate: 1.0 mL=min) showed that the purity of the compounds 4a–j was
greater than 99%.
Characterization Data of Compounds 4a–4j
Compound 4a. Mp 221–222 ꢀC (lit.[19] 218–220 ꢀC). 1H NMR (CDCl3)
d ¼ 2.97 (t, J ¼ 8.3 Hz, 2H), 4.03 (t, J ¼ 8.3 Hz, 2H), 7.18 (t, J ¼ 7.9 Hz, 1H), 7.28
(t, J ¼ 7.8 Hz, 1H), 7.34 (d, J ¼ 7.9 Hz, 1H), 7.42-7.54 (m, 3H), 7.65 (d, J ¼ 7.8 Hz,
1H), 7.68–7.78 (m, 2H), 8.28 (s, 1H). MS m=z (%) 246 (Mþ, 87), 245 (100), 217
(29), 189 (3), 173 (21), 165 (2), 143 (4), 115 (5), 97 (3). IR (KBr) n ¼ 3060, 2937,
2836, 1540, 1323, 1306, 1290, 1237, 1153, 1012, 776, 741, 717 cmꢃ1
.
1
Compound 4b. Mp 186–187 ꢀC. H NMR (CDCl3) d ¼ 2.97 (t, J ¼ 8.3 Hz,
2H), 3.87 (s, 3H), 4.02 (t, J ¼ 8.3 Hz, 2H), 7.01 (d, J ¼ 8.8 Hz, 2H), 7.18 (dd,
J1 ¼ 8.0 Hz, J2 ¼ 7.0 Hz, 1H), 7.29 (dd, J1 ¼ 7.1 Hz, J2 ¼ 8.0 Hz, 1H), 7.38 (d,
J ¼ 8.2 Hz, 1H), 7.66 (d, J ¼ 8.0 Hz, 1H), 7.72 (d, J ¼ 8.8 Hz, 2H), 8.14 (s, 1H). 13C
NMR (CDCl3) d ¼ 161.03, 159.03, 136.72, 129.98, 129.48, 128.05, 125.51, 124.45,
102.28, 119.96, 117.89, 114.05, 112.16, 55.39, 48.39, 19.33. MS m=z (%) 276 (Mþ,
100), 260 (7), 248 (11), 232 (8), 204 (7), 143 (3), 130 (4), 115 (1), 91 (1). HRMS calcd
for C18H16N2O: 276.1263; found: 276.1264. IR (KBr) n ¼ 2949, 2825, 1610, 1539,
1319, 1257, 1174, 1034, 847, 740, 594 cmꢃ1
.
1
Compound 4c. Mp 211–212 ꢀC. H NMR (CDCl3) d ¼ 1.42 (t, J ¼ 7.0 Hz,
3H), 2.93 (t, J ¼ 8.2 Hz, 2H), 3.97 (t, J ¼ 8.2 Hz, 2H), 4.05 (q, J ¼ 7.0 Hz, 2H), 6.95
(d, J ¼ 7.9 Hz, 2H), 7.16 (dd, J1 ¼ 7.0 Hz, J2 ¼ 8.0 Hz, 1H), 7.27 (dd, J1 ¼ 7.0 Hz,
J2 ¼ 8.0 Hz, 1H), 7.34 (d, J ¼ 8.2 Hz, 1H), 7.60–7.71 (m, 3H), 8.41 (s, 1H). 13C
NMR (CDCl3) d ¼ 160.46, 158.88, 136.52, 129.92, 129.36, 128.00, 125.59, 124.45,
120.33, 119.96, 117.86, 114.65, 112.03, 63.61, 48.58, 19.29, 14.77. MS m=z (%) 290
(Mþ, 100), 261 (21), 245 (9), 233 (13), 217 (7), 204 (12), 143 (5), 115 (3), 102 (1).

2814
J. DONG ET AL.
IR (KBr) n ¼ 3061, 2978, 2931, 1608, 1542, 1321, 1246, 1177, 842, 742 cmꢃ1. Anal.
calcd. for C19H18N2O: C, 78.59; H, 6.25; N, 9.65; Found: C, 78.57; H, 6.43; N, 9.81.
1
Compound 4d. Mp 191–192 ꢀC. H NMR (CDCl3) d ¼ 2.96 (t, J ¼ 8.3 Hz,
2H), 3.82 (s, 3H), 4.02 (t, J ¼ 8.3 Hz, 2H), 6.97–7.04 (m, 1H), 7.16 (t, J ¼ 7.4 Hz,
1H), 7.30–7.21 (m, 3H), 7.42–7.30 (m, 2H), 7.64 (d, J ¼ 8.0 Hz, 1H), 8.41 (s, 1H).
13C NMR (CDCl3) d ¼ 159.95, 159.38, 138.86, 136.61, 129.77, 127.81, 125.51,
124.57, 120.36, 120.31, 120.00, 117.83, 116.15, 112.85, 112.10, 55.41, 48.75, 19.26.
MS m=z (%) 276 (Mþ, 87), 275 (100), 260 (5), 245 (7), 232 (7), 217 (10), 204 (11),
143 (3), 115 (4), 102 (2), 77 (1). IR (KBr) n ¼ 3060, 2940, 2830, 1579, 1542, 1321,
1288, 1215, 1055, 1018, 750 cmꢃ1. Anal. calcd. for C18H16N2O: C, 78.24; H, 5.84;
N, 10.14; Found: C, 78.14; H, 5.93; N, 10.06.
1
Compound 4e. Mp 167–168 ꢀC. H NMR (CDCl3) d ¼ 2.97 (t, J ¼ 8.5 Hz,
2H), 3.85 (s, 3H), 4.10 (t, J ¼ 8.5 Hz, 2H), 7.05 (d, J ¼ 8.3 Hz, 1H), 7.08 (dd,
J1 ¼ 7.4 Hz, J2 ¼ 7.5 Hz, 1H), 7.14 (dd, J1 ¼ 7.1 Hz, J2 ¼ 7.2 Hz, 1H), 7.24 (d,
J ¼ 8.1 Hz, 1H), 7.32 (d, J ¼ 8.2 Hz, 1H), 7.44 (dd, J1 ¼ 8.2 Hz, J2 ¼ 8.3 Hz, 1H),
7.48 (dd, J1 ¼ 7.5 Hz, J2 ¼ 1.6 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H), 8.30 (s, 1H). 13C
NMR (CDCl3) d ¼ 158.84, 156.70, 136.57, 130.93, 130.56, 129.34, 127.73, 125.53,
124.42, 121.69, 120.13, 120.03, 116.68, 111.92, 111.77, 56.19, 49.02, 19.28. MS m=z
(%) 276 (Mþ, 100), 259 (45), 247 (60), 232 (11), 218 (23), 204 (13), 171 (5), 143
(5), 115 (4), 102 (2). IR (KBr) n ¼ 2938, 2837, 1600, 1543, 1491, 1464, 1320, 1300,
1246, 1012, 747 cmꢃ1. Anal. calcd. for C18H16N2O: C, 78.24; H, 5.84; N, 10.14;
Found: C, 77.91; H, 5.85; N, 10.13.
1
Compound 4f. Mp 123–124 ꢀC. H NMR (CDCl3) d ¼ 1.25 (t, J ¼ 7.0 Hz,
3H), 2.96 (t, J ¼ 8.5 Hz, 2H), 4.09 (t, J ¼ 8.5 Hz, 2H), 4.13 (q, J ¼ 7.0 Hz, 2H), 7.04
(d, J ¼ 8.2 Hz, 1H), 7.07 (dd, J1 ¼ 7.4 Hz, J2 ¼ 7.5 Hz, 1H), 7.14 (dd, J1 ¼ 7.1 Hz,
J2 ¼ 7.2 Hz, 1H), 7.22–7.24 (m, 1H), 7.32 (d, J ¼ 8.2 Hz, 1H), 7.42 (dd, J1 ¼ 8.2 Hz,
J2 ¼ 8.3 Hz, 1H), 7.52 (dd, J1 ¼ 7.5 Hz, J2 ¼ 1.6 Hz, 1H), 7.63 (d, J ¼ 8.0 Hz, 1H),
8.53 (s, 1H). 13C NMR (CDCl3) d ¼ 159.16, 155.96, 136.61, 130.92, 130.71, 129.55,
128.33, 125.44, 124.34, 121.81, 120.03, 120.00, 116.68, 113.24, 111.89, 64.90, 48.95,
19.33, 14.81. MS m=z (%) 290 (Mþ, 57), 275 (100), 261 (22), 245 (47), 233 (7), 217
(13), 144 (6), 115 (3), 102 (1). HRMS calcd. for C19H18N2O: 290.1419; found:
290.1420. IR (KBr) n ¼ 3060, 2980, 2943, 2891, 1601, 1538, 1493, 1453, 1319,
1306, 1244, 1154, 1123, 1042, 744 cmꢃ1
.
1
Compound 4g. Mp 192–193 ꢀC. H NMR (CDCl3) d ¼ 2.99 (t, J ¼ 8.6 Hz,
2H), 4.06 (t, J ¼ 8.6 Hz, 2H), 7.09–7.17 (m, 1H), 7.19–7.28 (m, 2H), 7.30–7.43 (m,
3H), 7.45 (dd, J ¼ 7.8 Hz, J2 ¼ 1.4 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H), 8.30 (s, 1H).
1
13C NMR (CDCl3) d ¼ 158.82, 137.00, 136.76, 132.38, 130.56, 130.41, 130.00,
128.34, 127.27, 125.43, 124.65, 120.29, 120.08, 116.86, 112.16, 48.96, 19.32. MS m=z
(%) 280 (Mþ, 69), 279 (100), 243 (12), 217 (33), 189 (3), 143 (4), 122 (5), 115 (4), 89
(2). IR (KBr) n ¼ 2942, 2875, 1590, 1543, 1433, 1320, 1294, 1062, 750 cmꢃ1. Anal.
calcd. for C17H13ClN2 (%): C, 72.73; H, 4.67; N, 9.98; Found: C, 72.81; H, 4.63;
N, 9.89.
Compound 4h. Mp 289–290 ꢀC (lit.[2a] 288–290 ꢀC). 1H NMR (CDCl3)
d ¼ 2.99 (t, J ¼ 8.3 Hz, 2H), 3.95 (s, 3H), 3.96 (s, 3H), 4.03 (t, J ¼ 8.3 Hz, 2H), 6.96

1-ARYL-3,4-DHIQS AND 1-ARYL-3,4-DHBCS
2815
(d, J ¼ 8.2 Hz, 1H), 7.20 (dd, J1 ¼ 7.2 Hz, J2 ¼ 7.7 Hz, 1H), 7.31 (dd, J1 ¼ 8.0 Hz,
J2 ¼ 8.3 Hz, 2H), 7.35–7.42 (m, 2H), 7.67 (d, J ¼ 8.0 Hz, 1H), 8.18 (s, 1H). MS m=z
(%) 306 (Mþ, 100), 289 (13), 275 (14), 247 (14), 232 (3), 204 (4), 137 (1), 115 (1),
102 (1). IR (KBr) n ¼ 3057, 2921, 1542, 1515, 1468, 1420, 1336, 1302, 1273, 1251,
1147, 1027, 747 cmꢃ1
.
1
Compound 4i. Mp 177–178 ꢀC. H NMR (CDCl3) d ¼ 2.97 (t, J ¼ 8.3 Hz,
2H), 4.02 (t, J ¼ 8.3 Hz, 2H), 6.05 (s, 2H), 6.93 (d, J ¼ 8.1 Hz, 1H), 7.19 (dd,
J1 ¼ 7.6 Hz, J2 ¼ 7.3 Hz, 1H), 7.27–7.33 (m, 3H), 7.40 (d, J ¼ 8.2 Hz, 1H), 7.66 (d,
J ¼ 8.0 Hz, 1H), 8.12 (s, 1H). 13C NMR (CDCl3) d ¼ 158.99, 149.05, 147.88,
136.83, 131.59, 127.92, 125.44, 124.45, 122.42, 120.24, 119.95, 117.91, 112.22,
108.40, 108.26, 101.41, 48.38, 19.35. MS m=z (%) 290 (Mþ, 100), 275 (2), 261 (11),
233 (4), 204 (11), 176 (2), 143 (3), 115 (2). HRMS calcd for C18H14N2O2:
290.1055; found: 290.1045. IR (KBr) n ¼ 3060, 2937, 1541, 1503, 1490, 1444, 1291,
1248, 1039, 740 cmꢃ1
.
Compound 4j. Mp 173–174 ꢀC (lit.[2a] 251 ꢀC). 1H NMR (CDCl3) d ¼ 2.96 (t,
J ¼ 8.2 Hz, 2H), 3.83 (s, 3H), 3.84 (s, 3H), 3.85 (s, 3H), 4.00 (t, J ¼ 8.2 Hz, 2H), 6.88
(s, 1H), 6.89 (s, 1H), 7.18 (dd, J1 ¼ 7.9 Hz, J2 ¼ 7.2 Hz, 1H), 7.30 (dd, J1 ¼ 8.0 Hz,
J2 ¼ 7.3 Hz, 1H), 7.43 (d, J ¼ 8.0 Hz, 1H), 7.67 (d, J ¼ 7.9 Hz, 1H), 9.04 (s, 1H).
MS m=z (%) 336 (Mþ, 100), 321 (15), 305 (17), 290 (9), 277 (18), 262 (5), 206 (5),
152 (3), 115 (2), 102 (1). IR (KBr) n ¼ 2938, 2834, 1580, 1539, 1506, 1413, 1372,
1342, 1127, 1005, 739 cmꢃ1. Anal. calcd. for C20H20N2O3 (%): C, 71.41; H, 5.99;
N, 8.33; Found: C, 71.61; H, 5.63; N, 8.38.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (No. 20972048)
and the Shanghai Educational Development Foundation (Dawn Program No.
03SG27) for the financial support of this work.
REFERENCES
1. (a) Christopher, J. A.; Atkinson, F. L.; Bax, B. D.; Brown, M. J. B.; Champigny, A. C.;
Chuang, T. T.; Jones, E. J.; Mosley, J. E.; Musgrave, J. R. 1-Aryl-3,4-dihydroisoquinoline
inhibitors of JNK3. Bioorg. Med. Chem. Lett. 2009, 19, 2230–2234; (b) Batra, S.; Sabnis,
Y. A.; Rosenthal, P. J.; Avery, M. A. Structure-based approach to falcipain-2 inhibitors:
synthesis and biological evaluation of 1,6,7-trisubstituted dihydroisoquinolines and iso-
quinolines. Bioorg. Med. Chem. 2003, 11, 2293–2299; (c) Bermejo, A.; Andreu, I.; Suvire,
F.; Leonce, S.; Caignard, D. H.; Renard, P.; Pierre, A.; Enriz, R. D.; Cortes, D.; Cabedo,
N. Syntheses and antitumor targeting G1 phase of the cell cycle of benzoyldihydroisoqui-
nolines and related 1-substituted isoquinolines. J. Med. Chem. 2002, 45, 5058–5068.
2. (a) Shen, Y.-C.; Chen, C.-Y.; Hsieh, P.-W.; Duh, C.-Y.; Lin, Y.-M.; Ko, C.-L. The prep-
aration and evaluation of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-b-carboline
derivatives as potential antitumor agents. Chem. Pharm. Bull. 2005, 53, 32–36; (b) Lee,
Y.-J.; Han, Y.-R.; Park, W.; Nam, S.-H.; Oh, K.-B.; Lee, H.-S. Synthetic analogs of
indole-containing natural products as inhibitors of sortase A and isocitrate lyase. Bioorg.
Med. Chem. Lett. 2010, 20, 6882–6885; (c) Rommelspacher, H.; Bruening, G.; Susilo, R.;

2816
J. DONG ET AL.
Nick, M.; Hill, R. Pharmacology of harmalan (1-methyl-3,4-dihydro-b-carboline). Eur. J.
Pharmacol. 1985, 109, 363–371.
3. (a) Chrzanowska, M.; Rozwadowska, M. D. Asymmetric synthesis of isoquinoline alka-
loids. Chem. Rev. 2004, 104, 3341–3370; (b) Noyori, R.; Hashiguchi, S. Asymmetric trans-
fer hydrogenation catalyzed by chiral ruthenium complexes. Acc. Chem. Res. 1997, 30, 97–
102; (c) Evanno, L.; Ormala, J.; Pihko, P. M. A highly enantioselective access to tetrahy-
droisoquinoline and b-carboline alkaloids with simple Noyori-type catalysts in aqueous
media. Chem. Eur. J. 2009, 15, 12963–12967; (d) Li, C.; Xiao, J. Asymmetric hydrogen-
ation of cyclic imines with an ionic CpꢄRh(III) catalyst. J. Am. Chem. Soc. 2008, 130,
13208–13209; (e) Hajipour, A. R.; Hantehzadeh, M. Asymmetric reduction of prochiral
cyclic imines to alkaloid derivatives by novel asymmetric reducing reagent in THF or
under solid-state conditions. J. Org. Chem. 1999, 64, 8475–8478.
4. (a) da Silva, W. A.; Rodrigues, M. T.; Shankaraiah, N.; Ferreira, R. B.; Andrade, C. K.
Z.; Pilli, R. A.; Santos, L. S. Novel supramolecular palladium catalyst for the asymmetric
reduction of imines in aqueous media. Org. Lett. 2009, 11, 3238–3241; (b)
Espinoza-Moraga, M.; Petta, T.; Vasquez-Vasquez, M.; Laurie, V. F.; Moraes, L. A.
B.; Santos, L. S. Bioreduction of b-carboline imines to amines employing Saccharomyces
bayanus. Tetrahedron: Asymmetry 2010, 21, 1988–1992; (c) Santos, L. S.; Fernandes, S. A.;
Pilli, R. A.; Marsaioli, A. J. A novel asymmetric reduction of dihydro-b-carboline deriva-
tives using calix[6]arene=chiral amine as a host complex. Tetrahedron: Asymmetry 2003,
14, 2515–2519.
5. (a) Martin, N. H.; Champion, S. L.; Belt, P. B. Regiospecific oxidation of substituted
1-benzyl-3,4-dihydro-isoquinolines using singlet oxygen. Tetrahedron Lett. 1980, 21,
2613–2616; (b) Capilla, A. S.; Romero, M.; Pujol, M. D.; Caignard, D. H.; Renard, P.
Synthesis of isoquinolines and tetrahydroisoquinolines as potential antitumor agents.
Tetrahedron 2001, 57, 8297–8303.
6. (a) Ivanov, I.; Nikolova, S.; Statkova-Abeghe, S. A simple method for the synthesis of
1-substituted b-carboline derivatives from tryptamine and carboxylic acids in polyphospho-
ric acid. Heterocycles 2005, 65, 2483–2492; (b) Garcia, M. D.; Wilson, A. J.; Emmerson, D.
P. G.; Jenkins, P. R. Regioselective photo-oxidation of 1-benzyl-4,9-dihydro-3H-b-
carbolines. Chem. Commun. 2006, 2586–2588; (c) Radchenko, O. S.; Novikov, V. L.;
Elyakov, G. B. A simple and practical approach to the synthesis of the marine sponge
pigment fascaplysin and related compounds. Tetrahedron Lett. 1997, 38, 5339–5342.
7. (a) Bischler, A.; Napieralski, B. A new method for the synthesis of isoquinolines. Ber.
1893, 26, 1903–1908; (b) Whaley, W. M.; Govindachari, T. R. Preparation of 3,4-dihy-
droisoquinolines and related compounds by Bischler–Napieralski reaction. Org. React.
1951, 6, 74–150; (c) Fodor, G.; Nagubandi, S. Correlation of the von Braun, Ritter, Bis-
chler–Napieralski, Beckmann, and Schmidt reactions via nitrilium salt intermediates.
Tetrahedron 1980, 36, 1279–1300; (d) Saito, T.; Yoshida, M.; Ishikawa, T. Triphosgene:
A versatile reagent for Bischler–Napieralski reaction. Heterocycles 2001, 54, 437–438;
(e) Hegedues, A.; Hell, Z.; Potor, A. A new, environmentally friendly method for the Bis-
chler–Napieralski cyclization using zeolite catalyst. Catal. Commun. 2006, 7, 1022–1024,
and the references cited therein; (f) Movassaghi, M.; Hill, M. D. A versatile cyclodehydra-
tion reaction for the synthesis of isoquinoline and b-carboline derivatives. Org. Lett. 2008,
10, 3485–3488.
8. (a) Okimoto, M.; Takahashi, Y.; Numata, K.; Sasaki, G. Electrochemical dehydrogena-
tion of 1,2,3,4-tetrahydroisoquinoline to 3,4-dihydroisoquinoline. Heterocycles 2005, 65,
371–375; (b) Murahashi, S.-I.; Okano, Y.; Sato, H.; Nakae, T.; Komiya, N. Aerobic
ruthenium-catalyzed oxidative transformation of secondary amines to imines. Synlett
2007, 1675–1678; (c) Misztal, S.; Cegla, M. Selective and efficient synthesis of 3,4-dihydro-
b-carboline derivatives. Synthesis 1985, 1134–1135.

1-ARYL-3,4-DHIQS AND 1-ARYL-3,4-DHBCS
2817
9. Ito, K.; Tanaka, H. Syntheses of 1,2,3,4-tetrahydroisoquinolines from N-sulfonyl-
phenethylamines and aldehydes. Chem. Pharm. Bull. 1977, 25, 1732–1739.
10. Audia, J. E.; Evrard, D. A.; Murdoch, G. R.; Droste, J. J.; Nissen, J. S.; Schenck, K. W.;
Fludzinski, P.; Lucaites, V. L.; Nelson, D. L.; Cohen, M. L. Potent, selective tetrahydro-b-
carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach
fundus. J. Med. Chem. 1996, 39, 2773–2780.
11. Ishikawa, T.; Manabe, S.; Aikawa, T.; Kudo, T.; Saito, S. Intramolecular catalytic Friedel–
Crafts reactions with allenyl cations for the synthesis of quinolines and their analogues.
Org. Lett. 2004, 6, 2361–2364.
12. Dong, J.; Shi, X.-X.; Yan, J.-J.; Xing, J.; Zhang, Q.; Xiao, S. Efficient and practical one-
pot conversions of N-tosyltetrahydroisoquinolines into isoquinolines and of N-tosyltetra-
hydro-b-carbolines into b-carbolines through tandem b-elimination and aromatization.
Eur. J. Org. Chem. 2010, 6987–6992.
13. Van Binst, G.; Baert, R.; Biesemans, M.; Mortelmans, C.; Salsmans, R. Benzo- and
indoloquinolizine derivatives. VII. The dehydrogenation of enamines in the synthesis of
benzo[c]substituted quinolizidines. Bull. Soc. Chim. Belg. 1976, 85, 1–9.
14. Yang, J.; Hua, W.-Y.; Wang, F.-X.; Wang, Z.-Y.; Wang, X. Design, synthesis, and inhi-
bition of platelet aggregation for some 1-o-chlorophenyl-1,2,3,4-tetrahydroisoquinoline
derivatives. Bioorg. Med. Chem. 2004, 12, 6547–6557.
15. Lantos, I.; Bhattacharjee, D.; Eggleston, D. S. Synthesis of 1-phenyl-5H-2-benzazepines
by ring expansion of 1-phenyl-1,2-dihydroisoquinolines. J. Org. Chem. 1986, 51, 4147–
4150.
16. Doi, S.; Shirai, N.; Sato, Y. Abnormal products in the Bischler-Napieralski isoquinoline
synthesis. J. Chem. Soc., Perkin Trans. 1 1997, 2217–2221.
17. Neuvonen, K.; Fueloep, F.; Neuvonen, H.; Koch, A.; Kleinpeter, E.; Pihlaja, K. Propa-
gation of polar substituent effects in 1-(substituted phenyl)-6,7-dimethoxy-3,4-dihydro-
and -1,2,3,4-tetrahydroisoquinolines as explained by resonance polarization concept. J.
Org. Chem. 2005, 70, 10670–10678.
18. Yamada, K.; Takeda, M.; Iwakuma, T. Asymmetric reduction of cyclic imines with chiral
sodium acyloxyborohydrides. J. Chem. Soc., Perkin Trans. 1 1983, 265–270.
19. Mohsen, A.; Omar, M. E.; Yamada, S. Studies on thioamides. IV. Extension of the cyclo-
desulfurization reaction to synthesize 1-substituted and 1,3-disubstituted-3,4-dihydro-9H-
pyrido[3,4-b]indole derivatives. Chem. Pharm. Bull. 1966, 14, 856–861.