Tetrahydroquinolines by lewis acid-promoted friedel-crafts cyclizations

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Tetrahydroquinolines by Lewis Acid-
promoted Friedel-Crafts Cyclizations
Richard A. Bunce a , Nicholas R. Cain a & John G. Cooper a
a Department of Chemistry, Oklahoma State University, Stillwater,
OK, 74078-3071, USA
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Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations, Organic Preparations and
Procedures International: The New Journal for Organic Synthesis, 45:1, 28-43
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Organic Preparations and Procedures International, 45:28–43, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2013.743420
Tetrahydroquinolines by Lewis Acid-promoted
Friedel-Crafts Cyclizations
Richard A. Bunce, Nicholas R. Cain, and John G. Cooper
Department of Chemistry, Oklahoma State University Stillwater,
OK, 74078-3071 USA
Two recent projects described approaches to 1,1-dimethyl-1,2,3,4-tetrahydronaphthalenes1
and 4,4-dimethyl-1,2,3,4-tetrahydroisoquinolines2 using acid-promoted Friedel-Crafts cy-
clizations. Both of these ring systems are of interest to us for the synthesis of structures with
potential biological activity. The current work explores a further use of this strategy for the
synthesis of tetrahydroquinolines bearing gem-dimethyl substituents at C4. Such tetrahy-
droquinolines have shown activity as peroxisome proliferator activated receptor agonists
and, thus, have potential in the treatment of type-2 diabetes.3–5
Several experiments using FeCl3·6H2O in dichloromethane,2,6,7 AlCl3 in benzene, and
ꢀR
Amberlyst-15 in benzene1 were performed on the parent substrate 4a to identify the best
protocol for the ring closure. In the current series, cyclization was complicated by the
relatively facile loss of the alcohol side-chain to give the N-aryl-p-toluenesulfonamides 6.
This side-chain degradation resulted in slightly lower yields of tetrahydroquinolines relative
to our previously reported tetrahydroisoquinolines.2 Indeed, it was found that the optimum
reagent for cyclization was dependent on both the nature and location of the substituent
group on the aromatic ring.
The required tetrahydroquinoline precursors were prepared in three steps from substi-
tuted anilines using a strategy that overlaps with a previous synthesis of 4-aminoquinolines
reported by Johnson and co-workers.8 Conjugate addition of anilines 1 to methyl acrylate
gave the 3-anilinopropionate esters 2 in 61–72% yields. Tosylation at nitrogen then afforded
sulfonamides 3 in 79–90%, and Grignard addition with methylmagnesium iodide furnished
the requisite precursors 4 in 60–90% yields (see Scheme 1).
Based upon our recent success using FeCl3·6H2O for the synthesis of tetrahydroiso-
quinolines from tertiary alcohols,2 we first examined this mild Lewis acid (Method A) for
the current tetrahydroquinoline cyclizations. The optimized conditions using FeCl3·6H2O
employed 2.0 equiv of the Lewis acid in chloroform at 60◦C for 2–6 h and gave yields
up to 78% with 12–28% loss of the alcohol side chain (see Table 1). As expected,2
Received July 17, 2012; in final form September 11, 2012.
Nick Cain and John Cooper were undergraduate research participants.
Address correspondence to Richard A. Bunce, Department of Chemistry, Oklahoma State Uni-
versityStillwater, OK 74078-3071, USA. E-mail: rab@okstate.edu
28

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
29
Table 1
Cyclization of Tetrahydroquinoline Derivatives
Cmpd
X
Methoda
Time
(h)
Yield (%) of
cyclizationb
Ratio of 5
5-X
6-X
7-X
8-X
4a
4a
4b
4c
4d
4e
4e
4f
H
H
A
B
A
A
A
A
B
A
B
A
B
A
B
A
4.0
1.0
4.0
4.0
4.0
2.0
1.0
2.0
0.5
6.0
1.0
6.0
1.0
4.0
68
62
59
78
74
76
80
0
63
65
78
44
74
62
2-CH3
3-CH3
4-CH3
3-OCH3
3-OCH3
4-OCH3
4-OCH3
3-C1
—
26
—
21
21
—
—
28
14
—
—
—
—
—
74
—
—
0
63
—
—
44
74
—
—
52
—
55
59
—
—
37
64
—
—
59
—
—
—
—
—
—
—
—
—
—
4f
4g
4g
4h
4h
4i
3-C1
4-C1
4-C1
2,3-(CH2)4
62
aMethod A: 2.0 equiv FeCl3-6H2O, CHC13, 60◦C; Method B: 1.5 equiv AlCl3 PhH, 80◦C.
bAll successful cyclizations were accompanied by 12–30% of fragmentation to give 6, identified by
their mps.
CO2CH3
CO2CH3
i
ii
iii
X
X
X
NH2
N
H
N
Ts
1
2
3
5
6
3
4
iv
OH
+
X
X
7
X
2
N 1
Ts
NH
Ts
N
8
Ts
4
6
5
i: CH2=CHCO2CH3, Δ, 61−72%; ii: p-TsCl, pyridine, 79-90%; iii: CH3MgBr, 60-90%;
iv: Method A: 2.0 equiv FeCl3·6H2O, CHCl3, Δ or Method B: 1.5 equiv AlCl3, PhH, Δ.
a: X = H; b: X = 2-CH3; c: X = 3-CH3; d: X = 4-CH3; e: X = 3-OCH3
f: X = 4-OCH3; g: X = 3-Cl; h: X = 4-Cl; i: X = 2,3-(CH2)4
Scheme 1
Synthesis of the tetrahydroquinoline precursors.

30
Bunce et al.
MCl3
O
H2O
MCl3
4a
6a
+
+
H
O
N
T
s
7
Scheme 2
Possible mechanism for loss of the alcohol side chain.
ortho-substituted substrates gave products with X at C8, para substrates gave X at C6,
and meta substrates gave a mixture having X at C7 (less sterically congested, major) and
at C5 (more sterically congested, minor). We speculate that loss of the side-chain from 4a
could take place by a Grob-type fragmentation9,10 via 7 to generate acetone, ethylene, and
the anion of the sulfonamide 6a (see Scheme 2). Since the sulfonamide is a relatively stable
anion, this reaction may or may not require pre-complexation of the nitrogen by iron.
In several cases, it was not possible to achieve satisfactory yields using FeCl3·6H2O.
In particular, substrates bearing heteroatom functional groups at C4, relative to the nitrogen
(e.g. 4f and 4h), gave poor results with this catalyst. For these cases as well as our other
heteroatom-substituted systems, 1.5 mole equiv of AlCl3 at 80◦C for 0.5–1 h (Method
B) provided greater yields of cyclized products (see Table 1) with less fragmentation.
This likely results from the greater reactivity of AlCl3,11 which promotes rapid formation
of the product without prolonged heating. Additionally, the anhydrous conditions used
with AlCl3 would disfavor dissociation of chloride ion and preclude nucleophile-initiated
substrate degradation. In contrast, the use of AlCl3 with alkyl-substituted substrates lowered
yields by 5–10% compared to the FeCl3·6H2O-catalyzed reactions. Finally, attempts to use
ꢀR
Amberlyst-15 for any of these ring closures led to an unacceptably high proportion of
side-chain cleavage.
In conclusion, we have developed a new synthesis of tetrahydroquinolines using a
Lewis acid-promoted Friedel-Crafts reaction. For unsubstituted and alkyl-substituted sub-
strates examined, FeCl3·6H2O proved superior, but when the substrate possessed het-
eroatom functionality, more reactive AlCl3 was necessary. We are continuing our efforts to
explore and optimize cyclizations of heterocyclic systems using mild electrophilic aromatic
substitutions.
Experimental Section
Unless otherwise indicated, all reactions were carried out under dry N2 in oven-dried
glassware. All reagents and solvents were used as received. Reactions were monitored by
thin layer chromatography (TLC) on silica gel GF plates (Analtech No. 21521). Larger-scale
separations were performed by preparative thin layer chromatography (PTLC) on 20-cm
× 20-cm silica gel GF plates (Analtech No. 02015) or flash column chromatography12
ꢀR
in quartz columns using silica gel (Davisil , grade 62, 60–200 mesh) mixed with UV-
active phosphor (Sorbent Technologies No. UV-05). Band elution for all chromatographic
methods was monitored using a hand-held UV lamp. Melting points were uncorrected.

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
31
FT-IR spectra were recorded from thin films on NaCl disks. 1H- and 13C-NMR spectra were
measured in CDCl3 at 300 MHz and 75 MHz, respectively, using (CH3)4Si as the internal
standard.
Representative Procedure for the Addition of Anilines to Methyl Acrylate.
Methyl 3-Anilinopropionate (2a)
The procedure of Johnson and co-workers was used.8 A mixture of 9.30 g (100 mmol) of
aniline (1a), 9.36 g (9.79 mL, 108 mmol) of methyl acrylate, and 1.00 mL of acetic acid was
refluxed for 15 h. The solution was cooled and distilled under high vacuum to afford 12.9 g
(72%) of 2a as a yellow oil, bp. 120–124◦C (1 mm Hg), [lit.8 bp. 156–160◦C (13–14 mm
Hg)]. IR: 3399, 1733 cm−1; 1H-NMR: δ 7.18 (t, J = 7.7 Hz, 2H), 6.72 (t, J = 7.7 Hz, 1H),
6.62 (d, J = 7.7 Hz, 2H), 4.00 (br s, 1H), 3.69 (s, 3H), 3.45 (t, J = 6.6 Hz, 2H), 2.62 (t,
J = 6.6 Hz, 2H); 13C-NMR: δ 172.6, 147.5, 129.3, 117.7, 113.0, 51.2, 39.3, 33.6.
Methyl 3-(2-Methylanilino)propionate (2b)
This compound was prepared as above from 10.7 g (100 mmol) of 2-methylaniline (1b),
9.36 g (9.79 mL, 108 mmol) of methyl acrylate, and 1.00 mL of acetic acid to give 13.5 g
(70%) of 2b as a yellow oil, bp. 118–122◦C (1 mm Hg). IR: 3426, 1734 cm−1; 1H-NMR:
δ 7.12 (t, J = 7.7 Hz, 1H), 7.05 (d, J = 7.1 Hz, 1H), 6.66 (t, J = 7.1 Hz, 1H), 6.61 (d,
J = 7.7 Hz, 1H), 3.97 (br s, 1H), 3.69 (s, 3H), 3.48 (t, J = 6.0 Hz, 2H), 2.65 (t, J = 6.0 Hz,
2H), 2.12 (s, 3H); 13C-NMR: δ 172.8, 145.4, 130.1, 127.0, 122.3, 117.1, 109.5, 51.6, 39.2,
33.5, 17.3.
Anal. Calcd for C11H15NO2: C, 68.39; H, 7.77; N, 7.25. Found: C, 68.59; H, 7.82; N,
7.14.
Methyl 3-(3-Methylanilino)propionate (2c)
This compound was prepared as above from 10.7 g (100 mmol) of 3-methylaniline (1c),
9.36 g (9.79 mL, 108 mmol) of methyl acrylate, and 1.00 mL of acetic acid to give 12.5 g
(65%) of 2c as a yellow oil, bp. 123–128◦C (1 mm Hg). IR: 3399, 1733 cm−1; 1H-NMR: δ
7.06 (t, J = 7.1 Hz, 1H), 6.54 (d, J = 7.1 Hz, 1H), 6.44 (s, 1H), 6.43 (d, J = 7.1 Hz, 1H),
3.92 (br s 1H), 3.68 (s, 3H), 3.43 (t, J = 6.0 Hz, 2H), 2.60 (t, J = 6.0 Hz, 2H), 2.26 (s, 3H);
13C-NMR: δ 172.6, 147.5, 139.0, 129.1, 118.6, 113.7, 110.0, 51.6, 39.3, 33.6, 21.5.
Anal. Calcd for C11H15NO2: C, 68.39; H, 7.77; N, 7.25. Found: C, 68.46; H, 7.80; N,
7.16.
Methyl 3-(4-Methylanilino)propionate (2d)
This compound was prepared as above from 10.7 g (100 mmol) of 4-methylaniline (1d),
9.36 g (9.79 mL, 108 mmol) of methyl acrylate, and 1.00 mL of acetic acid to give 13.1 g
(68%) of 2d as a yellow oil, bp. 121–125◦C (1 mm Hg). The distillate crystallized to a
1
light yellow solid on standing, mp. 54–56◦C. IR: 3383, 1733 cm−1; H-NMR: δ 6.99 (d,
J = 8.2 Hz, 2H), 6.55 (d, J = 8.2 Hz, 2H), 3.91 (br s, 1H), 3.69 (s, 3H), 3.43 (t, J = 6.0 Hz,

32
Bunce et al.
2H), 2.62 (t, J = 6.0 Hz, 2H), 2.24 (s, 3H); 13C-NMR: δ 172.9, 145.2, 129.8, 127.0, 113.2,
51.7, 39.7, 33.7, 20.4.
Anal. Calcd for C11H15NO2: C, 68.39; H, 7.77; N, 7.25. Found: C, 68.44; H, 7.78; N,
7.21.
Methyl 3-(3-Methoxyanilino)propionate (2e)
The procedure of Johnson and co-workers was used.8 A mixture of 6.15 g (50.0 mmol) of
3-methoxyaniline (1e), 4.64 g (4.86 mL, 54.0 mmol) of methyl acrylate, and 3 drops of
anhydrous stannic chloride in 5 mL of benzene was refluxed for 24 h. Concentration and
vacuum distillation of the crude mixture gave 6.37 g (61%) of 2e as a colorless oil, bp.
148–154◦C (1 mm Hg). IR: 3399, 2845, 1733 cm−1; 1H-NMR: δ 7.09 (t, J = 7.7 Hz, 1H),
6.29 (dd, J = 8.2, 2.2 Hz, 1H), 6.26 (dd, J = 8.2, 2.2 Hz, 1H), 6.18 (t, J = 2.2 Hz, 1H),
4.09 (br s, 1H), 3.77 (s, 3H), 3.70 (s, 3H), 3.44 (t, J = 6.3 Hz, 2H), 2.62 (t, J = 6.3 Hz,
2H); 13C-NMR: δ 172.7, 160.8, 148.8, 130.0, 106.1, 102.9, 99.0, 55.0, 51.7, 39.3, 33.5.
Anal. Calcd for C11H15NO3: C, 63.16; H, 7.18; N, 6.70. Found: C, 63.39; H, 7.26; N,
6.56.
Methyl 3-(4-Methoxyanilino)propionate (2f)
This compound was prepared as above by refluxing 6.16 g (50.0 mmol) of 4-methoxyaniline
(1f), 4.64 g (4.86 mL, 54.0 mmol) of methyl acrylate, and 3 drops of anhydrous stannic
chloride in 5 mL of benzene for 24 h. Concentration and vacuum distillation of the crude
mixture gave 6.69 g (64%) of 2f as a colorless oil, bp. 149–152◦C (1 mm Hg) [lit.8 bp.
143–152 (0.65 mm Hg)]. IR: 3384, 2834, 1733 cm−1; 1H-NMR: δ 6.78 (d, J = 8.8 Hz, 2H),
6.61 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.73 (br s, 1H), 3.69 (s, 3H), 3.40 (t, J = 6.3 Hz,
2H), 2.61 (t, J = 6.3 Hz, 2H); 13C-NMR: δ 172.8, 152.4, 141.6, 114.9, 114.6, 55.7, 51.7,
40.5, 33.7.
Methyl 3-(3-Chloroanilino)propionate (2g)
This compound was prepared as above by refluxing 6.38 g (50.0 mmol) of 3-chloroaniline
(1g), 4.64 g (4.86 mL, 54.0 mmol) of methyl acrylate, and 0.50 mL of acetic acid for
20 h. Vacuum distillation of the crude mixture gave 6.93 g (65%) of 2g as a colorless
oil, bp. 135–140◦C (1 mm Hg) [lit.8 bp. 194–198◦C (20 mm Hg)]. The distillate solidified
to a white solid on standing, mp 38–39◦C (lit.5 mp. 39.6–40.6◦C). IR: 3399, 1731 cm−1
;
1H-NMR: δ 7.06 (t, J = 8.2 Hz, 1H), 6.66 (d, J = 7.7 Hz, 1H), 6.58 (s, 1H), 6.47 (dd, J =
8.2, 2.2 Hz, 1H), 4.14 (br s, 1H), 3.70 (s, 3H), 3.42 (t, J = 6.0 Hz, 2H), 2.61 (t, J = 6.0 Hz,
2H); 13C-NMR: δ 172.6, 148.6, 135.0, 130.2, 117.4, 112.4, 111.2, 51.8, 39.1, 33.4.
Methyl 3-(4-Chloroanilino)propionate (2h)
This compound was prepared as above by refluxing 6.38 g (50.0 mmol) of 4-chloroaniline
(1h), 4.64 g (4.86 mL, 54.0 mmol) of methyl acrylate, and 0.50 mL of acetic acid for 20 h.
Vacuum distillation of the crude mixture gave 6.95 g (65%) of 2h as a colorless oil, bp.
146–148◦C (1 mm Hg). The distillate solidified to a white solid on standing, mp 59–60◦C.

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
33
IR: 3397, 1732 cm−1; 1H-NMR: δ 7.12 (d, J = 8.8 Hz, 2H), 6.54 (d, J = 8.8 Hz, 2H), 3.95
(br s, 1H), 3.69 (s, 3H), 3.41 (t, J = 6.3 Hz, 2H), 2.61 (t, J = 6.3 Hz, 2H); 13C-NMR: δ
172.6, 146.0, 129.1, 122.3, 114.1, 51.8, 39.5, 33.4.
Anal. Calcd for C10H12ClNO2: C, 56.21; H, 5.62; N, 6.56. Found: C, 56.33; H, 5.67;
N, 6.29.
Methyl 3-(5,6,7,8-Tetrahydro-1-naphthylamino)propionate (2i)
This compound was prepared as above by refluxing 3.67 g (25.0 mmol) of 5,6,7,8-
tetrahydro-1-naphthylamine (1i), 2.32 g (2.43 mL, 27.0 mmol) of methyl acrylate, and
0.50 mL of acetic acid for 20 h. Vacuum distillation of the crude mixture gave 4.13 g (71%)
of 2i as a yellow oil, bp. 157–162◦C (1 mm Hg) [lit.13 bp. 225–226◦C (32 mm Hg)]. IR:
1
3429, 1737 cm−1; H-NMR: δ 7.03 (t, J = 7.7 Hz, 1H), 6.52 (d, J = 7.7 Hz, 1H), 6.46
(d, J = 7.7 Hz, 1H), 3.92 (br s, 1H), 3.69 (s, 3H), 3.48 (t, J = 6.0 Hz, 2H), 2.73 (t, J =
6.0 Hz, 2H), 2.66 (t, J = 6.0 Hz, 2H), 2.38 (t, J = 6.0 Hz, 2H), 1.84 (m, 2H), 1.75 (m, 2H);
13C-NMR: δ 172.9, 145.1, 137.8, 126.0, 121.5, 118.5, 106.7, 51.7, 39.3, 33.6, 30.0, 23.7,
23.0, 22.6.
Anal. Calcd for C14H19NO2: C, 72.10; H, 8.15; N, 6.01. Found: C, 72.31; H, 8.24; N,
5.91.
Representative Procedure for Tosylation of the 3-Anilinopropionates.
Methyl N-Tosyl-3-anilinopropionate (3a)
The procedure of Johnson and co-workers was used.8 To a stirred solution of 5.00 g
(27.9 mmol) of 2a in 50 mL of pyridine was added 5.80 g (30.4 mmol) of p-toluenesulfonyl
chloride (p-TsCl) in small increments over a period of 5 min. The reaction was stirred at
room temperature for 10 min, and then heated at 100◦C (oil bath) for 15 min. After cooling,
75 mL of water was added, and the mixture was extracted with ether (3 × 75 mL). The
ether solution was washed three times with 3.0 M HCl, once with 0.5 M NaOH, once with
water, and once with saturated NaCl, then dried (MgSO4) and concentrated under vacuum.
The resulting tan crystals were recrystallized from ether-petroleum ether to give 8.45 g
(91%) of sulfonamide 3a as a tan solid, mp. 46–48◦C (lit.8 mp. 46.4–47.8◦C). IR: 1739,
1354, 1164 cm−1; 1H NMR: δ 7.48 (d, J = 8.2 Hz, 2H), 7.30 (m, 3H), 7.26 (t, J = 8.2 Hz,
2H), 7.03 (m, 2H), 3.84 (t, J = 7.7 Hz, 2H), 3.59 (s, 3H), 2.56 (t, J = 7.7 Hz, 2H), 2.42 (s,
3H); 13C-NMR: δ 171.3, 143.5, 138.9, 135.0, 129.4, 129.1, 128.8, 128.1, 127.7, 51.7, 46.8,
34.0, 21.5.
Methyl N-Tosyl-3-(2-methylanilino)propionate (3b)
This compound was prepared as above from 5.00 g (25.9 mmol) of 2b and 5.38 g
(28.2 mmol) of p-TsCl in 50 mL of pyridine. Workup gave 7.09 (79%) of sulfonamide 3b as
a light brown oil. IR: 1739, 1351, 1161 cm−1; 1H-NMR: δ 7.57 (d, J = 8.2 Hz, 2H), 7.29 (d,
J = 8.2 Hz, 2H), 7.28 (d, J = 7.7 Hz, 1H); 7.21 (td, J = 7.7, 1.1 Hz, 1H), 7.06 (td, J = 7.7,
1.1 Hz, 1H), 6.60 (d, J = 7.7 Hz, 1H), 4.04 (ddd, J = 15.4, 9.3, 6.6 Hz, 1H), 3.57 (s, 3H), 3.56
(obscured ddd, 1H), 2.61 (ddd, J = 15.9, 8.8, 6.0 Hz, 1H), 2.46 (obscured ddd, J ≈ 15.4,

34
Bunce et al.
9.3, 6.0 Hz, 1H), 2.44 (s, 3H), 2.34 (s, 3H); 13C-NMR: δ 171.3, 143.6, 139.9, 137.8, 135.5,
131.5, 129.5, 128.5, 128.1, 127.9, 126.4, 51.7, 47.5, 33.6, 21.5, 18.4.
Anal. Calcd for C18H21NO4S: C, 62.25; H, 6.05; N, 4.03. Found: C, 62.41; H, 6.01; N,
4.11.
Methyl N-Tosyl-3-(3-methylanilino)propionate (3c)
This compoundwaspreparedasabovefrom5.00g(25.9mmol)of 2cand5.38g(28.2mmol)
of p-TsCl in 50 mL of pyridine. Workup and recrystallization from ether-petroleum ether
gave 7.82 (87%) of sulfonamide 3c as a light tan solid, mp. 83–85◦C. IR: 1741, 1351,
1165 cm−1; 1H-NMR: δ 7.50 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.2 Hz, 2H), 7.18 (t, J =
7.7 Hz, 1H), 7.11 (d, J = 7.7 Hz, 1H), 6.90 (s, 1H), 6.77 (d, J = 7.7 Hz, 1H), 3.81 (t, J =
7.4 Hz, 2H), 3.60 (s, 3H), 2.55 (t, J = 7.4 Hz, 2H), 2.43 (s, 3H), 2.30 (s, 3H); 13C NMR:
δ 171.4, 143.5, 139.0, 138.8, 135.1, 129.8, 129.3, 128.9, 128.8, 127.7, 125.4, 51.6, 46.8,
33.9, 21.5, 21.2.
Anal. Calcd for C18H21NO4S: C, 62.25; H, 6.05; N, 4.03. Found: C, 62.31; H, 6.07; N,
3.98.
Methyl N-Tosyl-3-(4-methylanilino)propionate (3d)
This compound was prepared as above from 5.00 g (25.9 mmol) of 2d and 5.38 g
(28.2 mmol) of p-TsCl in 50 mL of pyridine. Workup and recrystallization from ether-
petroleum ether gave 7.72 (86%) of sulfonamide 3d as a light tan solid, mp. 56–57◦C. IR:
1741, 1351, 1165 cm−1; 1H-NMR: δ 7.49 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H),
7.10 (d, J = 8.2 Hz, 2H), 6.90 (d, J = 8.2 Hz, 2H), 3.81 (t, J = 7.4 Hz, 2H), 3.60 (s, 3H),
2.54 (t, J = 7.4 Hz, 2H), 2.43 (s, 3H), 2.33 (s, 3H); 13C-NMR: δ 171.4, 143.4, 138.2, 136.2,
135.1, 129.7, 129.4, 128.6, 127.7, 51.7, 46.8, 33.9, 21.5, 21.1.
Anal. Calcd for C18H21NO4S: C, 62.25; H, 6.05; N, 4.03. Found: C, 62.34; H, 6.09; N,
3.93.
Methyl N-Tosyl-3-(3-methoxyanilino)propionate (3e)
This compound was prepared as above (at 25◦C) from 5.00 g (23.9 mmol) of 2e and 5.02 g
(26.4 mmol) of p-TsCl in 50 mL of 1:1 benzene:pyridine. Workup gave 7.98 g (92%) of
sulfonamide 3e as a light yellow oil. IR: 2839, 1739, 1352, 1162 cm−1; 1H-NMR: δ 7.51
(d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.2 Hz, 2H), 7.19 (t, J = 8.2 Hz, 1H), 6.85 (dd, J = 8.2,
2.2 Hz, 1H), 6.63 (t, J = 2.2 Hz, 1H), 6.58 (d, J = 7.7 Hz, 1H), 3.82 (t, J = 7.4 Hz, 2H),
3.73 (s, 3H), 3.61 (s, 3H), 2.56 (t, J = 7.4 Hz, 2H), 2.42 (s, 3H); 13C-NMR: δ 171.3, 159.9,
143.5, 140.1, 129.6, 129.4, 128.2, 127.7, 120.6, 114.7, 114.0, 55.3, 51.6, 46.8, 33.9, 21.5.
Anal. Calcd for C18H21NO5S: C, 59.50; H, 5.79; N, 3.86. Found: C, 59.73; H, 5.84; N,
3.67.
Methyl N-Tosyl-3-(4-methoxyanilino)propionate (3f)
This compound was prepared as above (at 25◦C) from 5.00 g (23.9 mmol) of 2f and 5.02 g
(26.4 mmol) of p-TsCl in 50 mL of 1:1 benzene:pyridine. Workup gave 7.81 g (90%) of

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
35
sulfonamide 3f as a light yellow oil that crystallized on standing, mp. 42–44◦C (lit.8 mp.
43–44.5◦C). IR: 2841, 1740, 1315, 1162 cm−1; 1H-NMR: δ 7.49 (d, J = 8.2 Hz, 2H), 7.25
(d, J = 8.2 Hz, 2H), 6.93 (d, J = 9.3 Hz, 2H), 6.81 (d, J = 9.3 Hz, 2H), 3.80 (t, J = 7.4 Hz,
2H), 3.78 (s, 3H), 3.60 (s, 3H), 2.54 (t, J = 7.4 Hz, 2H), 2.42 (s, 3H); 13C-NMR: δ 171.4,
159.2, 143.4, 135.1, 131.3, 130.1, 129.4, 127.7, 114.2, 55.4, 51.6, 46.9, 33.9, 21.5.
Methyl N-Tosyl-3-(3-chloroanilino)propionate (3g)
This compound was prepared as per 3a from 5.00 g (23.9 mmol) of 2g and 5.02 g
(26.4 mmol) of p-TsCl in 50 mL of pyridine. Workup and recrystallization from benzene-
petroleum ether gave 7.81 g (89%) of sulfonamide 3g as white crystals, mp. 75–77◦C
(lit.8 mp. 77–78.2◦C). IR: 1739, 1351, 1161 cm−1; 1H-NMR: δ 7.48 (d, J = 8.2 Hz, 2H),
7.30–7.22 (complex m, 4H), 7.05 (s, 1H), 6.95 (d, J = 7.1 Hz, 1H), 3.81 (t, J = 7.1 Hz,
2H), 3.61 (s, 3H), 2.56 (t, J = 7.1 Hz, 2H), 2.44 (s, 3H); 13C-NMR: δ 171.1, 143.9, 140.3,
134.5, 134.4, 129.9, 129.5, 129.0, 128.4, 127.6, 127.0, 51.7, 46.7, 33.9, 21.5.
Methyl N-Tosyl-3-(4-chloroanilino)propionate (3h)
This compound was prepared as above from 5.00 g (23.9 mmol) of 2h and 4.91 g
(25.7 mmol) of p-TsCl in 50 mL of pyridine. Workup and recrystallization from benzene-
petroleum ether gave 7.91 g (90%) of sulfonamide 3h as white crystals, mp. 71–73◦C. IR:
1738, 1350, 1166 cm−1; 1H-NMR: δ 7.47 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H),
7.27 (d, J = 8.2 Hz, 2H), 6.98 (d, J = 8.2 Hz, 2H), 3.81 (t, J = 7.4 Hz, 2H), 3.61 (s, 3H),
2.55 (t, J = 7.4 Hz, 2H), 2.43 (s, 3H); 13C-NMR: δ 171.2, 143.8, 137.6, 134.6, 134.0, 130.1,
129.5, 129.3, 127.7, 51.7, 46.7, 33.9, 21.5.
Anal. Calcd for C17H18ClNO4S: C, 55.51; H, 4.90; N, 3.81. Found: C, 55.69; H, 4.96;
N, 3.71.
Methyl N-Tosyl-3-(5,6,7,8-tetrahydro-1-naphthylamino)propionate (3i)
This compound was prepared as above from 3.00 g (12.9 mmol) of 2i and 2.68 g (14.1 mmol)
of p-TsCl in 30 mL of pyridine. Workup gave 4.09 g (82%) of sulfonamide 3i as a yellow
1
oil that crystallized on standing, mp. 77–80◦C. IR: 1740, 1348, 1165 cm−1; H-NMR: δ
7.59 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 7.7 Hz, 1H), 6.96 (t,
J = 7.7 Hz, 1H), 6.40 (d, J = 7.7 Hz, 1H), 4.01 (ddd, J = 15.9, 9.9, 6.6 Hz, 1H), 3.58 (s,
3H), 3.49 (ddd, J = 14.3, 9.3, 5.5 Hz, 1H), 2.94 (m, 1H), 2.84–2.32 (complex m, 5H), 2.44
(s, 3H), 1.86 (m, 4H); 13C-NMR: δ 171.3, 143.5, 139.3, 139.2, 137.6, 135.5, 129.5, 129.4,
128.0, 125.4, 125.0, 51.7, 47.5, 33.3, 29.6, 25.6, 22.62, 22.60, 21.5.
Anal. Calcd for C21H25NO4S: C, 65.12; H, 6.46; N, 3.62. Found: C, 65.39; H, 6.54; N,
3.48.
Representative Procedure for Grignard Reaction of the Sulfonamide Esters.
N-Tosyl-3-anilino-2-methyl-2-butanol (4a)
A 250-mL, three-necked, round-bottomed flask, equipped with an addition funnel, a con-
denser and a magnetic stirrer, was charged with 0.96 g (40.0 mmol) of magnesium metal

36
Bunce et al.
and 5 mL of ether. To this mixture was slowly added a small portion (ca. 10 drops) of a
solution of 2.56 g (1.12 mL, 18.0 mmol) of methyl iodide in 25 mL of ether. Several of
the magnesium turnings were carefully broken up with a glass rod to initiate the reaction,
and the remainder of the methyl iodide solution was slowly added dropwise to maintain a
gentle reflux. Once added, the reaction was heated for 10 min to ensure complete formation
of the Grignard reagent. Heating was stopped, and a solution of 2.00 g (6.00 mmol) of 3a
was added dropwise over 15 min. The reaction was heated for an additional 15 min, then
cooled, added to ice-cold, saturated NH4Cl and extracted with ether (3 × 50 mL). The
combined organic extracts were washed with 5% Na2S2O3, water, and saturated NaCl, then
dried (MgSO4), and concentrated under vacuum to give a viscous light yellow oil that crys-
tallized on standing. Recrystallization from ether-petroleum ether afforded 1.44 g (72%)
1
of alcohol 4a as a white solid, mp. 101–102◦C. IR: 3525, 1345, 1162 cm−1; H-NMR: δ
7.47 (d, J = 8.2 Hz, 2H), 7.30 (m, 3H), 7.26 (t, J = 8.2 Hz, 2H), 7.06 (m, 2H), 3.69 (t,
J = 7.7 Hz, 2H), 2.42 (s, 3H), 1.64 (t, J = 7.7 Hz, 2H), 1.49 (br s, 1H), 1.21 (s, 6H);
13C-NMR: δ 143.4, 139.2, 135.0, 129.4, 129.0, 128.7, 127.8, 127.7, 70.0, 46.7, 41.4, 29.5,
21.5.
Anal. Calcd for C18H23NO3S: C, 64.86; H, 6.91; N, 4.20. Found: C, 64.89; H, 6.95; N,
4.13.
N-Tosyl 3-(2-Methylanilino)-2-methyl-2-butanol (4b)
This compound was prepared on the same scale as above from 2.08 g (6.00 mmol) of 3b.
Purification by recrystallization from ether-petroleum ether gave 1.64 g (79%) of alcohol
1
4b, mp. 101–103◦C. IR: 3520, 1343, 1157 cm−1; H-NMR: δ 7.57 (d, J = 8.2 Hz, 2H),
7.28 (coincident d, J = 8.2 and 7.7 Hz, 3H), 7.21 (t, J = 7.1 Hz, 1H), 7.06 (t, J = 7.7 Hz,
1H), 6.60 (d, J = 7.1 Hz, 1H), 3.90 (td, J = 12.4, 5.5 Hz, 1H), 3.33 (td, J = 12.4, 4.4 Hz,
1H), 2.44 (s, 3H), 2.39 (s, 3H), 1.79 (td, J = 12.4, 5.5 Hz, 1H), 1.51 (td, J = 12.4, 4.4 Hz,
1H), 1.34 (s, 1H), 1.19 (s, 3H), 1.15 (s, 3H); 13C-NMR: δ 143.3, 140.1, 138.3, 135.7, 131.3,
129.4, 128.2, 127.9, 127.8, 126.3, 69.8, 47.9, 41.5, 29.5, 29.4, 21.5, 18.6.
Anal. Calcd for C19H25NO3S: C, 65.71; H, 7.20; N, 4.03. Found: C, 65.69; H, 7.23; N,
4.01.
N-Tosyl 3-(3-Methylanilino)-2-methyl-2-butanol (4c)
This compound was prepared on the same scale as above from 2.08 g (6.00 mmol) of 3c.
Purification by recrystallization from ether-petroleum ether gave 1.83 g (88%) of alcohol
1
4c, mp. 103–104◦C. IR: 3523, 1347, 1165 cm−1; H-NMR: δ 7.48 (d, J = 8.2 Hz, 2H),
7.24 (d, J = 8.2 Hz, 2H), 7.17 (t, J = 7.7 Hz, 1H), 7.10 (d, J = 7.7 Hz, 1H), 6.93 (s,
1H), 6.77 (d, J = 7.7 Hz, 1H), 3.66 (t, J = 7.7 Hz, 2H), 2.42 (s, 3H), 2.31 (s, 3H),
1.68 (s, 1H), 1.63 (t, J = 7.7 Hz, 2H), 1.21 (s, 6H); 13C-NMR: δ 143.3, 139.0, 138.9,
135.0, 129.8, 129.3, 128.6, 127.7, 125.1, 69.9, 46.8, 41.4, 29.5, 21.5, 21.2 (one aromatic C
unresolved).
Anal. Calcd for C19H25NO3S: C, 65.71; H, 7.20; N, 4.03. Found: C, 65.66; H, 7.27; N,
3.95.

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
37
N-Tosyl 3-(4-Methylanilino)-2-methyl-2-butanol (4d)
This compound was prepared on the same scale as above from 2.08 g (6.00 mmol) of 3d.
Purification by recrystallization from ether-petroleum ether gave 1.88 g (90%) of alcohol
4d, mp. 94–95◦C. IR: 3524, 1347, 1161 cm−1; 1H-NMR: δ 7.48 (d, J = 8.2 Hz, 2H), 7.25
(d, J = 8.2 Hz, 2H), 7.11 (d, J = 8.2 Hz, 2H), 6.93 (d, J = 8.2 Hz, 2H), 3.65 (t, J =
7.7 Hz, 2H), 2.42 (s, 3H), 2.34 (s, 3H), 1.62 (t, J = 7.7 Hz, 2H), 1.56 (s, 1H), 1.21 (s, 6H);
13C-NMR: δ 143.3, 137.8, 136.4, 135.0, 129.6, 129.3, 128.4, 127.7, 70.0, 46.7, 41.3, 29.5,
21.5, 21.1.
Anal. Calcd for C19H25NO3S: C, 65.71; H, 7.20; N, 4.03. Found: C, 65.78; H, 7.17; N,
3.97.
N-Tosyl 3-(3-Methoxyanilino)-2-methyl-2-butanol (4e)
This compound was prepared on the same scale as above from 2.18 g (6.00 mmol) of 3e.
Purification by flash column chromatography (5–20% ether in hexanes) gave 1.63 g (75%)
of alcohol 4e as a white solid, mp. 112–114◦C. IR: 3525, 2839, 1349, 1162 cm−1; 1H-NMR:
δ 7.50 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 7.20 (t, J = 8.2 Hz, 1H), 6.84 (dd,
J = 8.2, 2.2 Hz, 1H), 6.65 (t, J = 2.2 Hz, 1H), 6.61 (d, J = 7.7 Hz, 1H), 3.75 (s, 3H),
3.66 (t, J = 7.7 Hz, 2H), 2.42 (s, 3H), 1.64 (t, J = 7.7 Hz, 2H and obscured s, 1H), 1.21
(s, 6H); 13C-NMR: δ 159.9, 143.4, 140.4, 135.0, 129.4, 129.3, 127.7, 120.4, 114.7, 113.6,
69.9, 55.3, 46.8, 41.4, 29.5, 21.5.
Anal. Calcd for C19H25NO4S: C, 62.81; H, 6.89; N, 3.86. Found: C, 62.90; H, 6.91; N,
3.75.
N-Tosyl 3-(4-Methoxyanilino)-2-methyl-2-butanol (4f)
This compound was prepared on the same scale as above from 2.18 g (6.00 mmol) of 3f.
Purification by flash column chromatography (5–20% ether in hexanes) gave 1.68 g (77%)
of alcohol 4f as a white solid, mp. 84–86◦C. IR: 3522, 2841, 1344, 1160 cm−1; 1H-NMR:
δ 7.48 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.82 (d,
J = 8.8 Hz, 2H), 3.80 (s, 3H), 3.6 (t, J = 7.7 Hz, 2H), 2.42 (s, 3H), 1.67 (br s, 1H), 1.63 (t,
J = 7.7 Hz, 2H), 1.21 (s, 6H); 13C-NMR: δ 158.9, 143.3, 135.0, 131.6, 129.9, 127.7, 114.1,
69.9, 55.3, 46.9, 41.3, 29.5, 21.5 (one aromatic C unresolved).
Anal. Calcd for C19H25NO4S: C, 62.81; H, 6.89; N, 3.86. Found: C, 62.87; H, 6.81; N,
3.77.
N-Tosyl 3-(3-Chloroanilino)-2-methyl-2-butanol (4g)
This compound was prepared on the same scale as above from 2.21 g (6.00 mmol) of 3g.
Purification by flash column chromatography (5–20% ether in hexanes) gave 1.46 g (66%)
of alcohol 4g as a white solid, mp. 87–89◦C. IR: 3523, 1351, 1161 cm−1; 1H-NMR: δ 7.47
(d, J = 8.2 Hz, 2H), 7.30–7.20 (complex m, 4H), 7.08 (s, 1H), 6.96 (dd, J = 7.1, 2.2 Hz,
1H), 3.65 (t, J = 7.7 Hz, 2H), 2.42 (s, 3H), 1.63 (t, J = 7.7 Hz, 2H and obscured s, 1H),
1.21 (s, 6H); 13C-NMR: δ 143.7, 140.5, 134.5, 134.3, 129.8, 129.5, 128.8, 128.0, 127.6,
126.7, 69.9, 46.6, 41.3, 29.5, 21.5.

38
Bunce et al.
Anal. Calcd for C18H22ClNO3S: C, 58.78; H, 5.99; N, 3.81. Found: C, 58.72; H, 5.95;
N, 3.84.
N-Tosyl 3-(4-Chloroanilino)-2-methyl-2-butanol (4h)
This compound was prepared on the same scale as above from 2.21 g (6.00 mmol) of 3h.
Purification by flash column chromatography (5–20% ether in hexanes) gave 1.44 g (65%)
1
of alcohol 4h as a white solid, mp. 111–113◦C. IR: 3521, 1347, 1161 cm−1; H-NMR: δ
7.46 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.2 Hz, 2H), 6.99 (d, J =
8.2 Hz, 2H), 3.66 (t, J = 7.7 Hz, 2H), 2.42 (s, 3H), 1.61 (t, J = 7.7 Hz, 2H and obscured
s, 1H), 1.21 (s, 6H), 13C-NMR: δ 143.6, 137.7, 134.6, 133.6, 129.9, 129.5, 129.2, 127.6,
69.9, 46.6, 41.2, 29.5, 21.5.
Anal. Calcd for C18H22ClNO3S: C, 58.78; H, 5.99; N, 3.81. Found: C, 58.86; H, 5.97;
N, 3.70.
N-Tosyl 3-(5,6,7,8-Tetrahydro-1-naphthyl)-2-methyl-2-butanol (4i)
This compound was prepared as above from 1.16 g (3.00 mmol) of 3i and 3.0 equiv. of
methylmagnesium bromide. Purification by flash column chromatography (5–20% ether in
hexanes) gave 0.84 g (72%) of alcohol 4i as a white solid, mp. 116–118◦C. IR: 3514, 1341,
1161 cm−1; 1H-NMR: δ 7.59 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 7.03 (d, J =
7.7 Hz, 1H), 6.95 (t. J = 7.7 Hz, 1H), 6.41 (d, J = 7.1 Hz, 1H), 3.86 (td, J = 12.6, 4.9 Hz,
1H), 3.29 (td, J = 12.6, 4.9 Hz, 1H), 3.00 (m, 1H), 2.79 (m, 3H), 2.44 (s, 3H), 1.79 (m,
5H), 1.49 (td, J = 12.6, 4.4 Hz, 1H), 1.37 (s, 1H), 1.17 (s, 3H), 1.14 (s, 3H); 13C-NMR:
δ 143.2, 139.3, 139.1, 138.2, 135.7, 129.34, 129.28, 128.0, 125.3, 124.8, 69.8, 48.0, 41.4,
29.7, 29.4, 25.7, 22.7, 22.6, 21.5.
Anal. Calcd for C22H29NO3S: C, 68.22; H, 7.49; N, 3.62. Found: C, 68.39; H, 7.52; N,
3.45.
Representative Procedures for the Ring Closure of Tetrahydroquinolines.
1-Tosyl-4,4-dimethyl-1,2,3,4-tetrahydroquinoline (5a)
Method A. A 15-mL, screw-top pressure vessel (Ace No. 8648 with Ace No. 5846 plug),
equipped with a magnetic stirrer was charged with 100 mg (0.298 mmol) of 4a and 5 mL
of dichloromethane. To the resulting solution was added 162 mg (0.600 mmol, 2 equiv.)
of FeCl3·6H2O, and the vessel was sealed under an atmosphere of argon. The mixture was
heated at 60◦C for 4 h, and then cooled, added to saturated NaCl and extracted with ether
(3 × 15 mL). [Note: Reaction times for other substrates are given in Table 1]. The combined
organic layers were washed once with saturated NaCl, dried (MgSO4), and concentrated
under vacuum. The crude product was purified using PTLC and eluted with 10% ether in
hexanes to afford two bands: Band 1, 64 mg (68%) of 5a as a viscous light yellow oil;
Band 2, 21 mg (28%) of 6a, mp. 101–102◦C (lit.14 mp. 102◦C). The spectral data for 6a
also matched those reported.14
Method B. A 50-mL, one-necked, round-bottomed flask, equipped with a condenser,
a magnetic stirrer and an argon atmosphere, was charged with a solution of 100 mg
(0.298 mmol) of 4a in 20 mL of benzene. The mixture was heated to reflux, 60 mg

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
39
(0.447 mmol, 1.5 equiv.) of AlCl3 was cautiously added, and the reaction mixture was
stirred at reflux for 30 min. The reaction was added to ice water and extracted with ether
(3 × 15 mL). The combined organic layers were washed with 5% NaHCO3, water and
saturated NaCl, then dried (MgSO4), and concentrated under vacuum. The crude product
was purified on a 20 cm × 20 cm PTLC plate eluted with 10% ether in hexanes to afford
three bands: Band 1, 5–10 mg of a mixture of alkenes from dehydration of the starting
alcohol; Band 2, 59 mg (62%) of 5a; Band 3, 7 mg (10%) of 6a.
1
The spectral data for 5a were: IR: 1355, 1162 cm−1; H-NMR: δ 7.81 (dd, J = 7.7,
1.6 Hz, 1H), 7.44 (d, J = 8.2 Hz, 2H), 7.30–7.10 (complex m, 3H), 7.18 (d, J = 8.2 Hz, 2H),
3.83 (t, J = 5.8 Hz, 2H), 2.36 (s, 3H), 1.36 (t, J = 5.8 Hz, 2H), 1.02 (s, 6H); 13C-NMR: δ
143.5, 138.6, 137.1, 135.4, 129.4, 127.2, 127.0, 126.2, 125.2, 124.9, 43.7, 35.8, 32.4, 31.2,
16.2.
Anal. Calcd for C18H21NO2S: C, 68.57; H, 6.66; N, 4.44. Found: C, 68.77; H, 6.73; N,
4.29.
1-Tosyl-4,4,8-trimethyl-1,2,3,4-tetrahydroquinoline (5b)
This compound was prepared as above from 100 mg (0.288 mmol) of 4b and 156 mg
(0.577 mmol) of FeCl3·6H2O according to Method A. Purification by PTLC eluted with
10% ether in hexanes gave two bands: Band 1, 56 mg (59%) of 5b as a white solid, mp.
120–121◦C; Band 2, 16 mg (21%) of 6b as a white powder, mp. 106–107◦C (lit.15 mp.
108◦C). The spectral data for 6b also matched those reported in the literature.16
The spectral data for 5b were: IR: 1354, 1340, 1162 cm−1; 1H-NMR: δ 7.40 (d, J =
8.2 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 7.12 (m, 3H), 4.11 (br s, 1H), 3.34 (br s, 1H), 2.52 (s,
3H), 2.39 (s, 3H), 1.58 (br s, 1H), 1.22 (br s, 1H), 1.04 (br s, 3H), 0.88 (br s, 3H); 13C-NMR:
δ 144.4, 142.0, 137.5, 137.1, 134.5, 129.4, 129.1, 128.0, 126.3, 124.5, 44.9, 34.8, 34.4 (br),
32.9, 30.1 (br), 21.5, 20.9.
Anal. Calcd for C19H23NO2S: C, 69.30; H, 6.99; N, 4.26. Found: C, 69.33; H, 6.97; N,
4.22.
1-Tosyl-4,4,7-trimethyl-1,2,3,4-tetrahydroquinoline (5c-A) and
1-Tosyl-4,4,5-trimethyl-1,2,3,4-tetrahydroquinoline (5c-B)17
This compound was prepared from 100 mg (0.288 mmol) of 4c and 156 mg (0.577 mmol)
of FeCl3·6H2O according to Method A. Purification by PTLC eluted with 5% ethyl acetate
in hexanes gave three bands: Band 1, 49 mg (52%) of 5c-A as a viscous light yellow oil;
Band 2, 25 mg (26%) of 5c-B as a light yellow viscous oil; Band 3, 12 mg (16%) of 6c as
a white powder, mp. 111–113◦C (lit15 mp. 114◦C). The spectral data for 6c also matched
those reported in the literature.16
The spectral data for 5c-A were: IR: 1354, 1343, 1165 cm−1; 1H-NMR: δ 7.64 (s, 1H),
7.45 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz, 1H), 6.95 (d, J =
7.1 Hz, 1H), 3.80 (t, J = 5.4 Hz, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 1.32 (t, J = 5.4 Hz, 2H),
0.99 (s, 6H); 13C-NMR: δ 143.4, 137.1, 135.8, 135.6, 135.2, 129.4, 127.2, 126.8, 126.2,
125.3, 43.8, 35.8, 32.1, 31.3, 21.5, 21.1.

40
Bunce et al.
Anal. Calcd for C19H23NO2S: C, 69.30; H, 6.99; N, 4.26. Found: C, 69.37; H, 7.02; N,
4.19.
The spectral data for 5c-B were: IR: 1351, 1340, 1161 cm−1; H-NMR: δ 7.65 (d,
J = 7.1 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 7.07 (t, J = 8.2 Hz,
1H), 6.96 (d, J = 7.1 Hz, 1H), 3.79 (t, J = 5.4 Hz, 2H), 2.45 (s, 3H), 2.37 (s, 3H), 1.41 (t,
J = 5.4 Hz, 2H), 1.11 (s, 6H); 13C-NMR: δ 143.3, 137.3, 137.2, 136.8, 136.3, 130.4, 129.4,
127.2, 125.7, 124.2, 43.3, 39.9, 33.4, 28.6, 23.6, 21.5.
1
Anal. Calcd for C19H23NO2S: C, 69.30; H, 6.99; N, 4.26. Found: C, 69.49; H, 7.08; N,
4.15.
1-Tosyl-4,4,6-trimethyl-1,2,3,4-tetrahydroquinoline (5d)
This compound was prepared from 100 mg (0.288 mmol) of 4d and 156 mg (0.577 mmol)
of FeCl3·6H2O according to Method A. Purification by PTLC eluted with 10% ether in
hexanes gave two bands: Band 1, 70 mg (74%) of 5d as a white powder, mp. 138–140◦C;
Band 2, 12 mg (16%) of 6d as a white powder, mp. 116–117◦C (lit.15 mp. 117◦C). The
spectral data for 6d also matched those reported in the literature.16
The spectral data for 5d were: IR: 1351, 1337, 1162 cm−1; 1H-NMR: δ 7.70 (d, J =
8.2 Hz, 1H), 7.44 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 7.03 (s, 1H), 6.99 (d, J =
8.2 Hz, 1H), 3.79 (t, J = 5.8 Hz, 2H), 2.36 (s, 3H), 2.31 (s, 3H), 1.31 (t, J = 5.8 Hz, 2H),
1.00 (s, 6H); 13C-NMR: δ 143.3, 138.4, 137.1, 134.7, 132.8, 129.4, 127.5, 127.2, 127.0,
124.9, 43.7, 35.7, 32.2, 31.3, 21.4, 21.0.
Anal. Calcd for C19H23NO2S: C, 69.30; H, 6.99; N, 4.26. Found: C, 69.25; H, 6.98; N,
4.16.
1-Tosyl-4,4-dimethyl-7-methoxy-1,2,3,4-tetrahydroquinoline (5e-A) and
1-Tosyl-4,4-dimethyl-5-methoxy-1,2,3,4-tetrahydroquinoline (5e-B)17
These compounds were prepared from 100 mg (0.275 mmol) of 4e and 55 mg (0.413 mmol)
of AlCl3 according to Method B. Purification by PTLC eluted with 5% ethyl acetate in
hexanes gave three bands: Band 1, 20 mg (21%) of 5e-B as a viscous light yellow oil; Band
2, 56 mg (59%) of 5e-A as a viscous light yellow oil; Band 3, 16 mg (11%) of 6e as a light
tan solid, mp. 65–67◦C (lit.15 mp. 68◦C).
The spectral data for 5e-A were: IR: 2835, 1356, 1341, 1167 cm−1; 1H-NMR: δ 7.48
(d, J = 8.2 Hz, 2H), 7.40 (d, J = 2.7 Hz, 1H), 7.19 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.8 Hz,
1H), 6.72 (dd, J = 8.8, 2.2 Hz, 1H), 3.82 (s, 3H), 3.82 (t, J = 5.8 Hz, 2H), 2.37 (s, 3H), 1.33
(t, J = 5.8 Hz, 2H), 0.99 (s, 6H); 13C-NMR: δ 157.4, 143.5, 137.0, 136.2, 130.7, 129.4,
127.7, 127.2, 112.4, 109.0, 55.3, 43.9, 35.8, 31.9, 31.3, 21.5.
Anal. Calcd for C19H23NO3S: C, 66.09; H, 6.66; N, 4.06. Found: C, 66.29; H, 6.73; N,
3.89.
The spectral data for 5e-B were: IR: 2840, 1351, 1339, 1167 cm−1; 1H-NMR: δ 7.47
(coincident d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 7.14 (t, J = 8.2 Hz, 1H), 6.71 (d,
J = 8.2 Hz, 1H), 3.79 (s, 3H), 3.78 (t, J = 5.5 Hz, 2H), 2.37 (s, 3H), 1.34 (t, J = 5.5 Hz, 2H),
1.10 (s, 6H); 13C-NMR: δ 158.9, 143.3, 137.6, 137.3, 129.4, 127.2, 127.0, 126.3, 118.3,
108.7, 55.2, 43.7, 38.9, 32.7, 27.9, 21.5.

Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
41
Anal. Calcd for C19H23NO3S: C, 66.09; H, 6.66; N, 4.06. Found: C, 66.32; H, 6.77; N,
3.90.
1-Tosyl-4,4-dimethyl-6-methoxy-1,2,3,4-tetrahydroquinoline (5f)
This compound was prepared as above from 100 mg (0.275 mmol) of 4f and 55 mg
(0.413 mmol) of AlCl3 according to Method B. Purification by PTLC eluted with 10%
ether in hexanes gave two bands: Band 1, 60 mg (63%) of 5f as a viscous light yellow oil;
Band 2, 21 mg (28%) of 6f as a white solid, mp. 114–115◦C (lit.14 mp. 114.7–115.5◦C).
The spectral data for 6f also matched those reported.14
The spectral data for 5f were: IR: 1351, 1163 cm−1; 1H-NMR: δ 7.76 (d, J = 8.4 Hz,
1H), 7.40 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.0 Hz, 1H), 6.75
(s, 1H), 3.81 (s, 3H), 3.78 (t, J = 5.8 Hz, 2H), 2.36 (s, 3H), 1.26 (t, J = 5.8 Hz, 2H), 0.97
(s, 6H); 13C-NMR: δ 157.1, 143.3, 140.4, 137.0, 129.4, 128.5, 127.3, 126.7, 112.5, 111.3,
55.3, 43.7, 35.3, 32.6, 31.3, 21.4.
Anal. Calcd for C19H23NO3S: C, 66.09; H, 6.66; N, 4.06. Found: C, 66.19; H, 6.69; N,
3.97.
1-Tosyl-4,4-dimethyl-5-chloro-1,2,3,4-tetrahydroquinoline (5g-A) and
1-tosyl-4,4-dimethyl-7-chloro-1,2,3,4-tetrahydroquinoline (5g-B)17
These compounds were prepared from 100 mg (0.272 mmol) of 4g and 54 mg (0.408 mmol)
of AlCl3 according to Method B. Purification by PTLC eluted with 5% ethyl acetate in
hexanes gave three bands: Band 1, 14 mg (14%) of 5g-B as a viscous yellow oil; Band
2: 66 mg (64%) of 5g-A as a viscous yellow oil; Band 3, 14 mg (17%) of 6g as a white
powder, mp. 135–137◦C (lit.18 mp. 138◦C). The spectral data for 6g also matched those
reported in the literature.16
1
The spectral data for 5g-A were: IR: 1354, 1341, 1165 cm−1; H-NMR: δ 7.87 (d,
J = 2.2 Hz, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.2 Hz,
1H), 7.09 (dd, J = 8.2, 2.2 Hz, 1H), 3.80 (t, J = 5.8 Hz, 2H), 2.38 (s, 3H), 1.36 (t, J =
5.8 Hz, 2H), 1.01 (s, 6H); 13C-NMR: δ 143.8, 136.9, 136.6, 136.5, 131.5, 129.6, 128.1,
127.2, 125.2, 124.3, 43.6, 35.6, 32.3, 31.0, 21.5.
Anal. Calcd for C18H20ClNO2S: C, 61.80: H, 5.72; N, 4.01. Found: C, 61.78; H, 5.77;
N, 4.13.
1
The spectral data for 5g-B were: IR: 1354, 1343, 1165 cm−1; H-NMR: δ 7.77 (dd,
J = 8.2, 1.1 Hz, 1H), 7.44 (d, J = 8.2 Hz, 2H), 7.22 (m, 3H), 7.11 (d, J = 8.2 Hz, 1H),
3.79 (t, J = 5.5 Hz, 2H), 2.39 (s, 3H), 1.41 (t, J = 5.5 Hz, 2H), 1.25 (s, 6H). 13C-NMR:
δ 143.8, 138.1, 137.2, 135.7, 134.3, 129.64, 129.58, 127.2, 126.6, 125.1, 43.4, 39.5, 34.1,
27.5, 21.5.
Anal. Calcd for C18H20ClNO2S: C, 61.80: H, 5.72; N, 4.01. Found: C, 61.89; H, 5.68;
N, 3.91.
1-Tosyl-4,4-dimethyl-6-chloro-1,2,3,4-tetrahydroquinoline (5h)
This compound was prepared from 100 mg (0.272 mmol) of 4h and 54 mg (0.408 mmol) of
AlCl3 in 10 mL of benzene according to Method B. Purification by PTLC with 10% ether

42
Bunce et al.
in hexanes gave two bands: Band 1, 70 mg (74%) of 5h, mp. 136–138◦C; Band 2, 14 mg
(18%) of 6h, mp. 96–98◦C (lit.14 mp. 97.4–98.8◦C). The spectral data for 6h also matched
those reported.14
The spectral data for 5h were: IR: 1354, 1165 cm−1; 1H-NMR: δ 7.79 (d, J = 8.8 Hz,
1H), 7.45 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.2 Hz, 2H), 7.20 (obscured d, J = 2.7 Hz,
1H), 7.14 (dd, J = 8.8, 2.7 Hz, 1H), 3.80 (t, J = 5.8 Hz, 2H), 2.38 (s, 3H), 1.33 (t, J =
5.8 Hz, 2H), 1.00 (s, 6H); 13C-NMR: δ 143.8, 140.5, 136.6, 134.0, 130.6, 129.6, 127.2,
127.0, 126.4, 126.3, 43.5, 35.3, 32.7, 31.0, 21.5.
Anal. Calcd for C18H20ClNO2S: C, 61.80: H, 5.72; N, 4.01. Found: C, 61.79; H, 5.74;
N, 3.98.
1-Tosyl-4,4-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[h]quinoline (5i)
This compound was prepared from 100 mg (0.258 mmol) of 4i and 140 mg (0.518 mmol)
of FeCl3·6H2O according to Method A. Purification by PTLC eluted with 10% ether in
hexanes gave two bands: Band 1, 59 mg (62%) of 5i as a viscous light yellow oil; Band 2,
9 mg (12%) of 6i as a white powder, mp. 117–118◦C.
The spectral data for 5i were: IR: 1353, 1161 cm−1; 1H-NMR: δ 7.46 (d, J = 8.2 Hz,
2H), 7.21 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 7.7 Hz, 1H), 6.97 (d, J = 7.7 Hz, 1H), 4.08
(dm, J = 14.3 Hz, 1H), 3.25 (m, 2H), 2.80 (m, 3H), 2.39 (s, 3H), 2.00–1.60 (complex m,
4H), 1.41 (m, 1H), 1.21 (m, 1H), 1.06 (s, 3H), 0.88 (s, 3H); 13C-NMR: δ 143.3, 138.9,
137.6, 137.2, 136.2, 134.2, 129.3, 128.0, 127.6, 123.9, 45.2, 35.0, 34.3, 32.6, 30.3, 29.0,
27.8, 22.9, 22.5, 21.5.
Anal. Calcd for C22H27NO2S: C, 71.54; H, 7.32; N, 3.79. Found: C, 71.79; H, 7.37; N,
3.68.
1
The spectral data for 6i were: IR: 3280, 1325, 1161 cm−1; H-NMR: δ 7.64 (d, J =
8.2 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 7.7 Hz, 1H), 7.02 (t, J = 7.7 Hz, 1H),
6.88 (d, J = 7.7 Hz, 1H), 6.49 (br s, 1H), 2.68 (br s, 2H), 2.39 (s, 3H), 2.33 (br s, 2H), 1.64
(distorted quintet, J = 3.3 Hz, 4H); 13C-NMR δ 143.6, 138.5, 136.8, 134.2, 129.9, 129.5,
127.1, 126.9, 125.8, 120.8, 29.6, 24.4, 22.6, 22.3, 21.5.
Anal. Calcd for C17H19NO2S: C, 67.77; H, 6.31; N, 4.65. Found: C, 67.72; H, 6.34; N
4.55.
Acknowledgments
J. G. C. thanks Oklahoma State University for a 2010–2011 Wentz Project Scholarship.
Funding for the 300 MHz NMR spectrometer of the Oklahoma Statewide Shared NMR
Facility was provided by NSF (BIR-9512269), the Oklahoma State Regents for Higher
Education, the W. M. Keck Foundation, and Conoco, Inc. Finally, the authors wish to
thank the OSU College of Arts and Sciences for funds to upgrade our departmental FT-IR
instruments.
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Tetrahydroquinolines by Lewis Acid-promoted Friedel-Crafts Cyclizations
43
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