Synthesis of tetrahydrobenzazepinesulfonamides and their rearrangement to diarylsulfones

Article abstract of DOI:10.1080/00397910500377495

A new class of diarylsulfones, in which tetrahydrobenzazepine comprises one of the aromatic moieties, has been synthesized via the acid-catalyzed rearrangement of several substituted benzazepinesulfonamides. The rearrangement is normally ortho but in at l

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Synthesis of
Tetrahydrobenzazepinesulfonamides and
Their Rearrangement to Diarylsulfones
Hui Ren a , Murray Zanger a & James R. McKee a
a Department of Chemistry & Biochemistry , University of the Sciences in
Philadelphia , Philadelphia, Pennsylvania, USA
Published online: 19 Aug 2006.
To cite this article: Hui Ren , Murray Zanger & James R. McKee (2006) Synthesis of
Tetrahydrobenzazepinesulfonamides and Their Rearrangement to Diarylsulfones, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:3, 355-363, DOI:
10.1080/00397910500377495
To link to this article: http://dx.doi.org/10.1080/00397910500377495
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Synthetic Communicationsw, 36: 355–363, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500377495
Synthesis of
Tetrahydrobenzazepinesulfonamides and
Their Rearrangement to Diarylsulfones
Hui Ren, Murray Zanger, and James R. McKee
Department of Chemistry & Biochemistry, University of the Sciences in
Philadelphia, Philadelphia, Pennsylvania, USA
Abstract: A new class of diarylsulfones, in which tetrahydrobenzazepine comprises
one of the aromatic moieties, has been synthesized via the acid-catalyzed rearrange-
ment of several substituted benzazepinesulfonamides. The rearrangement is normally
ortho but in at least one case a para isomer is also formed. Sulfones of this type
have been shown to possess potent anti-HIV activity.
Keywords: Acid-catalyzed rearrangements, benzazepine, sulfonamides, sulfones
INTRODUCTION
In earlier work from this laboratory, the rearrangement of tetrahydroquinoli-
nesulfonamides (A) to diarylsulfones (B) was described.[1] The reaction is
an extension of the acid-catalyzed rearrangement of N-alkylbenzenesulfonani-
lides,[1] originally described by Witt and Uermenyi[2] and expanded on by
Halberkamm.[3] In this reaction the benzenesulfonyl group migrates
primarily to the ortho position although in special cases some para isomer
is formed. The mechanism of rearrangement[1] for these sulfonamides (C)
has also been investigated. Recently diarylsulfones[4] and in particular
Received in the USA July 28, 2005
Address correspondence to Murray Zanger, Department of Chemistry & Bio-
chemistry, University of the Sciences in Philadelphia, 600 S. 43rd Street, Philadelphia,
PA 19104-4418, USA. Tel.: 215-596-8833; Fax: 215-596-8543; E-mail: m.zanger@
usip.edu
355

356
H. Ren et al.
several of the sulfones prepared in this laboratory have been shown to be
potent non-nucleoside reverse transcriptase inhibitors (NNRTI’s) of HIV.[5]
See Figure 1.
With this renewed interest in diarylsulfones, research in this lab was
initiated with the goal of preparing new diarylsulfones possessing a fused-ring
containing a nitrogen atom. Specifically the preparation and rearrangement
of sulfonamides derived from indoline (D) and tetrahydrobenzazepine (E)
were undertaken. Unfortunately the indolinesulfonamides did not undergo
acid-catalyzed rearrangement but simply hydrolyzed. This article describes
the synthesis and rearrangement of tetrahydrobenzazepine-sulfonamides.
RESULTS AND DISCUSSION
The preparation of 2,3,4,5-tetrahydrobenzazepine from a-tetralone (1) has
been described.[6] The tetralone is converted to an oxime (2), which, when
treated with polyphosphoric acid (PPA), undergoes a Beckmann rearrange-
ment to tetrahydrobenzazepinone (3).[7] Lithium aluminum hydride
reduction of the lactam yielded the tetrahydrobenzazepine (4).[8]
For this work the 7-chloro-2,3,4,5-tetrahydrobenzazepine (6) was also
desired to add diversity to the series and, because the 7-chloro isomer in the
tetrahydroquinoline series,[5] showed excellent activity. A novel synthesis of
(6) was achieved by chlorinating the lactam (3) using sulfuryl chloride and
then reducing the product (5) to compound (6). A small percentage of the
chlorolactam consisted of the 9-isomer but it could be removed by recrystalli-
zation. Scheme 1 outlines the synthetic routes.
The benzazepinesulfonamides were prepared by reacting compounds (4)
or (6) with benzenesulfonyl chloride or 2-nitrobenzenesulfonyl chloride to
give four sulfonamides, two of which (9, 10) were novel and two known
(7, 8) compounds.[9,10] When treated with 98% sulfuric acid, the four
amides rearranged to form five new sulfones (11–15). Compound (8) with a
2-nitro-group and no 7-substituent gave mainly the ortho rearranged
product (12) but also formed a small amount of the para sulfone (15)
(Scheme 2). The para isomer comprised about 10% of the rearranged product.
Figure 1. Sulfones and sulfonamides under investigation.

Synthesis of Aryltetrahydrobenzazepinesulfones
357
Scheme 1. (i) NH2OH, pyridine, MeOH, reflux; (ii) PPA, 1208, and then iced; (iii)
LiAlH4, THF, refluxed 4 h; (iv) SO2Cl2, benzene, 0–58, then rt, 3 h; (v) LiAlH4,
THF, refluxed 4 h.
Table 1 lists the sulfonamides and sulfones which were prepared and
characterized.
EXPERIMENTAL
All melting points are uncorrected. All infrared spectra (FT-IR) were recorded
with thin film on a KBr plate and only noteworthy absorptions (cm21) are
1
listed. H NMR spectra were recorded at 400 MHz with TMS as an internal
reference. All mass spectra were determined with a GC-MS. The results of
elemental analysis are within +0.3% of the theoretical values.
Synthesis of a-Tetralone Oxime (2)[6]
A mixture of 25.6 g (17.5 mmol) of a-tetralone (1), 25.7 g (37.2 mmol) of
hydroxylamine hydrochloride, 125 mL of pyridine, and 125 mL of methanol
were added to a 500-mL, three-necked, round-bottomed flask. The solution
was refluxed for 2 h, resulting in a clear green solution. Green crystals of
Scheme 2. (i) R2BzSO2Cl, 10% NaOH, warm to 508; (ii) 98% H2SO4 at 1058 for
20 min; pour over ice.

358
H. Ren et al.
Table 1. Preparation of sulfonamides and sulfones
No.
Type
R1
R2
Mp (8C)
Formula
Yield (%)
7a
8b
9
I
I
H
H
H
NO2
H
111–112
127.5–129
148–149
142.5–144
84–85.5
C16H17NO2S
78
58
95
79
45
20
52
49
2
C16H16N2O4S
C16H16ClNO2S
C16H15ClN2O4S
C16H17NO2S
I
Cl
Cl
10
11
12
13
14
15
I
NO2
H
II
II
II
II
II
H
H
Cl
NO2
H
89–91
C16H16N2O4S
C16H16ClNO2S
C16H15ClN2O4S
C16H16N2O4S
147–148.5
99–101.5
181–183
Cl
H@9
NO2
NO2
aCompound 7 is known (mp 108, Ref. [6]).
bCompound 8 is known (no data, Ref. [7]). H@9 ¼ 2-NO2PhSO2-group at position 7
(from para-rearrangement); isomer of compd. 12.
a-tetralone oxime were obtained after the solvent was evaporated. The sample
was further recrystallized from 95% ethanol to give 26 g of light green
crystals. Yield: 92.3%; mp: 106–108 8 (lit. mp: 100.5–101.5 8).[6] IR:
1
3248.17 cm21(O–H), 1638.53 cm21 (C55N), 951.17 cm21 (N–O); H NMR
(CDC13): d 7.92–7.04 (m, 4H, aromatics), 2.89–2.86 (t, 2H, CH2), 2.81–
2.78 (t, 2H, CH2), 1.95–1.89 (m, 2H, CH2). GC-MS: m/z 162 (Mþ).
Synthesis of l,3,4,5-Tetrahydro-2H-1-benzazepin-2-one (3)[7]
A mixture of 3.07 g (19.1 mmol) of (2) and 44.92 g of polyphosphoric acid
(PPA) were placed in a 500-mL beaker. Then the mixture was heated to
1208 in an oil bath under constant stirring. The color of the mixture
gradually darkened. The viscosity of the mixture, caused mainly by PPA,
decreased as the temperature reached 1208. The reaction was then kept at
120–1308 for another 10 min. The temperature was allowed to return to
room temperature, and then ice was added to the cherry-red reaction
mixture. Six or seven h later, a pale precipitate formed and was filtered and
washed with water, resulting in 2.43 g of (3). Yield: 78.14%; mp:143–1458
(lit. mp: 142.5–1438).[7] IR: 3187.67 cm21 (NH), 1661.18 cm21 (C–O);
1H NMR (CDCl3): d 7.64 (bs, 1H, NH), 7.28–6.98 (m, 4H, aromatics),

Synthesis of Aryltetrahydrobenzazepinesulfones
359
2.85–2.88 (t, 2H, CH2), 2.40–2.37 (t, 2H, CH2), 2.29–2.22 (m, 2H, CH2).
GC-MS: m/z 161 (Mþ).
Synthesis of 2,3,4,5-Tetrahydro-lH-l-benzazepine (4)[8]
Pulverized lithium aluminum hydride (1.5 g, 39.5 mmol) and 15 mL of dry
THF were placed into a 500-mL, three-necked, round-bottomed flask, and
the mixture heated to boiling. A solution of 3.7 g (22.9 mmol) of (3) in
150 mL of dry THF was added slowly at such a rate that the solvent
refluxed gently without external heating. When the addition was complete,
the solution was stirred and heated at reflux for 4 h. After the reaction
mixture cooled, water was added dropwise to destroy the excess LiAIH4. A
gray precipitate was removed by gravity filtration and washed with CHC13
several times. The gray precipitate was extracted with CHC13 using a
Soxhlet extraction apparatus for 6 h. The chloroform washings and chloroform
extract were combined and the solvent stripped to give 2.40 g (yield: 74.1%)
of a reddish viscous liquid. Compound (4) was reported to have a melting
point of 328.[8] The crude product was used directly to prepare tetrahydroben-
zazepinesulfonamides. IR: 3360.86 cm21 (NH), stretch absorption of C55O at
1661.18 cm21 disappeared; 1H NMR (CDC13): d 7.16–6.66 (m, 4H,
aromatics), 3.81 (bs, 1H, NH), 3.10–3.07 (t, 2H, CH2), 2.83–2.80 (t, 2H,
CH2), 1.85–1.81 (m, 2H, CH2), 1.71–1.67 (m, 2H, CH2).
Synthesis of 7-Chloro-2,3,4,5-tetrahydro-2H-l-
benzazepin-2-one (5)[11]
Dry benzene (20 mL) and 3 g (18.6 mmol) of (3) were placed in a round-
bottomed flask. To this solution, 3 mL of SO2Cl2 in 10 mL of dry benzene
was added dropwise, under constant stirring, while the temperature was
kept at 0-58 using an ice–water bath. The solution was stirred for an additional
40 min after the addition was complete. The solution was then stirred at room
temperature for 3 h longer. The solvent and excess SO2Cl2 were removed
using a water aspirator, leaving a yellow solid. The crude product (5) was
recrystallized from ethyl acetate or acetone to give 1.37 g of white crystals.
Yield 37.7%; mp: 161–1638 (lit. mp: 164–1668).[11] IR: 3306.27 cm21
1
(NH), 1667.67 cm21 (C55O); H NMR (DMSO-d6): d 9.56 (s, 1H, NH),
6.96–7.36 (3H, aromatics), 2.67–2.70 (t, 2H, CH2), 2.06–2.18 (m, 4H,
CH2CH2). GC-MS: m/z 195 (Mþ).
Synthesis of 7-Chloro-2,3,4,5-tetrahydro-lH-l-benzazepine (6)
Using the same procedure for (4),[8] 0.93 g (24.5 mmol) of pulverized lithium
aluminum hydride, 15 mL of dry THF, and 2.45 g (12.6 mmol) of (5) were

360
H. Ren et al.
reacted. A gray-white precipitate was collected by gravity filtration and
was washed with THF. After the THF was evaporated, 2.40 g of a pale solid
was obtained. Yield: 88.1%; mp 66–678. IR: 3374.99 cm21 (NH), stretch
absorption of C55O at 1667.67 cm21 disappeared; 1H NMR (CDC13): d
6.69–7.10 (4H, aromatics), 4.07 (bs, NH), 3.03–3.05 (t, 2H, CH2), 2.74–
2.76 (t, 2H, CH2), 1.79–1.83 (m, 2H, CH2), 1.64–1.68 (m, 2H, CH2).
GC-MS m/z 181 (Mþ).
Synthesis of 1-Benzenesulfonyl-2,3,4,5-tetrahydro-lH-l-
benzazepine (7)[9]
Compound (4) (3.10 g, 20 mmol) and 3.71 g (20 mmol) of benzenesulfonyl
chloride were placed in a 100-mL beaker. Aqueous sodium hydroxide
solution (10%) was added slowly under constant stirring. The reaction
mixture became warm and a gummy solid started to form. Enough aqueous
sodium hydroxide solution was added to keep the solution basic. The
solution was then warmed to 508 for several minutes. The supernatant
liquid was decanted, and the resulting gummy mass washed with water and
recrystallized (using charcoal) from ethanol to yield 4.60 g of light yellow
needles. Yield: 78.3%; mp: 111–1128. (lit. 1098).[9] IR: 1140.12 cm21 and
1
1379.10 cm21 (S55O); H NMR (CDCl3): d 7.11–7.76 (m, 9H, aromatics),
3.72–3.77 (bs, 2H, CH2), 2.36–2.39 (t, 2H, CH2), 1.80–1.85 (m, 2H, CH2),
1.56 (bs, 2H, CH2). GC-MS: m/z 287 (Mþ).
Synthesis of 1-[2-Nitrophenylsulfonyl]-2,3,4,5-tetrahydro-lH-l-
benzazepine (8)
Using the same procedure as (7), 2.02 g (13.7 mmol) of (4) and 3.18 g
(14.4 mmol) of 2-nitrobenzenesulfonyl chloride were reacted to yield 2.63 g
of light yellow needles. Yield: 57.8%; mp: 127.5–1298. IR: No NH absorption
at 3500–3100 cm21, 1153.46 cm21, and 1339.40 cm21 (SO); 1H NMR
(CDC13): d 7.84–7.70 (m, 4H, aromatics), 7.26–6.87 (m, 4H, aromatics),
3.77 (bs, 2H, CH2), 2.87–2.85 (t, 2H, CH2), 2.02–1.96 (m, 2H, CH2), 1.70
(bs, 2H, CH2). GC-MS: m/z 332 (Mþ).
Synthesis of 7-Chloro-l-(phenylsulfonyl)-2,3,4,5-tetrahydro-lH-l-
benzazepine (9)
Pyridine (5.3 mL) was added to a mixture of 0.96 g (5.5 mmol) of (6) and
1.75 g (9.9 mmol) of benzenesulfonyl chloride in a 25-mL, round-bottomed
flask. The solution turned red and was refluxed for 3 h, then cooled. The
reaction mixture was poured over ice, and a yellow product precipitated.

Synthesis of Aryltetrahydrobenzazepinesulfones
361
The solid was filtered and recrystallized from ethanol to give 1.2 g of white
needles. Yield: 94.7%; mp 148–1498; IR: 1158.42 cm21 and 1343.41 cm21
(S55O); H NMR (CDCl3): d 1.55 (bs, 2H, CH2), 1.78–1.83 (m, 2H, CH2),
1
2.29–2.32 (t, 2H, CH2), 3.71 (bs, 2H, CH2), 7.12–7.75 (8H, aromatics).
GC-MS: m/z 321 (Mþ); Anal. calcd. for C16H16ClNO2S: C, 59.72%; H,
5.01%; N, 4.35%. Found: C, 59.53%; H, 4.87%; N, 4.43%.
Synthesis of 7-Chloro-1-[2-Nitrophenylsulfonyl]-2,3,4,5-tetrahydro-
lH-l-benzazepine (10)
Using the same procedure as (9), a mixture of 0.92 g (5.08 mmol) of (6) and
2.02 g (9.11 mmol) of 2-nitrobenzenesulfonyl chloride were reacted and
recrystallized from hexane/acetone to give 1.47 g of orange or yellow
crystals. Yield: 78.9%; mp 142.5–1448; IR: 1158.82 cm21 and 1355.22 cm21
1
(S55O); H NMR (CDC13): d 1.69 (bs, 2H, CH2), 1.94–2.00 (m, 2H, CH2),
2.80–2.81 (t, 2H, CH2), 3.71 (bs, 2H, CH2), 6.82–7.25 (m, 3H, aromatics),
7.63–7.85 (m, 4H, aromatics). GC-MS: MS: m/z 366 (Mþ).
Synthesis of 9-(Phenylsulfonyl)-2,3,4,5-tetrahydro-lH-l-benzazepine
(11): Rearrangement of (7)
A mixture of 2.0 g (6.96 mmol) of l-(phenylsulfonyl)-2,3,4,5-tetrahydro-lH-1-
benzazepine (7) and 8 mL of conc. H2SO4 was placed in a 25-mL Erlenmeyer
flask. The flask was stoppered loosely with a cork, and the mixture gradually
colored to a deep red. When the solid dissolved completely, the solution was
heated in an oven at 1058 for 20 min, cooled, and then poured onto ice with
stirring until a gummy solid formed. The gummy solid was filtered and
washed thoroughly with ice water until the washings were neutral. The
product of (7) was recrystallized from methanol to give 0.89 g of yellow
1
crystals, mp: 84–85.58. Yield: 44.5%. IR: 3396.39 cm21 (NH); H NMR
(CDCl3): d 1.60–1.62 (m, 2H, CH2), 1.69–1.72 (m, 2H, CH2), 2.79–2.85
(m, 4H, CH2), 6.11 (bs, 1H, NH), 6.89–7.90 (m, 8H, aromatics). GC-MS:
m/z: 287 (Mþ). Anal. calcd. for: C16H17NO2S: C, 66.87%; H, 5.41%.
Found: C, 66.87%; H, 4.87%.
Synthesis of 9-[2-Nitrophenylsulfonyl]-2,3,4,5-tetrahydro-lH-1-
benzazepine (12) and 7-[2-Nitrophenylsulfonyl]-2,3,4,5-tetrahydro-
lH-1-benzazepine (15): Rearrangement of (8)
A mixture of 2.0 g (6.0 mmol) of l-[2-nitrophenylsulfonyl]-2,3,4,5-tetrahydro-
lH-1-benzazepine (8) and 6 mL of conc. H2SO4 was placed in a 25-mL
Erlenmeyer flask and loosely stoppered with a cork. The mixture gradually

362
H. Ren et al.
colored. When the solid dissolved completely, the solution was heated in an
oven at 1058 for 15 min, cooled, and poured onto ice with stirring until a
gummy solid formed. The gummy solid was filtered and washed thoroughly
with ice water until the washings were neutral. The gummy solid was
extracted for 15 h with ether using a Soxhlet extraction apparatus. The ether
extract, after removal of solvent, yielded a yellow solid.
The crude sample contained two isomeric diarylsulfones: 9-[2-nitrophenyl-
sulfonyl]-2,3,4,5-tetrahydro-lH-l-benzazepine (12) (major) and 7-[2-nitrophe-
nylsulfonyl]-2,3,4,5-tetrahydro-lH-l-benzazepine (15) (minor). To effect
separation, the crude sample was chromatographed on a silica-gel plate using
an eluant of hexane and ethyl acetate (hexane–EtOAc ¼ 60: 10 and gradually
increased to (hexane–EtOAc ¼ 50: 50). The product, 9-[2-nitrophenylsulfo-
nyl]-2,3,4,5-tetrahydro-lH-l-benzazepine (12), was first eluted (TLC Rf 0.44
(hexane–EtOAc ¼ 50 : 50) as an orange or light yellow crystal (0.20 g) with a
melting point at 89–918. Yield: 20%. Next to elute as a yellow crystal
(0.02 g) with a melting point of 181–1838 was 7-[2-nitrophenylsulfonyl]-
2,3,4,5-tetrahydro-lH-l-benzazepine (15). The TLC Rf was 0.26 (hexane–
EtOAc ¼ 50 : 50). Yield: 2%. The molar ratio of (12) to (15) was about 10: 1.
For 9-[2-nitrophenylsulfonyl]-2,3,4,5-tetrahydro-lH-l-benzazepine (12),
1
IR: 3410.66 cm21 (NH); H NMR (CDC13): d 8.20–8.16 (m, 1H), 7.81–
7.74 (m, 3H), 7.67–7.65 (dd, 1H), 7.33–7.32 (dd, 1H), 6.90–6.86 (t, 1H),
6.12 (bs, 1H), 3.03–3.01 (t, 2H), 2.88–2.85 (t, 2H), 1.80–1.75 (m, 2H),
1.73–1.66 (m, 2H); GC-MS: m/z 332 (Mþ). Anal. calcd. for C16H16N2O4S:
C, 57.82%; H, 4.85%; N, 8.43%. Found: C, 57.63%; H, 5.02%; N, 8.48%.
For 7-[2-nitrophenylsulfonyl]-2,3,4,5-tetrahydro-lH-l-benzazepine (15),
1
IR: 3387.60 cm21 (NH); H NMR (CDCl3) d 8.30–8.28 (dd, 1H), 7.75–
7.65 (m, 5H), 6.88–6.86 (d, 2H), 3.25–3.23 (t, 2H), 2.91–2.88 (t, 2H),
1.92–1.84 (m, 2H), 1.80–1.75 (m, 2H); GC-MS: m/z 332 (Mþ).
Synthesis of 7-Chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-lH-l-
benzazepine (13): Rearrangement of (9)
The experimental procedure is similar to the rearrangement of (7); 3.11 g (9)
and 10 mL of conc. sulfuric acid were heated in an oven for 20 min, forming a
dark, clear solution. The solution was cooled and poured onto ice, resulting in
a light orange precipitate. The sample was extracted for 12 h with ether using a
Soxhlet apparatus to obtain the crude product, which was recrystallized from
ether (by allowing the ether to evaporate until incipient crystallization)
to produce 1.66 g of pure product. Yield: 51.8%; mp: 147–148.58;
IR: 3397.71 cm21 (NH); 1H NMR (CDCl3): d 1.60–1.64 (m, 2H, CH2),
1.68–1.72 (m, 2H, CH2), 2.76–2.78 (t, 2H, CH2), 2.82–2.85 (t, 2H, CH2),
6.08 (bs, 1H, NH), 7.26–7.90 (m, 7H, aromatics). GC-MS: m/z 321 (Mþ).
Anal. calcd. for C16H16ClNO2S: C, 59.72%; H, 5.01%; N, 4.35%. Found:
C, 59.92%; H, 5.02%; N, 4.41%.

Synthesis of Aryltetrahydrobenzazepinesulfones
363
Synthesis of 7-Chloro-9-[2-nitrophenylsulfonyl]-2,3,4,5-tetrahydro-
lH-l-benzazepine (14): Rearrangement of (10)
The experimental procedure was similar to the rearrangement of (7). A
mixture of 2.19 g (10) and 5 mL of conc. H2SO4 were heated for 20 min.
Unlike the rearrangement of (8) where two isomeric sulfones were
obtained, the rearrangement of 7-chloro-l-[2-nitrophenylsulfonyl]-2,3,4,5-tet-
rahydro-lH-l-benzazepine (10) only led to 7-chloro-9-[2-nitrophenylsulfonyl]-
2,3,4,5-tetrahydro-1H-1-benzazepine. This was developed on prep-scale
silica-gel TLC plates (CHCl3–EtOAc; 9 : 1) to give 1.08 g of yellow
1
crystals. Yield: 49.3%; mp 99–101.58; IR: 3408.95 cm21 (NH); H NMR
(CDC13): d 1.70–1.81 (m, 4H, CH2CH2), 2.82–2.85 (t, 2H, CH2), 3.05–
3.08 (t, 2H, CH2), 7.27–8.21 (m, 6H, aromatics). GC-MS: m/z 366 (Mþ).
Anal. calcd. for C16H15ClN2O4S: C, 52.39%; H, 4.12%. Found: C, 52.47%;
H, 4.14%.
CONCLUSION
The syntheses described can be used to prepare a new class of diarylsulfone in
which one of the aromatic moieties possesses a fused azepine ring. These
compounds, like their tetrahydroquinoline analogs, may possess anti-HIV
activity.
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1. Gennaro, A.; Zanger, M. J. Org. Chem. 1971, 36, 375.
2. (a) Witt, O. N.; Uermenyi, D. Ber. 1913, 46, 296; (b) Witt, O. N.; Truttwin, H. Ber.
1914, 47, 2786.
3. (a) Halberkamm, J. Ber. 1921, 54, 1665, 1833; (b) Halberkamm, J. Ber. 1922,
55, 3074.
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