An expeditious concise synthesis of benzo[ b ]pyrano[2,3- d ]oxepines and dibenzo[ b, d ]oxepines

Article abstract of DOI:10.1055/s-0029-1218006

An efficient concise synthesis of 4-methylthio-2-oxo-5,6-dihydro-2H- benzo[b]pyrano[2,3-d]oxepine-3-carbonitriles has been delineated through condensation-cyclization of 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones and methyl 2-cyano-3,3-dimethylthioacrylate

Full text of DOI:10.1055/s-0029-1218006

2992
LETTER
An Expeditious Concise Synthesis of Benzo[b]pyrano[2,3-d]oxepines and
Dibenzo[b,d]oxepines
S
ynthesisof Benzo
i
[
b
]pyr
s
a
no[2,3-
d
h
n
d Dibenzo[
b
u
d
]oxepines K. Tandon,*a Hardesh K. Maurya,a Balendu Kumar,a Brijesh Kumar,b Vishnu Ji Ram*a
a
Department of Chemistry, Lucknow University, Lucknow 226007, U.P., India
Fax +91(522)2623405; E-mail: vjiram@yahoo.com
b
Division of SAIF, Central Drug Research Institute, Lucknow, 226001, India
Received 15 July 2009
A comprehensive literature survey revealed that mainly
four possible dibenzoxepine ring systems: dibenzo[b,d]-,
dibenzo[b,e]-, dibenzo[b,f]-, and dibenzo[c,e]oxepines
are reported depending upon the site of fusion of benzene
Abstract: An efficient concise synthesis of 4-methylthio-2-oxo-
5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepine-3-carbonitriles has
been delineated through condensation–cyclization of 3,4-dihydro-
2H-benzo[b]oxepin-5(2H)-ones and methyl 2-cyano-3,3-dimeth-
ylthioacrylate in DMF using powdered KOH as a base. A base- with oxepine ring. The chemistry and pharmacology of
induced reaction of 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones
dibenzo[b,e]-, dibenzo[b,f]-, and dibenzo[c,e]oxepines
and 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitrile in the pres-
ence of powdered KOH in DMF gave an isomeric mixture of (E)-
are explored extensively while dibenzo[b,d]oxepine is
still underdeveloped. The diverse pharmacological activi-
and
(Z)-2-(4-phenyl-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]ox-
ties, fascinating chemistry,8 and meagerly explored ring
system necessitated to develop an easy access to the syn-
thesis of dibenzo[b,d]oxepines to explore their chemistry
and biodynamic properties.
epin-2-ylidene)acetonitriles. However, the ring transformation of 6-
aryl-4-(sec-amino)-2H-pyran-2-one-3-carbonitriles from 3,4-dihy-
dro-2H-benzo[b]oxepin-5(2H)-ones under analogous reaction con-
ditions
exclusively
gave
8-phenyl-10-(sec-amino)-6,7-
dihydrodibenzo[b,d]oxepine-11-carbonitriles.
Earlier, compounds of this ring system have been
synthesized9 by treatment of biphenyl-2-yloxyacetyl chlo-
ride with AlCl3 as dibenzo[b,d]oxepin-5-one in moderate
yield. These are also obtained by thermal decomposition
of 2¢-phenyldiphenylether-2-sulfonyl chloride at 250–
260 °C as tribenzo[b,d,f]oxepines.10 Junjappa et al. have
reported11,12 the synthesis of this ring system by the reac-
tion of cyclic 2-oxoketenedithioacetals with propargyl-
magnesium bromide and allylmagnesium bromide
separately. These are also obtained by irradiation of 9,10-
epoxy-9,10-dihydrophenanthrene under nitrogen blanket
in benzene.13 Further, irradiation of 2-phenethyloxyaryl
bromide in acetonitrile13 also gave similar product.13
Keywords: 2-pyranone, benzo[b]pyrano[2,3-d]oxepine, diben-
zo[b,d]oxepine, ring-transformation reaction
Dibenzoxepine framework is commonly present as sub-
structure in numerous natural products of therapeutic im-
portance.1 Cularinoids, a group of sixty isoquinoline
alkaloids, are characterized by the presence of dibenzox-
epine skeleton. The oxidized cularinoids,2 such as 3,4-di-
oxocularines I and aristocularines II, are known to display
significant cytotoxic activity against both wild-type and
adriamycin-resistant cell lines. They are also effective
against H-29 human colon adenocarcinoma and MDA-
MB-231 human breast cancer cells3,4 and found useful as
nuclear hormone receptor modulators.5 Besides these,
they are extensively in use for the treatment of anxiety,
depression, and schizophrenic psychoses.6,7
Recently, dibenzo[b,d]oxepines have been prepared by
intramolecular cyclization of 1-bromo-2-phenethoxy ben-
zene in the presence of a catalyst generated from
Pd(OAc)2 and 2-(diphenylphospheno)-2¢-(N,N-dimethyl-
amino)biphenyl.14 An improved synthesis has also been
reported through cyclization of 1-bromo-2-phenethoxy-
benzenes in the presence of Pd(OAc)2 and PCY3·HBF4 in
conjunction with Cs2CO3 and 2,2-dimethylpropionic acid
in mesitylene at 135 °C.15 Oxidative coupling of substitut-
ed phenyl phenylacetate by thallium(III)trifluoroacetate
(TTFA) or phenyl iodine(III)bis(trifluoroacetate) (PIFA)
has also been reported as an alternative route16 for the con-
struction of lactonized benzo[b,d]oxepines.
O
Me
Me
N
O
N
O
MeO
MeO
MeO
MeO
O
O
OMe
OMe
aristocularine (II)
3,4-dioxocularine (I)
Our synthetic strategy is based on the use of 6-aryl-4-
methylsulfanyl-2H-pyrans-2-one-3-carbonitriles 2 as pre-
cursors, obtainable from the reaction of aryl methyl ke-
tone and methyl 2-cyano-3,3-dimethylthioacrylate17 (1).
Amination18 of 2 with sec-amine in boiling ethanol afford-
ed 6-aryl-4-(sec-amino)-2H-pyran-2-one-3-carbonitriles
3 (Scheme 1).
Figure 1 Natural isoquinoline alkaloids with benzoxepine frame-
work
SYNLETT 2009, No. 18, pp 2992–2996
x
x
.x
x
.2
0
0
9
Advanced online publication: 08.10.2009
DOI: 10.1055/s-0029-1218006; Art ID: G23409ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Benzo[b]pyrano[2,3-d]oxepines and Dibenzo[b,d]oxepines
2993
3,4-Dihydro-2H-benzo[b]oxepin-5(2H)-ones 4, used as a the reaction of 6-aryl-4-sec-amino-2H-pyran-2-one 3 and
source of carbanion for the construction of various ben- 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones under
4
zo[b]pyrano[2,3-d]oxepins have been obtained by the analogous reaction conditions exclusively gave 8-phenyl-
reaction of phenol with g-butyrolactone with subsequent 10-sec-amino-1-yl-6,7-dihydrodibenzo[b,d]oxepine-11-
cyclization of isolated acid in PPA.19 The benzo[b]ox- carbonitriles 6 by following path A (Scheme 3).
epin-5-ones 4 on reaction with methyl 2-cyano-3,3-dime-
The molecular makeup of 6-aryl-4-methylthio-2H-pyran-
thylthioacrylate (1) at room temperature in the presence of
2-one-3-carbonitriles 2 revealed the presence of three
KOH exclusively gave 4-methylthio-2-oxo-5,6-dihydro-
electrophilic sites C-2, C-4, and C-6 in which the latter is
2H-benzo[b]pyrano[2,3-d]oxepine-3-carbonitriles
5
the most electron deficient due to extended conjugation
and the presence of an electron-withdrawing CN substitu-
ent at position 3 of the pyran ring. Thus, C-6 position of
the pyran ring is attacked by carbon nucleophiles, gener-
ated in situ from 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-
ones 4 in the presence of powdered KOH. The progress of
the reaction was clearly observed by evolution of carbon
dioxide bubbles. The completion of reaction was moni-
tored by silica gel coated TLC plates.
(Scheme 2).
N(R3)2
SMe
MeOOC
MeS
CN
CN
O
CN
DMF
KOH
HN(R3)2
+
ArCOMe
EtOH
Ar
SMe
Ar
O
O
O
2
3
1
2,3 Ar
Ph
N(R3)2
piperidin-1-yl
1,2,3,4-tetrahydroisoquinolin-2-yl
piperidin-1-yl
piperidin-1-yl
–
Thus, an equimolar mixture of 6-aryl-4-methylthio-2H-
pyran-2-one-3-carbonitriles 2 and bicyclic ketone 4 was
stirred with anhydrous KOH in DMF for 2–3 hours at
room temperature, and the reaction mixture was poured
onto crushed ice with vigorous stirring followed by neu-
tralization with 10% aqueous HCl. The resulting precipi-
tate was filtered, washed with water, and dried. The crude
product was purified by silica gel column chromatogra-
phy and compound isolated was identified as an isomeric
mixture of (E)- and (Z)-2-{4-phenyl-5,6-dihydro-2H-
benzo[b]pyrano-[2,3-d]oxepin-2-ylidene}acetonitriles 7.
However, compound 6 was obtained by stirring a mixture
of 6-aryl-4-sec-amino-2H-pyran-2-one 3 and 4 under
analogous reaction conditions in the presence of pow-
dered KOH in DMF at room temperature.
4-ClC6H4
1-naphthyl
2-thienyl
4-MeC6H4
Scheme 1 Synthesis of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbo-
nitriles 2 and 6-aryl-4-(sec-amino)-2H-pyran-2-one-3-carbonitriles 3
O
CN
O
O
SMe
NC
COOMe
SMe
DMF
KOH
+
O
MeS
R
O
R
4
1
5
Yield (%)
5
R
In these reactions 3,4-dihydro-2H-benzo[b]oxepin-
5(2H)-ones 4 have been employed either as a source of
carbanion or as precursors for the construction of various
4-methylthio-2-oxo-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]-
oxepine-3-carbonitriles 5.
a
b
c
H
59
55
65
21
10-Me
10-OMe
8,10-(Me)2
d
The common initial step in the synthesis of 6 and 7 is for-
mation of Michael adduct by attack of a carbanion gener-
ated in situ from 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-
ones 4 at C-6 of the pyran ring and thereafter, reaction fol-
lowed either path A or B depending upon the nature of
substrate. The Michael adduct so formed underwent ring
opening in situ followed by recyclization involving C-3 of
pyran ring and carbonyl function of bicyclic ketone 4 to
yield exclusively 6. In the formation of 7, the Michael ad-
duct underwent enolization followed by Michael addition
with subsequent elimination of methyl mercaptan as de-
picted in Scheme 3.
Scheme 2 Synthesis of 5,6-dihydro-4-methylthio-2-oxo-2H-ben-
zo[b]pyrano[2,3-d]oxepine-3-carbonitriles
The reaction of 6-aryl-4-methylthio-2H-pyran-2-one-3-
carbonitriles 2 and 4 in DMF using powdered KOH as a
base exclusively gave an isomeric mixture (E)- and (Z)-2-
{4-phenyl-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepin-2-
ylidene}acetonitriles 7 instead of 8-aryl-10-methylthio-
6,7-dihydrobenzo[b,d]oxepine-11-carbonitriles 6 (R1 = SMe),
by following path B (Scheme 3). Attempts to separate the
E- (minor) and Z-isomer (major) under different reaction
conditions failed due to their very close Rf and were iden-
tified only by NMR spectroscopy. Use of different bases
such as NaH and Na2CO3 in lieu of KOH did not change
the course of reaction and improved the yield.
All the synthesized compounds were characterized by
spectroscopic analyses.20
In conclusion, we have developed a novel, simple, and
economical synthesis of congested 5,6-dihydro-2H-ben-
zo[b]pyrano[2,3-d]oxepines 5 from the reaction of 3,4-di-
hydro-2H-benzo[b]oxepin-5(2H)-ones 4 and methyl 2-
cyano-3,3-dimethylthioacrylate (1) in the presence of
KOH in DMF. We have also developed an efficient syn-
A different synthetic strategy was followed to obtain 6 by
using 6-aryl-4-sec-amino-2H-pyran-2-one 3 as a precur-
sor in lieu of 2 for the ring-transformation reaction. Thus,
Synlett 2009, No. 18, 2992–2996 © Thieme Stuttgart · New York

2994
V. K. Tandon et al.
LETTER
R2
nitrile 3 and 6-aryl-4-methylthio-2H-pyran-2-one 2 with
3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones 4 separately
through C–C insertion not reported so far.
O
CN
+
R1
Ar
O
O
O
Table 1 Synthesis of Compounds 6 and 7
4
2, 3
6, 7 Compound
Mp (°C) Yield (%)
DMF
KOH
R2 = sec-amino
R2 = SMe
path A
path B
N
CN
6a
144
40
OH
O
OMe
O
O
CN
R2
Ar
CN
R2
Ar
O
O
O
O
R1
R1
O
H
N
O
CN
O
OMe
6b
188
36
CN
OH
O
R1
CN
OH
R1
O
R2
R2
Ar
O
Ar
O
O
H
– CO2
– CO2
N
C
N
CN
CN
OH
6c
102
38
R1
R1
R2
OMe
R2
:
OH
Ar
Ar
Cl
O
O
O
H
– H2O
N
C=N
Ar
R2
CN
6d
128
30
R1
R2
Me
O
10
11
CN
1
9
2
R1
3
8
Ar
S
O
O
7
4
O
6
CN
5
– R2H
6
O
Me
7a
7b
7c
116
200
154
39
55
38
CN
O
O
CN
Ar
O
O
OMe
7
Cl
Scheme 3 A plausible mechanism for the synthesis of 2-(4-phenyl-
5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepin-2-ylidene)acetonitri-
les 7 and 8-phenyl-10-sec-amino-6,7-dihydrobenzo[b,d]oxepine-11-
carbonitriles 6
O
CN
O
OMe
thesis of dibenzo[b,d]oxepine 6 and an isomeric mixture
of (E)- and (Z)-2-(4-phenyl-5,6-dihydro-2H-benzo[b]py-
rano[2,3-d]oxepin-2-ylidene)acetonitriles 7 by the reac-
tion of 6-aryl-4-sec-amino-2H-pyran-2-one-3-carbo-
O
Synlett 2009, No. 18, 2992–2996 © Thieme Stuttgart · New York

LETTER
Synthesis of Benzo[b]pyrano[2,3-d]oxepines and Dibenzo[b,d]oxepines
2995
(14) Campeau, L.-C.; Parisien, M.; Leblanc, M.; Fagnou, K.
Table 1 Synthesis of Compounds 6 and 7 (continued)
J. Am. Chem. Soc. 2004, 126, 9186.
(15) Lafrance, M.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc.
2007, 129, 14570.
(16) Taylor, S. R.; Ung, A. T.; Pyne, S. G.; Skelton, B. W.; White,
A. H. Tetrahedron 2007, 63, 11377.
(17) (a) Tominaga, Y.; Ushirogochi, A.; Matsuda, Y.
J. Heterocycl. Chem. 1987, 24, 1557. (b) Ram, V. J.;
Verma, M.; Hussaini, F. A.; Shoeb, A. J. Chem. Res., Synop.
1991, 98. (c) Ram, V. J.; Verma, M.; Hussaini, F. A.; Shoeb,
A. Liebigs Ann. Chem. 1991, 1229.
6, 7 Compound
Mp (°C) Yield (%)
CN
O
Me
7d
202
155
39
31
Cl
O
(18) Ram, V. J.; Nath, M.; Srivastava, P.; Sarkhel, S.; Maulik,
P. R. J. Chem. Soc., Perkin Trans. 1 2000, 3719.
(19) Tandon, V. K.; Khanna, J. M.; Anand, N. Tetrahedron 1990,
46, 2871.
CN
O
Me
7e
(20) Data for Compounds
General Procedure for the Synthesis of 4-Methylthio-2-
oxo-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepine-3-
carbonitriles (5)
Me
O
A mixture of 3,4-dihydro-2H-benzo[b]oxepin-5 (2H)-one (1
mmol) and methyl 2-cyano-3,3-dimethylthioacrylate (1, 1
mmol) in DMF (8 mL) in the presence of powdered KOH (2
mmol) for 5 h. Excess of DMF was removed under reduced
pressure and the residue poured onto crushed ice with
vigorous stirring. The aqueous suspension was neutralized
with 10% HCl (5 mL) and the precipitate obtained was
filtered, washed with H2O, and purified on silica gel column,
using 40% hexane in CH2Cl2 as eluent.
Compound 5c: yellow solid; yield 65%; mp 178 °C; IR
(KBr): 2956, 2361, 2216 (CN), 1722 (C=O), 1585, 1489,
1271, 1212, 1037, 840, 761, 668, 502 cm–1. 1H NMR (300
MHz, CDCl3): d = 2.87 (t, J = 6 Hz, 2 H), 3.01 (s, 3 H,
SCH3), 3.83 (s, 3 H, OCH3), 4.47 (t, 2 H, J = 6.0 Hz, OCH2),
7.03 (s, 1 H, ArH), 7.28 (d, J = 9 Hz, 2 H, ArH). 13C NMR
(300 MHz, CDCl3): d = 18, 27, 55, 75, 93, 112 (2 C), 114,
115, 120, 123, 124, 150, 155, 158, 168. MS: m/z = 315 [M+].
ESI-HRMS: m/z calcd for C16H14NO4S: 316.0626 [M+ + 1];
found: 316.0643.
Acknowledgment
VKT and VJR are thankful to CSIR, New Delhi for financial
support and Sophisticated Analytical Instrument Facility, CDRI,
Lucknow, for providing spectroscopic data.
References and Notes
(1) (a) Bentley, K. W. In The Isoquinoline Alkaloids, Part 5,
Vol. 1; Ravindranath, B., Ed.; Hartwood Academic:
Banglore, 1998, 93–106. (b) Castedo, L.; Suau, R. In The
Alkaloids, Part 6, Vol. 29; Brossi, A., Ed.; Academic Press:
Orlando, 1986, 287–324.
(2) Rodriguez de Lera, A.; Suau, R.; Castedo, L. J. Heterocycl.
Chem. 1987, 24, 313.
(3) Suau, R.; Lopez-Romero, J. M.; Rico, R.; Alonso, F. J.;
Lobo, C. Tetrahedron 1996, 52, 11307.
(4) (a) Wijeratne, E. M. K.; Gunatilaka, A. L.; Kingston, D. G.
I.; Haltiwanger, R. C.; Ehghleston, D. S. Tetrahedron 1995,
51, 7877. (b) Suau, R.; Rico, R.; Lopez-Romero, J. M.;
Najera, F.; Ruiz, A.; Ortiz-Lopez, F. J. Arkivoc 2002, (v), 62.
(5) (a) Richey, R. N.; Yu, H. Org. Process Res. Dev. 2009, 13,
315. (b) Coghlan, M. J.; Green, J. E.; Grese, T. A.; Jadhav,
P. K.; Matthews, D. P.; Steinberg, M. I.; Fales, K. R.; Bell,
M. G. WO 2004052847 A2, 2004.
(6) (a) Olivera, R.; SanMartin, R.; Churruca, F.; Dominguez,
E. J. Org. Chem. 2002, 67, 7215; and references cited
therein. (b) Dominguez, E. Trends Heterocycl. Chem. 2003,
9, 259. (c) Mercep, M.; Mesic, M.; Pesic, D. WO
2003099822, 2003. (d) Peggy, P. M.; Wilson, P. D. Org.
Lett. 2003, 5, 4911.
General Procedure for the Synthesis of 8-Phenyl-10-
(sec-amino)-6,7-dihydrodibenzo[b,d]oxepine-11-
carbonitriles (6)
A mixture of 3,4-dihydrobenzo[b]oxepine-5 (2H)-ones 4 (1
mmol) and 6-phenyl-4-(sec-amino)-2H-pyran-2-one-3-
carbonitriles 3 (1 mmol) in DMF (6 mL) was stirred for
3 h in the presence of powdered KOH (2 mmol). After
completion of the reaction, content was poured onto crushed
ice with vigorous stirring and neutralized with 10% HCl.
The precipitate obtained was filtered, washed with H2O, and
dried. The crude product was purified through silica gel
column using a mixture of hexane–CH2Cl2 (7:3) as eluent
and repurified by abs. MeOH.
(7) Review: Missir, A.; Limban, C.; Stecoza, C.; Morusciag, L.;
Chirita, I. Farmacia (Bucharest) 1998, 46, 17.
(8) Kumar, S.; Ila, H.; Junjappa, H. Tetrahedron 2007, 63,
10067.
(9) Harrow, T. A.; Harrison, C. E.; Williamson, W. R. N.
J. Chem. Soc.C 1971, 2098.
(10) Neale, A. J.; Rawlings, T. J.; McCall, E. B. Tetrahedron
1965, 21, 1299.
(11) Balu, M. P.; Singh, G.; Ila, H.; Junjappa, H. Tetrahedron
Lett. 1986, 27, 117.
(12) (a) Gupta, A. K.; Ila, H.; Junjappa, H. Tetrahedron Lett.
1987, 28, 1459. (b) Singh, G.; Ila, H.; Junjappa, H.
Tetrahedron Lett. 1984, 25, 5095.
(13) Brightwell, N. E.; Griffin, G. W. J. Chem. Soc., Chem.
Commun. 1973, 37.
Compound 6a: white solid; yield 44%; mp 144 °C. IR
(KBr): 3069, 2934, 2850, 2804, 2370, 2218 (CN), 1573,
1496, 1439 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.52–
1.69 (m, 6 H), 3.06 (m, 2 H), 3.20 (m, 4 H), 3.79 (s, 3 H),
4.24 (m, 2 H), 6.97–7.03 (m, 2 H), 7.08 (s, 1 H), 7.24 (d, 1
H, J = 3.0 Hz), 7.38–7.48 (m, 5 H). 13C NMR (300 MHz,
CDCl3): d = 24, 26 (2 C), 28, 53 (2 C), 55, 78, 105, 115, 116,
118, 119, 122, 127 (2 C), 128 (3 C), 132 (2 C), 140, 143, 146,
148, 155, 156. MS: m/z = 411 [M+ + 1], 412 [M+ + 2]. ESI-
HRMS: m/z calcd for C27H27N2O2: 411.20725 [M+ + 1];
found: 411.20728.
General Procedure for the Synthesis of 2-{4-Phenyl-5,6-
dihydro-2H-benzo[b]pyrano[2,3-d]oxepin-2-ylidene}-
acetonitriles (7)
A mixture of 3,4-dihydrobenzo[b]oxepine-5 (2H)-ones 4 (1
mmol), 6-(4-phenyl-4-methylthio)-2-oxo-2H-pyran-3-
Synlett 2009, No. 18, 2992–2996 © Thieme Stuttgart · New York

2996
V. K. Tandon et al.
LETTER
carbonitriles 2 (1 mmol) and powdered KOH (2 mmol) in
DMF (8 mL) was stirred for 3 h.The reaction mixture was
poured onto crushed ice with vigorous stirring. The aqueous
phase was neutralized with 10% HCl, and the precipitate
obtained was filtered, washed with H2O, and purified on
silica gel column using hexane–CH2Cl2 mixture (7:3) as
eluent.
Compound 7b: red colored solid; yield 55%; mp 200 °C; IR
(KBr): 3077, 2927, 2834, 2368, 2189 (CN), 1639, 1570,
1490, 1404 cm–1. 1H NMR (300 MHz, CDCl3): d (Z-isomer,
70%) = 2.50 (s, 2 H, CH2), 3.89 (s, 3 H, OCH3), 4.26 (s, 2 H,
OCH2), 6.18 (s, 1 H, CH), 6.65–7.43 (m, 8 H, ArH); d (E-
isomer, 30%) = 2.41 (s, 2 H, CH2), 3.83 (s, 3 H, OCH3), 4.35
(s, 2 H, OCH2), 6.65 (s, 1 H, CH), 6.65–7.43 (m, 8 H, ArH).
13C NMR (300 MHz, CDCl3): d = 31, 55, 65, 72, 110, 112,
115, 116, 117, 118, 119, 122 (2 C), 129 (2 C), 135 (2 C), 146,
150, 151, 155, 164. MS: m/z = 378 [M+], 380 [M+ + 2]. ESI-
HRMS: m/z calcd for C22H17ClNO3: 378.0897 [M+ + 1];
found: 378.0889.
Synlett 2009, No. 18, 2992–2996 © Thieme Stuttgart · New York

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