Anionic cyclization of (N,N-Dimethylamino)[2-(prop-2-yn-1-yloxy)aryl]- acetonitriles

Article abstract of DOI:10.1055/s-0028-1088061

The cyclization of (N,N-dimethylamino)[2-(prop-2-yn-1-yloxy)aryl] acetonitriles is carried out under phase-transfer conditions using powdered sodium hydroxide and benzyltriethylammonium chloride as catalyst in dimethyl sulfoxide to afford mixtures of a me

Full text of DOI:10.1055/s-0028-1088061

PAPER
2029
Anionic Cyclization of (N,N-Dimethylamino)[2-(prop-2-yn-1-yloxy)aryl]-
acetonitriles
A
nionic cycliza
a
tion deusz Zdrojewski, Joanna Musielak, Andrzej Joꢀczyk*
Warsaw University of Technology, Faculty of Chemistry, Koszykowa St. 75, 00-662 Warszawa, Poland
Fax +48(22)6282741; E-mail: anjon@ch.pw.edu.pl
Received 6 February 2009; revised 13 February 2009
It has been reported that 2-(dialkylamino)phenylacetoni-
triles can be alkylated in the presence of a mixture of con-
centrated aqueous and solid sodium hydroxide and
benzyltriethylammonium chloride (TEBAC) as a phase-
Abstract: The cyclization of (N,N-dimethylamino)[2-(prop-2-yn-
1-yloxy)aryl]acetonitriles is carried out under phase-transfer condi-
tions using powdered sodium hydroxide and benzyltriethylammoni-
um chloride as catalyst in dimethyl sulfoxide to afford mixtures of
a methylenechromane and a methylchromene via favored 6-exo-dig transfer catalyst (PTC system18–20), at elevated tempera-
ture.21 On the other hand, efficient intermolecular addition
and 6-endo-dig processes, respectively. Several of the chromenes
rearranged into benzofuranone derivatives during column chroma-
of 2-phenylalkanenitriles to ethynes occurred on treat-
tography on alumina and the formation of these is rationalized.
ment with solid sodium hydroxide, benzyltriethylammo-
nium chloride as the catalyst and dimethyl sulfoxide22 or
Key words: phase-transfer catalysis, carbanions, cyclizations, het-
erocycles, intramolecular vinylation
cesium tert-butoxide in N-methyl-2-pyrrolidinone.17 The
former conditions were also suitable for intermolecular
vinylation of 2-(dialkylamino)arylacetonitriles23–25 and 2-
substituted N-(benzylidene)glycinonitriles.26 Based on the
above,21–26 we have investigated the phase-transfer-cata-
lyzed intramolecular addition reactions of aminonitriles 3,
which are easily prepared from salicylic aldehydes 1a–e
(Scheme 1 and Table 1).
Compounds which possess both an acidic site and a suit-
ably located carbon–carbon triple bond, on treatment with
a base, generate anions which can undergo intramolecular
addition to the triple bond via exo- and/or endo-dig
cyclization1 leading to the formation of carbo- or hetero-
cyclic products.
Aldehydes 1 were O-alkylated with propargyl bromide
under phase-transfer conditions (10% aqueous sodium
hydroxide, benzyltriethylammonium chloride, toluene) to
give alkynes 2 which were converted into the required
aminonitriles 3 via the Strecker reaction. Subsequent an-
ionic cyclization of compounds 3 was carried out in the
presence of powdered sodium hydroxide, benzyltriethyl-
ammonium chloride as the catalyst and dimethyl sulfox-
ide (solid–liquid system), under mild conditions, to give
chromanes 4 or mixtures of 4 and chromenes 5 (Scheme
1).
According to Baldwin’s rules,1 formation of exo products
4 should occur by way of favored 6-exo-dig cyclization,
while endo products 5 are formed by a favored 6-endo-dig
process (Scheme 2). Production of exo-4 occurs through
straightforward carbanion attack on the carbon–carbon
triple bond of 3 to generate 4–, yet a similar process lead-
ing to endo-5 requires propargyl to allenyl ether rear-
rangement in 3, prior to cyclization. Alternatively, the
There are several examples in the literature of such car-
banionic cyclizations. These include cyclizations of sub-
stituted derivatives of malonic2–5 and acetoacetic acid
esters,2,5–7 a-substituted methyl acetate derivatives,5 alky-
nyl ketones,7–9 o-alkynyl-10 and o-propargyloxyacetophe-
nones,11 propargyl ethyl malonates,12 ethyl N-(2-
ethynyloxyphenyl)malonamate13 and nitro-substituted
compounds.14 The one-pot reaction of dimethyl 2-oxo-cy-
cloalkane-1,3-dicarboxylates with 1,4-dibromobut-2-yne
produced substituted dihydrofurans in 92–100% yield.15
Cyclizations of a-cyanocarbanions generated from suit-
ably substituted a-aminonitriles using lithium diisopropy-
lamide (followed by oxidation of the crude intermediates
with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone),16 or
from phenylacetonitrile, or w-ethynylalkyl-a-substituted-
benzylsulfones, using catalytic amounts of cesium hy-
droxide,17 produced either mixtures of substituted pyr-
roles and azetidines,16 or 2-exo-methylenecyclopentanes
or hexanes,17 respectively.
NMe2
NC
NMe2
NC
NMe2
Me2NH⋅HCl
NaCN, H2O
X
Y
X
Y
X
Y
X
Y
X
Y
O
O
(i)
CN
(ii)
+
Br
5–30 °C, 24 h
O
O
O
OH
O
1
2
3
4
5
Scheme 1 Reagents and conditions: (i) 10% aq NaOH, toluene, TEBAC, 60 °C, 3–10 h; (ii) powdered NaOH, DMSO, TEBAC, 35 °C, 2 h.
SYNTHESIS 2009, No. 12, pp 2029–2034
x
x.
x
x
.
2
0
0
9
Advanced online publication: 27.04.2009
DOI: 10.1055/s-0028-1088061; Art ID: Z02009SS
© Georg Thieme Verlag Stuttgart · New York

2030
T. Zdrojewski et al.
PAPER
Table 1 2-Propargyloxyarylcarbaldehydes 2, Aminonitriles 3, and the Anionic Cyclization Products 4 and 5
Compd
1a
X, Y
Time (h)a
Yield (%) of 2
Yield (%) of 3
Yield (%) of 4
Yield (%) of 5
Ratio of 4:5b
H, H
3
4
88
83
79
85
55
80
82
77
48
73
32
48
36
21d
30
44
30
1:2
2:1
5:1
1:0
5:1
1b
5-Cl, H
5-Br, H
H, 3-MeO
5,6-(CH)4
c
1c
5
–
1d
4
c
1e
10
–
a Reaction time for the conversion of 1 into 2.
b Determined on the basis of 1H NMR spectroscopy.
c Decomposed with the formation of 9 during column chromatography.
d Competitive oxidation of 3d– decreased the yield of the cyclization product.
highly basic vinyl anion 4– may undergo a [1,3]-proton According to route ‘a’, the latent carbonyl group in ami-
shift to yield allyl anion 5– which gives 5 on protonation.
nonitrile 5 is unmasked during column chromatography
giving chromone 6 which undergoes addition of cyanide
to form 7–. The latter affords the heterocyclic product 9
via a ring-opening/ring-closing process. The base-
induced ring-opening of chromenes has been described
previously.27,28 In route ‘b’, aminonitrile 5 can exist in
equilibrium with the strongly electrophilic immonium salt
10 which can easily add a cyanide anion to form enamine
11. Hydrolysis of the latter gives a b-cyanoketone which
after deprotonation produces 7–, which is further trans-
formed into 9 via the processes described above. Some of
the steps presented in route ‘b’ have already been reported
in the reactions of vinylaminonitriles.24
The compositions of the crude reaction mixtures of 4 and
5, after cyclization, were determined by integration of the
signals of the dimethylamino groups in the 1H NMR spec-
tra.
Attempted isolation of cyclic products 4 and 5 by column
chromatography on alumina led to pure exo-4 while endo-
5 was transformed into heterocycle 9. Two possible routes
‘a’ and ‘b’ leading from 5 to 9 are shown in Scheme 3.
NMe2
NC
NMe2
X
Y
X
Y
Products 4 and 5 contain a masked carbonyl group and
hence are precursors of the corresponding 3-methylene-
chroman-4-ones and 3-methylchromone derivatives 6.
However, attempted unmasking of the carbonyl groups23
in 4 and 5 under typical conditions (benzene–aqueous
copper sulfate solution, or water–ethanolic copper sulfate
solution) failed; a complex mixture of products was ob-
tained instead.
H+
CN
PTC
4
3
O
O
4–
3–
NC
NMe2
NC
NMe2
X
Y
X
Y
H+
5
O
O
In conclusion, we have demonstrated that a phase-transfer
catalytic system can be used to achieve anionic cycliza-
tion of aminonitriles 3. Some of the chromenes 5 proved
to be unstable during column chromatography on alumina
and underwent rearrangement into benzofuranones 9.
5–
Scheme 2 Intramolecular cyclization leading to chromanes 4 and
chromenes 5
O
O
O
NC
NMe2
X
X
Y
X
Y
X
Y
CN–
a
O
CN
O
CN
Y
O
O
7–
5
6
8–
1. H2O
2. B–
b
– Me2NH
N
N
O
CN–
N
O
O
X
Y
X
X
Y
X
Y
X
H+
CN
CN
O
O
CN–
CN
O
O
Y
Y
10
11
9–
9
Scheme 3 Possible routes leading to the formation of heterocycle 9
Synthesis 2009, No. 12, 2029–2034 © Thieme Stuttgart · New York

PAPER
Anionic Cyclization
2031
Column chromatography was carried out on Fluka 5016A alumi-
num oxide (basic) using EtOAc–hexane (1:5 v/v) as eluent. Gas
chromatography (GC) was performed using an Agilent 6850 Series
13C NMR: d = 56.0, 60.8, 76.9, 78.2, 117.7, 118.8, 124.9, 131.0,
149.4, 152.8, 190.6.
Anal. Calcd for C11H10O3: C, 69.46; H, 5.30. Found: C, 69.50; H,
5.38.
1
GC System fitted with a HP–50+ (30 m) column. H NMR (400
MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra were re-
corded on a Varian Mercury 400BB spectrometer; chemical shifts
(d) are given in ppm relative to tetramethylsilane (TMS); coupling
constants (J) are given in Hz. MS and HRMS spectra were obtained
using an AMD 604 (Intectra) apparatus. Elemental analyses were
performed on a Perkin Elmer 2400 Series II CHNS/O microanalyz-
er. Melting points were measured on a capillary apparatus and are
uncorrected. Aldehydes 1 and propargyl bromide (80 wt% solution
in toluene) were commercial grade (Aldrich).
2-(Prop-2-yn-1-yloxy)-1-naphthaldehyde (2e)
Mp 107–110 °C.
1H NMR: d = 2.58 (t, J = 2.4 Hz, 1 H, CCH), 4.95 (d, J = 2.4 Hz, 2
H, CH2), 7.36–7.49 (m, 2 H, ArH), 7.59–7.68 (m, 1 H, ArH), 7.79
(d, J = 8.0 Hz, 1 H, ArH), 8.07 (d, J = 9.2 Hz, 1 H, ArH), 9.27 (d,
J = 8.0 Hz, 1 H, ArH), 10.91 (s, 1 H, CHO).
13C NMR: d = 57.0, 76.5, 79.4, 108.3, 124.5, 126.5, 127.7, 127.9,
129.0, 129.8, 130.6, 138.9, 157.8, 190.0.
(Prop-2-yn-1-yloxy)benzaldehydes and (Prop-2-yn-1-
yloxy)naphthaldehyde 2; General Procedure
Anal. Calcd for C14H10O2: C, 79.98; H, 4.79. Found: C, 79.90; H,
4.82.
To a stirred solution of aldehyde 1 (50 mmol) and TEBAC (0.11 g,
0.5 mmol) in toluene (70 mL) was added a solution of NaOH (2.4
g, 0.06 mol) in H2O (22 mL). The mixture was stirred (ca. 0.5 h) and
then propargyl bromide (55 mmol, 80 wt% in toluene) was added
dropwise. Stirring was continued at 60 °C until aldehyde 1 was no
longer detected by GC (3–10 h, Table 1). The reaction mixture was
allowed to cool and the organic phase was separated. The aq phase
was extracted with toluene (3 ꢀ 20 mL) and the combined organic
phase was washed with H2O (30 mL) and dried (MgSO4). Follow-
ing evaporation of the solvent, the crude product was crystallized
from C6H6 or from a mixture of C6H6–cyclohexane.
(N,N-Dimethylamino)[2-(prop-2-yn-1-yloxy)aryl]acetonitriles
3; General Procedure
To a stirred, chilled (ca. 5 °C) suspension of aldehyde 2 (25 mmol)
and dimethylamine hydrochloride (3.1 g, 38 mmol) in MeCN (25
mL), a solution of NaCN (1.9 g, 38 mmol) in H2O (2 mL) was added
dropwise whilst maintaining the temperature of the reaction mixture
below 10 °C. The mixture was stirred for ca. 24 h at 30 °C until al-
dehyde 2 could no longer be detected by GC. The reaction mixture
was cooled, diluted with H2O (25 mL) and extracted with C6H6
(5 ꢀ 20 mL). The combined extracts were washed with H2O (10
mL) and dried (MgSO4). After evaporation of the solvent the crude
residue was distilled and/or crystallized from Et2O or a mixture of
C6H6–cyclohexane.
2-(Prop-2-yn-1-yloxy)benzaldehyde (2a)
Mp 66–69 °C (Lit.29 66–68 °C).
1H NMR: d = 2.56 (t, J = 2.4 Hz, 1 H, CCH), 4.80 (d, J = 2.4 Hz, 2
H, CH2), 6.94–7.89 (m, 4 H, ArH), 10.46 (s, 1 H, CHO).
13C NMR: d = 56.0, 76.4, 77.5, 113.1, 121.5, 125.3, 128.3, 135.7,
159.7, 189.5.
(N,N-Dimethylamino)[2-(prop-2-yn-1-yloxy)phenyl]acetoni-
trile (3a)
Bp 107–108 °C (0.1 Torr); mp 35–36 °C.
1H NMR: d = 2.35 [s, 6 H, N(CH3)2], 2.52 (X of ABX, JAX = JBX
2.4 Hz, 1 H, CCH), 4.75, 4.81 (AB of ABX, JAB = 16 Hz, 2 H, CH2),
=
Anal. Calcd for C10H8O2: C, 74.99; H, 5.03. Found: C, 75.13; H,
4.99.
5.16 (s, 1 H, CH), 7.03–7.50 (m, 4 H, ArH).
13C NMR: d = 41.6 (2C), 56.4, 56.8, 75.9, 77.9, 113.0, 115.2, 121.2,
122.5, 129.5, 130.2, 154.7.
5-Chloro-2-(prop-2-yn-1-yloxy)benzaldehyde (2b)
Mp 75–76 °C.
1H NMR: d = 2.59 (t, J = 2.4 Hz, 1 H, CCH), 4.81 (d, J = 2.4 Hz, 2
H, CH2), 7.07 (d, J = 9.2 Hz, 1 H, ArH), 7.49 (dd, J = 9.2, 2.8 Hz, 1
H, ArH), 7.78 (d, J = 2.8 Hz, 1 H, ArH), 10.38 (s, 1 H, CHO).
Anal. Calcd for C13H14N2O: C, 72.87; H, 6.59; N, 13.07. Found: C,
72.81; H, 6.52; N 13.14.
13C NMR: d = 56.6, 76.9, 77.1, 114.9, 126.3, 127.3, 128.0, 135.1,
158.0, 188.1.
[5-Chloro-2-(prop-2-yn-1-yloxy)phenyl](N,N-dimethylami-
no)acetonitrile (3b)
Mp 68–70 °C.
1H NMR: d = 2.35 [s, 6 H, N(CH3)2], 2.53 (X of ABX, JAX = JBX
2.4 Hz, 1 H, CCH), 4.72, 4.78 (AB of ABX, JAB = 16 Hz, 2 H, CH2),
5.08 (s, 1 H, CH), 7.00 (d, J = 8.8 Hz, 1 H, ArH), 7.33 (dd, J = 8.8,
2.4 Hz, 1 H, ArH), 7.46 (d, J = 2.4 Hz, 1 H, ArH).
13C NMR: d = 41.6 (2C), 56.4, 56.8, 75.9, 77.9, 113.0, 115.2, 121.2,
122.5, 129.5, 130.2, 154.7.
Anal. Calcd for C10H7ClO2: C, 61.72; H, 3.63; Cl, 18.22. Found: C,
61.54; H, 3.60; Cl, 18.13.
=
5-Bromo-2-(prop-2-yn-1-yloxy)benzaldehyde (2c)
Mp 93–95 °C (Lit.29 89–91 °C).
1H NMR: d = 2.59 (t, J = 2.4 Hz, 1 H, CCH), 4.82 (d, J = 2.4 Hz, 2
H, CH2), 7.02 (d, J = 9.2 Hz, 1 H, ArH), 7.63 (dd, J = 9.2, 2.4 Hz, 1
H, ArH), 7.93 (d, J = 2.4 Hz, 1 H, ArH), 10.38 (s, 1 H, CHO).
Anal. Calcd for C13H13ClN2O: C, 62.78; H, 5.27; N, 11.26; Cl,
14.25. Found: C, 62.79; H, 5.25; N, 11.23; Cl, 14.31.
13C NMR: d = 56.6, 76.7, 77.3, 114.6, 115.3, 126.7, 131.1, 138.0,
158.5, 188.1.
[5-Bromo-2-(prop-2-yn-1-yloxy)phenyl](N,N-dimethylami-
no)acetonitrile (3c)
Mp 66–69 °C.
Anal. Calcd for C10H7BrO2: C, 50.24; H, 2.95; Br, 33.42. Found: C,
50.09; H, 2.99; Br, 33.60.
1H NMR: d = 2.36 [s, 6 H, N(CH3)2], 2.53 (X of ABX, JAX = JBX
2.4 Hz, 1 H, CCH), 4.72, 4.79 (AB of ABX, JAB = 16 Hz, 2 H, CH2),
5.08 (s, 1 H, CH), 6.95 (d, J = 8.8 Hz, 1 H, ArH), 7.45 (dd, J = 8.8,
2.4 Hz, 1 H, ArH), 7.60 (d, J = 2.4 Hz, 1 H, ArH).
13C NMR: d = 41.8 (2C), 56.6, 56.8, 76.4, 77.3, 113.8, 114.8, 115.0,
124.9, 133.0, 154.0.
=
3-Methoxy-2-(prop-2-yn-1-yloxy)benzaldehyde (2d)
Mp 43–44 °C.
1H NMR: d = 2.48 (t, J = 2.4 Hz, 1 H, CCH), 3.91 (s, 3 H, OCH3),
4.89 (d, J = 2.4 Hz, 2 H, CH2), 7.16–7.20 (m, 2 H, ArH), 7.44–7.49
(m, 1 H, ArH), 10.50 (s, 1 H, CHO).
Synthesis 2009, No. 12, 2029–2034 © Thieme Stuttgart · New York

2032
T. Zdrojewski et al.
PAPER
4-(N,N-Dimethylamino)-3-methyl-4H-chromene-4-carboni-
Anal. Calcd for C13H13BrN2O: C, 53.26; H, 4.47; N, 9.56; Br, 27.26.
Found: C, 53.21; H, 4.40; N, 9.54; Br, 27.36.
trile (5a)
Yellowish crystals; mp 68–70 °C (cyclohexane).
(N,N-Dimethylamino)[3-methoxy-2-(prop-2-yn-1-yloxy)phe-
nyl]acetonitrile (3d)
Mp 64–67 °C.
1H NMR: d = 2.34 [s, 6 H, N(CH3)2], 2.51 (X of ABX, JAX = JBX
2.4 Hz, 1 H, CCH), 3.87 (s, 3 H, OCH3), 4.71, 4.83 (AB of ABX,
JAB = 16 Hz, 2 H, CH2), 5.23 (s, 1 H, CH), 6.95 (d, J = 8.8 Hz, 1 H,
ArH), 6.94–7.14 (m, 2 H, ArH).
1H NMR: d = 1.99 (d, J = 1.4 Hz, 3 H, CH3), 2.21 [s, 6 H, N(CH3)2],
6.77 (q, J = 1.4 Hz, 1 H, CH), 7.03–7.54 (m, 4 H, ArH).
13C NMR: d = 14.9, 38.9 (2C), 61.2, 106.9, 114.0, 116.7, 118.0,
=
123.3, 128.9, 129.8, 139.8, 151.1.
Anal. Calcd for C13H14N2O: C, 72.87; H, 6.59; N, 13.07. Found: C,
72.63; H, 6.55; N, 12.95.
13C NMR: d = 41.6 (2C), 55.8, 57.5, 60.4, 75.4, 79.1, 113.3, 115.4,
120.7, 124.3, 128.5, 144.6, 152.7.
(2-Methyl-3-oxo-2,3-dihydro-1-benzofuran-2-yl)acetonitrile
(9a)
Anal. Calcd for C14H16N2O2: C, 68.83; H, 6.60; N, 11.47. Found: C,
68.72; H, 6.52; N, 11.43.
White powder; yield: 6%; mp 54–55 °C (C6H6).
1H NMR: d = 1.58 (s, 3 H, CH3), 2.72, 2.87 (AB, JAB = 16.8 Hz, 2
H, CH2), 7.10–7.18 (m, 2 H, ArH), 7.64–7.73 (m, 2 H, ArH).
13C NMR: d = 21.0, 26.7, 84.6, 113.8, 115.0, 118.8, 122.8, 125.1,
139.1, 170.9, 200.3.
(N,N-Dimethylamino)[2-(prop-2-yn-1-yloxy)-1-naphthyl]aceto-
nitrile (3e)
Mp 72–73 °C.
1H NMR: d = 2.42 [s, 6 H, N(CH3)2], 2.55 (X of ABX, JAX = JBX
=
Anal. Calcd for C11H9NO2: C, 70.58; H, 4.85; N, 7.48. Found: C,
70.52; H, 4.99; N, 7.29.
2.4 Hz, 1 H, CCH), 4.85, 4.94 (AB of ABX, JAB = 16 Hz, 2 H, CH2),
5.32 (s, 1 H, CH), 7.37–7.67 (m, 3 H, ArH), 7.82 (d, J = 8.4 Hz, 1
H, ArH), 7.89 (d, J = 9.2 Hz, 1 H, ArH), 8.33 (d, J = 8.4 Hz, 1 H,
ArH).
13C NMR: d = 43.5 (2C), 53.2, 56.8, 76.5, 79.4, 109.9, 113.5, 118.6,
122.9, 125.5, 125.7, 129.3, 130.1, 130.3, 137.2, 153.0.
Residue from 3b
The sticky oil partially solidified and was triturated with cyclohex-
ane (5 mL) to give pure isomer 5b. The organic layer containing 4b
was filtered through alumina to remove tars.
Anal. Calcd for C17H16N2O: C, 75.25; H, 6.10; N, 10.60. Found: C,
77.29; H, 6.12; N, 10.68.
6-Chloro-4-(N,N-dimethylamino)-3-methylenechromane-4-
carbonitrile (4b)
White crystals; mp 69–71 °C (cyclohexane).
Intramolecular Vinylation of Aminonitriles 3; General Proce-
dure
1H NMR: d = 2.27 [s, 6 H, N(CH3)2], 4.59, 4.95 (AB of ABMX,
JAB = 12 Hz, JAX = JBX = 0.8 Hz, JBM = 1.6 Hz, 2 H, CH2), 5.42 (M
To a stirred (under nitrogen) solution of aminonitrile 3 (10 mmol)
and TEBAC (50 mg, 0.2 mmol) in DMSO (15 mL), powdered
NaOH (2.4 g, 60 mmol) was added in one portion, at r.t. A slight
exotherm was observed and the temperature of the mixture in-
creased to ca. 30 °C. Stirring was continued at 35 °C until aminoni-
trile 3 was no longer detected by GC (usually 2 h). The mixture was
quenched with H2O (50 mL) and extracted with C6H6 (5 ꢀ 10 mL).
The combined organic extract was washed with H2O (20 mL) and
brine (20 mL), and then dried (MgSO4). After removing the solvent,
the resulting residue consisting of 4 and 5 was treated as described
below.
of ABMX, JBM = 1.6 Hz, 1 H, CH), 5.76 (X of ABMX, JAX
JBX = 0.8 Hz, 1 H, CH), 6.80 (d, J = 8.8 Hz, 1 H, ArH), 7.23 (dd,
J = 8.8, 2.4 Hz, 1 H, ArH), 7.39 (d, J = 2.4 Hz, 1 H, ArH).
13C NMR: d = 39.7 (2C), 66.8, 67.9, 113.7 116.8, 119.0, 120.9,
124.7, 128.6, 131.0, 136.9, 151.8.
=
Anal. Calcd for C13H13ClN2O: C, 62.78; H, 5.27; N, 11.26. Found:
C, 62.71; H, 5.29; N, 11.33.
6-Chloro-4-(N,N-dimethylamino)-3-methyl-4H-chromene-4-
carbonitrile (5b)
Yellowish crystals; mp 120–124 °C (dec.; cyclohexane–C6H6).
Residue from 3a
1H NMR: d = 1.97 (d, J = 1.6 Hz, 3 H, CH3), 2.21 [s, 6 H, N(CH3)2],
6.77 (q, J = 1.6 Hz, 1 H, CH), 7.00 (d, J = 8.8 Hz, 1 H, ArH), 7.30
(dd, J = 8.8, 2.4 Hz, 1 H, ArH), 7.49 (d, J = 2.4 Hz, 1 H, ArH).
13C NMR: d = 14.7, 38.8 (2C), 60.9, 106.7, 115.5, 117.6, 118.1,
128.3, 128.4, 129.9, 139.6, 149.6.
The mixture of products 4a and 5a was distilled (Kugelrohr, 115-
125 °C/0.2 Torr) to afford a yellowish oil which partially crystal-
lized. The crystals were separated and were identified as being pre-
dominantly chromene 5a. The oil containing mostly chromane 4a
was chromatographed on alumina to give pure 4a; residual 5a in the
oil rearranged into 9a.
Anal. Calcd for C13H13ClN2O: C, 62.78; H, 5.27; N, 11.26. Found:
C, 62.74; H, 5.33; N, 11.20.
4-(N,N-Dimethylamino)-3-methylenechromane-4-carbonitrile
(4a)
Yellowish oil.
Residue from 3c
Column chromatography gave pure 4c and 9c. The NMR data for
chromene 5c are taken from the proton and carbon spectra of the
mixture of crude 4c/5c (5:1). No other data are presented for 5c.
1H NMR: d = 2.27 [s, 6 H, N(CH3)2], 4.59, 4.96 (AB of ABMX,
JAB = 12 Hz, JAX = JBX = 0.8 Hz, JBM = 1.6 Hz, 2 H, CH2), 5.39 (M
of ABMX, JBM = 1.6 Hz, 1 H, CH), 5.74 (X of ABMX, JAX = JBX
0.8 Hz, 1 H, CH), 6.84–6.97 (m, 2 H, ArH), 7.24–7.44 (m, 2 H,
ArH).
=
6-Bromo-4-(N,N-dimethylamino)-3-methylenechromane-4-car-
bonitrile (4c)
Yellow oil.
13C NMR: d = 39.7 (2C), 66.6, 68.1, 114.1, 116.0, 117.5, 119.5,
1H NMR: d = 2.24 [s, 6 H, N(CH3)2], 4.59, 4.94 (AB of ABMX,
119.8, 129.2, 131.0, 137.5, 153.1.
J
AB = 12 Hz, JAX = JBX = 0.8 Hz, JBM = 1.6 Hz, 2 H, CH2), 5.42 (M
of ABMX, JBM = 1.6 Hz, 1 H, CH), 5.76 (X of ABMX,
AX = JBX = 0.8 Hz, 1 H, CH), 6.75 (d, J = 8.8 Hz, 1 H, ArH), 7.36
(dd, J = 8.8, J = 2.4 Hz, 1 H, ArH), 7.51 (d, J = 2.4 Hz, 1 H, ArH).
Anal. Calcd for C13H14N2O: C, 72.87; H, 6.59; N, 13.07. Found: C,
72.77; H, 6.46; N, 12.86.
J
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PAPER
Anionic Cyclization
2033
13C NMR: d = 39.6 (2C), 66.6, 67.7, 111.6, 113.5, 116.7, 119.4,
121.3, 131.3, 133.8, 136.6, 152.2.
1H NMR: d = 2.41 [s, 6 H, N(CH3)2], 4.60, 4.68 (AB of ABMX,
JAB = 12 Hz, JAM = 1.2 Hz, JBM = 0.6 Hz, 2 H, CH2), 5.65 (M of AB-
MX, JAM = 1.2 Hz, JBM = 0.6 Hz, 1 H, CH), 5.80 (s, X of ABMX, 1
H, CH), 7.06 (d, J = 9.2 Hz, 1 H, ArH), 7.37–7.80 (m, 4 H, ArH),
8.86 (d, J = 8.8 Hz, 1 H, ArH).
Anal. Calcd for C13H13BrN2O: C, 53.26; H, 4.47; N, 9.56. Found: C,
52.89; H, 4.21; N, 9.39.
6-Bromo-4-(N,N-dimethylamino)-3-methyl-4H-chromene-4-
carbonitrile (5c)
13C NMR: d = 39.4 (2C), 62.8, 68.7, 109.7, 118.5, 118.9, 124.1,
124.5, 127.1, 128.6, 129.8, 132.1, 132.3, 133.8, 153.7.
1H NMR: d = 1.97 [d, J = 1.6 Hz, 3 H, CH3), 2.21 (s, 6 H, N(CH3)2],
6.75 (q, J = 1.6 Hz, 1 H, CH), 6.94 (d, J = 8.8 Hz, 1 H, ArH), 7.43
(dd, J = 8.8, 2.4 Hz, 1 H, ArH), 7.63 (d, J = 2.4 Hz, 1 H, ArH).
Anal. Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C,
77.22; H, 6.32; N, 10.51.
13C NMR: d = 14.7, 38.7 (2C), 60.7, 106.6, 115.4, 115.8, 117.5,
118.4, 131.1, 132.7, 139.5, 149.9.
1-(N,N-Dimethylamino)-2-methyl-1H-benzo[f]chromene-1-car-
bonitrile (5e)
1H NMR: d = 2.01 (d, J = 1.6 Hz, 3 H, CH3), 2.46 [s, 6 H, N(CH3)2],
6.80 (q, J = 1.6 Hz, 1 H, CH), the aromatic signals overlapped with
those of 4e.
(6-Bromo-2-methyl-3-oxo-2,3-dihydro-1-benzofuran-2-yl)ace-
tonitrile (9c)
Yellow oil; yield: 15%.
(2-Methyl-1-oxo-1,2-dihydronaphtho[2,1-b]furan-2-yl)acetoni-
trile (9e)
White crystals; yield: 13%; mp 97–99 °C (C6H6).
1H NMR: d = 1.68 (s, 3 H, CH3), 2.79, 2.96 (AB, JAB = 16.8 Hz, 2
H, CH2), 7.29 (d, J = 9.2 Hz, 1 H, ArH), 7.47–7.56 (m, 1 H, ArH),
7.66–7.71 (m, 1 H, ArH), 7.87 (d, J = 8.2 Hz, 1 H, ArH), 8.15 (d,
J = 9.2 Hz, 1 H, ArH), 8.70 (d, J = 8.2 Hz, 1 H, ArH).
1H NMR: d = 1.59 (s, 3 H, CH3), 2.74, 2.88 (AB, JAB = 16.8 Hz, 2
H, CH2), 7.08 (dd, J = 8.8, 0.8 Hz, 1 H, ArH), 7.73–7.82 (m, 2 H,
ArH).
13C NMR: d = 21.1, 25.7, 85.6, 114.7, 115.4, 115.6, 120.6, 127.6,
141.7, 169.8, 198.8.
Anal. Calcd for C11H8BrNO2: C, 49.65; H, 3.03; N, 5.26. Found: C,
49.71; H, 2.93; N, 5.02.
13C NMR: d = 21.1, 25.8, 85.6, 111.1, 113.8, 115.1, 123.1, 125.8,
128.7, 129.2, 129.5, 130.2, 141.1, 173.8, 199.6.
MS (EI, 70 eV): m/z (%) = 237 (80, M+), 197 (100), 154 (20), 126
(25).
Residue from 3d
Column chromatography afforded pure 4d and the product of oxi-
dation of carbanion 3d–: 3-methoxy-N,N-dimethyl-2-(prop-2-yn-1-
yloxy)benzamide 3d¢.
HRMS (EI): m/z calcd for C15H11NO2: 237.07898; found:
237.07929.
4-(N,N-Dimethylamino)-8-methoxy-3-methylenechromane-4-
Anal. Calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C,
75.90; H, 4.63; N, 5.96.
carbonitrile (4d)
Yellow oil.
1H NMR: d = 2.27 [s, 6 H, N(CH3)2], 3.87 (s, 3 H, OCH3), 4.72, 5.03
(AB of ABMX, JAB = 12 Hz, JAX = JBX = 0.8 Hz, JBM = 1.6 Hz, 2 H,
CH2), 5.41 (M of ABMX, JBM = 1.6 Hz, 1 H, CH), 5.74 (X of AB-
MX, JAX = JBX = 0.8 Hz, 1 H, CH), 6.88–6.93 (m, 2 H, ArH), 7.01–
7.07 (m, 1 H, ArH).
Acknowledgment
This work was financially supported by Warsaw University of
Technology.
13C NMR: d = 39.8 (2C), 56.0, 67.0, 68.0, 112.4 114.2, 116.2, 119.5,
120.1, 121.0, 137.4, 142.8, 148.7.
References
Calcd for C14H16N2O2: C, 68.83; H, 6.60; N, 11.47. Found: C,
68.69; H, 6.64; N, 7.01.
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White crystals; yield: 44%; mp 54–55 °C (C6H6).
1H NMR: d = 2.48 (t, J = 2.5 Hz, 1 H, CCH), 2.87 (s, 3 H, NCH3),
3.11 (s, 3 H, NCH3), 3.87 (s, 3 H, OCH3), 4.69 (s, 2 H, CH2), 6.84
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Residue from 3e
Column chromatography afforded pure compounds 4e and 9e. The
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1-(N,N-Dimethylamino)-2-methylene-2,3-dihydro-1H-ben-
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White crystals; mp 86–92 °C (C6H6).
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Synthesis 2009, No. 12, 2029–2034 © Thieme Stuttgart · New York