Electrophilic activation of acetyl-substituted heteroaromatic compounds

Article abstract of DOI:10.1021/jo001035k

The chemistry of acetyl-substituted pyridines, thiazoles, quinoline, isoquinolines, and pyrazine (1-9 and 28) has been studied. These heteroarenes (1-8) condense with benzene in good yields (74-96%) in the Bronsted superacid, CF₃SO₃H (triflic acid). In these acid-catalyzed hydroxyalkylation reactions, compounds 1-8 are significantly more reactive than acetophenone. It is proposed that compounds 1-8 readily form dicationic electrophiles in triflic acid.

Full text of DOI:10.1021/jo001035k

J . Org. Chem. 2000, 65, 8997-9000
8997
Electr op h ilic Activa tion of Acetyl-Su bstitu ted Heter oa r om a tic
Com p ou n d s
Douglas A. Klumpp,* Manuel Garza, Gregorio V. Sanchez, J r., Siufu Lau, and Sarah de Leon
Department of Chemistry, California State Polytechnic University, 3801 West Temple Avenue,
Pomona, California 91768
daklumpp@csupomona.edu
Received J uly 10, 2000
The chemistry of acetyl-substituted pyridines, thiazoles, quinoline, isoquinolines, and pyrazine (1-9
and 28) has been studied. These heteroarenes (1-8) condense with benzene in good yields (74-
9
3 3
6%) in the Bronsted superacid, CF SO H (triflic acid). In these acid-catalyzed hydroxyalkylation
reactions, compounds 1-8 are significantly more reactive than acetophenone. It is proposed that
compounds 1-8 readily form dicationic electrophiles in triflic acid.
In tr od u ction
In hydroxyalkylation reactions catalyzed by Bronsted
superacids, very high reactivity has been observed for
some aldehydes and ketones, and this has been attributed
The acid-catalyzed condensation of ketones and alde-
hydes with aromatic compounds is known as the hy-
8
to the formation of dicationic electrophiles (eq 3). The
1
droxyalkylation reaction. This widely used reaction has
dicationic electrophiles can be formed by either of two
routes: by protonation of the carbonyl group along with
been applied to the preparation of plastics (phenol-
2
formaldehyde resins), dyes and pigments (for example,
8
,9
an adjacent base-site (eq 3) or by double protonation
3
malachite green), and other products such as porphy-
of the carbonyl group (eq 4).10 Given the value of this
rins.4 The hydroxyalkylation reaction is useful when
electron-rich arenes are condensed with the ketone or
aldehyde. With less reactive aromatic compounds such
as benzene or chlorobenzene, the ketone or aldehyde
must have a strong electron-withdrawing group in order
for the condensation to take place. For example, 2,2,2-
trifluoroacetophenone condenses with benzene in CF
3
-
SO H (triflic acid, TfOH), and DDT is prepared by the
3
acid-catalyzed condensation of chloral or its hydrate with
chlorobenzene (eqs 1-2).5
,6
synthetic chemistry, we have been exploring the scope
and utility of these methods of electrophilic activation
in hydroxyalkylation reactions. In the following paper,
we report our studies of the hydroxyalkylation reaction
involving acetyl-substituted heteroarenes and related
systems.
Recently, there has been significant interest in the
chemistry of dicationic and superelectrophilic species.
7
(
1) (a) Hofmann, J . E.; Schriesheim, A. In Friedel-Crafts and
Related Reaction; Olah, G. A., Ed.; Wiley: New York, 1964; Vol 2, pp
97-640. (b) March, J . Advanced Organic Chemistry, 4th ed; Wiley:
New York, 1992; pp 548-549.
2) Chenier, P. J . Handbook of Industrial Chemistry, 2nd ed.;
VHC: New York, 1992; p 293.
3) (a) Krahler, S. E. In The Chemistry of Synthetic Dyes and
5
(
(7) (a) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 767. (b)
Stable Carbocation Chemistry; Prakash, G. K. S., Schleyer, P. v. R.,
Eds.; Wiley: New York, 1997. (c) Yokoyama, A.; Ohwada, T.; Shudo,
K. J . Org. Chem. 1999, 64, 611.
(8) (a) Klumpp, D. A.; Lau, S. L. J . Org. Chem. 1999, 64, 7309. (b)
Klumpp, D. A.; Garza, M.; Lau, S.; Shick, B.; Kantardjieff, K. J . Org.
Chem. 1999, 64, 7635.
(9) (a) Yamazaki, T.; Saito, S.-i.; Ohwada, T.; Shudo, K. Tetrahedron
Lett. 1995, 36, 5749. (b) Olah, G. A.; Rasul, G.; York, C.; Prakash, G.
K. S. J . Am. Chem. Soc. 1995, 117, 11211. (c) Klumpp, D. A.; Garza,
M.; J ones, A.; Mendoza, S. J . Org. Chem. 1999, 64, 6702.
(10) (a) Saito, S.; Ohwada, T.; Shudo, K. J . Am. Chem. Soc. 1995,
117, 11081. (b) Saito, S.; Ohwada, T.; Shudo, K. J . Org. Chem. 1996,
61, 8089.
(
Pigments; Lubs, H. A., Ed.; Krieger Publishing Co.: Malabar, FL, 1955;
p 275. (b) Colour Index, 3rd Ed; 1971; Vol. 4, p 4380.
(
4) (a) The Porphyrins; Dolphin, D., Ed.; Academic Press: New York,
978. For recent examples, see: (b) Kral, V.; Sessler, J . L.; Zimmerman,
R. S.; Seidel, D.; Lynch, V.; Andrioletti, B. Angew. Chem., Int. Ed. Engl.
000, 39, 1055. (c) Rao, P. D.; Littler, B. J .; Geier, G. R., III; Lindsey,
J . S. J . Org. Chem. 2000, 65, 1084
5) (a) Chem. Abstr. 1979, 90, 86986u. (b) U.S. Pat. Appl. 891,872,
978. (c) Kray, W. D.; Rosser, R. W. J . Org. Chem. 1977, 42, 1186.
6) (a) Bailes, R. J . Chem. Educ. 1945, 22, 122. (b) Mosher, J . Ind.
Eng. Chem. 1946, 38, 916.
1
2
(
1
(
1
0.1021/jo001035k CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/28/2000

8
998 J . Org. Chem., Vol. 65, No. 26, 2000
Klumpp et al.
Ta ble 1. Resu lts fr om th e Rea ction of
Acetyl-Su bstitu ted Ar en es (1-9) w ith Ben zen e in
CF 3SO3H
With prolonged reaction time and heating, isoquinoline
does give a trace quantity of 18, but the major product
is 19 (isolated in 57% yield, eq 5). When a pure sample
9
6 6
of 18 is reacted with TfOH and C H at 50 °C, only
product 18 is observed in the resulting product mixture.
This suggests that the product distribution for 1-acetyl-
isoquinoline (9) is the result of a kinetically controlled
reaction. Reaction with the second C H may be inhibited
6 6
by unfavorable steric effects arising from the peri posi-
tion. In addition to acetyl-substituted heteroaromatics,
some acyl-substituted heteroarenes condense with C
in TfOH. Compound 20 is prepared in 94% yield from
-propionylpyridine, but reaction of 21 gives a mixture
6 6
H
4
of at least 6 diphenylated products (eq 6). The product
mixture suggests that intramolecular hydride transfer-
(s) may be involved and that the resulting cationic
intermediates give the mixture of products.
Resu lts a n d Discu ssion
The above results suggest an obvious question: why
is the acetyl group of acetophenone unreactive toward
benzene in superacid, but the analogous heteroaromatic
compounds react in good to excellent yields? In the case
of acetophenone, the carbonyl group is fully protonated
Although it has been reported that acetophenone is
unreactive toward benzene in TfOH,11 the acetylpyridines
(
1-3) give the respective condensation products (10-12)
in excellent yields (Table 1). Compounds similar to 10-
1
2
1
2 are known to have fungicidal activity, estrogen
16
in TfOH, but the resulting carboxonium ion is stabilized
1
3
synthetase inhibitory activity, and other biological
activities.14 To our knowledge, the only other published
synthetic route to compounds 10-12 involves the depro-
tonation and alkylation of diphenylpyridylmethanes.15
The sterically crowded pyridine 13 is also prepared in
good yield from 2,6-diacetylpyridine (4). The acetyl-
substituted thiazoles (5 and 6), quinoline (7), and iso-
quinoline (8) likewise give the respective condensation
products 14-17.
by inductive and resonance effects. Shudo and Ohwada
have reported kinetic evidence for diprotonation of aryl
16
ketones; however, diprotonated intermediates from
acetophenone must be formed in extremely low concen-
tration. Thus, acetophenone is unreactive toward benzene
in the hydroxyalkylation reaction catalyzed by TfOH. The
acetyl-substituted heteroarenes possess strong base-sites
which are fully protonated in acid, so that upon subse-
quent protonation of the carbonyl groups, reactive dica-
tionic electrophiles can be generated (Scheme 1). We
propose that the reactivity of the heteroaromatic com-
pounds stems from their ability to form appreciable
concentrations of the diprotonated electrophiles. The
enhanced reactivity of dicationic electrophiles was first
(
11) Ohwada, T.; Yamagata, N.; Shudo, K. J . Am. Chem. Soc. 1991,
1
16, 1364.
(
(
12) Whaley, J . W.; Taylor, H. M. Phytopathology 1970, 60, 771.
13) J ones, C. D.; Winter, M. A.; HIrsch, K. S.; Stamm, N.; Taylor,
H. M.; Holden, H. E.; Davenport, J . D.; Krumkalns, E. V.; Suhr, R. G.
J . Med. Chem. 1990, 33, 416.
(
14) Franklin, M. R. J . Pharmacology 1993, 46, 683.
(
15) (a) Martensson, O.; Nilsson, E. Acta Chem. Scand. 1961, 15,
1
021. (b) Eisch, J . J .; Kovacs, C. A.; Chobe, P.; Boleslawski, M. P. J .
Org. Chem. 1987, 52, 4427
(16) Saito, S.; Sato, Y.; Ohwada, T.; Shudo, K. J . Am. Chem. Soc.
1994, 116, 2312.

Electrophilic Activation of Heteroaromatic Compounds
J . Org. Chem., Vol. 65, No. 26, 2000 8999
Sch em e 1
recognized by Olah and co-workers, and it is thought to
be the result of electrostatic and inductive effects.17,7a
In addition to the acetyl-substituted arenes 1-9,
ketones 22, 23, and 25-27 were reacted under similar
conditions. The substituted acetophenone (22) does not
condense with benzene in TfOH and it can be recovered
quantitatively. Although diprotonated species are likely
formed from 22 in superacid, the protonated acetyl group
is not sufficiently electrophilic to react with benzene. This
seems to suggest that dicationic electrophiles only show
high reactivity when the charge centers are conjugated
or in close proximity. When ketone 23 is reacted with
benzene in TfOH, the condensation does not occur and
compound 23 can also be recovered. Protonation must
only occur at the pyridyl rings (24) and consequently no
reaction occurs at the carbonyl group. In general, het-
eroarenes having more than one strong base-site were
unreactive to the condensation chemistry. Even at el-
evated temperature, compounds 25-27 do not condense
2-Acetylpyridine (1) also condenses with toluene and
chlorobenzene, but despite high yields for these conver-
sions, the reactions occur with poor regioselectivities. No
reaction is seen with o-dichlorobenzene or nitrobenzene
even when 1 is reacted with a large excess of TfOH at
80 °C. When 1 is reacted with C
6 6
H and a large excess of
H
2
SO (100 h at 50 °C), no reaction is seen. This is
4
consistent with the proposed mechanism for the hydroxy-
alkylation reactions (Scheme 1). Superacidic conditions
are required because weaker acids such as H SO are
2 4
unable to generate diprotonated intermediates.
6 6
with C H in TfOH.
Con clu sion
Despite having two base sites on the heterocyclic ring,
acetylpyrazine (28) does condense with C in TfOH (eq
). Product 29 is formed, which suggests an equilibrium
between intermediates 32 and 33 in TfOH. Product 30
is formed as the other major product from 28. When the
reaction is conducted at elevated temperature (50 °C),
product 31 is also formed as a minor product. It is not
presently clear how the pyrazine ring is phenylated to
give 30 and 31, but further studies are in progress.
6
H
6
We have found that acetyl-substituted pyridines, thia-
zoles, quinoline, isoquinoline, and pyrazine condense with
benzene in hydroxyalkylation reactions in the Bronsted
7
3 3
superacid, CF SO H. These acetylheteroarenes are sig-
nificantly more reactive than acetophenone in the hy-
droxyalkylation reaction. Due to inductive and electro-
static effects, the protonated heteroaromatic rings
contribute significantly to the electrophilic activation of
carboxonium ion intermediates.
The condensation of 2-acetylpyridine (1) with C
be accomplished in 4 h at 25 °C using an excess of TfOH
14 equiv). When lower quantities of TfOH or shorter
6 6
H can
(
Exp er im en ta l Section
reaction times are used, the condensation product is
accompanied by significant quantities of compound 34
Triflic acid was purchased from 3M Co. and distilled under
an inert atmosphere immediately prior to use.18 The acetyl-
substituted arenes were purchased from commercial suppliers
(eq 8). An equilibrium is likely established between 35
and 36 (eq 9). With highly acidic conditions and longer
reactions, 35 is formed and this leads to product 10.
(
18) (a) For a review of TfOH chemistry, see: Stang, P. J .; White,
M. R. Aldrichim. Acta 1983, 16, 15. (b) Olah, G. A.; Prakash, G. K. S.;
Sommer, J . In Superacids; Wiley: New York, 1985. (c) TfOH may be
quantitatively recycled; for a procedure, see: Booth, B. L.; El-Fekky,
T. A. J CS Perkin I 1979, 2441.
(
17) (a) Olah, G. A.; Germain, A.; Lin, H. C.; Forsyth, D. J . Am.
Chem. Soc. 1975, 97, 3928. (b) Olah, G. A.; Hartz, N.; Rasul, G.;
Prakash, G. K. S. J . Am. Chem. Soc. 1993, 115, 6985.

9
000 J . Org. Chem., Vol. 65, No. 26, 2000
Klumpp et al.
+
and used as received. Compound 7 was prepared by the
reaction of CH MgBr with 4-quinolinecarboxaldehyde and
subsequent oxidation with SeO . Compound 8 was prepared
by the reaction of CH MgBr with 2-isoquinolinecarbonitrile;
309 (M ); HRMS m/z calcd for C23
H
19N 309.1517, found
3
309.1522.
2
Rea ction of 1-Acetylisoqu in olin e (9). A 0.2 g (1.2 mmol)
portion of compound 9 was reacted with TfOH (10 mL) and
C H (2 mL) at 50 °C for 24 h. As described in the general
6 6
procedure, the product mixture was worked up, and the
products were isolated by column chromatography (9:1 hex-
anes/ether).
3
compound 21 was prepared by the reaction of 1-decylmagne-
sium bromide with 2-pyridinecarbonitrile. Compound 22 was
prepared by acylation of 4-(3-phenylpropyl)pyridine using
1
9
3
AlCl and acetyl chloride. High-resolution mass spectra were
recorded at the Mass Spectrometry Facility at the University
1
-(1,1-Dip h en yleth yl)isoqu in olin e (18): 0.004 g (0.014
1
of California, Riverside. H NMR spectra were recorded at 300
1
mmol, 1% yield); mp 134-137 °C (C
6 6
H ); H NMR δ 2.32, 7.10-
1
3
MHz and C NMR spectra were recorded at 125 MHz. All
NMR spectra were recorded from CDCl solutions.
7
.38 (m, 11H), 7.47 (m, 1H), 7.59 (d, J ) 5.7 Hz, 1H), 7.63 (d,
3
J ) 8.7 Hz, 1H), 7.77 (d, J ) 5.7 Hz, 1H), 8.55 (d, J ) 5.7 Hz,
Gen er a l P r oced u r e for th e P r ep a r a tion of Con d en sed
13
1
1
3
H); C NMR δ 34.1, 57.1, 120.7, 125.9, 126.2, 127.5, 127.7,
P r od u cts 10-19. A 0.2 g portion of the acetyl-substituted
28.2, 128.9, 129.0, 129.1, 137.5, 141.1, 147.5, 165.2; EI MS
heteroarene was dissolved in 1.0 mL of C
6
H
6
, and to this
+
09 (M ).
solution was added 5.0 mL of triflic acid. This mixture was
stirred at room temperature (6 was reacted at 50 °C) for 4-12
h and then poured over several grams of ice. The resulting
solution was made basic with concentrated NaOH and ex-
1
-(1-P h en yleth en yl)isoqu in olin e (19): 0.158 g (0.69
1
mmol, 57% yield); mp 41-45 °C (C
0.6 Hz, 1H), 6.13 (d, J ) 0.6 Hz, 1H), 7.25-7.33 (m, 6H),
.47 (m, 1H), 7.66 (m, 1H), 7.85 (d, J ) 8.4 Hz, 1H), 8.01 (d, J
8.4 Hz, 1H), 8.59 (d, J ) 5.7 Hz, 1H); C NMR δ 118.0,
20.5, 126.2, 126.9, 127.1, 127.4, 127.7, 128.2, 128.7, 129.0,
6 6
H ); H NMR δ 5.53 (d, J
)
7
tracted with CHCl
3
. The organic phase was washed with H
2
O
13
)
1
1
and brine and then dried with MgSO
4
. Removal of the solvent
under reduced pressure then provided the product. The
product(s) was then purified by recrystallization or column
chromatography.
+
30.3, 136.8, 142.5; EI MS 231 (M ); HRMS m/z calcd for
C
17
H
12N (M - H) 230.0970, found 230.0961.
4
-(1,1-Dip h en ylp r op yl)p yr id in e (20): mp 41-44 °C
2
-(1,1-Dip h en yleth yl)p yr id in e (10): mp 51-54 °C (CHCl
3
,
1
(
CHCl
Hz, 2H), 7.30-7.62 (m, 12H), 8.7 (m, 2H); C NMR δ 10.1,
2.0, 58.8, 124.4, 126.2, 128.0, 129.1, 145.5, 149.3, 156.4; EI
3
); H NMR δ 0.98 (t, J ) 7.2 Hz, 3H), 2.83 (q, J ) 7.2
1
5a
1
lit. mp 54-56 °C); H NMR δ 2.27 (s, 3H), 7.01 (d, J ) 8.1
13
Hz, 1H), 7.11-7.15 (m, 4H), 7.20-7.32 (m, 7H), 7.55 (dt, J )
3
1
1
.8, 7.5, 1H), 8.65 (m, 1H); 13C NMR δ 29.4, 55.1, 121.0, 123.6,
+
MS 273 (M ); HRMS m/z calcd for C20
73.1506.
Rea ction of 2-a cetylp yr a zin e (28). A 0.305 g (2.5 mmol)
portion of compound 28 was reacted with TfOH (7 mL) and
(1 mL) at 50 °C for 24 h. As described in the general
H19N 273.1392, found
+
26.9, 128.0, 128.6, 135.8, 148.3, 148.9, 167.1; EI MS 259 (M );
2
HRMS m/z calcd for C19H17N 259.1361, found 259.1369.
3
-(1,1-Dip h en ylet h yl)p yr id in e (11): mp 108-110 °C
1
(
7
CHCl ); H NMR δ 2.21 (s, 3H), 7.07-7.10 (m, 4H), 7.18-
3
6 6
C H
.32 (m, 7H), 7.38 (m, 1H), 8.41 (d, J ) 2.4 Hz, 1H), 8.46 (dd,
procedure, the product mixture was worked up and the
products were isolated by column chromatography (3:1 hex-
anes/ether).
13
J ) 1.2, 4.5 Hz, 1H); C NMR δ 30.2, 51.1, 122.7, 126.3, 128.1,
1
28.5, 136.1, 144.4, 147.2, 147.8, 150.1; EI MS 259 (M+);
20
+
HRMS m/z calcd for C19
4
H
18N (MH ) 260.1439, found 260.1430.
);
2
-(1,1-Dip h en yleth yl)p yr a zin e (29): 0.0623 g (0.24 mmol,
-(1,1-Diph en yleth yl)pyr idin e (12): mp 87-90 °C (CHCl
3
1
1
7
1
1
0% yield); H NMR δ 2.25 (s, 3H), 7.09-7.14 (m, 4H), 7.24-
1
H NMR δ 2.17 (s, 3H), 7.02-7.10 (m, 6H), 7.25-7.31 (m, 6H),
.34 (m, 6H), 8.0.36 (d, J ) 1.5 Hz, 1H), 8.41 (d, J ) 2.4 Hz,
8
1
.50 (d, J ) 6.0 Hz, 1H); 13C NMR δ 29.7, 52.3, 123.8, 126.4,
13
H), 8.58 (dd, J ) 1.5, 2.4 Hz, 1H); C NMR δ 29.1, 53.4, 126.5,
+
28.1, 128.5, 147.2, 149.5, 157.9; EI MS 259 (M ); HRMS m/z
+
28.2, 128.4, 141.7, 143.4, 145.1, 147.0, 162.7; EI MS 260 (M );
calcd for C19
H17N 259.1361, found 259.1358.
HRMS m/z calcd for C18
2
16 2
H N 260.1313, found 260.1323.
2
,6-Bis-(1,1-d ip h en yleth yl)p yr id in e (13): mp 138-140 °C
-Acetyl-6-p h en ylp yr a zin e (30): 0.0616 g (0.311 mmol,
1
(
7
CHCl
3
); H NMR δ 2.13 (s, 6H), 6.84 (d, J ) 7.8 Hz, 2H), 7.06-
1
1
7
(
2% yield); mp 158-159 °C (CHCl
3
); H NMR δ 2.73 (s, 3H),
.10 (m, 8H), 7.18-7.26 (m, 12H), 7.40 (t, J ) 7.8, 1H); 13
C
.52-7.55 (m, 3H), 8.07 (m, 2H), 9.05 (d, J ) 1.5 Hz, 1H), 9.25
NMR δ 29.2, 55.2, 120.0, 125.6, 127.5, 128.7, 135.7, 148.7,
13
d, J ) 1.5 Hz, 1H); C NMR δ 25.9, 127.4, 129.2, 130.8, 135.4,
1
4
65.2; EI MS 439 (M+); HRMS m/z calcd for C33
H
28N (M - H)
+
1
40.5, 142.9, 145.6, 155.1, 199.1; EI MS 198 (M ); HRMS m/z
calcd for C12 O 198.0793, found 198.0793.
-(1,1-Dip h en yleth yl)-6-p h en ylp yr a zin e (31): 0.0224 g
38.2222, found 438.2212.
10 2
H N
2
-(1,1-Diph en yleth yl)th iazole (14): mp 46-48 °C (CHCl
3
);
2
1
H NMR δ 2.29 (s, 3H), 7.16-7.20 (m, 4H), 7.23-7.32 (m, 7H),
1
(
0.07 mmol, 3% yield); H NMR δ 2.27 (s, 3H); 7.14-7.17 (m,
7
1
.82 (d, J ) 3.3 Hz, 1H). 13C NMR δ 29.8, 53.4, 119.3, 126.8,
4
8
2
H), 7.25-7.34 (m, 7H), 7.47-7.50 (m, 2H), 7.99-8.02 (m, 2H),
+
28.1, 128.1, 142.5, 147.6, 178.9; EI MS 265 (M ); HRMS m/z
13
.38 (d, J ) 1.5 Hz, 1H), 9.03 (d, J ) 1.5 Hz, 1H); C NMR δ
calcd for C17
H15NS 265.0925, found 265.0930.
9.3, 46.3, 126.7, 127.0, 128.5, 128.7, 129.2, 129.4, 129.9, 131.3,
+
2
,4-Dim eth yl-5-(1,1-diph en yleth yl)th iazole (15): mp 58-
136.5, 140.7, 144.4, 147.4; EI MS 336 (M ); HRMS m/z calcd
for C H N (M - H) 335.1548, found 335.1544.
1
6
3
1
1 °C (CHCl ); H NMR δ 1.90 (s, 3H), 2.19 (s, 3H), 2.54 (s,
3
2
4
19
2
13
H), 7.20-7.28 (m, 10); C NMR δ 17.5, 18.8, 31.3, 48.7, 126.6,
+
27.9, 128.2, 140.6, 147.4, 147.9, 161.4; EI MS 293 (M ); HRMS
m/z calcd for C19
H
19NS 293.1238, found 293.1234.
Ack n ow led gm en t. The support of the NIH (SO6-
GM53933-0251) is gratefully acknowledged. We also
thank Cal Poly University, Pomona, for partial support
through a Research, Scholarship, and Creative Activi-
ties Grant.
3
-(1,1-Dip h en yleth yl)qu in olin e (16): mp 126-128 °C
1
(
(
8
1
1
3
6 6
C H ); H NMR δ 2.31 (s, 3H), 7.14-7.18 (m, 4H), 7.20-7.37
m, 6H), 7.46-7.55 (m, 2H), 7.96 (m, 2H), 8.09-8.12 (m, 1H),
.80 (d, J ) 1.8 Hz, 1H); 13C NMR δ 30.4, 51.5, 126.7, 126.9,
27.9, 128.1, 128.2, 128.3, 128.9, 129.1, 129.4, 129.5, 133.4,
+
34.6, 152.5; EI MS 309 (M ); HRMS m/z calcd for C23
09.1517, found 309.1514.
19
H N
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 10-20 and 29-31. This material is
available free of charge via the Internet at http://pubs.acs.org.
3
-(1,1-Dip h en yleth yl)isoqu in olin e (17): mp 117-120 °C
1
(
6 6
C H ); H NMR δ 2.39 (s, 3H), 7.19-7.36 (m, 10H), 7.39 (s,
1
H), 7.54-7.68 (m, 3H), 7.97 (d, J ) 8.1 Hz, 1H), 9.32 (s, 1H);
C NMR δ 29.7, 55.0, 119.4, 126.4, 127.1, 127.2, 127.5, 128.2,
28.3, 128.6, 129.1, 130.5, 136.2, 148.6, 152.1, 161.2; EI MS
1
3
J O001035K
1
(
20) By gas chromatography, the yields of the products were
(
19) Vogel, A. I. In Practical Organic Chemistry, 5th ed.; Furness,
considerably higher than that measured for the isolated yields. Due
to poorly resolved fractions in the chromatography, some product was
lost.
B. S., Hannaford, A. J ., Smith, P. W. G., Tatchell, A. R., Eds.;
Longman: Singapore, 1989; pp 1008-1009.