Synthesis of benzo[f]isoindole-4,9-diones

Article abstract of DOI:10.1021/jo801056e

(Chemical Equation Presented) A synthesis of benzo[f]isoindole-4,9-diones 1 is presented starting from the reaction of 2,3-bis(bromomethyl)-1,4- dimethoxynaphthalene 15 with primary amines affording 2,3-bis(aminomethyl)-1,4- dimethoxynaphthalenes 14, which could be converted by CAN-mediated oxidation in one step to benzo[f]isoindole-4,9-diones 1. An alternative synthesis of benzo[f]isoindole-4,9-diones 1 starts from 2,3-bis(bromomethyl)-1,4- naphthoquinone 9 via 2,3-dihydrobenzo[f]isoindoles 10 which spontaneously oxidize.

Full text of DOI:10.1021/jo801056e

Synthesis of Benzo[f]isoindole-4,9-diones
Sven Claessens,† Jan Jacobs,† Sam Van Aeken,‡ Kourosch Abbaspour Tehrani,‡ and
Norbert De Kimpe*,†
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent UniVersity, Coupure Links
653, B-9000 Ghent, Belgium, and Laboratory of Organic Chemistry, Department of Applied Biological
Sciences and Engineering, Faculty of Sciences, Vrije UniVersiteit Brussel, Pleinlaan 2,
B-1050 Brussels, Belgium
norbert.dekimpe@ugent.be
ReceiVed May 16, 2008
A synthesis of benzo[f]isoindole-4,9-diones 1 is presented starting from the reaction of 2,3-bis(bromo-
methyl)-1,4-dimethoxynaphthalene 15 with primary amines affording 2,3-bis(aminomethyl)-1,4-dimetho-
xynaphthalenes 14, which could be converted by CAN-mediated oxidation in one step to benzo[f]isoindole-
4,9-diones 1. An alternative synthesis of benzo[f]isoindole-4,9-diones 1 starts from 2,3-bis(bromomethyl)-
1,4-naphthoquinone 9 via 2,3-dihydrobenzo[f]isoindoles 10 which spontaneously oxidize.
Introduction
During the past years, research was conducted at our
departments toward the synthesis of quinones bearing annelated
N-heterocyclic rings.1 In this way, we managed to synthesize
6-deoxybostrycoidin2 and several naturally occurring 2-azaan-
thraquinone analogues.3 Only recently, a pathway was developed
for the synthesis of 3-alkyl-2-aza-1-cyano-4-hydroxyanthraquino-
nes.4 Having experience in quinones with annelated pyridine
moieties, it was felt necessary to synthesize the related quinones
with annelated five-membered rings, i.e., benzo[f]isoindole-4,9-
diones 1, because of the link with natural product chemistry.
The heterocyclic core of benzo[f]isoindole-4,9-diones 1 is found
in natural products such as Reniera indole 2, which has been
isolated from the blue sponge Reniera sp.5 Azamonosporascone
FIGURE 1. Isoindoles of interest.
† Ghent University.
3 has been isolated from Monosporascus cannonballus, a fungus
responsible for crop losses of musk melon and watermelon.6
Bhimamycin C 4 and Bhimamycin D 5 were isolated from a
terrestrial streptomycete7 and display bioactivities against human
ovarian cancer cell lines,8 are EP4 receptor agonists in the
treatment of pain,9 and are inhibitors of HIV-1 integrase.10
‡ Vrije Universiteit Brussel.
(1) (a) Jacobs, J.; Kesteleyn, B.; De Kimpe, N. Tetrahedron 2008, 64, 7545–
7554. (b) Jacobs, J.; Mbala Mavinga, B.; Kesteleyn, B.; Diels, G.; De Kimpe,
N. Tetrahedron 2008, 64, 6364–6371. (c) Jacobs, J.; Kesteleyn, B.; De Kimpe,
N. Tetrahedron 2008, 64, 4985–4992. (d) Jacobs, J.; Deblander, J.; Kesteleyn,
B.; Abbaspour Tehrani, K.; De Kimpe, N. Tetrahedron 2008, 64, 5345–5353.
(e) For a review, see: Claessens, S.; Verniest, G.; Jacobs, J.; Van Hende, E.;
Habonimana, P.; Nguyen Van, T.; Van Puyvelde, L.; De Kimpe, N. Synlett 2007,
829–850. (f) Jacobs, J.; Claessens, S.; Kesteleyn, B.; Huygen, K.; De Kimpe,
N. Tetrahedron 2007, 63, 2503–2510.
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2005, 61, 2295–2300.
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269. (b) Parker, K. A.; Cohen, I. D.; Padwa, A.; Dent, W. Tetrahedron Lett.
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10.1021/jo801056e CCC: $40.75
Published on Web 09/06/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 7555–7559 7555

Claessens et al.
SCHEME 1
SCHEME 2
Although these benzo[f]isoindole-4,9-diones 1 have attracted
considerable attention in the literature, only a limited number
of synthetic pathways were developed toward compounds having
a benzo[f]isoindole-4,9-dione core. These pathways are mainly
based upon 1,3-dipolar cycloaddition of pyridinium or isoquino-
linium ylids across 1,4-naphthoquinones,11 1,3-dipolar cycload-
ditions of azomethine ylids generated from amino acids12 or
nitrile oxides,13 via an unusual rearrangement of 2,3-diacety-
lenyl-1,4-naphthoquinone with hydrazide,14 starting from the
annelated thiophenes15 and a photochemical addition of 2,3-
diphenyl-2H-azirine to 1,4-naphthoquinone.16 The synthesis of
2-methyl-2H-benzo[f]isoindole-4,9-dione is based on the nu-
cleophilic displacement of both methylthio groups in 2,3-
bis(methylthiomethyl)-1,4-naphthoquinone with methylamine,
followed by oxidation by oxygen to afford the benzo[f]isoin-
dole.17 The rearrangement of 2-azaanthraquinones employing
2,3-dichloro-5,6-dicyanopyrazine as the cyclization partner also
resulted in the formation of benzo[f]isoindole-4,9-diones.18
Drawbacks of these methods are the use of non-straightforward
methods, unavailability of precursors and low yields. Therefore,
a short and straightforward synthesis of this interesting class of
compounds is of primordial importance.
Results and Discussion
We were interested in synthesizing 2-alkyl-2H-benzo[f]isoin-
dole-4,9-diones 1 with only substituents on the nitrogen for
which only one existing synthesis pathway is described by
Thomson et al.17 According to this procedure, only the 2-methyl
substituted benzo[f]isoindole 8 was prepared making use of an
alkylthiolation reaction of 2,3-dimethyl-1,4-naphthoquinone 6.
Subsequent reaction of 2,3-bis(methylthiomethyl)-1,4-naphtho-
quinone 7 with methylamine resulted in 2-methyl-2H-ben-
zo[f]isoindole-4,9-dione 8 in a combined yield of 28%.
In order to avoid the use of expensive 2,3-dimethyl-1,4-
naphthoquinone 6, an alternative entry was sought. At first, it
was thought that the reaction of primary amines with 2,3-
bis(bromomethyl)-1,4-naphthoquinone 9 would have some good
chance to succeed, giving a short and straightforward synthesis
of benzo[f]isoindoles-4,9-diones 1. 2,3-Bis(bromomethyl)-1,4-
naphthoquinone 9 was prepared according to literature by a
double bromomethylation procedure starting from 1,4-naphtho-
quinone.19 An alternative procedure reported in literature
consists of the radical bromination of 2,3-dimethyl-1,4-naph-
thoquinone 6.20 The latter procedure is not preferred because it
is also starting from 2,3-dimethyl-1,4-naphthoquinone 6. Com-
pound 9 proved to have limited stability and should be used
within one week. Benzo[f]isoindole-4,9-diones 1a and 1b were
obtained in reasonable yield after reaction of 2,3-bis(bromo-
methyl)-1,4-naphthoquinone 9 with isopropylamine or tert-
butylamine in diethyl ether at 0 °C for 30 minutes (Scheme 1).
After the first substitution reaction, a second intramolecular
nucleophilic substitution takes place to form 2,3-dihydro-
benzo[f]isoindoles 10a and 10b. These intermediates 10a,b are
(10) Verschueren, W. G.; Dierynck, I.; Amssoms, K. I. E.; Hu, L.; Boonants,
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Chem. 1994, 31, 187–192. (c) Monnier, K.; Schmitt, G.; Laude, B.; Theobald,
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S.; Silva, A. M. S.; Cavaleiro, J. A. S.; Makarova, E. A.; Lukyanets, E. A. J.
Org. Chem. 2006, 71, 8352–8356. (b) Galezowski, M.; Gryko, D. T. J. Org.
Chem. 2006, 71, 5942–5950. (c) Pearson, W. H.; Stoy, P.; Mi, Y. J. Org. Chem.
2004, 69, 1919–1939. (d) Silva, A. M. G.; Tome, A. C.; Neves, M. G. P. M. S.;
Silva, A. M. S.; Cavaleiro, J. A. S. J. Org. Chem. 2002, 67, 726–732. (e) Likussar,
W.; Michelitsch, A.; Schubert-Zsilavecz, M.; Gusterhuber, D. Monatsh. Chem.
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Michelitsch, A. Monatsh. Chem. 1991, 122, 383–387. (g) Myers, J. A.; Moore,
L. D., Jr.; Whitter, W. L.; Council, S. L.; Waldo, R. M.; Lanier, J. L.; Omoji,
B. J. Org. Chem. 1980, 45, 1202–1206. (h) Uchida, T.; Tsubokawa, S.; Harihara,
K.; Matsumoto, K. J. Heterocycl. Chem. 1978, 15, 1303–1307.
(13) Huisgen, R.; Stangl, H.; Sturm, H. J.; Wagenhofer, H. Angew. Chem.
1962, 74, 31.
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1510. (b) Marecki, P. E.; Butke, G. P. J. Heterocycl. Chem. 1983, 20, 1497–
1500.
(16) Gilgen, P.; Jackson, B.; Hansen, H. J.; Heimgartner, H.; Schmid, H.
HelV. Chim. Acta 1974, 57, 2634–2643.
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1980, 282–288.
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Chem. Soc. 1996, 7, 169–172.
(20) Thomson, R. H. J. Chem. Soc. 1953, 1196–1199.
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7556 J. Org. Chem. Vol. 73, No. 19, 2008

Synthesis of Benzo[f]isoindole-4,9-diones
SCHEME 3
SCHEME 4
SCHEME 5
not stable and are oxidized spontaneously by oxygen in the air
to the benzo[f]isoindole-4,9-diones 1a and 1b in 61% and 56%,
respectively.
The obtained yields are rather moderate and it was felt that
there was room for more improvement. During the course of
our research towards 2-azaanthraquinones it was found that the
reaction of amine 11 with cerium(IV) ammonium nitrate (CAN)
did not give the expected oxidation towards a quinone but
resulted in 3-bromo-1,4-dimethoxy-2-naphthaldehyde 12 in a
yield of 79% instead (Scheme 2).
The aminomethyl moiety is not stable against CAN and
becomes oxidized to the aldimine, which is hydrolyzed in situ
to give the corresponding aldehyde. Here it was realized that
this unexpected side-reaction can be directed to our favor.
Therefore, the following retrosynthetic scheme was devised
(Scheme 3). Based on the observation that CAN oxidizes
aminomethyl moieties towards aldehydes, it is possible to obtain
compounds 13 which will ring close to form the targeted
compounds 1.
At first, a reliable synthesis of 2,3-bis(bromomethyl)-1,4-
dimethoxynaphthalene 15 was required. The known 2,3-bromo-
methyl-3-methyl-1,4-dimethoxynaphthalene 1721 was bromi-
nated in a radicalar way using 1.5 equivalents of N-bromo
succinimide (NBS) and a catalytic amount of dibenzoyl peroxide
(BPO) upon heating under reflux in tetrachloromethane. In this
way, the target compound 15 was prepared in 58% overall yield
starting from menadione 16 on a multigram scale (Scheme 4).
A more straightforward synthesis of 2,3-bis(bromomethyl)-1,4-
dimethoxynaphthalene 15 was found in the double bromom-
ethylation reaction of 1,4-dimethoxynaphthalene 18 using
hydrobromic acid (33 wt% in acetic acid) with a large excess
of paraformaldehyde at room temperature for 12 hours. This
resulted in the synthesis of 2,3-bis(bromomethyl)-1,4-dimethox-
ynaphthalene 15 in 82% yield (Scheme 4).
Next, it was realized that the reaction of 2,3-bis(bromo-
methyl)-1,4-dimethoxynaphthalene 15 with primary amines will
result in double substitution products 14a–f and not in the
formation of 4,9-dimethoxy-2,3-dihydro-1H-benzo[f]isoindoles
21. The fact that this reaction prefers to undergo twice an
intermolecular substitution instead of chosing an intramolecular
ring closure can be explained by the rules of Baldwin (Scheme
6). Presuming the ring closure is based on two successive SN2-
type substitutions, an intramolecular ring closure can occur
because 5-exo-tet reactions are favored. This should result in
4,9-dimethoxy-2,3-dihydro-1H-benzo[f]isoindoles 21. However,
the bromide is benzylic and there is an electron-donating ortho-
substituent present. As a consequence, this compound will very
easily form ortho-quinodimethane 20 Via an electron push
mechanism, and the amine will add in a Michael-type way. An
intramolecular ring closure of compound 20 is disfavored
because it would be a 5-endo-trig ring closure.
Therefore, a second intermolecular substitution reaction is
occurring, which gives rise to a double substitution product 14.
Although it can be stated that Baldwin’s rules are not obliged
J. Org. Chem. Vol. 73, No. 19, 2008 7557

Claessens et al.
SCHEME 6
SCHEME 7
to be followed, they provide a good mechanistic explanation
for this reaction.
lecularly attacks the aldehyde in a favored 5-exo-trig ring closure
reaction resulting in hemiaminals 22a-f. Subsequently, hy-
droxide expulsion to generate an iminium ion and subsequent
aromatization by loss of a proton gave rise to the targeted
benzo[f]isoindole-4,9-diones 1a-f in 54-87% yield.
Subsequently, it was thought that the formation of ben-
zo[f]isoindole-4,9-diones 1 should be possible starting from the
previously obtained double substitution products 14, using a
CAN-mediated oxidation (Scheme 7). It was reasoned that a
first equivalent of CAN will oxidize one aminomethyl moiety
to the corresponding monoaldehyde, after which a ring closure
of the second aminomethyl moiety across the formed aldehyde
will occur. Subsequently, further oxidation will result in the
targeted benzo[f]isoindole-4,9-diones 1. To confirm this state-
ment, several 2,3-bis(aminomethyl)-1,4-dimethoxynaphthalenes
14a-f were synthesized and subjected to reaction with CAN
in aqueous acetonitrile. Using the theoretically required amount
of CAN and conducting the reaction at 0 °C for 3 h gave nicely
and in one step the predicted benzo[f]isoindole-4,9-diones 1a-f.
Mechanistically, the reaction probably proceeds via the monoal-
dehyde 13a-f. The second unreacted amino moiety intramo-
Conclusions
It has been found that reaction of 2,3-bis(bromomethyl)-1,4-
dimethoxynaphthalene 15 with primary amines results in the
formation of double substitution products 14. However, based
on the observation that aminomethyl moieties are oxidized by
cerium(IV) ammonium nitrate toward the corresponding alde-
hydes 13, 2,3-bis(aminomethyl)-1,4-dimethoxynaphthalenes 14
were converted into the targeted benzo[f]isoindole-4,9-diones
1a-f. The latter compounds were also prepared starting from
2,3-bis(bromomethyl)-1,4-naphthoquinone 9.
7558 J. Org. Chem. Vol. 73, No. 19, 2008

Synthesis of Benzo[f]isoindole-4,9-diones
bis(bromomethyl)-1,4-dimethoxynaphthalene 15 (0.15 g, 0.4 mmol)
in diethyl ether (5 mL) was added the appropriate amine (5 equiv)
at room temperature. The reaction mixture was stirred for 3 h after
which it was filtered, and the solvent was evaporated in vacuo to
yield the (1,4-dimethoxynaphthalene-2,3-diyl)dimethylamine 14,
which was used in the next step without purification (yield
95-99%). (1,4-Dimethoxynaphthalene-2,3-diyl)bis(N-tert-butyl)di-
Experimental Section
1. 2,3-Bis(bromomethyl)-1,4-dimethoxynaphthalene 15. Method
A: Starting from 2-Bromomethyl-3-methyl-1,4-dimethoxynaph-
thalene 17. 2-Bromomethyl-3-methyl-1,4-dimethoxynaphthalene 721
(11.6 g, 39.5 mmol) was dissolved in tetrachloromethane (100 mL)
and NBS (10.32 g, 1.5 equiv) and BPO (2.5 g, 0.2 equiv) were
added. The reaction mixture was stirred and heated under reflux
for 8 h in daylight, after which it was cooled down in an ice bath
to 0 °C. The reaction mixture was filtered, and the solvent was
evaporated (tetrachloromethane was recovered and washed with
sulfuric acid for reuse). The crude residue was purified by
recrystallization (ether/petroleum ether) to yield 2,3-bis(bromo-
methyl)-1,4-dimethoxynaphthalene as orange crystals 15 (79%,
11.6 g).
1
methylamine 14a: red-pink crystals, mp 72.1 °C. H NMR (300
MHz, CDCl3): δ 1.26 (18H, s, 2 × C(CH3)3), 3.96 (4H, s, 2 ×
CH2), 3.98 (6H, s, 2 × MeO), 7.44-7.50 (2H, m, 2 × CHar),
8.02-8.07 (2H, m, 2 × CHar). 13C NMR (75 MHz, CDCl3): δ 29.1
(6 × CH3), 38.7 (2 × CH2), 51.1 (2 × Cquat), 63.0 (2 × MeO),
122.6 (2 × CHar), 125.9 (2 × CHar), 128.4 (2 × Cquat), 130.2 (2 ×
C
quat), 151.1 (2 × Cquat). IR (ATR): νmax 3314, 1356 cm-1. MS
(ES+) m/z (%): 359 (M + H+, 100). Anal. Calcd for C22H34N2O2:
C 73.70, H 9.56, N 7.81. Found: C 73.48, H 9.71, N 7.75.
4. General Procedure for the Synthesis of Benzo[f]isoindole-
4,9-diones 1a,b Starting from 2,3-Bis(bromomethyl)-1,4-naphtho-
quinone 9. To a stirred solution of 2,3-bis(bromomethyl)-1,4-
naphthoquinone 9 (0.25 g, 0.72 mmol) in diethyl ether (5 mL) was
added the appropriate amine at 0 °C. The reaction mixture was
stirred for 30 min and subsequently filtered over a silica patch.
The filter cake was washed and the solvent evaporated in vacuo to
yield crude benzo[f]isoindole-4,9-dione 1a,b. The crude reaction
mixture was purified by flash chromatography. 2-tert-Butyl-2H-
benzo[f]isoindole-4,9-dione 1a: Purification by flash chromatogra-
phy over aluminium oxide (EtOAc/petroleum ether 1:4) provided
a yellow powder (0.052 g, 93%), mp 172-173 °C. 1H NMR (500
MHz, CDCl3): δ 1.63 (9H, s, 3 × CH3), 7.62 (2H, s, CH-1 and
CH-3), 7.68–7.70 (2H, m, 2 × CHar), 8.25 (2H, dd, J ) 3.4, 5.8
Hz, 2 × CHar). 13C NMR (126 MHz, CDCI3): δ 30.5 (3 × CH3),
57.5 (Cquat), 121.8 (CH-1 and CH-3), 122.6 (2 × Cquat), 126.9 (2 ×
CHar), 133.0 (2 × CHar), 135.6 (2 × Cquat), 180.4 (2 × CdO). IR
(ATR): νmax 3125, 1648, 1531, 1221, 970, 710 cm-1. MS (EI, 70
eV) m/z (%): 254 (M + H+, 100). Anal. Calcd for C16H15NO2: C
75.87, H 5.97, N 5.53, found: C 75.69, H 6.10, N 5.46.
5. General Procedure for the Synthesis of Benzo[f]isoindole-
4,9-diones 1 using CAN-Oxidation of (1,4-Dimethoxynaphthalene-
2,3-diyl)dimethylamine 14. To a stirred solution of (1,4-dimethoxy-
naphthalene-2,3-diyl)dimethylamine 14 (1.3 mmol) in acetonitrile
(5 mL) was added CAN (4.04 g, 4 equiv) in water (5 mL) at 0 °C.
The reaction mixture was allowed to reach ambient temperature
over a period of 30 min. The reaction was diluted with water (10
mL) and extracted with ethyl acetate (3 × 10 mL). The organic
solution was dried over MgSO4. The solvent was evaporated in
vacuo, and the crude reaction mixture was purified by flash
chromatography over silica gel using dichloromethane as eluens.
2-tert-Butyl-2H-benzo[f]isoindole-4,9-dione 1a: yield 81%; spectral
data, vide supra.
Method B: Starting from 1,4-Dimethoxynaphthalene 18. 1,4-
Dimethoxynaphthalene 18 (8.0 g, 118 mmol) was dissolved in a
30% solution of hydrobromic acid in acetic acid (85 mL). To this
mixture was added paraformaldehyde (34 g, 1.15 mol), and the
mixture was stirred at room temperature for 12 h. The reac-
tion mixture was then quenched with water and extracted with
diethyl ether. The combined organic phases were subsequently
washed with a saturated sodium bicarbonate solution, a saturated
sodium bisulfite solution, and brine and dried over MgSO4. After
concentration in vacuo, purification by column chromatography on
silica gel (EtOAc/cHexane 1:12) yielded 2,3-bis(bromomethyl)-1,4-
dimethoxynaphthalene as white crystals 15 (82%, 13.2 g), mp
117-118 °C.22 1H NMR (250 MHz, CDCl3): δ 8.09 (2H, dd, J )
3.3, 6.4 Hz), 7.54-7.58 (2H, m), 5.01 (4H, s), 4.07 (6H, s). 13C
NMR (63 MHz, CDCl3): δ 152.2 (Cquat), 129.0 (Cquat), 127.4 (CHar),
125.8 (Cquat), 123.2 (CHar), 62.6 (CH3), 24.7 (CH2). IR (ATR): νmax
1352, 1213, 1036, 778, 711 cm-1. MS (EI, 70 eV) m/z (%): 376/
374/372 (M+, 18/35/18), 296 (23), 295 (97), 294 (21), 293 (96),
214 (50), 200 (94), 199 (100), 171 (52), 141 (78), 139 (62), 128
(79), 115 (83). Anal. Calcd for C14H14Br2O2: C 44.95, H 3.77.
Found: C 45.21, H 3.89.
2. 2,3-Bis(bromomethyl)-1,4-naphthoquinone 9. Method A:
Starting from 2,3-Bis(bromomethyl)-1,4-dimethoxynaphthalene
15. To a flask containing a solution of 2,3-bis(bromomethyl)-1,4-
dimethoxynaphthalene 15 (0.374 g, 1 mmol) in acetonitrile/
dichloromethane 4:1 (5 mL) was added dropwise an aqueous
solution of CAN (1.64 g, 3 equiv in 1 mL H2O). After 30 min of
stirring at room temperature, the reaction mixture was diluted with
ethyl acetate (5 mL), poured in water (10 mL), extracted with ethyl
acetate (3 × 5 mL), and dried over MgSO4. Evaporation of the
solvent and chromatography on silica gel (petroleum ether/ethyl
acetate 92:8) yielded 2,3-bis(bromomethyl)-1,4-naphthoquinone 9
as yellow crystals (0.3 g, 87%).
Method B: Starting from 1,4-Naphthoquinone. This method has
been developed by Ferreira19 and yielded 2,3-bis(bromomethyl)-
1,4-naphthoquinone 9 in 43%. Only 1H NMR spectra were
reported.19 Other spectral data are completed here. Mp: 153-154
°C (lit. 154 °C,19 153-154 °C20). 1H NMR (300 MHz, CDCl3): δ
4.56 (4H, s, 2 × CH2), 7.73-7.79 (2H, m, 2 × CHar), 8.10-8.16
(2H, m, 2 × CHar). 13C NMR (75 MHz, CDCl3): δ 20.6 (2 × CH2),
127.0 (2 × CHar), 131.7 (2 × Cquat), 134.5 (2 × CH2), 143.6 (Cquat),
182.4 (2 × CdO). IR (ATR): νmax 1668 cm-1. MS (ES+) m/z (%):
342/344/346 (M+, 100).
Acknowledgment. This work was financially supported by
the Flemish Institute for the Promotion of Scientific-Techno-
logical Research in Industry (IWT) and the Fund for Scientific
Research-Flanders (FWO-Vlaanderen).
Supporting Information Available: General experimental
methods, spectral data of compounds 14b-f and 1b-f, and 1H
NMR and 13C NMR spectra of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
3. General Procedure for the Preparation of (1,4-Dimethoxy-
naphthalene-2,3-diyl)dimethylamine 14. To a stirred solution of 2,3-
(22) Illescas, B. M.; Martin, N.; Seoane, C. J. Org. Chem. 1997, 62, 7585–
7591.
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