A new approach to the synthesis of benzylidene derivatives of 1-(α-aminobenzyl)-2-naphthols (Betti bases), promising chiral inductors

Full text of DOI:10.1016/j.mencom.2007.06.020

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 239–240
A new approach to the synthesis of benzylidene
derivatives of 1-(α-aminobenzyl)-2-naphthols
(
Betti bases), promising chiral inductors
a
a
a
Victor F. Zheltukhin, Kirill E. Metlushka, Dilyara N. Sadkova,
b
b
a
Charles E. McKenna, Boris A. Kashemirov and Vladimir A. Alfonsov*
a
b
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy
of Sciences, 420088 Kazan, Russian Federation. Fax: +7 8432 75 5322; e-mail: alfonsov@iopc.knc.ru
Department of Chemistry, University of Southern California, Los Angeles, CA 90089-0744, USA.
Fax: +1 213 740 0930; e-mail: mckenna@usc.edu
DOI: 10.1016/j.mencom.2007.06.020
A new approach to the synthesis of precursors of Betti bases is described, in which β-naphthol reacts with 1,3,5-triaryl-
,4-diazapenta-1,4-dienes (3:2) in refluxing benzene.
2
Interest in identifying new, readily accessible enantiopure chiral
compounds for use as inductors (chirality carriers) or starting
materials in asymmetric synthesis continues unabated. To a
considerable extent, this is due to current requirements for the
benzaldehyde and ammonia in ethanol solution at room tempe-
rature for several days4 results in imine A, which exists in
solution in tautomeric equilibrium with two diastereomeric trans-
,5
and cis-1,3-diaryl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazine
1
6(a)–(c)
synthesis of enantiomerically pure pharmaceuticals and resulting
structures B and C.
The imine is then hydrolysed with
6
recent progress in the chemistry of pure enantiomers. 1-(α-Amino-
benzyl)-2-naphthols, eponymously called Betti bases, are quite
suitable for these purposes because they are easy to synthesise,
the starting reagents are readily available, and separation of the
hydrochloric acid to give an amine hydrochloride, yielding after
4,5
treatment with alkali the free base, which can be separated.
Subsequently, a few other methods for the synthesis of similar
compounds were suggested.7
(a)–(f)
The product yields reported
2
,3(a)–(r)
enantiomers is straightforward.
in the above literature sources range from satisfactory to good.
The key compounds in all these syntheses are primary con-
densation products A, B and C. In this study, we suggest a new
approach to the synthesis of these Betti bases precursors. The
method involves the reaction of β-naphthol 1 with 1,3,5-triaryl-
The classical synthesis of the simplest member of the
series, 1-(α-aminobenzyl)-2-naphthol, Betti base itself, involves
several steps. The three-component condensation of β-naphthol,
X
2
,4-diazapenta-1,4-dienes 2 in a molar ratio of 3:2 in refluxing
†
benzene for 5–17 h according to Scheme 1.
The completion of the reaction can be easily determined by
cessation of ammonia evolution. All products were obtained as
crystalline compounds after the reaction mixture was cooled or
the solvent was removed. Reaction products 3a–e were isolated
OH
+
3
2 X
C
H
N
N
C
X
H
H
1
2
in yields from 88% to quantitative.
The yields of 2 are high (72–97%)8
(a)–(c)
for the majority
X
X
of substituted benzaldehydes used. Thus, the overall yields of
compounds 3a–e obtained using our method exceed those
reported in literature (Table 1). All the reactions occur without
formation of by-products. The structures of the end products
N
C
H
3
–
NH3
OH
1
were established by H NMR, IR spectroscopy, elemental analyses
†
General method for the synthesis of compounds 3a–e. β-Naphthol
3
A
(0.03–0.055 mol) was dissolved with heating in anhydrous benzene
(30–35 ml) and compound 2 (0.02–0.036 mol) was added (molar ratio
2
:β-naphthol = 2:3). The reaction mixture was refluxed until ammonia
X
X
X
X
evolution ceased, which required 5 to 17 h depending on the substituent
H
H
N
at the aryl fragment in compound 2.
N
If the product was formed as a crystalline precipitate, it was filtered
off, the filtrate was concentrated to half volume, and the precipitate that
formed was separated again. If the product did not precipitate at once,
the solvent was removed in vacuo from the reaction mixture, and the
viscous residue was triturated with a small amount of diethyl ether. The
resulting crystalline compound was dried in a vacuum of a water-jet
O
O
3
B
3C
a X = Br
b X = Cl
c X = H
d X = OMe
e X = NMe2
3(m),6(c)
pump and recrystallised from a suitable solvent.
The yields, melting points, and fractions of tautomers A, B and C
calculated from the integral intensities of characteristic proton signals in
1
Scheme 1
the H NMR spectra of the products obtained are listed in Table 1.
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Mendeleev Commun., 2007, 17, 239–240
Table 1 Yields, melting points, and fractions of tautomers A, B and C in CDCl solutions for compounds 3a–e.
3
1
Yield /
overall
yield (%)
Tautomer fractions (%) ( H NMR)
Published data
Mp/°C
Product
X
Mp/°C
a
A
B
C
Yield (%)
Reference
3
3
3
3
3
a
b
c
d
e
Br
Cl
H
OMe
NMe2
94 / 70
88 / 78
94 / 92
99 / 96
96 / 86
184–185b
153–154
145–147
182–184
224–226
13.8
15.5
26.9
56.9
92.2
78.3
77.0
63.8
37.8
7.0
7.9
7.5
9.3
5.3
0.8
48
78
90
76
—
125–126
155–156
145–147
182–184
—
3(m)
6(c)
6(c)
6(c)
—
a
b
Yields of 3a–e with the count of yields of 2a–e. The melting point of 3a from different experiments was checked repeatedly. Spectral and elemental analysis
3
(m)
data for the synthesised compound correspond to the structure of 3a and are consistent with published data.
and, for known compounds, by comparison of their spectro-
scopic constants with literature values.
C.-S. Da, Z.-Q. Xin, R. Wang, M. C. K. Choi and A. S. C. Chan, Org.
Lett., 2001, 3, 2733; (e) Y. Wang, X. Li and K. Ding, Tetrahedron:
Asymmetry, 2002, 13, 1291; (f) J. Lu, X. Xu, C. Wang, J. He, Y. Hu and
H. Hu, Tetrahedron Lett., 2002, 43, 8367; (g) Y. Zhang, L. Zhang,
Z. Guo and L. Zhu, J. Coord. Chem., 2002, 55, 1393; (h) K. Li, Z. Zhou,
L. Wang, Q. Zhou and C. Tang, Main Group Met. Chem., 2002, 25,
663; (i) M. R. Saidi and N. Azizi, Tetrahedron: Asymmetry, 2003, 14,
389; (j) J.-X. Ji, L.-Q. Qiu, C. W. Yip and A. S. C. Chan, J. Org. Chem.,
6(c)
As expected, in agreement with published data, compounds
3
a–e in CDCl solution exist as mixtures of tautomers A, B
3
and C due to ring–chain tautomerism. Their % fractions in the
mixture as determined by integration of the HC1 and HC3 signals
are shown in Table 1. One can see from Table 1 that the
presence of donor substituents in starting compound 2 results in
the formation of products in which imine form A predominates,
whereas acceptor substituents stabilise oxazine forms B and C.
Indeed, the hitherto unknown bis(dimethylamino) derivative 3e‡
containing the strongest n electron pair-donor (dimethylamino)
groups at the para positions of both phenyl rings is charac-
terised by the highest fraction of imine form A, namely, 92.2%.
In summary, we have presented a new method for the
synthesis of Betti base precursors by reaction of β-naphthol
with 1,3,5-triaryl-2,4-diazapenta-1,4-dienes. The new method
provides Betti bases in high yield and purity, facilitating
subsequent separation into the individual enantiomers.
2
003, 68, 1589; (k) X. Xu, J. Lu, Y. Dong, R. Li, Z. Ge and Y. Hu,
Tetrahedron: Asymmetry, 2004, 15, 475; (l) Y. Dong, J. Sun, X. Wang,
X. Xu, L. Cao and Y. Hu, Tetrahedron: Asymmetry, 2004, 15, 1667; (m)
I. Szatmári, T. A. Martinek, L. Lázár, A. Koch, E. Kleinpeter, K. Neuvonen
and F. Fülöp, J. Org. Chem., 2004, 69, 3645; (n) X. Xu, J. Lu, R. Li,
Z. Ge, Y. Dong and Y. Hu, Synlett., 2004, 122; (o) I. Szatmári,
A. Hetényi, L. Lázár and F. Fülöp, J. Heterocycl. Chem., 2004, 41, 367;
(p) X. Wang, Y. Dong, J. Sun, X. Xu, R. Li and Y. Hu, J. Org. Chem.,
2005, 70, 1897; (q) S. Dahmen and M. Lormann, Org. Lett., 2005, 7,
4
597; (r) J.-X. Ji, J. Wu, T. T.-L. Au-Yeung, C.-W. Yip, R. K. Haynes
and A. S. C. Chan, J. Org. Chem., 2005, 70, 1093.
M. Betti, Gazz. Chim. Ital., 1900, 30, II, 310.
M. Betti, Org. Synth. Coll. Vol., 1941, I, 381.
4
5
6 (a) H. E. Smith and N. E. Cooper, J. Org. Chem., 1970, 35, 2212;
(
(
b) H. Mohrle, C. Miller and D. Wendisch, Chem. Ber., 1974, 107, 2675;
c) I. Szatmári, T. A. Martinek, L. Lázár and F. Fülöp, Tetrahedron,
This study was supported by the Civilian Research and
Development Foundation (grant no. RUC2-2638-KA-05).
2
003, 59, 2877.
(a) V. P. Mamaev and V. M. Ignat’ev, Izv. Akad. Nauk SSSR, Ser. Khim.,
965, 1107 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1965, 14, 1074);
b) M. Betti and A. Torichelli, Gazz. Chim. Ital., 1903, 33, 1; (c) M. R.
7
1
(
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1
-[a-(4''-Dimethylaminobenzylidene)amino-4'-dimethylaminobenzyl]-
1
naphth-2-ol 3e: yield 96%; mp 224–226 °C (benzene). H NMR (CDCl )
3
d: (tautomer A) 2.90 (s, MeN), 3.03 (s, Me'N), 6.34 (s, CHN), 8.43 (s,
CH=N); (tautomer B) 2.90 (s, MeN), 2.98 (s, Me'N), 5.64 (s, CHN),
5
.74 (s, CHO); (tautomer C) 2.96 (s, MeN), 3.00 (s, Me'N), 5.80 (s,
CHN), 5.93 (s, CHO); (tautomers A + B + C) 6.65–7.92 (m, CHarom).
Found (%): C, 80.09; H, 7.24; N, 9.95. Calc. for C H N O (%): C,
2
8
29
3
7
9.40; H, 6.90; N, 9.91. For the tautomer ratios, see Table 1.
Received: 30th November 2006; Com. 06/2833
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