tert-Amino effect in naphthalene proton sponges: a novel approach to benzo[h]quinoline and quino[7,8:7',8']quinoline derivatives

Article abstract of DOI:10.1016/j.mencom.2010.01.014

2-Vinyl- and 2,7-divinyl-1,8-bis(dimethylamino)naphthalenes with strong -M substituents in the β-positions of vinyl groups have been shown to undergo a tert-amino-type rearrangement providing a new and facile route to benzo[h]quinoline and quino[7,8:7',8']quinoline derivatives.

Full text of DOI:10.1016/j.mencom.2010.01.014

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 36–38
tert-Amino effect in naphthalene proton sponges: a novel approach
to benzo[h]quinoline and quino[7,8:7',8']quinoline derivatives
Maria A. Povalyakhina, Alexander F. Pozharskii,* Olga V. Dyablo,
Valery A. Ozeryanskii and Oksana V. Ryabtsova
Department of Chemistry, Southern Federal University, 344090 Rostov-on-Don, Russian Federation.
Fax: +7 863 297 5146; e-mail: apozharskii@sfedu.ru
DOI: 10.1016/j.mencom.2010.01.014
2-Vinyl- and 2,7-divinyl-1,8-bis(dimethylamino)naphthalenes with strong –M substituents in the β-positions of vinyl groups
have been shown to undergo a tert-amino-type rearrangement providing a new and facile route to benzo[h]quinoline and
quino[7,8:7',8']quinoline derivatives.
Recently, we have disclosed that acidic treatment of secondary
and tertiary alcohols of type 1 on the basis of 1,8-bis(dimethyl-
amino)naphthalene (proton sponge) generates naphthyl-2-methyl
carbocations 2, which then undergo a fast transformation into
1,1,3-trimethyl-2,3-dihydroperimidinium salts 4.1 The process
involves hydride anion transfer from the neighbouring N–Me
group to the carbenium centre followed by the peri-cyclization
of intermediate methyleneimmonium salt 3 (Scheme 1). These
were the first examples of the so-called tert-amino effect2,3 in
proton sponges.
Monoaldehyde 5 has been shown to react easily with these
methylene-active compounds in alcohol or toluene solution under
ambient conditions. However, in the latter solvent, an addition
of piperidine is needed whereas in EtOH an external catalyst is
not necessary.† We were able to isolate in a pure state only
alkenes 6c,d. As regards alkenes 6a,b, though their formation
in the reaction mixture can be monitored spectrophotometri-
cally, they are rapidly transformed into benzo[h]quinolines 8a,b.‡
Thus, the presence of an electron-deficient α-carbon atom in the
polarized vinyl group of compounds 6a,b initiates spontaneous
hydride transfer from the neighbouring N-methyl group fol-
lowed by the tetrahydropyridine ring closure. Apparently, the
way of cyclization of methyleneimmonium cation 7 is due to a
higher nucleophilicity of the side-chain carbanionic centre as
compared with the 8-NMe2 group. Moreover, the peri-cycliza-
H
H
Me
Me2N N
C
H
Ph
Me2N
NMe2
OH
Ph
hydride
shift
H+
R
R
H
H
Me
Me2N
C
H
1
2
Me2N
NMe2
N
R
H2C
CHO
R
H2C
R'
Me
Me
Me2N
CH2
N
Me2N
N
R'
CH(R)Ph
CH(R)Ph
5
6a–e
Ha Hb
Mea
b
Me
R
Me
Me2N
Me
N
CH2
3a
3b
N
N
R'
Hd
Hc
hydride
shift
Me
R
Me2N
N
R'
CH(R)Ph
7
8a–e
4
R = H, Ph (70–100%)
a R = R' = CN
Ha
Ha
O
Scheme 1
Hb
Meb
b R + R' =
Here we report another kind of tert-amino effect in this
series in which cyclization proceeds with the participation of an
electron-deficient ortho-substituent instead of the peri-NMe2
group, providing a new and convenient approach to inacces-
sible4,5 benzo[h]quinoline and quino[7,8:7',8']quinoline systems.
2-Vinyl- and 2,7-divinyl-1,8-bis(dimethylamino)naphthalenes
(6 and 10, respectively) were employed as starting compounds,
which were prepared by the Knoevenagel condensation of earlier
described6 2-formyl- and 2,7-diformyl-1,8-bis(dimethylamino)-
naphthalenes (5 and 9, respectively) with malonodinitrile, dime-
done, tosylacetonitrile and ethyl cyanoacetate (Schemes 2 and 3).
O
Hb
Mea
O
S
c R = CN, R' =
Me
O
d R = CN, R' = CO2Et
e R = CN, R' = CO2Me
Scheme 2
As reported earlier, both the parent proton sponge7 and its derivatives8
can effectively function as basic catalysts in the Knoevenagel reaction.
†
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© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 36–38
tion, similar to that depicted in Scheme 1, should only proceed
after rotation of the –N+(Me)=CH2 function around the Carom–N
bond (cf. 3a ® 3b), that requires some extra energy.
N(4)
C(17)
C(16)
C(12)
C(18)
C(15)
N(2)
C(11)
N(1)
N(3)
We have found that the isomerization of alkenes 6c,d into
benzo[h]quinolines 8c,d can be conducted almost quantitatively
by simply heating the solid samples or by keeping their solu-
tions in polar solvents such as DMSO or EtOH at room
temperature. Interaction of aldehyde 5 with ethyl cyanoacetate
in methanol (room temperature, 72 h) is accompanied by re-
esterification yielding benzo[h]quinoline 8e.
C(14)
C(9)
C(1)
C(13)
C(10)
C(5)
C(2)
C(3)
C(8)
C(7)
C(4)
C(6)
For dicyano-substituted benzo[h]quinoline 8a, a single-
crystal X-ray study has been performed confirming its structure
(Figure 1).§ The naphthalene plane of 8a is notably twisted
[torsion C(2)–C(3)···C(7)–C(8) is 9.6°] with the amine nitrogens
being out of the plane and 2.81 Å apart indicating that 8a and
its analogues are still sterically distorted molecules.
Figure 1 Molecular structure of 8a in representation of atoms via thermal
ellipsoids at p = 30%. Selected bond lengths and distances (Å), valence and
torsion angles (°): N(1)–C(1) 1.402(2), N(2)–C(9) 1.406(2), N(1)···N(2)
2.808(2); N(1)–C(1)–C(10) 120.87(14), N(2)–C(9)–C(10) 120.16(13),
C(9)–C(10)–C(1) 125.31(14); N(1)–C(1)–C(2)–C(3) 174.30(15), C(7)–
C(8)–C(9)–N(2) 171.46(13), C(6)–C(5)–C(10)–C(1) 169.07(14).
2,7-Dialdehyde 9 behaves towards the selected methylene-
active reagents in a similar manner. Its interaction with malono-
dinitrile and ethyl cyanoacetate provides dialkenes 10a,c,‡ which
under above mentioned conditions are easily converted into
quino[7,8:7',8']quinolines 11a,c. Reaction of 9 with dimedone,
as in the case of 5, produces compound 11b in a one-pot
process. All yields are near 98%.
donor ability of the peri-NMe2 groups. The suggested method
is synthetically useful for the construction of benzo[h]quinolines,
quino[7,8:7',8']quinolines and, possibly, other naphthalene-based
heterocyclic systems, including chiral compounds.
Me2N
NMe2
In summary, our study has disclosed an earlier unknown type
of proton sponge reactivity reflecting a rather high hydride
R
OHC
CHO H2C
R'
‡
All new structures gave correct analytical and spectral data. Some experi-
mental details and selected spectral characteristics [1H NMR (250 MHz),
IR (paraffin oil)] are as follows.
9
6c: A mixture of 5 (0.07 g, 0.29 mmol), tosylcyanomethane (0.057 g,
0.29 mmol) and piperidine (0.025 g, 0.29 mmol) in 4 ml of EtOH was
kept at room temperature for 24 h. Wine-coloured solid (0.106 g, 87%)
was filtered off, washed with cold EtOH and dried in vacuo. IR (n/cm–1):
2211 (CºN). 1H NMR (CDCl3) d: 2.44 (s, 3H, CMe), 2.73 (s, 6H,
8-NMe2), 3.21 (s, 6H, 1-NMe2), 7.03 (dd, 1H, H-7, 3J 7.4 Hz, 2J 1.4 Hz),
Me2N
NMe2
R
R
R'
R'
10a–c
3
7.28–7.41 (m, 5H, H-3,5,6,3',5'), 7.79 (d, 1H, H-4, J 8.8 Hz), 7.89 (d,
2H, H-2',6', 3J 8.4 Hz), 8.38 (s, 1H, –CH=). On heating the crystals are
discoloured at 140–145 °C without melting due to a conversion into 8c.
8c: Method A. A sample of 6c (0.07 g, 0.17 mmol) was heated in an
argon atmosphere at 140–180 °C until full discolouration. Slightly beige
crystals, mp 219–221 °C (from MeOH). Yield 0.063 g (90%). IR (n/cm–1):
2231 (CºN). 1H NMR (CDCl3) d: 2.51 (s, 3H, 4'-Me), 2.63 (br. s, 3H,
10-NMe2a), 2.85 (br. s, 3H, 10-NMe2b), 2.99 (s, 3H, 1-NMe), 3.16 (dd,
1H, 4-CH2c, 2J 16.4 Hz, 4J 2.2 Hz), 3.75 (d, 1H, 4-CH2d, 2J 16.4 Hz), 3.89
(br. d, 1H, 2-CH2a, 2J 13.3 Hz), 4.03 (br. d, 1H, 2-CH2b, 2J 13.3 Hz),
6.92–7.00 (m, 2H, H-5,9), 7.28–7.34 (m, 3H, H-6,7,8), 7.49 (d, 2H,
H-3',5', 3J 8.2 Hz), 7.97 (d, 2H, H-2',6', 3J 8.2 Hz).
Hb Ha
Ha Hb
R
R
Me
R'
Hd
Hc
N
N
R'
Hd
Me
Hc
11a–c
a R = R' = CN
Ha
Ha
O
Method B. A solution of 6c (0.07 g, 0.17 mmol) in DMSO (3 ml) was
kept at room temperature for 48 h. After vacuum evaporation of the
solvent, a pure sample of 8c (0.07 g, 100%) was obtained.
Hb
Meb
b R + R' =
O
Hb
Mea
10a: A mixture of dialdehyde 9 (0.07 g, 0.26 mmol), malonodinitrile
(0.019 g, 0.29 mmol) and piperidine (0.022 g, 0.26 mmol) in PhMe (8 ml)
was kept at room temperature for 24 h. The deposited wine-coloured
crystals of 10a (0.084 g, 88%) were filtered off and washed with cold
(0 °C) toluene (3 ml) to give pure compound. IR (n/cm–1): 2219, 2193
c R = CN, R' = CO2Et
Scheme 3
1
§
(CºN). H NMR (CDCl3) d: 3.25 (s, 12H, NMe2), 7.39 (d, 2H, H-3,6,
X-ray diffraction data. Crystals of 8a (obtained by slow evaporation of
3J 8.8 Hz), 7.85 (s, 2H, –CH=), 7.92 (d, 2H, H-4,5, 3J 8.8 Hz). On
heating the crystals are discoloured between 145–155 °C converting,
without melting, into 11a.
saturated solution of 8a in n-hexane, C18H18N4, M = 290.36) are mono-
clinic, space group P21/c, at 100 K: a = 7.1632(5), b = 12.3083(9) and
c = 17.4259(11) Å, V = 1517.12(18) Å3, Z = 4, dcalc = 1.271 Mg m–3,
m(MoKα) = 0.078 mm–1, F(000) = 616. Intensities of 4923 reflections
were measured with a CAD4 Enraf-Nonius diffractometer [l(MoKα) =
= 0.71072 Å, q/2q-scans, 2qmax = 27.99°] and 4420 independent reflec-
tions (Rint = 0.0294) were used in a further refinement. The refinement
converged to wR2 = 0.0911 and GOF = 1.014 for all independent reflec-
tions [R1 = 0.0480 was calculated against F for 2959 observed reflections
with I > 2s(I)]. All calculations were performed using SHELXTL PLUS 5.0.
CCDC 758607 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2010.
11a: Method A. Dialkene 10a (0.07 g, 0.19 mmol) was heated under
argon at 145–155 °C until full discolouration. This gave 0.067 g (96%)
of 11a with mp 251–253 °C (from MeOH). IR (n/cm–1): 2251 (CºN).
1H NMR (CDCl3) d: 3.03 (s, 6H, NMe), 3.66 (br. d, 4H, 4-CH2, 9-CH2,
2J 13.3 Hz), 3.84 (m, 2H, 2-CH2a, 11-CH2a), 4.07 (m, 2H, 2-CH2b,
11-CH2b), 7.07 (d, 2H, H-5,8, 3J 8.4 Hz), 7.38 (d, 2H, H-6,7, 3J 8.4 Hz).
Method B. A solution of 10a (0.07 g, 0.19 mmol) in 3 ml of DMSO
was kept at room temperature for 48 h, providing after evaporation of the
solvent pure 11a (0.07 g, 100%).
For characteristics of compounds 6d, 8a,b,d,e, 10c and 11b,c, see
Online Supplementary Materials.
– 37 –

Mendeleev Commun., 2010, 20, 36–38
3 (a) C. Zhang, S. Murarka and D. Seidel, J. Org. Chem., 2009, 74, 419;
We are grateful to Dr. Z. A. Starikova (A. N. Nesmeyanov
Institute of Organoelement Compounds of the Russian Academy
of Sciences, Moscow) for performing the X-ray diffraction
study of compound 8a. This work was supported by the Russian
Foundation for Basic Research (grant no. 08-03-00028).
(b) S. Murarka, C. Zhang and D. Seidel, Org. Lett., 2009, 11, 129.
4 L. A. Kurasov, A. F. Pozharskii and V. V. Kuz’menko, Zh. Org. Khim.,
1983, 19, 859 (in Russian).
5 H. A. Staab and T. Saupe, Angew. Chem., Int. Ed. Engl., 1988, 27, 865.
6 A. F. Pozharskii, A. V. Degtyarev, O. V. Ryabtsova, V. A. Ozeryanskii,
M. E. Kletskii, Z. A. Starikova, L. Sobczyk and A. Filarowski, J. Org.
Chem., 2007, 72, 3006.
Online Supplementary Materials
7 I. Rodriguez, G. Sastre, A. Corma and S. Iborra, J. Catal., 1999, 183, 14.
8 N. V. Vistorobskii and A. F. Pozharskii, Zh. Org. Khim., 1991, 27, 1543
(in Russian).
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2010.01.014.
References
1 O. V. Ryabtsova, A. F. Pozharskii, A. V. Degtyarev and V. A. Ozeryanskii,
Mendeleev Commun., 2006, 313.
2 O. Meth-Cohn and H. Suschitzky, Adv. Heterocycl. Chem., 1972, 14, 211.
Received: 19th August 2009; Com. 09/3380
– 38 –