2-α-hydroxybenzhydryl- and 2,7-di(α-hydroxybenzhydryl)-1,8- bis(dimethylamino)naphthalenes: The first examples of stabilization of in/out proton sponge conformers by intramolecular hydrogen bonding. The most flattened amino group ever participating in IHB

Article abstract of DOI:10.1016/j.tetlet.2005.04.045

2-(α-Hydroxybenzhydryl)- 6 and 2,7-di(α-hydroxybenzhydryl)-1,8- bis(dimethylamino)naphthalenes 8 have been shown to exist in crystals as in/out conformers stabilized by O-H?N intramolecular hydrogen bonding. In agreement with X-ray studies, the NMR data a

Full text of DOI:10.1016/j.tetlet.2005.04.045

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3973–3976
2-a-Hydroxybenzhydryl- and 2,7-di(a-hydroxybenzhydryl)-1,8-
bis(dimethylamino)naphthalenes: the first examples of stabilization
of in/out proton sponge conformers by intramolecular hydrogen
bonding. The most flattened amino group ever participating in IHB
Alexander F. Pozharskii,a,* Oksana V. Ryabtsova,a Valery A. Ozeryanskii,a
Alexander V. Degtyarev,a Zoya A. Starikova,b Lucjan Sobczykc and Alexander Filarowskic
aDepartment of Chemistry, Rostov State University, Zorge 7, 344090 Rostov-on-Don, Russian Federation
bA.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, 119991 Moscow,
Russian Federation
cFaculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
Received 28 January 2005; revised 7 April 2005; accepted 12 April 2005
Abstract—2-(a-Hydroxybenzhydryl)- 6 and 2,7-di(a-hydroxybenzhydryl)-1,8-bis(dimethylamino)naphthalenes 8 have been shown
to exist in crystals as in/out conformers stabilized by O–Hꢀ ꢀ ꢀN intramolecular hydrogen bonding. In agreement with X-ray studies,
the NMR data are also consistent with 7 retaining its in/out form in solution, whilst for 8 superimposed equilibrating in/out–out/in
conformers are observed.
ꢀ 2005 Elsevier Ltd. All rights reserved.
It is known that strong steric and electronic repulsion of
peri-NMe2 groups in 1,8-bis(dimethylamino)naphtha-
lene (proton sponge) 1 (Scheme 1) results not only in
exceptionally high basicity (pKa = 12.1, H2O, 25 ꢁC)
but also in severe distortion of the molecular structure.1
Thus, the naphthalene ring in 1 loses its planarity and
the NMe2 groups adopt the in/in (trans) conformation
shown in Scheme 2a.2 Two specific features of this form
are: (1) division of the N-methyl groups into two sorts,
one lying approximately in the ring plane and the other
perpendicular to it, and (2) orientation of the axes of the
non-bonded electron pairs into the inter-nitrogen space
and at opposite sides (trans) of the mean ring plane. This
conformation is also typical for many other proton
sponges.1b,c
Recently, we disclosed that dramatic structural changes
take place in derivatives of compound 1 bearing bulky
Me
Me
Me
Me
Me N
NMe
2
Me
2
Me
Me
Me
O
H
H
H
R
R
N
N
O
O
N
N
R
Ph
Ph
Ph
Ph
Ph
Ph
for 8
1 R = H
2 R = I
8a
6 R = H
7 R = Br
8 R = C(OH)Ph
3 R = SMe
4 R = SiMe
5 R = Br
3
2
Scheme 1.
*
Corresponding author. Tel./fax: +7 8632975146; e-mail addresses: apozharskii@chimfak.rsu.ru; vv_ozer2@chimfak.rsu.ru
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.045

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A. F. Pozharskii et al. / Tetrahedron Letters 46 (2005) 3973–3976
Scheme 2. Possible dimethylamino group conformations in naphthalene proton sponges (white rectangles stand for side view of the mean ring plane).
substituents in positions 2 and 7 (ortho).3 For example,
in diiodide 2 and di(sulfide) 3 both the nitrogen atoms
are nearly planar and the NMe2 groups are almost per-
pendicular to the ring plane which, unlike that in 1, re-
tains its planarity. This conformation was named in/in
(in plane) since the nitrogen pyramids remain slightly di-
rected towards each other and the almost pure p-orbitals
of the unshared electron pairs lie in the ring plane
(Scheme 2b). Even bigger changes occur in the 2,7-
bis(trimethylsilyl) derivative 4 for which the in/out con-
formation was registered for the first time (Scheme 2c),
though the Ôout-nessÕ of the inverted NMe2 group was
relatively small (the sum of the valency angles at the Ôin-
vertedÕ nitrogen atom equals 355.3ꢁ).3 Presumably, reali-
zation of the in/out form in the case of 4 is caused by
spatial repulsion exerted by the extraordinary bulkiness
of the trimethylsilyl group and by the relatively weak
n ! d interaction between the nitrogen and silicon
atoms.
Alcohols 6–8 were obtained in good yields from the
corresponding bromides (e.g., 5), which were treated
successively with n-butyllithium and benzophenone (see
General procedure for details).9 For alcohols 6 and 8,
single crystal X-ray measurements were conducted at
115 K.10 As expected, both compounds exist in the solid
state as in/out conformers fixed by O–Hꢀ ꢀ ꢀN hydrogen
bonding (Figs. 1 and 2).
˚
˚
The Nꢀ ꢀ ꢀN distances (6: 2.921 A; 8: 2.915 A) are very
˚
close to that of 4 (2.925 A) and are significantly larger
2b
˚
than in the parent sponge 1 (2.804 A at 100 K ).
Undoubtedly, the methyls of the inverted nitrogen atom
arranged between the amine nitrogens cause this
enlargement. The IHB in molecules 6 and 8 has several
peculiarities. Firstly, the sum of the valence angles at
their inverted nitrogens lie in the range of 350–351ꢁ
against 355ꢁ for compound 4. This means that the
Ôout-nessÕ of the chelated NMe2 group in 6 and 8
is somewhat higher and therefore the IHB provides
a stronger stabilization of the in/out form than the
n,d-interaction in 4. Secondly, the IHB in 6 (\O–
From the above, one could assume that the in/out
conformation might be more strongly stabilized via
other types of interactions, such as intramolecular
hydrogen bonding (IHB) or charge-transfer complexes.
To check this assumption, in the present work we have
prepared and studied alcohols 6–8 containing a-hydroxy-
benzhydryl groups in the ortho-positions of the parent
proton sponge 1.
Hꢀ ꢀ ꢀN = 152.3ꢁ) and especially in diol
8
(\O–
Hꢀ ꢀ ꢀN = 162.7ꢁ) tends to be more linear than in the ani-
line counterparts 9a,b (\O–Hꢀ ꢀ ꢀN = 145.0ꢁ and 150.9ꢁ,
respectively).4 Obviously, this is caused by the enhanced
planarity of the 1-NMe2 groups in the proton sponge
derivatives that provides better directionality of the lone
(a)
(b)
Figure 1. General view and atom numbering scheme for a molecule of alcohol 6 (a) and part of one of the endless chains along the b axis showing
intra- and intermolecular H-bonding between molecules of 8 (b).

A. F. Pozharskii et al. / Tetrahedron Letters 46 (2005) 3973–3976
3975
Figure 2. View of proton sponge molecules along the average ring plane with the amino groups closer to the viewer as wireframe CIF generated
models (without 2,7-substituents and hydrogens): 1 (a), 6 (b), 8 (c).
nitrogen electron pair axis towards the hydroxylic
hydrogen. Notably, the Cambridge Structural Database
contains no information on any other amines with such
planar amino groups involved in IHB of the O–Hꢀ ꢀ ꢀN
or N–Hꢀ ꢀ ꢀN type. Finally, the Nꢀ ꢀ ꢀO distances in com-
pounds 6 and 8 are also shorter than in aniline alcohols
9a,b, testifying the strength of IHB in the former.
dynamically equivalent at 298 K in either 1H or 13C
NMR spectra. One possible explanation would involve
a fast (on the NMR time scale) equilibration of the
two superimposed in/out conformers, 8 and 8a, taking
place in solution at ambient temperature (Scheme 1).
Clear-cut evidence for this equilibration is the shift
of the two-proton peak for the OH-groups to dH
6.94 ppm, that is, between the OH-signals for
compounds 6 and 10. However, there is another way
to explain the equivalence of the two half-moieties of
compound 8 based on the interconversion of the
NMe2 groups, which should be an extremely fast pro-
cess. In such a case, both OH groups would be oriented
towards the nitrogen atoms, but the lone electron pairs
are engaged in hydrogen bond formation, either to
one, or to another OH group. Full explanation of the
process requires additional studies, which are presently
underway.
Me N
NMe
2
R
2
H
R
N
O
Ph
Ph
Ph
Ph
HO
10
9a R = Me
9b R = Et
The intramolecular O–Hꢀ ꢀ ꢀN hydrogen bonds in both 6
and 8 with participation of the inverted dimethylamino
group are characterized by a broad IR band of low
intensity in the region 2500–3000 cmꢁ1 (solid state).
The red shift of this band correlates with its length
Acknowledgements
This work was supported by the Russian Foundation
for Basic Research (grant RFBR 05-03-32110).
˚
˚
(2.626 A for 6 and 2.613 and 2.599 A for 8—two inde-
pendent molecules in the unit cell). The low intensity
of the intramolecular m(OHꢀ ꢀ ꢀN) IR band can be
explained in terms of a geometrical effect:5 in our case
the hydrogen bond is markedly bent. Also one cannot
exclude some coupling between the motion of the proton
and the electrons as postulated by Witkowski6 that
seems to be common in the, so-called, resonance-as-
sisted hydrogen bonds.7 The intermolecular O–Hꢀ ꢀ ꢀO
References and notes
1. (a) Alder, R. W. Chem. Rev. 1989, 89, 1215–1223; (b)
Llamas-Saiz, A. L.; Foces-Foces, C.; Elguero, J. J. Mol.
Struct. 1994, 328, 297–323; (c) Pozharskii, A. F. Russ.
Chem. Rev. 1998, 67, 1–24.
2. (a) Einspahr, H.; Robert, J.-B.; Marsh, R. E.; Roberts, J.
D. Acta Crystallogr. 1973, B29, 1611–1617; (b) Mallinson,
P. R.; Wozniak, K.; Wilson, C. C.; McCormack, K. L.;
Yufit, D. S. J. Am. Chem. Soc. 1999, 121, 4640–4646.
3. Pozharskii, A. F.; Ryabtsova, O. V.; Ozeryanskii, V. A.;
Degtyarev, A. V.; Kazheva, O. N.; Alexandrov, G. G.;
Dyachenko, O. A. J. Org. Chem. 2003, 68, 10109–10122.
4. Al-Masri, H. T.; Sieler, J.; Lo¨nnecke, P.; Blaurock, S.;
Domasevitch, K.; Hey-Hawkins, E. Tetrahedron 2004, 60,
333–339.
˚
hydrogen bonds in 8 (of 2.769 A) show usual behaviour
and are characterized by an intense IR band located at
ca. 3330–3340 cmꢁ1. The formation of intramolecular
O–Hꢀ ꢀ ꢀN hydrogen bonds is also well evidenced by a
drop in the intensity of the Bohlman bands of the
m(C–H) vibrations located at ca. 2780 and 2825 cmꢁ1
.
1
It follows from H and 13C NMR spectra that com-
pounds 6 and 7 also retain their in/out forms stabilized
by IHB in solution. In fact, the OH-proton peak, in both
alcohols, is situated near dH 10.5 ppm, whereas in the
spectrum of 4-(a-hydroxybenzhydryl)-1,8-bis(dimethyl-
amino)naphthalene 108 where there is no possibility
of forming IHB, the signal is much more upfield (d
3.42 ppm). It should be emphasized that both the
NMe2 and C(OH)Ph2 groups, as well as the meta- and
para-protons of the naphthalene core of diol 8 are
5. Filarowski, A.; Koll, A. Vib. Spectrosc. 1998, 17, 123.
6. Witkowski, A. Phys. Rev. 1990, 41A, 3511.
`
´
7. Alkorta, I.; Elguero, J.; Mo, O.; Yan˜ez, M.; Del Bene,
J. E. Mol. Phys. 2004, 102, 2563.
8. Pozharskii, A. F.; Ryabtsova, O. V.; Vistorobskii, N. V.;
Starikova, Z. A. Russ. Chem. Bull. 2000, 49, 1097–1102.
9. General procedure for the preparation of 6–8. To a
solution of dibromide 5 (0.200 g, 0.54 mmol) in dry ether
(3 mL) cooled to ꢁ30 ꢁC, a 1.6 M hexane solution of
BunLi (0.34 mL, 0.54 mmol) was added. The solution of
the monolithium derivative thus formed was treated with a

3976
A. F. Pozharskii et al. / Tetrahedron Letters 46 (2005) 3973–3976
solution of benzophenone (0.098 g, 0.54 mmol) in dry
2-(a-Hydroxybenzhydryl)-7-bromo-1,8-bis(dimethylamino)-
naphthalene (7): 1H NMR (250 MHz, CDCl3, 25 ꢁC)
d/ppm: 2.54 (s, 6H, NMe2), 2.83 (s, 6H, NMe2), 6.80–8.55
(d, 1H, H-3), 7.33–7.79 (m, 13H, H-4, H-5, H-6, Ph), 10.42
(s, 1H, OH).
ether (2 mL) at ꢁ30 ꢁC. The reaction mixture was kept for
20 min at ꢁ30 ꢁC and then for 40 min at 20 ꢁC before
being poured into water (10 mL). The organic layer was
separated and the water layer was extracted with ether
(3 · 3 mL). The combined organic extracts were dried over
Na2SO4, evaporated to dryness and the residue was
purified by PTLC on Al2O3 yielding 80% of bromoalcohol
7 as a yellowish oil.
2,7-Di(a-hydroxybenzhydryl)-1,8-bis(dimethylamino)naph-
thalene (8): 1H NMR (250 MHz, CDCl3, 25 ꢁC) d/ppm:
2.43 (s, 12H, NMe2), 6.66–8.78 (d, 2H, H-3, H-6), 6.94 (s,
2H, OH, exchangeable with D2O), 7.13–7.28 (m, 22H, H-
4, H-5, Ph). 13C NMR (125 MHz, CD2Cl2, 25 ꢁC) d/ppm:
44.95, 83.83, 124.10, 127.35, 128.05, 128.54, 129.81,
132.81, 136.47, 142.65, 147.80, 150.01. IR (fluoroluble
suspension)m/cmꢁ1: 3333, 3083, 3057, 3022, 3003, 2989,
2955, 2924, 2867, 2835, 2801, 2784, 1599, 1582, 1522, 1504,
1490, 1445, 1368, 1353. IR (CCl4)m/cmꢁ1: 3608, near 3100
(broad band), 3086, 3062, 3025, 2929, 2904, 2807, 1492,
1447, 1370, 1312, 1172, 1096, 1054, 1033, 1024, 931, 892,
654, 640, 596, 550. IR (CD2Cl2) m/cmꢁ1: 3592, near 3050
(broad band), 3086, 3063, 3026, 2929, 1600, 1583, 1523,
1490, 1447, 1318, 1232, 1172, 1102, 840.
This procedure was repeated with 2 equiv of n-BuLi to
give 21% of 6 as pale-yellow crystals with mp 154.5–
155.5 ꢁC (from hexanes); with 2 equiv of both n-BuLi and
benzophenone, a 15% yield of 8 was obtained as yellowish
crystals with mp 273 ꢁC (from CHCl3). Compounds 6–8
gave analytical and spectral data consistent with their
structures. The NMR and IR data are as follows.
2-(a-Hydroxybenzhydryl)-1,8-bis(dimethylamino)naphtha-
1
lene (6): H NMR (250 MHz, CDCl3, 25 ꢁC) d/ppm: 2.56
(s, 6H, NMe2), 2.57 (s, 6H, NMe2), 6.77–8.49 Hz (d, 1H,
H-3), 7.22–7.37 (m, 12H, H-6, H-7, Ph), 7.40–8.48 (d, 1H,
H-4), 7.49–8.10 and 1.16 (dd, 1H, H-5), 10.56 (s, 1H, OH,
exchangeable with D2O). 13C NMR (125 MHz, CD2Cl2,
25 ꢁC) d/ppm: 43.40, 47.53, 83.71, 118.12, 125.56, 125.64,
126.14, 127.06, 127.89, 128.38, 128.57, 128.76, 136.96,
143.61, 146.06, 149.70, 152.66. IR (fluoroluble suspension)
m/cmꢁ1: 3082, 3058, 3018, 2995, 2980, 2928, 2854, 2827,
2783, 1595, 1582, 1551, 1503, 1478, 1459, 1444, 1433, 1372,
1350, 1334.
10. Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication numbers CCDC 248980–248981. Copies
of the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.cam.
ac.uk].