Experimental and theoretical studies on the nature of weak nonbonded interactions between divalent selenium and halogen atoms

Article abstract of DOI:10.1021/jo048436a

(Chemical Equation Presented). To investigate the nature of weak nonbonded selenium...halogen interactions (Se...X interactions; X = F, Cl, and Br), three types of model compounds [2-(CH₂X)C₆H ₄SeY (1-3), 3-(CH₂

Full text of DOI:10.1021/jo048436a

Experimental and Theoretical Studies on the Nature of Weak
Nonbonded Interactions between Divalent Selenium and Halogen
Atoms
Michio Iwaoka,*,† Takayuki Katsuda, Hiroto Komatsu, and Shuji Tomoda*
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba,
Meguro-ku, Tokyo 153-8902, Japan
miwaoka@tokai.ac.jp; tomoda@selen.c.u-tokyo.ac.jp
Received September 6, 2004
To investigate the nature of weak nonbonded selenium‚‚‚halogen interactions (Se‚‚‚X interactions;
X ) F, Cl, and Br), three types of model compounds [2-(CH2X)C6H4SeY (1-3), 3-(CH2X)-2-C10H6-
SeY (4-6), and 2-XC6H4CH2SeY (7-9); Y ) CN, Cl, Br, SeAr, and Me] were synthesized, and their
77Se NMR spectroscopic behaviors were analyzed in CDCl3. The gradual upfield shifts of 77Se NMR
absorptions observed for series 1-3 and 4-6 suggested that the strength of Se‚‚‚X interaction
decreases in the order of Se‚‚‚F > Se‚‚‚Cl > Se‚‚‚Br. The quantum chemical calculations at the
B3LYP/631H level using the polarizable continuum model (PCM) revealed that the most stable
conformer for 1-3 is the one with an intramolecular short Se‚‚‚X atomic contact in CHCl3 (ꢀ ) 4.9)
and also that the nX f σ*Se-Y orbital interaction (ESe‚‚‚X) can reasonably explain the order of strength
for the Se‚‚‚X interactions. On the other hand, the 77Se NMR absorptions observed for series 7-9
did not shift significantly from the reference compounds (C6H5CH2SeY), indicating the absence of
the Se‚‚‚X interaction for 7-9 presumably due to attenuation of basicity for the halogen atom that
is substituted directly to the aromatic ring. These observations suggested that the nX f σ*Se-Y
orbital interaction is a dominant factor for formation of weak Se‚‚‚X interactions. Electron correlation
was also suggested to be important for the stability.
Introduction
applied to asymmetric synthesis2 but also because they
may play an important role in the catalytic cycle of
glutathione peroxidase mimics.3 Moreover, the non-
bonded interactions would serve as potential analogues
to those involving a divalent sulfur (S) atom, which exists
commonly in biomolecules.4
The high reactivity of organoselenium reagents allows
the insertion of various functional groups to organic
compounds under mild conditions with high stereoselec-
tivity. For this reason, organoselenium chemistry has
been widely applied in the synthesis of various organic
compounds.1 In view of the molecular design of useful
selenium reagents, it is of valuable importance to inves-
tigate weak nonbonded interactions involving a divalent
selenium (Se) atom because the interactions should play
a role in the molecular recognition to a substrate as well
as in the molecular conformation. Nonbonded interac-
tions involving a divalent Se have also attracted much
attention not only because they have been successfully
We have recently succeeded in evaluation of nonbonded
interactions between Se and second-row atoms (N, O, and
(2) (a) Fujita, K.; Iwaoka, M.; Tomoda, S. Chem. Lett. 1994, 923-
926. (b) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. Tetrahedron
1997, 53, 2029-2048. (c) Fragale, G.; Wirth, T. Eur. J. Org. Chem.
1998, 1361-1369. (d) Fragale, G.; Neuburger, M.; Wirth, T. Chem.
Commun. 1998, 1867-1868.
(3) (a) Iwaoka, M.; Tomoda, S. J. Chem. Soc., Chem. Commun. 1992,
1165-1167. (b) Iwaoka, M.; Tomoda, S. J. Am. Chem. Soc. 1994, 116,
2557-2561. (c) Wirth, T.; Ha¨uptli, S.; Leuenberger, M. Tetrahedron:
Asymmetry 1998, 9, 547-550. (d) Mugesh, G.; Singh, H. B. Chem. Soc.
Rev. 2000, 29, 347-357. (e) Mugesh, G.; Panda, A.; Singh, H. B.;
Punekar, N. S.; Butcher, R. J. J. Am. Chem. Soc. 2001, 123, 839-850.
(f) Back, T. G.; Moussa, Z. J. Am. Chem. Soc. 2002, 124, 12104-12105.
(4) (a) Iwaoka, M.; Takemoto, S.; Okada, M.; Tomoda, S. Chem. Lett.
2001, 132-133. (b) Iwaoka, M.; Takemoto, S.; Okada, M.; Tomoda, S.
Bull. Chem. Soc. Jpn. 2002, 75, 1611-1625. (c) Iwaoka, M.; Takemoto,
S.; Tomoda, S. J. Am. Chem. Soc. 2002, 124, 10613-10620.
* To whom correspondence should be addressed.
† Current address: Department of Chemistry, School of Science,
Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292,
Japan.
(1) (a) Organoselenium Chemistry: A Practical Approach; Back, T.
G., Ed.; Oxford University Press: New York, 1999. (b) Organoselenium
Chemistry: Modern Developments in Organic Synthesis; Wirth, T., Ed.;
Springer-Verlag: Berlin, 2000.
10.1021/jo048436a CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/02/2004
J. Org. Chem. 2005, 70, 321-327
321

Iwaoka et al.
CHART 1
CHART 3
CHART 2
SCHEME 1
F).5-7 It was found that the strength of the interactions
decreases in the order of Se‚‚‚N > Se‚‚‚O > Se‚‚‚F as the
electron-donating ability of the second-row atom de-
creases. However, the general properties of the non-
bonded interactions between Se and heavy-row atoms
have not been well elucidated though such interactions
may be important for the excellent high asymmetric
induction reported by Tiecco and co-workers:8 The chiral
selenium reagent, which may possibly have an intramo-
lecular Se‚‚‚S interaction, exhibited much better asym-
metric yields than the corresponding chiral selenium
reagent with an Se‚‚‚O interaction. In our previous
paper,9 heavy-row atom effects on the strength of non-
bonded Se‚‚‚X (X ) F, Cl, and Br) interactions were
studied for the first time by use of series of 2-(halo-
methyl)benzeneselenenyl derivatives [2-(CH2X)C6H4SeY,
1-3] (Chart 1). The Se‚‚‚X interactions were suggested
to attenuate as the X atom goes down in the periodic
table. Herein, we present the full account on the
Se‚‚‚halogen interactions, including extended studies by
use of the naphthalene analogues [3-(CH2X)-2-C10H6SeY,
4-6] (Chart 2) and (2-halophenyl)methaneselenenyl
derivatives [2-XC6H4CH2SeY, 7-9] (Chart 3), which have
the halogen atom (X) and the selenenyl group (SeY)
interchanged in the parent compounds 1-3.
3a-e) were synthesized according to Scheme 1. Disele-
nide 2d was synthesized from bis[2-(hydroxymethyl)-
phenyl] diselenide (11) by use of thionyl chloride. Simi-
larly, diselnide 3d was prepared by the reaction of 11
with hydrobromic acid in acetic acid at 90 °C. Obtained
2d and 3d were then converted to selenenyl chlorides 2b
and 3b, selenenyl bromides 2c and 3c, and selenenyl
cyanides 2a and 3a, respectively, by common proce-
dures.5-7 Methyl selenides 2e and 3e were synthesized
from 11 by reductive methylation of the diselenide
linkage followed by halogenation of the hydroxyl group.
All compounds were identified with 1H, 13C, and 77Se
NMR spectra, although selenenyl chloride 3b was con-
taminated with a small amount of 2b and selenenyl
chloride 2b slowly decomposed to diselenide 2d at room
temperature. For these selenenyl chlorides, further pu-
rification was not performed because of the instability.
To investigate Se‚‚‚X (X ) F, Cl, and Br) interactions
in other series of compounds, 3-halomethyl-2-naphtha-
leneselenenyl derivatives (4a,d, 5a,d, and 6a,d) were also
synthesized from bis(3-hydroxymethy-2-naphthyl) di-
selenides (14), which was prepared from methyl 3-amino-
2-naphthoate (12), according to the similar procedures
to the syntheses of 1a,d, 2a,d, and 3a,d (Scheme 2). The
X-ray crystal structure of 6d have revealed that the
intramolecular nonbonded Se‚‚‚Br interaction really
exists though it should be very weak [rSe‚‚‚Br ) 3.7356(4)
Å].9
Results and Discussion
Synthesis of Model Compounds. 2-(Fluoromethyl)-
benzeneselenenyl derivatives (1a-e) have been fully
characterized in the literature.7 The other two series of
2-(halomethyl)benzeneselenenyl derivatives (2a-e and
The common procedures were also employed for the
syntheses of (2-halophenyl)methaneselenenyl derivatives
(7-9), which have X and SeY groups at the mutually
opposite sites upon the benzyl fragment of 1-3, and the
reference compounds 10 (Scheme 3). In these compounds,
the basicity of the halogen atom (X) is largely decreased,
compared with that in the parent compounds 1-3, due
to the resonance effect between the lone pair of the
halogen atom (nX) and the aromatic π electrons. Com-
pounds 7-10 were identified with 1H, 13C, and 77Se NMR
spectra, although phenylmethaneselenenyl bromide (10c)
(5) (a) Iwaoka, M.; Tomoda, S. Phosphorus, Sulfur Silicon Relat.
Elem. 1992, 67, 125-130. (b) Iwaoka, M.; Tomoda, S. J. Am. Chem.
Soc. 1996, 118, 8077-8084.
(6) (a) Komatsu, H.; Iwaoka, M.; Tomoda, S. Chem. Commun. 1999,
205-206. (b) Iwaoka, M.; Komatsu, H.; Katsuda, T.; Tomoda, S. J. Am.
Chem. Soc. 2004, 126, 5309-5317.
(7) (a) Iwaoka, M.; Komatsu, H.; Tomoda, S. Chem. Lett. 1998, 969-
970. (b) Iwaoka, M.; Komatsu, H.; Katsuda, T.; Tomoda, S. J. Am.
Chem. Soc. 2002, 124, 1902-1909.
(8) Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini, F.;
Bagnoli, L.; Temperini, A. Angew. Chem., Int. Ed. 2003, 42, 3131-
3133.
(9) Iwaoka, M.; Katsuda, T.; Tomoda, S.; Harada, J.; Ogawa, K.
Chem. Lett. 2002, 518-519.
322 J. Org. Chem., Vol. 70, No. 1, 2005

Weak Nonbonded Selenium‚‚‚Halogen Interactions
SCHEME 2
SCHEME 3
TABLE 1. 77Se NMR Data (δSe and JSe‚‚‚F) for
could not be obtained as a pure product probably due to
the high reactivity. Selenenyl chloride derivatives (Y )
Cl) were not synthesized because they are highly labile
and could not be obtained as pure materials.
2-(CH2X)C6H4SeY (1-3) and 3-(CH2X)-2-C10H6SeY (4-6)a
X ) F
X ) Cl
X ) Br
Y
compd
δSe
JSe‚‚‚F (Hz) compd δSe
compd δSe
77Se NMR Chemical Shifts. It is well established that
77Se NMR chemical shifts (δSe) are sensitive to the
environment around the Se atom.10 We recently demon-
strated that the magnitude of the downfield shift of 77Se
NMR can be used as a quantitative experimental probe
for the strength of nonbonded Se‚‚‚O interactions.11
Therefore, the δSe values observed for the model com-
pounds were analyzed to characterize the nature of
Se‚‚‚halogen interactions.
CN
1a
4a
1b
1c
1d
4d
1e
288.6b
84.2b
80.4
2a
5a
2b
2c
2d
5d
2e
284.1
285.6
966.5
798.2
442.2c
460.6
165.1
3a
6a
3b
3c
3d
6d
3e
280.0
282.1
956.1
788.6
437.0
459.6
165.2
289.6
Cl
Br
SeAr
978.5b
801.0b
437.3b
454.0
80.1b
43.1b
23.6b
19.0
Me
161.1b
22.7b
a 77Se NMR spectra were measured at 95.35 MHz in CDCl3 at
298 K with Me2Se as an external standard. b The data from ref 7.
c The data from ref 5a.
The 77Se NMR chemical shifts (δSe) observed for a
benzene series 1-3 and a naphthalene series 4-6 are
listed in Table 1 along with the values of JSe‚‚‚F coupling
constants observed for fluorine compounds 1a-e and
4a,d. As reported previously,7 the strength of the Se‚‚‚F
interaction for 1a and 1e is 1.23 and 0.85 kcal/mol,
respectively, in CD2Cl2, and the observation of the J
coupling between Se and F atoms is a direct experimental
evidence for the presence of an intramolecular Se‚‚‚F
interaction for 1a-e. Comparison of the JSe‚‚‚F values
suggested that the strength of the Se‚‚‚F interaction
decreases in the order a (Y ) CN) > b (Y ) Cl) > c (Y )
Br) > d (Y ) SeAr) > e (Y ) Me).
3a-e (X ) Br), it is clear that the 77Se NMR absorptions
(δSe) shift toward upfield (∆δSe < 0) with the periodic row
of halogen atom X going down, although those for
compounds d (Y ) SeAr) and e (Y ) Me) remain
approximately in the same position. Since the downfield
shift of δSe can be a good index for the strength of
nonbonded Se‚‚‚O interactions,11 the observed tendency
of δSe suggested that the strength of the Se‚‚‚X interac-
tions for a-c decreases in the order of Se‚‚‚F > Se‚‚‚Cl
> Se‚‚‚Br, while those for d and e would not change
significantly by the periodic row of X.
Almost the same argument can be applied to naph-
thalene analogues 4-6. Thus, the presence of the similar
Se‚‚‚X (X ) F, Cl, and Br) interactions was characterized
for 4-6.
The above considerations were reasonably supported,
at least in part, when the δSe values for series 1-3 were
compared with those for the corresponding reference
compounds (i.e., 2-MeC6H4SeY; Y ) CN, Cl, Br, SeAr,
When the 77Se NMR chemical shifts (δSe) for 1a-e
(X ) F) are compared with those for 2a-e (X ) Cl) and
(10) Luthra, N. P.; Odom, J. D. In The Chemistry of Organic
Selenium and Tellurium Compounds Volume 1; Patai, S., Rappoport,
Z., Eds.; John Wiley & Sons: Chichester, 1986; Chapter 6, pp 189-
241.
(11) Iwaoka, M.; Tomoda, S. Phosphorus, Sulfur Silicon Relat. Elem.,
submitted.
J. Org. Chem, Vol. 70, No. 1, 2005 323

Iwaoka et al.
TABLE 2. 77Se NMR Data (δSe and JSe‚‚‚F) for
2-XC6H4CH2SeY (7-10)a
7 (X ) F)
8 (X ) Cl) 9 (X ) Br) 10 (X ) H)
Y
δSe
JSe‚‚‚F (Hz)
δSe
δSe
δSe
a
c
CN
292.9
(295.7)b
1166.7
8.6
287.7
(284.7)b
1166.6
400.1
288.5
(285.0)b
1166.1
402.3
286.0
(291)c
Br
d
d
1167.4
405.7
d SeAr 406.1
FIGURE 1. Rapid equilibrium between three possible con-
formers A, B, and C for 1-3.
(395.1)b
168.1
(395.9)b
168.6
(401.4)b
172.8
e
Me
174.3
d
(173)c
observed. This suggested the presence of weak Se‚‚‚F
interaction for 7a in solution. However, the JSe‚‚‚F coupling
could not be detected for 7c-e.
a 77Se NMR spectra were measured at 95.35 MHz in CDCl3 at
298 K with Me2Se as an external standard. b The data from ref
12. c The data from ref 13. d The nuclear spin coupling was not
observed between 77Se and 19F.
Possible Conformers in Solution. Under the condi-
tions of NMR measurements (in CDCl3 at 298 K), 1-3
must attain an equilibrium among more than two con-
formers (Figure 1): Conformer A has close atomic contact
between Se and X with an almost linear X‚‚‚Se-Y atomic
alignment, conformer B has the C-X bond away from
the Se-Y bond, and conformer C has both the C-X and
Se-Y bonds titled out of the aromatic plane to the same
direction. The values of δSe observed for 1-3, therefore,
represent the weighted average of the δSe values over
these conformers: they should be affected by both the
relative stability of Conformer A to the other conformers
(∆EA) and the degree of the nonbonded Se‚‚‚X contact
[i.e., rrel ) rSe‚‚‚X/(vdwSe + vdwX), where rSe‚‚‚X is a non-
bonded distance between Se and X atoms and vdwX is
the van der Waals radius of X].
QC Calculations and the NBO Analysis. To inter-
pret the observed 77Se NMR data, quantum chemical
(QC) calculations were performed on 1-3 by using the
Gaussian 98 program package.14 The three possible
conformers (conformers A, B, and C) were reasonably
located for each model compound. For diselenide d (Y )
SeAr), the Ar group was simplified to a Me group to save
on computation time. As illustrated in Figure 2, the two
possible subconformers were further considered for con-
former A of d′ (Y ) SeMe): One has the SeMe group
tilted inward with respect to the aromatic plane (endo)
and the other has the SeMe group tilted outward (exo).
Similarly, endo and exo subconformers were defined for
conformers B and C. Relative energies (in kcal/mol) of
all possible conformers obtained for 1-3 both in vacuo
and in CHCl3 (ꢀ ) 4.9) are listed in Table 3.
and Me). Although only one δSe value was reported in
the literature for these references (δSe ) 162 for 2-MeC6H4-
SeMe10), those for others could be roughly estimated by
the following procedures. First, the δSe value for C6H5-
SeMe, which does not have a methyl substituent at the
ortho position, was 202.10 Second, comparison of the δSe
value with that for 2-MeC6H4SeMe (δSe ) 162) led to the
assumption that the 2-Me group causes about 40 ppm
upfield shift of 77Se NMR. Third, application of the same
substituent effect allowed estimation of the δSe values for
2-MeC6H4SeY (Y ) CN, Cl, Br, and SeAr) as 282, 1002,
829, and 424, respectively, by using the δSe values of 322,
1042, 869, and 464 reported for nonsubstituted C6H5SeY
(Y ) CN, Cl, Br, and SeAr).10 Thus, for the cases of
selenocyanates (a, Y ) CN) and diselenides (d, Y ) SeAr),
the presence of weak intramolecular Se‚‚‚X interactions
for series 1-3 is supported by the downfield shifts of 77Se
NMR with respect to the reference compounds, i.e.,
2-MeC6H4SeCN [δSe ) 282 (estimated)] and 2-MeC6H4-
SeSeC6H4(2-Me) [δSe ) 424 (estimated)]. For methyl
selenides (e, Y ) Me), the δSe values for 1-3e are not
essentially different from that for the reference, i.e.,
2-MeC6H4SeMe (δSe ) 162). This suggests that the Se‚‚‚X
interactions must be very weak. On the other hand, for
selenenyl chlorides (b, Y ) Cl) and selenenyl bromides
(c, Y ) Br), the 77Se NMR absorptions of 1-3 appear in
upfield with respect to the reference compounds, i.e.,
2-MeC6H4SeCl [δSe ) 1002 (estimated)] and 2-MeC6H4-
SeBr [δSe ) 829 (estimated)]. The reasons for the upfield
shifts of 77Se NMR, which may be inconsistent with the
presence of Se‚‚‚X interactions, are not clear. However,
we tentatively assume that the upfield shifts are due to
the effect of electron correlation, which should be small
for the reference compounds but would be large for 1-3.
The significance of electron correlation for formation of
weak Se‚‚‚halogen interactions is discussed later.
At the B3LYP/631H level (see the Experimental Sec-
tion for this abbreviation) in vacuo, conformer A with an
intramolecular Se‚‚‚X interaction was found to be ener-
getically lowest except for 1d′, 1e, 2e, and 3e: conformer
B-exo is the most stable conformer for diselenide 1d′
(∆EA ) +0.17 kcal/mol), and conformer C is a global
energy minimum for methyl selenides 1e, 2e, and 3e
(∆EA ) +0.03, +0.30, and +0.36 kcal/mol, respectively).
Table 2 lists the 77Se NMR data (δSe and JSe‚‚‚F
)
observed for 7-10 along with the literature values12,13
in parentheses. The values of δSe for 7-9 were almost
unchanged from the reference compounds 10 except for
7a, suggesting that the Se‚‚‚X interactions are not
present in this type of selenium compounds. Only for the
case of 7a, a significant downfield shift of δSe (∆δSe ) 6.9
ppm) and a small JSe‚‚‚F coupling (JSe‚‚‚F ) 8.6 Hz) were
(14) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.;
Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels,
A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.;
Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma,
K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.;
Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle,
E. S.; Pople, J. A. Gaussian 98; Gaussian, Inc.: Pittsburgh, PA, 1998.
(12) Fredga, A.; Gronowitz, S.; Ho¨rnfeldt, A.-B. Chem. Scr. 1975, 8,
15-19.
(13) Christiaens, L.; Piette, J.-L.; Laitem, L.; Baiwir, M.; Denoel,
J.; Llabre`s, G. Org. Magn. Reson. 1976, 8, 354-356.
324 J. Org. Chem., Vol. 70, No. 1, 2005

Weak Nonbonded Selenium‚‚‚Halogen Interactions
FIGURE 2. Two possible structures of conformer A for diselenides 1-3d′ (Y ) SeMe): (a) endo conformer, (b) exo conformer.
TABLE 3. Relative Energies of Three Possible Conformers Calculated for 1-3a
1 (X ) F)
CHCl3
2 (X ) Cl)
CHCl3
3 (X ) Br)
c
c
c
Y
conformer
vacuob
vacuob
vacuob
CHCl3
a
CN
A
0.00
1.21
3.66
0.00
0.51
3.70
0.00
1.14
2.91
0.17
0.62
0.82
0.00
0.74
1.85
0.03
0.23
0.00
0.00
1.44
2.36
0.00
0.83
2.96
0.00
1.45
2.16
0.00
0.36
1.14
0.39
0.74
1.44
0.00
0.63
0.48
0.00
1.41
2.01
0.00
0.49
1.16
0.00
d
1.13
0.00
0.44
d
0.00
1.80
1.09
0.00
1.11
1.04
0.00
d
1.03
0.00
1.10
d
0.00
d
1.66
0.00
d
1.19
0.00
d
0.00
d
1.05
0.00
d
1.22
0.00
d
B
C
b
c
Cl
A
B
C
Br
A
B
C
1.13
0.00
0.28
d
1.37
0.00
0.03
d
d′
SeMe
A-endo
A-exo
B-endo
B-exo
C-endo
C-exo
A
0.67
0.25
0.83
0.30
d
2.08
1.61
1.72
0.00
d
d
d
0.44
0.85
0.36
d
2.74
2.69
0.00
d
e
Me
B
C
0.00
0.20
0.00
0.28
a The values are given in kcal/mol. b The relative energies with unscaled zero-point energies (ZPE) calculated in vacuo at the B3LYP/
631H//B3LYP/631H level. c The relative energies calculated in CHCl3 at the B3LYP/631H (SCRF ) PCM, solvent ) CHCl3)//B3LYP/
631H level with the same ZPE as in vacuo. d Optimized structures could not be located.
TABLE 4. Selected Structural Parameters and nX
f
The unique character of the methyl selenides may be due
to intramolecular C-H‚‚‚Se and C-H‚‚‚X hydrogen bonds
as discussed previously.7b In contrast, it was found that
conformer A is always most stable at the B3LYP/631H
(SCRF ) PCM) level using Tomasi’s polarizable con-
tinuum model (PCM)15 in CHCl3 solution (ꢀ ) 4.9),
suggesting that conformer A must be a major conformer
for all compounds under the conditions of NMR measure-
ments. Thus, the δSe values for 1-3 (Table 1) would be
mostly reflected by the degree of the nonbonded Se‚‚‚X
contact (rrel), i.e., the strengths of the Se‚‚‚X interactions.
Structural parameters obtained for conformer A of
model compounds 1-3 are summarized in Table 4. It is
obvious that the smaller the relative nonbonded Se‚‚‚X
atomic distance to the sum of the van der Waals radii
(rrel), the more linear the nonbonded X‚‚‚Se-Y angle
(θX‚‚‚Se-Y) and the smaller the dihedral angle between the
aromatic plane and the CH2-X bond (ωAr-C). Although
the extent of the atomic contact was only marginal
especially for 2a-e and 3a-e, the tendency suggested
the presence of linear and weak X‚‚‚Se-Y interactions.
Indeed, the X-ray structure of 6d has shown a small but
distinct Se‚‚‚Br atomic contact as described earlier.9 It
is also important to note that the rrel values obtained at
the Hartree-Fock level were significantly larger than
σ*SeY Orbital Interaction Energies (ESe‚‚‚X) Obtained for
Conformer A’s of 1-3a
b
d
e
f
rSe‚‚‚X
(Å)
θX‚‚‚Se-Y ωAr-C
ESe‚‚‚X
c
X
compd
Y
rrel
(deg)
(deg) (kcal/mol)
F
1a
1b
1c
1d′
1e
2a
2b
2c
2d′
2e
3a
3b
3c
3d′
3e
CN
2.79 0.83
2.69 0.80
2.76 0.82
168.8
170.7
168.6
171.4
169.6
165.9
132.2
129.8
165.1
168.7
166.3
122.7
125.1
165.7
170.0
49.4
47.0
51.2
55.9
58.1
72.9
85.4
87.1
79.1
80.2
76.6
92.6
91.2
81.7
83.7
4.33
7.03
5.71
2.68
1.89
1.96
0.27
0.18
1.00
0.62
1.82
0.12
0.16
1.03
0.67
Cl
Br
SeMeg 2.94 0.87
Me
CN
Cl
2.99 0.89
3.48 0.95
3.86 1.06
3.89 1.07
Cl
Br
SeMeg 3.65 1.00
Me
CN
Cl
3.68 1.01
3.65 0.97
4.13 1.10
4.09 1.09
Br
Br
SeMeg 3.80 1.01
Me
3.85 1.03
a The geometry optimization and NBO analysis were carried
out at the B3LYP/631H level. See Figure 1 for the definition of
conformer A. b Nonbonded Se‚‚‚X atomic distances. c Nonbonded
Se‚‚‚X atomic distances normalized by the sum of the van der
Waals radii (vdwSe + vdwX): Se‚‚‚F 3.37 Å; Se‚‚‚Cl 3.65 Å; Se‚‚‚Br
3.75 Å. d The X‚‚‚Se-Y angles. e The dihedral angles along the
Ar-CH2X bond. f The second-order perturbation energies due to
the nX f σ*SeY orbital interaction. g Data for the endo conformer.
those obtained at the B3LYP level. This strongly suggests
that the electron correlation plays significant roles in the
stability of Se‚‚‚X interactions.
(15) Miertus, S.; Scrocco, E.; Tomasi, J. Chem. Phys. 1981, 55, 117-
129.
J. Org. Chem, Vol. 70, No. 1, 2005 325

Iwaoka et al.
To evaluate the magnitude of the Se‚‚‚X orbital inter-
action, natural bond orbital (NBO) analysis16 was per-
formed for conformers A’s. The calculated NBO second-
order perturbation energies due to the nX f σ*Se-Y orbital
interaction (ESe‚‚‚X) are listed in the last column of Table
4. The ESe‚‚‚X values decreased in the order of 1 > 2 ≈ 3
for all substituents Y. The trend is not only in accord with
the benzene ring, also supports importance of the nX f
σ*Se-Y orbital interaction.
It should be noted that the effect of electron correlation
is also important for the stability of Se‚‚‚halogen interac-
tions because the nonbonded Se‚‚‚F7b and Se‚‚‚O6b atomic
distances were significantly longer at the Hartree-Fock
level which does not include the effect of electron cor-
relation sufficiently. On the other hand, the effect of
structural constraints (e.g., the difference in the C-X
bond lengths) would be small because the QC calculations
at B3LYP/631H level revealed that the values of rrel for
the bimolecular complex between CH3X and PhSeCl were
0.84, 0.94, and 0.95 for the CH3F, CH3Cl, and CH3Br
complexes, respectively,9 reproducing the tendency of the
rrel values calculated for 1-3 (see Table 4).
the tendency of the structural parameters (rrel, θX‚‚‚Se-Y
,
and ωAr-C) but also consistent with the tendency of 77Se
NMR chemical shifts observed for 1-3, except for the
cases of d and e. As to the δSe values for d and e,
contributions from the other conformers than Conformer
A may be significant (Table 3).
The Nature of Se‚‚‚X Interactions. According to the
NMR analysis and QC calculations, it is proved that the
linear (or hypervalent) Se‚‚‚halogen interactions are very
weak in general, but there is the distinct tendency that
the interaction gets weaker as the interacting halogen
atom (X) gets heavier; i.e., Se‚‚‚F > Se‚‚‚Cl > Se‚‚‚Br.
The tendency seems to be simply explained by the
electrostatic character of the Se‚‚‚X interactions at a
glance. However, more elaborate considerations should
be required for understanding the nature of the interac-
tions.
The electrostatic hypothesis should not work for sev-
eral reasons. First, even for the case of Se‚‚‚F interaction
characterized for 1a-e,7 it has been clearly demonstrated
on the basis of the observed marginal polar solvent effects
that the major stabilization factor is not the electrostatic
interaction between a positively charged Se and a nega-
tively charged F atom but the nX f σ*Se-F orbital
interaction. Second, the relative stability of conformer A
(∆EA), which has an intramolecular Se‚‚‚X interaction,
with respect to the other conformers increases in CHCl3
from that in vacuo (see Table 3). This is opposed to the
electrostatic hypothesis because conformer A must be
destabilized in CHCl3 if the electrostatic character is
important. Third, the δSe values for 7-9 are almost
unchanged from the reference compounds 10, suggesting
that the Se‚‚‚X interactions are not present for the model
compounds that have the SeY and X groups interchanged
upon the benzyl fragment of 1-3. Since the atomic
charges of the Se and X atoms should not change largely
by the replacement, contribution from the other factors
than the electrostatic one is strongly suggested to the
stability of the Se‚‚‚X interactions.
On the other hand, the nX f σ*Se-Y orbital interaction
can reasonably explain the tendency of strength for the
Se‚‚‚X interactions. It has recently been demonstrated
that the basicity of organic halides decreases as the X
goes from F to Br.17 The data of ESe‚‚‚X listed in Table 4
are in accord with the order of the basicity. We suggest
that the basicity of the heavier halogen atom is reduced
by the larger exchange repulsions between the lone pairs
of the Se atom and those remained on the halogen atom.
This would result in the weaker nX f σ*Se-Y orbital
interaction although the energy level of the nX orbital is
higher for the heavier atom. In addition, absence of Se‚‚‚X
interactions for 7-9, whose halogen atom possesses
significantly reduced basicity due to the resonance with
Conclusions
The nature of nonbonded Se‚‚‚halogen interactions
were investigated by using three types of model com-
pounds: 2-(CH2X)C6H4SeY (1-3), 2-(CH2X)C10H6SeY (4-
6), and 2-XC6H4CH2SeY (6-8). The 77Se NMR analyses
and the theoretical calculations revealed the following
points.
1. On the basis of the 77Se NMR analysis of model
compounds 1-3, the strength of the Se‚‚‚X interactions
decreases in the order of Se‚‚‚F > Se‚‚‚Cl > Se‚‚‚Br.
2. The similar Se‚‚‚X interactions can be characterized
for 4-6 by comparison of the 77Se NMR chemical shifts.
3. QC calculations of 1-3 at the B3LYP/631H level
using the polarizable continuum model (PCM) in CHCl3
solution (ꢀ ) 4.9) suggested that conformer A with an
intramolecular Se‚‚‚X interaction is the most stable
conformer in the solutions.
4. The order of the strength, i.e., Se‚‚‚F > Se‚‚‚Cl >
Se‚‚‚Br, is consistent with the NBO second-order pertur-
bation energies due to the nX f σ*Se-Y orbital interaction
(ESe‚‚‚X) calculated for 1-3.
5. With much lower halogen basicity, Se‚‚‚X interac-
tions do not exist for 7-9, except for 7a.
6. Electron correlation should also play an important
role in the weak nonbonded Se‚‚‚X interactions.
According to these considerations, it can be concluded
that the strength of Se‚‚‚X interactions decreases as the
X atom goes down in the periodic table. The heavy-row
atom effect would be mainly attributed to the decrease
of basicity for heavier halogen atoms. The-heavier-the-
weaker rule found for Se‚‚‚halogen interactions will be
useful not only for molecular design of various types of
organoselenium compounds but also for understanding
other types of noncovalent interactions, in which a
halogen atom is involved as an electron donating group.
Experimental Section
General experimental methods and synthetic procedures for
1-10 are provided in the Supporting Information.
Calculation and NBO Analysis. All computational cal-
culations were carried out by using the Gaussian 98 program
package.14 Geometries were fully optimized with Beck’s three-
parameter hybrid functional method (B3LYP).20 Huzinaga’s
(16) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88,
899-926.
(17) Ouvrard, C.; Berthelot, M.; Laurence, C. J. Chem. Soc., Perkin
Trans. 2 1999, 1357-1362.
(18) Taffarel, E.; Chirayil, S.; Thummel. R. P. J. Org. Chem. 1994,
59, 823-828.
(19) Ichihara, J.; Matsuo, T.; Hanafusa, T.; Ando, T. J. Chem. Soc.,
Chem. Commun. 1986, 793-794.
326 J. Org. Chem., Vol. 70, No. 1, 2005

Weak Nonbonded Selenium‚‚‚Halogen Interactions
43321/4321/311 basis sets21 were used for Se and Br, and
standard 6-31G(d,p) basis sets were employed for other atoms.
Combination of these basis sets is denoted here as 631H.
Vibrational frequencies and zero-point energies (ZPE) were
also calculated. All structures were characterized as potential
energy minimums at the B3LYP/631H level by verifying that
all vibrational frequencies are real. Single-point energies with
ZPE were calculated at the same level in vacuo and at the
B3LYP/631H (SCRF ) PCM) level using Tomasi’s polarizable
continuum model (PCM)15 in the CHCl3 solution (ꢀ ) 4.9). To
evaluate the orbital interaction energy between the halogen
lone pair (nX) and the selenium antibonding orbital (σ*SeY),
NBO second order-perturbation analysis16 was performed at
the B3LYP/631H level by applying the value of 0.05 for the
eval parameter.
Acknowledgment. This work was supported by
Grants in Aid for Scientific Research Nos. 11120210 and
10133207 from the Ministry of Education, Science and
Culture, Japan.
Supporting Information Available: General experimen-
tal methods, synthetic procedures for 1-10, copies of 1H, 13C,
and 77Se NMR spectra for 2a-c,e, 3a-c,e, 5a, 6a, 7a,c,e, 8c,e,
9c,e, and 10c,e and Cartesian coordinates for conformers A-C
of 1a-e, 2a-e, and 3a-e and those for the bimolecular
complexes of PhSeCl with CH3F, CH3Cl, or CH3Br. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(20) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785-
789. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
(21) Gaussian Basis Sets for Molecular Calculations; Huzinaga, S.,
Ed.; Elsevier: Amsterdam, 1984.
JO048436A
J. Org. Chem, Vol. 70, No. 1, 2005 327