Formation of meso-1,2-bis(dimethylamino)-1,2-diphenylethane by oxidative C-C coupling reaction

Article abstract of DOI:10.1515/znb-2005-1011

The title compound was obtained from the reaction of N,N- dimethylbenzylamine with n-butyl lithium and sulfur in tetrahydrofuran at room temperature. Its molecular structure was investigated by means of single crystal X-ray diffraction and quantum chemica

Full text of DOI:10.1515/znb-2005-1011

Formation of meso-1,2-Bis(dimethylamino)-1,2-diphenylethane by
Oxidative C-C Coupling Reaction
Holger Fleischera and Dieter Schollmeyerb
a Institut fu¨r Anorganische Chemie und Analytische Chemie, Johannes Gutenberg-Universita¨t Mainz,
Duesbergweg 10 – 14, D-55099 Mainz
b Institut fu¨r Organische Chemie, Johannes Gutenberg-Universita¨t Mainz,
Duesbergweg 10 – 14, D-55099 Mainz
Reprint requests to Dr. H. Fleischer. Fax: (49) 6131 392 5336. E-mail: fleische@uni-mainz.de
Z. Naturforsch. 60b, 1083 – 1087 (2005); received August 1, 2005
The title compound was obtained from the reaction of N,N-dimethylbenzylamine with n-butyl
lithium and sulfur in tetrahydrofuran at room temperature. Its molecular structure was investigated
by means of single crystal X-ray diffraction and quantum chemical DFT methods. The formation of
meso-1,2-bis(dimethylamino)-1,2-diphenylethane is likely to be due to an unusual α-deprotonation
of N,N-dimethylbenzylamine, instead of the well known ortho-lithiation, with a subsequent oxida-
tive C-C coupling of the anions. Ab initio calculations of the corresponding α- and o-deprotonated
anions of N,N-dimethylbenzylamine showed the former to be more stable than the latter, due to de-
localisation of the negative charge over the π-system of the phenyl ring. The choice of solvent and
temperature is seen as the main reason for the unusual course of the reaction.
Key words: 1,2-Bis(dimethylamino)-1,2-Diphenylethane, C-C Coupling, Crystal Structure,
ab initio Calculation
Introduction
N,N-dimethylbenzylamine from the reaction of tri-n-
butyl[α-(dimethylamino)benzyl]stannane with n-BuLi
in hexane at 0 ◦C, and to investigate its molecular struc-
ture in the solid state [6].
C-C coupling reactions of benzaldehyde or benza-
mide derivatives are useful synthetic tools in order to
get 1,2-diamino-1,2-diphenylethane derivatives. See-
bach and co-workers reported on reductive C-C cou-
pling reactions of benzaldehyde and its derivatives by
low-valent Ti and VIV reagents to give N,N,Nꢀ,Nꢀ-
tetraalkyl-1,2-diarylethylenediamines [1]. Selvakumar
and Harrod developed a titanocene-catalyzed reduc-
tive amide coupling using organosilanes as reducing
agents [2].
Reaction of sulfur, selenium or tellurium with aryl
lithium or Grignard reagents is a suitable method for
the formation of C-E bonds (E = S, Se, Te) [7]. Sev-
eral o-lithiated benzyl derivatives were successfully
converted to the respective thiols [8], (di)selenides
or (di)tellurides [9]. We report a hitherto unknown
α-deprotonation of N,N-dimethylbenzylamine by n-
BuLi and the oxidative dimerization of the result-
ing anion to give meso-1,2-bis(dimethylamino)-1,2-
diphenylethane.
More than 40 years ago, Hauser and co-workers in-
vestigated the reaction of N,N-dimethylbenzylamine
with organometallic compounds. They reported that
n-BuLi exclusively deprotonates an o-position, while
sodium alkyls deprotonate the CH2-group, to give
the α-metallated product [3, 4]. On exchange of Na+
for Li+ a rearrangement with metallation of the o-
position takes place at slightly elevated tempera-
tures. Reich and co-workers investigated the solution
structure of the o-lithiated N,N-dimethylbenzylamine
and found several dimers to coexist at tempera-
tures below −55 ◦C [5]. Boche et al. succeeded
in isolating the diethylether adduct of α-lithiated
Results and Discussion
Formation of meso-1,2-bis(dimethylamino)-
1,2-diphenylethane
Addition of lithiated N,N-dimethylbenzylamineto a
suspension of sulfur in THF at −78 ◦C and acid workup
gives 2-((N,N-dimethylamino)methyl)thiophenol in
moderate to good yields, as was reported in the liter-
ature [8, 10] and confirmed in our own syntheses (see
Scheme 1). When the reaction was carried out in such
c
0932–0776 / 05 / 1000–1083 $ 06.00 ꢀ 2005 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
Unauthenticated
Download Date | 9/26/18 4:21 PM

1084
H. Fleischer – D. Schollmeyer · Formation of meso-1,2-Bis(dimethylamino)-1,2-diphenylethane
Table 1. Selected structural data of meso-1,2-bis(di-
methylamino)-1,2-diphenylethane from a single crystal XRD
experiment and B3LYP/6-31G(d) (designated as DFT) ge-
˚
ometry optimization. Distances are given in A, angles in
degree.a
XRD DFT
XRD DFT
117.3(3) 117.8
121.7(4) 121.4
119.8(4) 120.0
119.6(4) 119.4
120.6(4) 120.4
121.0(4) 121.1
119.2(3) 119.4
109.8(3) 110.6
113.5(3) 113.2
110.9(3) 111.4
116.1(3) 116.7
111.7(3) 113.4
C(1)-C(2) 1.370(4)1.402 C(2)-C(1)-C(6)
C(1)-C(6) 1.395(5)1.404 C(1)-C(2)-C(3)
C(1)-C(7) 1.528(4)1.531 C(4)-C(3)-C(2)
C(2)-C(3) 1.386(5)1.397 C(5)-C(4)-C(3)
C(3)-C(4) 1.378(6)1.394 C(4)-C(5)-C(6)
C(4)-C(5) 1.356(6)1.397 C(5)-C(6)-C(1)
C(5)-C(6) 1.383(5)1.394 C(2)-C(1)-C(7)
C(7)-N(8) 1.485(4)1.476 N(8)-C(7)-C(7)#1
C(7)-C(7)#1 1.526(6)1.556 C(7)#1-C(7)-C(1)
N(8)-C(10) 1.434(5)1.456 C(10)-N(8)-C(9)
N(8)-C(9) 1.456(4)1.456 C(10)-N(8)-C(7)
C(9)-N(8)-C(7)
C(2)-C(1)-C(7)-N(8) −93.8(4)−96.2
C(2)-C(1)-C(7)-C(7)#1 139.1(4) 135.7
C(1)-C(7)-N(8)-C(10) −60.5(4)−61.8
Scheme 1. Different reactions of N,N-dimethylbenzylamine
with n-BuLi / S8. Reaction conditions: i:◦ n-BuLi in hex-
ane/diethylether, 0 ◦C; ii: 1. S8, THF, −78 C, 2. HCl, 0 ◦C;
C(1)-C(7)-N(8)-C(9)
68.0(4) 69.7
◦
◦
iii: 1. S8, THF, 20 – 25 C, 2. HCl, 20 – 25 C. The dimeric
a
C-H bond lengths were fixed in the refinement of the XRD data:
structure of II is according to Reich et al. [5].
2 – 6
˚
C
− H = 0.93, C7 − H = 0.98, C9/10 − H = 0.96 A. Sym-
metry transformations used to generate equivalent atoms: #1 −x,
−y+1, −z.
◦
obtained by sublimation (10−3 mbar, 150 C). Hence,
product selectivity depends on the reaction tempera-
ture. It must depend further on the solvent, since re-
action of n-BuLi with N,N-dimethylbenzylamine at
room temperature, either in pure diethylether or in a
mixture of diethylether with hexane and benzene, led
to the o-lithiated product, as was established by analy-
ses of subsequent reaction products [3, 4].
An ab initio investigation of the isolated anions (see
Fig. 1) at the MP2/6-31G(d) level revealed 2 (negative
charge at C7) to be more stable than 1 (negative charge
at C6) by 72 kJ mol−1. The main reason for the stabi-
lization of 2 is the resonance of the p-type lone pair
at C7 (α-C) with the aromatic system of the phenyl
ring, as was established by a second order perturbation
theory analysis of the Fock matrix in a natural bond
orbital (NBO) basis [11]. Without being restricted to
it, 2 adopted Cs symmetry, under which the respective
orbital interaction is at its maximum.
Fig. 1. MP2/6-31G(d) optimized molecular structures of
N,N-dimethylbenzylamine anions 1: Deprotonation in o-
position at C6 2: Deprotonation in α-position at C7. View
is along the bond from C7 to C1, the phenyl ring is oriented
horizontally.
Thus, the tautomer anion 2 appears to be favored
if the deprotonated N,N-dimethylbenzylamine is sep-
arated from the Li+ ion, such that no stabilization
a way that sulfur was added to a solution of [2-((N,N- of the o-lithiated form by means of intramolecular
dimethylamino)methyl)phenyl]lithiumin THF at room N···Li interaction can occur. THF is known to strongly
temperature, a brown-red and highly viscous product coordinate to Li+ and is thus feasible to produce a
instead of a yellow oil was obtained. From the former, separation of that cation from the deprotonated N,N-
meso-1,2-bis(dimethylamino)-1,2-diphenylethane was dimethylbenzylamine. This suggestion is supported
Unauthenticated
Download Date | 9/26/18 4:21 PM

H. Fleischer – D. Schollmeyer · Formation of meso-1,2-Bis(dimethylamino)-1,2-diphenylethane
1085
˚
Table 2. Selected bond distances (in A) at the α-C atom of
some 1,2-diamino-1,2-diphenylethane derivatives from sin-
gle crystal XRD experimentsa.
ꢀ
r(Cα –Ci)b r(Cα –Cα
)
r(Cα –N) Reference
meso-A
rac-B
rac-C
rac-D
(2R,3R,5S,6S)-E
(2R,3R,5S,6S)-F
(1R,2R)-G
meso-H
1.528
1.516
1.530
1.523
1.517
1.506
1.520
1.522
1.526
1.564
1.503
1.545
1.540
1.543
1.551
1.637
1.485
1.482
1.483
1.471
1.469
1.461
1.460
1.471
this work
[12]
[13]
[14]
[15]
[15]
[16]
[17]
b
a
For molecular structures of compounds A – H see Scheme 2; Ci
Fig. 2. ORTEP diagram of meso-1,2-bis(dimethylamino)-
1,2-diphenylethane. Displacement ellipsoids are at the 50%
probability level.
designates the ipso C atom of the phenyl ring.
sis [11], the preference for that conformation can be
attributed to a π −σ∗ interaction between the aromatic
system and the C-N bond. The sum of the bond an-
gles at N(8) is 338.7◦. Table 2 compares bond distances
at the α-C atom to those of some other 1,2-diamino-
1,2-diphenylethane derivatives. For r(Cα –Ci) no sig-
nificant differences occur between reference A and the
ꢀ
other compounds. r(Cα –Cα ) is shorter in A than in the
other compounds, which is likely to be a consequence
of reduced repulsion of the substituents at the two Cα
ꢀ
atoms (cf. the very long Cα –Cα bond in H).
Scheme 2. Molecular structures of compounds given in Ta-
ble 2.
The agreement between the XRD and the B3LYP/6-
31G(d) structure is good for bond distances and even
very good for bond angles. This is rather surpris-
ing, since the XRD experiment gives an rα structure
at 298 K in the solid state, while the DFT geome-
try optimization leads to an re structure of an iso-
lated molecule. These results suggest that intermolecu-
lar forces in the solid state do not have a significant im-
pact on the molecular structure. This conclusion is sup-
ported by the torsion angles given in Table 1. Torsion
angles are “soft” structural parameters, i. e. their mag-
nitude can be substantially changed with small energy
efforts. The four torsion angles in Table 1 give the rel-
ative orientations of the dimethylamino group and the
phenyl ring, i. e. they define the shape of the molecule.
Hence, since the agreement between XRD and DFT
torsions is quite high, meso-1,2-bis(dimethylamino)-
1,2-diphenylethane is not distorted to a significant de-
gree by packing forces in the solid state.
by results of Reich et al., who reported that spin-
6
spin coupling of Li to 13C and 15N in a solution of
2-[(dimethylamino)methyl]phenyllithium in THF dis-
◦
appears at temperatures above −55 C [5]. Since dis-
sociation and charge separation are likely to increase
the entropy of the system, it can be rationalized why
formation of 2 is favored at higher temperatures in this
solvent. The oxidative C-C coupling, leading to the for-
mation of 1,2-bis(dimethylamino)-1,2-diphenylethane,
is due to the action of sulfur on the anions. Preference
for any mechanism of the coupling reaction would be
too speculative at the present stage.
Structural investigations
The single crystal X-ray structure shows meso-1,2-
bis(dimethylamino)-1,2-diphenylethane to exhibit in-
version symmetry in the solid state. The six C atoms
of the phenyl ring are coplanar, intra-ring-C-C-C an-
gles summing to 720◦. The heavy atom torsion an-
gles of the C6H5CH unit are within 1.0◦ from to 0
or 180◦. The C(1)-C(7)-N(8) plane is nearly orthog-
onal to the plane of the phenyl ring. On the basis of a
Experimental Section
General procedures
N,N-dimethylbenzylamine, diethylether, THF and chlo-
roform were purified by distillation according to standard
second order perturbation calculation in an NBO ba- procedures.
Unauthenticated
Download Date | 9/26/18 4:21 PM

1086
H. Fleischer – D. Schollmeyer · Formation of meso-1,2-Bis(dimethylamino)-1,2-diphenylethane
Table 3. Crystal data for meso-1,2-bis(dimethylamino)-1,2-
diphenylethane.
The combined organic phases were dried over Na2SO4, the
solvents were distilled off under normal pressure to leave
36.2 g of a red-brown, highly viscous crude product. Heat-
Empirical formula
FW [g mol−1
C18H24N2
268.39
◦
]
ing this product to 150 C under high-vacuum conditions
(p = 10−3 mbar) led to the sublimation of pale yellow crys-
tals (less than 500 mg). The product could be identified
by 1H NMR spectroscopy as meso-1,2-bis(dimethylamino)-
1,2-diphenylethane. Crystals suitable for single crystal X-ray
diffraction were taken from the sublimate. No other reaction
products could by isolated or identified in the mixture.
Temperature [K]
Wavelength [A]
298(2)
1.54178
˚
Crystal size [mm]
Crystal system
Space group
0.43×0.32×0.23
monoclinic
P21/c
6.0537(12)
6.9486(10)
19.422(4)
107.20(2)
2, 1.142
˚
a [A]
˚
b [A]
˚
c [A]
β [◦]
Crystal structure determination
Z, ρcalcd [g cm−3
]
µ [mm−1
F(000)
]
0.507
292
The diffraction experiment was performed on a Tur-
boCAD 4 (Nonius) diffractometer. The crystal structure
was solved by direct methods and difference Fourier tech-
niques (SIR-92) [18]. Structural refinement was against F2
(SHELXL-97) [19]. Details of the crystal structure determi-
nation and the crystal data are given in Table 3 [20].
θ-Range
Limiting indices
4.77 ≤ θ ≤ 73.04◦
0 ≤ h ≤ 7, 0 ≤ k ≤ 8,
−24 ≤ l ≤ 23
1721
Reflections measured
Unique reflections
Refl. |F| > 4σ(F)
R[|F| > 4σ(F)]a
wR2
1570
1570
0.0892
0.2513
1.078
0.310 and −0.468
Theoretical methods
goodness-of-fit on F2
largest diff. peak
Ab initio and density functional theory (DFT) cal-
culations were performed with the GAUSSIAN98 soft-
ware package [21]. The molecular structure of meso-1,2-
bis(dimethylamino)-1,2-diphenylethane was fully optimized
using a 6-31G(d) basis set and DFT employing a combina-
tion of local, gradient-corrected, and exact exchange func-
tionals according to the prescription of Becke [22] and the
and hole [10−3 e·nm−3
]
a
R = ||F |−|F ||/ |F |.
∑
∑
o
c
o
Synthesis of meso-1,2-bis(dimethylamino)-1,2-diphenyl-
ethane
Under an Ar atmosphere, 100 ml of a 2.5 M solution gradient-corrected correlation functional of Lee, Yang and
of n-BuLi in hexane was slowly added to a stirred solution Parr [B3LYP/6-31G(d)] [23]. The geometries of the mono-
of N,N-dimethylbenzylamine (33.8 g, 0.25 mol) in 250 ml anions of N,N-dimethylbenzylamine, obtained by deproto-
of THF. When no more gas was evolved, sulfur (8.02 g, nation of the α- or the o-position, were fully optimized with
0.25 mol) was added in small portions. The reaction mix- the same basis set and second order perturbation theory ac-
ture was stirred for another 4 h, before 100 ml of H2O, cording to Møller and Plesset [MP2/6-31G(d)]. With the re-
25 ml of 10 M HCl and 100 ml of diethylether were added. spective model chemistry, analysis of the bonding situation in
Organic and aqueous phase were separated, and the latter an NBO basis was performed [11]. All stationary points were
extracted five times with a total of 500 ml of chloroform. characterized by calculation of analytical force constants.
[1] a) R. Imwinkelried, D. Seebach, Helv. Chim. Acta 67,
1496 (1984); b) C. Betschart, D. Seebach, Helv. Chim.
Acta 70, 2215 (1987); c) C. Betschart, B. Schmidt,
D. Seebach, Helv. Chim. Acta 71, 1999 (1988).
[2] K. Selvakumar, J. F. Harrod, Angew. Chem. 113, 2187
(2001); Angew. Chem. Int. Ed. 40, 2129 (2001).
[3] F. N. Jones, M. F. Zinn, C. R. Hauser, J. Am. Chem.
Soc. 85, 663 (1963).
[6] G. Boche, M. Marsch, J. Harbach, K. Harms, B. Ledig,
F. Schubert, J. C. W. Lohrenz, H. Ahlbrecht, Chem.
Ber. 126, 1887 (1993).
[7] E. Mu¨ller (ed.), Methoden der Organischen Chemie
Houben/Weyl, 4th edition, vol. IX: Sulfur, Selenium
and Tellurium Compounds, Georg Thieme Verlag,
Stuttgart (1955).
[8] D. M. Knotter, H. L. van Maanen, D. M. Grove, A. L.
Spek, G. van Koten, Inorg. Chem. 30, 3309 (1991).
[9] a) H. B. Singh, M. Sudha, A. A. West, T. A.
Hamor, J. Chem. Soc., Dalton Trans. 907 (1990);
b) A. Panda, G. Mugesh, H. B. Singh, R. J. Butcher,
Organometallics 18, 1986 (1999).
[4] W. H. Puterbaugh, C. R. Hauser, J. Am. Chem. Soc. 85,
2467 (1963).
¨
[5] H. J. Reich, B. O. Gudmundsson, J. Am. Chem. Soc.
118, 6074 (1996).
Unauthenticated
Download Date | 9/26/18 4:21 PM

H. Fleischer – D. Schollmeyer · Formation of meso-1,2-Bis(dimethylamino)-1,2-diphenylethane
1087
[10] H. Fleischer, D. Schollmeyer, A. Piou, manuscript in
preparation
[11] a) A. E. Reed, R. B. Weinstock, F. Weinhold, J. Chem.
Phys. 83, 735 (1985); b) A. E. Reed, L. A. Curtiss,
F. Weinhold, Chem. Rev. 88, 899 (1988).
Centre, CCDC-277670. Copies of the data can be ob-
tained free of charge on application to The Director,
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: int.code+(1223)336-033; e-mail for inquiry: file-
serv@ccdc.cam.ac.uk).
[12] M. C. Elliot, E. Williams, S. T. Howard, J. Chem. Soc.,
Perkin Trans. 2, 201 (2002).
[13] M.-C. P. Yeh, C.-N. Chuang, C.-H. Yu, Tetrahedron
Lett. 38, 7387 (1997).
[14] K. Bambridge, M. J. Begley, N. Simpkins, Tetrahedron
Lett. 35, 3391 (1994).
[15] M. H. Nantz, P. A. Lee, D. M. Bender, A. H. Roohi, J.
Org. Chem. 57, 6653 (1992).
[16] M. D. Jones, F. A. A. Paz, J. E. Davies, B. F. G. John-
son, Acta Crystallogr. 59E, 0455 (2003).
[17] B. Bracke, E. Volckaerts, A. T. H. Lenstra, H. J. Geise,
Bull. Soc. Chim. Belg. 99, 797 (1990).
[18] A. Altomare, G. Cascarano, C. Giacovazzo,
A. Guagliardi, M. C. Burla, G. Polidori, M. Ca-
malli, J. Appl. Crystallogr. 27, 435 (1994).
[19] G. M. Sheldrick, SHELXL-97 Program for crystal
structure refinement, University of Go¨ttingen, Ger-
many (1997).
[21] Gaussian 98, Revision A.6, M. J. Frisch, G. W.
Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, V. G. Zakrzewski, J. A. Mont-
gomery, Jr., R. E. Stratmann, J. C. Burant, S. Dap-
prich, J. M. Millam, A. D. Daniels, K. N. Kudin,
M. C. Strain, O. Farkas, J. Tomasi, V. Barone,
M. Cossi, R. Cammi, B. Mennucci, C. Pomelli,
C. Adamo, S. Clifford, J. Ochterski, G. A. Peters-
son, P. Y. Ayala, Q. Cui, K. Morokuma, D. K. Mal-
ick, A. D. Rabuck, K. Raghavachari, J. B. Foresman,
J. Cioslowski, J. V. Ortiz, B. B. Stefanov, G. Liu,
A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts,
R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y.
Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,
P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, J. L.
Andres, C. Gonzalez, M. Head-Gordon, E. S. Replogle,
J. A. Pople, Gaussian, Inc., Pittsburgh PA (1998).
[22] A. D. Becke, J. Chem. Phys. 98, 5648 (1993).
[20] Crystallographic data for the structure have been de- [23] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B37, 785
posited with the Cambridge Crystallographic Data (1988).
Unauthenticated
Download Date | 9/26/18 4:21 PM