Synthesis of [15N,15N']-N,N,N',N'-tetramethyl-ethylenediamine and its use in solvation studies of [6Li]-n-butyllithium [18]

Full text of DOI:10.1021/ja970557n

J. Am. Chem. Soc. 1997, 119, 5479-5480
5479
Synthesis of [15N,15N′]-N,N,N′,N′-Tetramethyl-
ethylenediamine and Its Use in Solvation Studies of
[6Li]-n-Butyllithium
Delia Waldmu¨ller,† Barbara J. Kotsatos,‡
Michael A. Nichols,*,‡ and Paul G. Williard*,†
Department of Chemistry, Brown UniVersity
ProVidence, Rhode Island 02912-9000
Department of Chemistry, John Carroll UniVersity
UniVersity Heights, Ohio 44118
ReceiVed February 21, 1997
N,N,N′,N′-Tetramethylethylenediamine (TMEDA) is widely
used as a ligand or cosolvent in organic syntheses, particularly
when organolithium reagents are involved.1 TMEDA has been
shown to improve product yields, alter product distributions and
increase reaction rates primarily through solvation and chelation
of the lithium cations.1a In order to elucidate the exact
mechanisms by which these reactions take place, methods which
permit the direct observation of the solvation of organolithium
bases such as lithium amides and alkyllithium compounds must
be developed and employed. While 6Li, 15N, 13C, and 31P NMR
techniques have been used to directly determine the aggregation
states of lithium amides1a,b,2 and alkyllithium compounds1c,3 and
their solvation by hexamethylphosphoramide (HMPA),4 rela-
tively few NMR studies have been reported using an [15N]-
labeled ligand, either covalently attached to the organolithium
compound2f,4a or as a free ligand in solution,5 to directly observe
solvation of the lithium cation. Herein, we report the synthesis
Figure 1. NMR spectra for a 0.14 M [6Li]-n-BuLi solution in the
presence of 1.1-1.2 equiv of [15N,15N′]TMEDA in toluene-d8 at -110
°C: (A) 6Li NMR spectrum; (B) ) 15N NMR spectrum. The 6Li-15N
coupling constant is 2.0 Hz in each spectrum. Line broadening of 0
Hz was applied to each spectrum. The 6Li (44.15 MHz) and 15N (30.408
MHz) NMR spectra are referenced to external 0.02 M [6Li]OCD3/CD3-
OD (δ ) 0 ppm) and 98% aniline/DMSO-d6 (δ ) 50 ppm) solutions,
respectively.9
† Brown University.
‡ John Carroll University.
§ Author to whom all correspondence should be sent: M. A. Nichols,
John Carroll University.
(1) (a) For leading references and a historical discussion of TMEDA’s
use in organolithium chemistry, see: Collum, D. B. Acc. Chem. Res. 1992,
25, 448-54. (b) Lucht, B. L.; Bernstein, M. P.; Remenar, J. E.; Collum,
D. B. J. Am. Chem. Soc. 1996, 118, 10707-18 and references therein. (c)
Seebach, D. Angew. Chem., Int. Ed. Engl. 1988, 27, 1624 and references
therein. (d) Snieckus, V. Chem. ReV. 1990, 90, 879.
(2) (a) Collum, D. B. Acc. Chem. Res. 1993, 26, 227-234 and references
therein. (b) Wanat, R. A.; Collum, D. B.; Van Duyne, G.; Clardy, J.; DePue,
R. T. J. Am. Chem. Soc. 1986, 108, 3415. (c) Jackman, L. M.; Scarmoutzos,
L. M. J. Am. Chem. Soc. 1987, 109, 5348-55. (d) Sugaswa, K.; Shindo,
M.; Noguchi, H.; Koga, K. Tetrahedron Lett. 1996, 37, 7377-80. (e)
Hilmersson, G.; Davidsson, O. J. Org. Chem. 1995, 60, 7660-9. (f) Sato,
D.; Kawasaki, H.; Shimada, I.; Arata, Y.; Okamura, K.; Date, T.; Koga, K.
J. Am. Chem. Soc. 1992, 114, 761-3.
Scheme 1. The Synthesis of [15N,15N′]TMEDA (IV) from
[15N]Potassium Phthalimide (I) Where All Nitrogen Atoms
Are [15N]-labeled (98%)9
(3) (a) Bauer, W. J. Am. Chem. Soc. 1996, 118, 5450-5. (b) For leading
references to this group’s work, see: Bauer, W.; Schleyer, P. v. R. In
AdVances in Carbanion Chemistry; Snieckus, V., Ed.; JAI: New York,
1992; p 89. (c) For leading references to this group’s work, see: Guenther,
H.; Eppers, O.; Hausmann, H.; Huels, D.; Mons, H.-E.; Klein, K.-D.;
Maercker, A. HelV. Chim. Acta 1995, 78, 1913-32. (d) For leading
references to this group’s work, see: DeLong, G. T.; Pannell, D. K.; Clarke,
M. T.; Thomas, R. D. J. Am. Chem. Soc. 1993, 115, 7013-7014. (e) For
leading references to this group’s work, see: Fraenkel, G.; Martin, K. V.
J. Am. Chem. Soc. 1995, 117, 10336. (f) Seebach, D.; Gabriel, J.; Hassig,
R. HelV. Chim. Acta 1984, 67, 1083-99. (g) Seebach, D.; Hassig, R.;
Gabriel, J. HelV. Chim. Acta 1983, 66, 308-37. (h) Gunther, M.; Moskau,
D.; Bast, P.; Schmalz, D. Angew. Chem., Int. Ed. Engl. 1987, 26, 1212.
(4) (a) Reich, H. J.; Gudmundsson, B. O. J. Am. Chem. Soc. 1996, 118,
6074-5. (b) Reich, H. J.; Borst, J. P.; Dykstra, R. R.; Green, D. P. J. Am.
Chem. Soc. 1993, 115, 8728-41. (c) Jackman, L. M.; Chen, X. J. Am.
Chem. Soc. 1992, 114, 403-11. (d) Riech, H. J.; Borst, J. P. J. Am. Chem.
Soc. 1991, 113, 1835-7. (e) Riech, H. J.; Green, D. P. J. Am. Chem. Soc.
1989, 111, 8729-31. (f) Romesberg, F. E.; Bernstein, M. P.; Gilchrist, J.
H.; Harrison, A. T.; Fuller, D. J.; Collum, D. B. J. Am. Chem. Soc. 1993,
115, 3475-83. (g) Romesberg, F. E.; Gilchrist, J. H.; Harrison, A. T.;
Fuller, D. J.; Collum, D. B. J. Am. Chem. Soc. 1991, 113, 5751-7. (h)
Barr, D.; Doyle, M. J.; Mulvey, R. E.; Raithby, P. R.; Reed, D.; Snaith, R.;
Wright, D. S. J. Chem. Soc., Chem. Commun. 1989, 318. (i) Raithby, P.
R.; Reed, D.; Snaith, R.; Wright, D. S. Angew. Chem., Int. Ed. Engl. 1991,
30, 1011.
of [15N,15N′]TMEDA and its use in the solvation studies of
[6Li]-n-butyllithium (n-BuLi) in toluene-d8 at -110 °C using
6Li and 15N NMR.
We prepared [15N,15N′]TMEDA in three steps starting from
[15N]potassium phthalimide,6 I, which was reacted with 1,2-
dibromoethane at 170-180 °C for 12 h to yield [15N,15N′]-
diphthalimidoethane, II (Scheme 1).7 Alkaline hydrolysis of
II lead to [15N,15N′]ethylenediamine (EDA), which was subse-
quently isolated as the [15N,15N′]EDA‚2HCl salt, III. The key
(6) Purchased from Aldrich Chemical Co.; 98% isotopic enrichment.
(7) Modified from the reported procedure: Salzberg, P. L.; Supniewski,
J. W. Organic Syntheses; Wiley: New York, 1941; Collect. Vol. I, pp 119-
21. Other procedures have been published, see: Soai, K.; Ookawa, A.;
Kato, K. Bull. Chem. Soc. Jpn. 1982, 55, 1671-72. Landini, D.; Rolla, F.
Synthesis 1976, 6, 389-91.
(5) (a) Lucht, B. L.; Collum, D. B. J. Am. Chem. Soc. 1996, 118, 3529-
30. (b) Lucht, B. L.; Collum, D. B. J. Am. Chem. Soc. 1996, 118, 2217-
25. (c) Falcone, M. A. M.S. Thesis, John Carroll University, University
Heights, OH 44118, 1996.
S0002-7863(97)00557-X CCC: $14.00 © 1997 American Chemical Society

5480 J. Am. Chem. Soc., Vol. 119, No. 23, 1997
Communications to the Editor
step is the Eschweiler-Clarke8 methylation of [15N,15N′]-IV
with formaldehyde in formic acid to yield the desired [15N,15N′]-
TMEDA, IV, in 11% overall percent yield from [15N]-I.9
sample in toluene-d8 containing unlabeled TMEDA was ana-
lyzed at -110 °C, the appearance of the R-13C resonance of
n-BuLi was identical to the one obtained using the [15N,15N′]-
TMEDA. Therefore, no long-range 15N-13C coupling is
occurring. Evidence of slow interaggregate exchange was
obtained when the sample was warmed to -96 or -78 °C; the
broad R-13C resonance sharpened to yield a well-resolved
pentuplet having a 6Li-13C coupling constant of 8.1 Hz, which
is in agreement with previous 13C,6Li NMR solution studies of
n-BuLi, where dimers were observed in hydrocarbon solutions
in the presence of TMEDA.3g,15 The future use of [15N,15N′]-
TMEDA to probe solvation of other organolithium compounds
will undoubtedly provide further insight into the solution
structures and reactivities of important organolithium compounds
and those results will be reported in due course.16
Figure 1 shows the 6Li NMR (A) and 15N NMR (B) spectra
recorded for a 0.14 M solution of [6Li]-n-BuLi10 in the presence
of 1.1-1.2 equiv of [15N,15N′]TMEDA. The spectra were
recorded at -110 °C in toluene-d8, and both spectra clearly
depict triplets11 having 6Li-15N coupling constants of 2.0 Hz.12
The splitting of the 15N (1:1:1) and 6Li resonances (1:2:1) leads
unambiguously to the conclusion that each 6Li cation is attached
to two 15N atoms, while each 15N amine atom is attached to
only one 6Li cation. The coupling pattern and the observation
of only one 15N resonance strongly suggests that TMEDA must
6
be chelating the Li cations in a dimeric aggregate having a
similar structure to our reported (n-BuLi‚TMEDA)2 X-ray
crystal structure.13 The 13C NMR resonance of the R-carbon
of [6Li]-n-BuLi was broad and was not the resolved pentuplet
predicted from the 6Li-13C coupling for a dimeric aggregate.11
Two explanations can be proposed: long-range coupling of a
Acknowledgment. This work was supported by the National
Institutes of Health through grant GM-35980 to P.G.W. Funding was
also provided to M.A.N. through a Summer Research Fellowship from
the JCU Graduate School and to B.J.K. in the form of a BP America
Summer Undergraduate Research Fellowship. A Kresge Science
Initiative Grant was used to purchase the NMR and GC/MS instruments
at JCU.
6
TMEDA 15N nucleus to the R-13C nucleus through the Li
nucleus and/or slow interaggregate exchange due to the low
temperature used (-110 °C).14 When an identical [6Li]-n-BuLi
Supporting Information Available: Experimental syntheses and
spectral characterization data for compounds II-IV and NMR spectra
from the [6Li]-nBuLi‚[15N,15N′]TMEDA experiment (18 pages). See
any current masthead page for ordering and Internet access instructions.
(8) (a) McElvain, S. M.; Bannister, L. W. J. Am. Chem. Soc. 1954, 76,
1126. (b) Clarke, H. T.; Gillespie, H. B.; Weisshaus, S. Z. J. Am. Chem.
Soc. 1933, 55, 4571.
(9) See the Supporting Information for the synthetic details and spectral
1
6
characterization of II-IV and H, 13C, Li, and 15N NMR spectra for the
[6Li]-n-BuLi‚[15N,15N′]TMEDA solution in toluene-d8 at -110 °C.
(10) Synthesized by the “sono-reflux” of 1-chlorobutane with 6Li metal
(obtained from Oak Ridge National Laboratories). For a similar procedure,
see: Arnett, E. M.; Fisher, F. J.; Nichols, M. A.; Ribeiro, A. A. J. Am.
Chem. Soc. 1990, 112, 801-8.
JA970557N
(15) Solid-state NMR (CP/MAS) studies of TMEDA and alkyllithium
compounds have been reported, see: Baumann, W.; Oprunenko, Y.;
Guenther, H. Z. Naturforsch. A 1995, 50, 429.
(11) The coupling of the 6Li and 15N (or 13C) resonances is governed by
(16) When solutions of [6Li]-n-BuLi containing less than 1 equiv of
6
1
6
the equation 2nI + 1, where n ) 1 for Li and /2 for 15N (or 13C). The
[15N,15N′]TMEDA are analyzed using Li and 15N NMR, both spectra are
coupling of Li and 15N has been discussed in ref 2a.
extremely complicated. When 2 equiv of [15N,15N′]TMEDA is present,
the spectra are essentially the same as that seen in Figure 1, with some line
broadening due to increased ligand exchange. The 6Li triplet can be resolved
using resolution enhancement. In contrast, when an excess of an [15N]mon-
odentate ligand is added to a [6Li,15N]lithium amide, all 6Li-15N coupling
is lost: see ref 5b,c.
6
(12) Previously reported 15N-6Li coupling constants for chelating and
solvating amine groups range from 1.3 to 3.7 Hz. See refs 2f, 4a, and 5.
(13) Nichols, M. A.; Williard, P. G. J. Am. Chem. Soc. 1993, 115,
11568-72.
(14) We thank a reviewer for these suggestions.