8078 J. Am. Chem. Soc., Vol. 123, No. 33, 2001
Reich et al.
7.41-7.57 (m, 3H), 7.8-7.85 (m, 2H). 13C{1H} NMR (CDCl3, 75.45
Compound 1 forms a mixed dimer with PhLi, which also
shows the features of high kinetic and thermodynamic stability
in dissociation to monomers compared to nonchelated analogues.
Thus, even a single chelating group stabilizes a dimeric structure.
2
MHz): δ 127.3 (o), 128.6 (m), 131.9 (p), 133.4 (i, JC-N ) 8.3 Hz),
1
170.0 (CdO, JC-N ) 15.3 Hz).
Benzylamine-[15N]. LiAlH4 (0.78, 20.6 mmol) was suspended in
35 mL of dry THF and cooled to 0 °C. [15N]-Benzamide (0.84 g, 6.9
mmol) in 10 mL of THF was added dropwise to the stirred suspension.
The mixture was refluxed for 12 h and slowly cooled to 0 °C, and
then 1 mL of 15% NaOH and 4 mL of water were added. The mixture
was stirred for several minutes and filtered, and the clear filtrate was
dried (Na2SO4). The solvent was evaporated (no heating) to give 0.69
g (93%) of a clear pale yellow liquid which was used without further
Experimental Section
General. All reactions requiring a dry anoxic atmosphere were
performed in glassware flame-dried or dried overnight in a 110 °C oven,
sealed with septa, and flushed with N2. Tetrahydrofuran (THF) and
diethyl ether (ether) were freshly distilled under N2 from sodium
benzophenone ketyl. Dimethyl ether (Me2O, bp -24.8 °C) was
condensed from a pressurized gas cylinder into a graduated conical
tube cooled to -78 °C, n-BuLi was added, and the dry Me2O was
passed by cannula into the desired vessel cooled to -78 °C. N,N,N′,N′′-
Tetramethylethylenediamine (TMEDA), N,N,N′,N′′,N′′-pentamethyl-
diethylenetriamine (PMDTA), and hexamethylphosphoric triamide
(HMPA) were distilled from CaH2 under reduced pressure (if required)
and stored under N2 over 4 Å molecular sieves. Common lithium
reagents were handled by septum and syringe-based techniques and
titrated against dry 1-propanol in THF with 1,10-phenanthroline as an
indicator.45 Et6Li38b (from EtBr and 6Li metal) and n-Bu6Li13b (n-BuCl
and 6Li metal) were prepared by literature methods. All reported reaction
temperatures are those of the cooling baths. Thin-layer chromatography
(TLC) was conducted on silica gel 60 F254 plates and visualized by
ultraviolet irradiation. Melting and boiling points are reported uncor-
rected. Kugelrohr distillation temperatures refer to the pot temperature.
Mass spectra were obtained on a Kratos MS-80 spectrometer.
1
purification. H NMR (CDCl3, 300 MHz): δ 1.69 (br-s, 2H), 3.86 (s,
2H), 7.21-7.32 (m, 5H). 13C{1H} NMR (CDCl3, 75.45 MHz): δ 46.4
(CH2, JC-N ) 3.8 Hz), 126.7 (d), 127.0 (d), 128.5 (d), 143.2 (s).
N,N-Dimethylbenzylamine-[15N]. Benzylamine-[15N] (0.69 g, 6.4
mmol) and formaldehyde (1.9 mL, 25.5 mmol) were dissolved in 30
mL of MeOH. The solution was cooled to 0 °C, and NaCNBH3 (0.56
g, 8.9 mmol) and ZnCl2 (0.61 g, 4.5 mmol) in 20 mL of MeOH were
added dropwise (slowly, 1 h). The solution was slowly warmed to room
temperature over 2 h and then cooled to 0 °C, and NaOH (2 M, 50
mL) was added. The MeOH was removed and the residue extracted
with ether (4 × 30 mL). Pentane was added and the solution washed
with water (2 × 50 mL) and brine (1 × 50 mL) and dried (Na2SO4).
The solvent was evaporated (no heating) to give 0.50 g (57%) of a
clear yellow liquid. Kugelrohr distillation (85-95 °C, 20 Torr) gave
0.29 g (33%) of a clear, colorless liquid. 1H NMR (CDCl3, 300 MHz):
δ 2.23 (d, JH-N ) 0.8 Hz, 6H), 3.41 (s, 2H), 7.24-7.33 (m, 5H). 13C-
{1H} NMR (CDCl3, 75.45 MHz): δ 45.2 (CH3, JC-N ) 4.5 Hz), 64.3
(CH2, JC-N ) 3.8 Hz), 127.0 (d), 128.2 (d), 129.1 (d), 138.7 (s). MS:
M+ ) 136.1020 (calcd for C9H1315N ) 136.1018).
Routine NMR Spectroscopy. Routine 1H and 13C nuclear magnetic
resonance (NMR) spectra were obtained on Bruker AC-300, AVANCE
or AM-360 and AM-500 spectrometers. All spectra were acquired in
CDCl3 or C6D6, with tetramethylsilane (TMS, δ 0.00) as an internal
Quantitation of Aryllithium Reagents. The concentrations of the
aryllithium solutions were determined by the following methods: (1)
quenching of the RLi solution with Me2S2 or Me3SiCl and determination
of the quantity of sulfide or silane produced by GC and/or proton NMR
spectroscopy; (2) in some cases where the crude lithium reagent
prepared by Li/Sn exchange was used, quantitative transmetalation was
assumed; (3) HMPA has been shown to bind lithium reagents
stoichiometrically in THF and ether solutions,15j thus the initial addition
of HMPA or PMDTA to the aryllithium reagent was assumed to
complex in stoichiometric fashion; integration of the complexed versus
the noncomplexed species in the 6Li NMR spectrum allowed determi-
nation of the aryllithium reagent concentration. Quantitative complex-
ation was confirmed by examination of the 31P NMR spectra for free
HMPA.
1
reference for H NMR and CDCl3 (δ 77.0) or C6D6 (δ 128.0) for 13C
NMR spectra. Routine 119Sn NMR spectra were obtained on a Bruker
AM-360 spectrometer (unlocked) and were acquired in protio-THF,
with tetramethylstannane (δ 0.00) as an internal reference.
Low-Temperature Multinuclear NMR Spectroscopy. All low-
temperature multinuclear NMR experiments were conducted on a
Bruker AVANCE-360 or AM-360 spectrometer equipped with a 10-
mm wide-bore broadband probe at the following frequencies: 360.148
MHz (1H), 90.556 MHz (13C), 52.984 MHz (6Li), 139.905 MHz (7Li),
and 145.785 MHz (31P).
All spectra were taken of samples in a combination of the protio
solvents THF, ether, and/or Me2O with the spectrometer unlocked. 13
C
NMR spectra were referenced internally to the C-2 carbon of THF (δ
67.96), the C-2 carbon of ether (δ 66.57), or Me2O (δ 60.25). Lorentzian
2-Lithio-N,N-dimethylbenzylamine (1). A typical procedure for
preparation of 1 (using the method of Hauser1a) is as follows: N,N-
dimethylbenzylamine (2.99 g, 22.1 mmol) and 20 mL of ether were
added to a dried and N2-flushed 100-mL storage flask equipped with
a stopcock and a septum. The solution was cooled to 0 °C, and 9.6 mL
of 2.20 M n-BuLi in hexane (21.1 mmol, 0.95 equiv) was added
dropwise. The resulting yellow solution was kept at room temperature
for 7 d, during which time transparent crystals formed. The supernatant
was removed by cannula transfer, and the crystals were washed with
ether (3 × 15 mL). The crystals (87% yield) were used for the
preparation of NMR samples or dissolved in THF to give a stock
solution (typically 1.0-1.5 M) used for subsequent reactions. Similar
procedures were used with n-Bu6Li and/or 15N-enriched N,N-dimeth-
ylbenzylamine.
An alternate method was also used. Et6Li (0.304 g 8.67 mmol) was
dissolved in 8.0 mL of ether. The solution was cooled to -78 °C, and
N,N-dimethylbenzylamine (1.30 mL, 8.65 mmol) was added. The
resulting clear yellow solution was warmed to room temperature and
kept for 7 d. The supernatant was removed via cannula, and the crystals
were washed with ether (3 × 15 mL) and dried in vaccuo. The crystals
were stored in a glovebox until used.
6
multiplication (LB) of 2-3 Hz was applied to 13C NMR spectra. Li
and 7Li NMR spectra were referenced externally to 0.3 M LiCl/MeOH
(δ 0.00) or internally to Li+(HMPA)4 (δ -0.40). 31P NMR spectra were
referenced externally to 1.0 M PPh3/THF (δ -6.00) or internally to
free HMPA (δ 26.40). Probe temperatures were measured externally
by ejecting the sample and inserting a thermocouple into the probe or
internally with the 13C chemical shift thermometer (Me3Si)3CH.15g
Benzamide-[15N].46 15NH4Cl (98%, 0.5 g, 9.2 mmol) was dissolved
in 7 mL of water in a one-neck round-bottom flask. The water was
covered with a layer of benzene (1-2 mL), the flask was cooled in an
ice bath, and to it was added (by pipet inserted through the benzene
layer) a solution of NaOH (0.79 g, 19.7 mmol in 5 mL of water),
followed immediately by benzoyl chloride (1.1 mL, 9.4 mmol) in 40
mL of benzene. The ice bath was removed, the flask fitted with a
septum, and the solution stirred at room temperature for 1.5 h
(precipitate of benzamide). The solution was cooled in ice, and the
solid was filtered, washed with water and cold benzene, and allowed
to air-dry to give 0.91 g of benzamide. A further 54 mg of benzamide
(total yield of 86%) was obtained by extracting the solvent and rinsing
the flask with CH2Cl2. The product was used without further purifica-
After completion of the NMR experiment, some samples were
quenched with Me2S2 to give N,N-dimethyl-2-(methylthio)benzyl-
amine.47 1H NMR (CDCl3, 300 MHz): δ 2.26 (s, 6H), 2.46 (s, 3H),
3.46 (s, 2H), 7.07-7.15 (m, 1H), 7.16-7.31 (m, 3H). 13C{1H} NMR
(CDCl3, 75.4 MHz): δ 15.67 (CH3), 45.37 (CH3), 62.00 (CH2), 124.22
(CH), 124.89 (CH), 127.63 (CH), 129.72 (CH), 136.61 (C), 138.71
1
1
tion. H NMR (CDCl3, 300 MHz): δ 6.25 (d, JN-H ) 88.6 Hz, 2H),
(45) Watson, S. C.; Eastman, J. F. J. Organomet. Chem. 1967, 9, 165-
168.
(46) Geller, B. A.; Samosvat, L. S. J. Gen. Chem. (USSR) 1960, 30,
1594-1597.