3
34
B. R. Taft et al.
PRACTICAL SYNTHETIC PROCEDURES
MHz, respectively. Mass spectral data were acquired on a VF
Autospec or an analytical VG-70-250-HF instrument.
(300 mL), 1% aq HCl (225 mL), sat. aq NaHCO (300 mL), H O
3
2
(3 × 225 mL), and brine (300 mL). The organics were then dried
over anhydrous Na SO and concentrated in vacuo to afford the title
2
4
Bis(4-chlorobenzyl) Hydrazine-1,2-dicarboxylate (4)
A clear solution of 4-chlorobenzyl alcohol (2; 14.258 g, 100.0
mmol) in anhyd THF (40 mL) was added dropwise via cannula at 0
compound as orange crystalline flakes; yield: 23.020 g (99%);
mp 107–108 °C.
1
H NMR (400 MHz, CDCl ): d = 7.38 (s, 8 H), 5.40 (s, 4 H).
3
°
1
C to an off-white slurry of 1,1¢-carbonyldiimidazole (16.215 g,
00.0 mmol) in anhyd THF (50 mL). The resulting clear, pale yel-
low solution was stirred and warmed to r.t. over 2 h. Hydrazine
1.55 mL, 49.5 mmol) and freshly distilled Et N (14.02 mL, 101.0
1
3
C NMR (100 MHz, CDCl ): d = 160.1, 135.4, 132.1, 130.4, 129.2,
3
7
0.1.
(
HRMS-ESI: m/z calcd for C H Cl N O + Na [M + Na]+:
3
16 12 2 2 4
mmol) were sequentially added and the solution was refluxed in an
0 °C oil bath for 12 h. After cooling, the solution was concentrated
in vacuo leading to an amorphous white solid that was transferred
3
89.0066, found: 389.0083.
8
to a fritted Büchner funnel and washed (vacuum filtration) with cold Acknowledgment
H O (5 × 150 mL) and 1:4 Et O–hexanes (2 × 100 mL). The color-
2
2
Financial support provided by the NSF is warmly acknowledged.
less solid was then collected and dried in vacuo to afford the title
compound; yield: 16.598 g (91%); R = 0.45 (1:1 EtOAc–hexanes,
f
KMnO stain); mp 177–179 °C.
4
References
1
H NMR (400 MHz, DMSO-d ): d = 9.35, 8.98 (NH rotamers, 2 H),
6
(
(
1) Toy, P. H.; But, T. Y. S. Chem. Asian J. 2007, 2, 1340.
2) Dembinski, R. Eur. J. Org. Chem. 2004, 2763.
7
.45–7.28 (m, 8 H), 5.08 (s, 4 H).
1
3
C NMR (100 MHz, DMSO-d ): d = 156.5, 135.7, 132.8, 129.8,
6
(3) (a) Lipshutz, B. H.; Chung, D. W.; Rich, B.; Corral, R. Org.
1
28.9, 65.3.
Lett. 2006, 8, 5069. (b) Our originally reported R for the
hydrazine dicarboxylate 4 is misleading, as the material was
impure due to the presence of residual imidazole.
f
HRMS-ESI: m/z calcd for C H Cl N O + Na [M + Na]+:
1
6
14
2
2
4
3
91.0222; found: 391.0227.
(4) Optimum results were achieved using CDI and CBA
Di-p-chlorobenzyl Azodicarboxylate (DCAD, 1)
obtained from Alfa Aesar.
Freshly distilled pyridine (5.21 mL, 64.67 mmol) and NBS (11.51
g, 64.67 mmol) were sequentially added to a slurry of 4 in toluene
(5) Imidazole is water soluble while 4 is not. Use of 1:1
hexanes–Et O leads to substantial loss of product 4.
2
(250 mL). After stirring the resulting orange cloudy mixture for 2 h,
Exposure time of the product to solvent can be minimized by
using vacuum filtration.
the mixture was diluted with toluene (375 mL, to completely dis-
solve all solids) and washed with H O (300 mL), sat. aq Na S O
2
2
2
3
Synthesis 2009, No. 2, 332–334 © Thieme Stuttgart · New York