1
038
N. Florini et al. / Tetrahedron: Asymmetry 20 (2009) 1036–1039
6
8
10
6
COOCH CH3
COOH
2
4
4
4
4
N
N
N
6
8
10
1
6
1
2
COOCH CH
3
COOH
2
COOCH CH
2
x 2 HCl
2
3
COOH
7
5
7
9
11
5
H
3
C3
N 5
H C3
3
COOCH CH3
5
2
11
COOH
7
9
7
Figure 1. Compound 5 (C numbered for NMR assignments).
Figure 2. Compound 6 (C numbered for NMR assignments).
with THF. Next the filtrate was dried and 20 mL of methanol was
added to it and the mixture solution was left to stand. The next
morning HCl gas was bubbled through the reaction mixture for
and 120 mL of aqueous 2 M NaOH in a 250 mL one-necked reaction
vessel and heated in oil bath to reflux for 6 h. After this period the
solvents were evaporated by rotary evaporator and then 150 mL of
3
0 min, which caused the solution to turn yellow and a light yellow
precipitate was formed. This precipitate was filtered out by G4 fil-
ter, washed with Et O, and dried. The product was a yellow pow-
der. Yield: 2.336 g (75.3%) The product was identified by NMR
3
M aqueous HCl was added. After this treatment the solvent was
2
again stripped off by rotary evaporator. The rest was washed thrice
with 30 mL of i-PrOH and then filtered cold (0 °C), first on a Bückner
funnel and then filtered on Celite and washed with 30 mL portions of
cold (0 °C) i-PrOH. A white, solid product was obtained. Yield:
4.824 g (98.0%). The product was characterized by melting point,
elemental analysis, and NMR and UV/CD spectroscopy. Melting
1
spectroscopy. NMR: H NMR (200.13 MHz, DMSO-d
6
, ppm): 1.30,
3
2
3
(
(
d, 3H, J 6.85 Hz (CH
CH
3
)); 2.98, (dd, Jab 13.20 Hz, Ja 6.20 Hz, H
a
HH
A
3
bA
3
3
2
)); 3.18, (dd, J 5.87 Hz, H
b
(CH
2
)); 3.54, (sex, JH 6.60 Hz, J
a
Hb
þ
5
.87 Hz (CH)); 8.67, s, (NH3 ). 13C NMR (50.29 MHz, DMSO-
D
6
,
ppm): 16.69 (CH
3 2
); 42.11 (CH ); 45.41 (CH).
point: 238 °C (dec). Anal. Calcd for
C
11
H
20Cl
2
N
2
O
8
ꢄ1 i-PrOH,
: C, 38.28; H, 6.43; N, 6.38. Found: C, 38.6; H, 7.3; N,
.2 NMR: H NMR (400.13 MHz, H O/D O (3:1), pH 10 buffer
C
6
14 2 2 9
H28Cl N O
0
0
3
.4. Preparation of (S)-N,N,N ,N -tetrakis[(ethoxy-carbonyl)methyl]-
1
2
2
1
,2-diaminopropane 5
3
(3)
HH
4 4 3
NH OH/NH Cl, ppm): 1.28, (d, 3H, J 6.95 Hz (C H )); 2.86, (dd,
3
(1)
3
(1)
1
3
D
H, J 10.6 Hz, (H
a
C
H
2
)); 2.96, (dd, 1H J 4.28 Hz, (H
H , C H)). C NMR (100.63 MHz, H
2
b
C
H
2
));
O/
A
a
Ab
In a 500 mL one-necked reaction vessel, equipped with an
external magnetic stirrer, a suspension of 1,2-diaminopropane
dihydrochloride, 4, 2.51 g (17.09 mmol) and anhyd tripotassium
(4,5)
(2)
13
.35–3.72, (m, 10H (C
O (3:1) pH 10 buffer NH
2
(3)
2
(5)
4
OH/NH
4
Cl, ppm): 10.9 (C
H
3
); 54.2
(2)
(1)
(4)
(6)
(
C
H
2
); 55.5 (C H); 56.5 (C
H
ꢂ
2
); 58.2 (C
H
2
); 174.9 (C @O);
phosphate, K
AN) was prepared. To this solution, while stirring at rt ethylbro-
moacetate, BrCH COOEt, 38.1 g (341.8 mmol) was added in one
portion. Then the reaction mixture was stirred at rt for 6 days. After
this period the solvent and most of the excess BrCH COOEt were
3
PO
4
, 36.23 g (170.9 mmol) in 180 mL of acetonitrile
(7)
20
D
1
+
77.6 (C @O). Polarimetry: ½
a
¼ þ24:7 (c 25.20, CH OH). Lit.:
3
(
7
47.0 (without additional details) (Fig. 2).
2
Acknowledgment
2
removed by distillation (2 mmHg). To the solid product 180 mL
of 3 M aqueous HCl was added, which resulted in the complete dis-
solution of this solid. The aqueous solution was then extracted
The (Italian) Ministry of University and Research (MIUR, con-
tract no. RBPR05NWWC) is acknowledged for support of this work.
2
twice with 70 mL portions of Et O. Then the reaction vessel, with
an Allihn condenser, containing the aqueous phase was immersed
in an ice/water bath and to the solution solid NaOH was added un-
til a pH of 14 was reached. At this point, the aqueous solution was
References
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2
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2
4
2
was evaporated in a rotary evaporator. The product was a yellow
oil. Yield: 6.146 g (86.0%).
The product was characterized by elemental analyses, infrared
and NMR spectroscopy, and polarimetry.
2
(a) Bartha, K.; Csékei, M.; Csihony, S.; Mehdi, H.; Horváth, I. T.; Pusztai, Z.; Vlád,
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4.0; H, 7.8; N, 6.9. Infrared: (KBr pellet, cm ): 2981, s, 2875, s, (
C–NH–); 1745, s, ( C@O); 1466, m, 1447, m, ( C–NH–); 1370, s, (d
C–NH–); 1190, s, ( –O–CH ). NMR (assigned with ref. to Fig. 1): H
NMR (200.13 MHz, CDCl
34 2 8
H N O : C, 54.55; H, 8.13; N, 6.70. Found: C,
ꢁ1
5
m
m
m
x
1
3
1
29, 5735–5743; (g) Markovitch, O.; Agmon, N. Mol. Phys. 2008, 106, 485–495.
3
(3)
3
, ppm): 1.27, (d, 3H, J 7.10 Hz, (C
HH
H
H
3
));
));
4. (a) Pályi, G.; Zucchi, C.; Bencze, L.; Caglioti, L. In New Avenues in Bioinformatics;
Seckbach, J., Rubin, J., Eds.; Springer: Berlin, 2004; pp 81–98; (b) Losada, M.; Xu,
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Int. Ed. 2007, 46, 7738–7740.
5. (a) Faglioni, F.; Lazzeretti, P.; Pályi, G. Chem. Phys. Lett. 2007, 435, 346–349; (b)
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3
(10+11)
3 a
H )); 2.57, (dd, 1H, (H
C(1)
1
2
J
(
(
.30, (t, 12H, J 7.30 Hz, (C
2
HH
3
2
(1)
.95, (dd, 1H, J 6.46 Hz, Jab 13.50 Hz (H
b
C
H
2
)); 3.11, (sex, 1H,
HH
(2)
3
6.65 Hz (C H)); 3.59,3 (s, 4H (NC(5)H
HH
2
)); 3.63, (s, 4H
NC(4)
H
2
)); 4.17, (q, 8H,
J
7.26 Hz (OC
(8+9)
H
2
)). 13C NMR
HH
(
10+11)
(3)
50.29 MHz, CDCl
3
, ppm): 14.86 (OCH
2
C
H
3
); 15.37 (C
H
H
3
);
);
2.53 (C(
0.42 (O–C
5)
(4)
(2)
(1)
7. Dwyer, F. P.; Garvan, F. L. J. Am. Chem. Soc. 1959, 81, 2955–2957.
5
6
H
2
(
–N); 55.55 (C
); 60.35 (O–C
@O). Polarimetry: ½
H
2
–N); 56.28 (C H); 58.48 (C
2
8.
(a) Gansow, O. A.; Loeffler, P. A.; Davis, R. E.; Willcott, M. R., III; Lenkinski, R. E. J.
Am. Chem. Soc. 1973, 95, 3389–3390; (b) Kabuto, K.; Sasaki, Y. J. Chem. Soc.,
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Sasaki, Y. Tetrahedron: Asymmetry 1992, 3, 1357–1360.
9)
(8)
(6)
H
2
H
2
); 171.3 (C @O); 172.1
¼ þ1:4 (c 8.53, CHCl ).
(7)
20
(
C
aꢂ
3
D
0
0
3
.5. Preparation of (S)-N,N,N ,N -tetrakis[(hydroxy-carbonyl)-
9.
Smith, R.; Bullock, J. L.; Brethworth, F. C.; Martell, A. E. J. Org. Chem. 1949, 14,
355–361.
methyl]-1,2-diamino-propane dihydrochloride 6
1
0. (a) Curme, G. O., Jr.; Chitwood, H. C.; Clarck, J. W. (to Carbide and Carbon Chem.
Corp.) U.S. Patent 2,384,816, 1945.; (b) Chitwood, H. C. (to Carbide and Carbon
Chem. Corp.) U.S. Patent 2,384,817, 1945.; (c) Kozlov, Yu. M.; Babich, V. A. Zh.
Obshch. Khim. 1981, 51, 1115–1119.
0
0
(
S)-N,N,N ,N -Tetrakis[(ethoxycarbonyl)-methyl]-1,2-diamino-
propane, 5.46 g (13.1 mmol), was suspended in 30 mL of methanol