The synthesis of N-(β-triphenylgermanyl)-propionyl-α-amino-benzylphosphonates

Article abstract of DOI:10.1081/SCC-100104839

A series of N-(β-triphenylgermanyl)propionyl-α-amino-benzylphosphonates was synthesized by reaction of β-triphenylgermanyl propionic acid with α-aminophosphonates under very mild conditions. The structures of products were determined by ¹H NMR,

Full text of DOI:10.1081/SCC-100104839

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THE SYNTHESIS OF N-(β-TRIPHENYLGERMANYL)-
PROPIONYL-α-AMINOBENZYLPHOSPHONATES
Yong Ye a , Qiang Zeng a & Lun-Zu Liu a
a State Key Laboratory of Elemento-Organic Chemistry , Institute of Elemento-Organic
Chemistry, Nankai University , Tianjin, 300071, P.R. China
Published online: 09 Nov 2006.
To cite this article: Yong Ye , Qiang Zeng & Lun-Zu Liu (2001) THE SYNTHESIS OF N-(β-TRIPHENYLGERMANYL)-
PROPIONYL-α-AMINOBENZYLPHOSPHONATES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:15, 2373-2378, DOI: 10.1081/SCC-100104839
To link to this article: http://dx.doi.org/10.1081/SCC-100104839
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SYNTHETIC COMMUNICATIONS, 31(15), 2373–2378 (2001)
THE SYNTHESIS OF
N-(b-TRIPHENYLGERMANYL)-
PROPIONYL-a-AMINO-
BENZYLPHOSPHONATES
Yong Ye,* Qiang Zeng, and Lun-Zu Liu
State Key Laboratory of Elemento-Organic Chemistry,
Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P.R. China
ABSTRACT
A
series of N-(b-triphenylgermanyl)propionyl-a-amino-
benzylphosphonates was synthesized by reaction of b-triphe-
nylgermanyl propionic acid with a-aminophosphonates under
very mild conditions. The structures of products were det-
ermined by 1H NMR, 31P NMR, IR, MS and elemental
analyses. The structure of 3a was confirmed by single-Crystal
X-ray diffraction studies.
b-Triphenylgermanyl propionic acid and its derivatives have recently
attracted a great deal of attention due to their strong anti-inflammatory,
antibiotics and anticancer properties.1–3 a-aminophosphates also are
reported to exhibit diverse biological activities, such as potent antibiotics,4
enzyme inhibitors,5 and pharmacological agents.6 It is conceivable that the
*Corresponding author.
2373
Copyright & 2001 by Marcel Dekker, Inc.
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2374
YE, ZENG, AND LIU
incorporation of the two moieties into one structural unit might produce an
unexpected effect on the biological activity.
Several methods for the preparation of a-aminophosphonates are avail-
able: a) addition of P-H function to imines and enamines,7 b) conversion of
the corresponding 1-hydroxyalkanephosphonates,8,9 c) Strecker-type reac-
tion of an aldehyde, ammonium acetate and diethylphosphite.10 However,
method a) and b) require rigid experimental conditions, and method c) pro-
vide lower yields (32–59%).
In this paper, we adopt a facile and direct route to have >80% yield of
compound 1 (shown in Scheme). The title compounds are readily obtained in
good yields using DMAP as catalyst under very mild conditions. The struc-
ture of compounds 3a–1 were determined by 1H NMR and elemental analy-
sis. Some of them were confirmed by IR, 31P NMR. Their related data are
shown in Table 1 and 2.
Scheme.
The structure of 3a was confirmed by MS spectrometry and Single-
Crystal X-ray diffraction studies. The crystal is the triclinic space group
with a ¼ 9.7753(5), b ¼ 11.5773(5), c ¼ 13.5059(6) A, V ¼ 1457.63(12) A3,
a ¼ 104.1850(10), b ¼ 95.9710(10), g ¼ 96.7270(10)ꢀ, Z ¼ 2, Mt ¼ 574.13,
Dc ¼ 1.308 g/cm3, ꢀ ¼ 0.7107 A, m ¼ 1.139 mmꢁ1, and F(000) ¼ 596. The
structure was refined to R ¼ 0.0257, wR ¼ 0.0705 for 5080 observed reflec-
tions with I>2 s (I). The molecular structure is shown in Fig.
Figure.

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b-TRIPHENYLGERMANYL PROPIONIC ACID
Table 1. Physical Data of Compounds 3a–l
Elementary analysis
2375
(%, calcd.)
Yield
R3 (%)
m.p
(ꢀC)
Compd.
3a
R
H
R1
H
R2
C6H5-
C
H
N
Me 86.0 130–132 63.58
6.07
2.60
(63.85) (5.98) (2.33)
Et 82.0 136–138 62.95 5.94 2.66
(62.78) (5.58) (2.44)
CH2O2C6H3- nPr 81.2 144–146 61.71
6.11 2.53
(61.43) (5.85) (2.05)
p-MeO-C6H4- nPr 83.5 142–144 63.60
6.18 2.03
(63.66) (6.36) (2.12)
Ph 77.8 168–170 65.48 4.92 2.11
(65.56) (4.78) (1.91)
p-MeO-C6H4- iBu 76.8 134–136 64.60
7.08 2.08
(64.50) (6.70) (2.00)
Et 84.7 136–138 64.14 6.59 2.58
(64.33) (6.17) (2.27)
Et 79.0 138–140 65.31 6.47 2.12
(65.26) (6.53) (2.18)
CH2O2C6H3- Me 83.5 134–136 59.33 5.04 2.14
(59.27) (5.10) (2.23)
p-MeO-C6H4- Me 87.0 128–130 61.60 5.58 2.26
(61.63) (5.63) (2.32)
Ph 76.6 158–160 66.96 5.51 1.82
(67.00) (5.46) (1.78)
Me Me CH2O2C6H3- nPr 74.6 152–154 64.22
6.53 1.86
(64.16) (6.58) (1.92)
3b
3c
3d
3e
3f
H
H
H
H
H
H
H
C6H5-
H
H
H
p-ClC6H4-
H
3g
3h
3i
Me C6H5-
Me Me C6H5-
H
H
H
H
3j
3k
3l
Me Me p-ClC6H4-
EXPERIMENTAL
Melting points were uncorrected. Elemental analyses were carried on a
Yanaco CHN Corder MT-3 apparatus. IR spectra were recorded as KBr
1
pellets on a BRUCK spectrometer. H NMR and 31P NMR spectra were
measured by using a Brucker AC-P200 spectrometer with TMS and 85%
H3PO4 as the internal and external reference respectively and with CDCl3 as
the solvent. MS Spectra was performed on a HP5988A spectrometer.
Compound 2 were synthesized according to literature.11

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YE, ZENG, AND LIU
Table 2. 1H and 31P NMR Data of Compounds 3a–l
d (ppm)
Compd.
3a
1.85 (m, 2H, CH2Ge); 2.36 (m, 2H, CH2C=0); 3.28 (d, 3H, OMe); 3.69
3
2
(d, 3H, OMe); 5.54 (dd, 1H, CHP, JPH=15.13 Hz, JHH=9.38 Hz);
7.24–7.43 (m, 20H, Ph); 24.24
3b
3c
1.01 (t, 3H, CH3); 1.28 (t, 3H, CH3); 1.85 (m, 2H, GeCH2); 2.36 (m, 2H,
CH2 C=O); 6.52 (br, 1H, NH); 3.52–3.68 (m, 4H, 2OCH2); 5.54 (dd, 1H,
2
3
CHP, JPH=11.48 Hz, JHH=9.38 Hz); 7.24–7.45 (m, 20H, Ph)
0.77 (t, 3H, CH3); 0.89 (t, 3H, CH3); 1.50–1.71 (m, 4H, CH2); 1.85
(m, 2H, GeCH2); 2.36 (m, 2H, CH2C=O); 3.65–4.10 (m, 4H, OCH2);
5.54 (dd, 1H, CHP); 5.91 (s, 2H, OCH2O); 6.50 (br, 1H, NH); 6.7–6.9
(m, 3H, Ph); 7.24–7.45 (m, 15H, Ph); 21.91
3d
0.73 (t, 6H, CH2CH3); 0.89 (t, 6H, CH2CH3); 1.80 (m, 2H, GeCH2);
1.5–1.7 (m, 8H, CH2CH3); 2.32 (m, 2H, CH2C=O); 3.51 (m, 2H,
OCH2); 3.92 (m, 2H, OCH2); 3.83 (s, 3H, OCH3); 5.45 (dd, 1H, CHP,
2
3JHH=9.4 Hz, JPH=15.12 Hz); 6.42 (br, 1H, NH); 6.83 (d, 2H,
CH=COMe); 7.24–7.45 (m, 17H, Ph); 22.19
3e
3f
1.85 (m, 2H, GeCH2); 2.74 (m, 2H, CH2C=O); 6.50 (br, 1H, NH); 5.66
2
(dd, 1H, CHP, JPH=11.48 Hz); 7.11–7.42 (m, 29H, Ph)
0.72 (d, 6H, CH3); 0.88 (d, 6H, CH3); 1.20 (m, 2H, CHMe); 1.88 (m, 2H,
CH2Ge); 2.40 (m, 2H, CH2C=O); 3.3–3.7 (m, 4H, OCH2); 3.85 (s, 3H,
OMe); 5.52 (dd, 1H, CHP); 6.67 (br, 1H, NH); 6.88 (d, 2H,
CH=COMe); 7.32–7.45 (m, 17H, Ph)
3g
1.02 (t, 3H, CH2CH3); 1.22 (t, 3H, CH2CH3); 1.13 (d, 3H, CHCH3); 2.52
(m, 1H, CHC=O); 3.7–4.1 (m, 4H, OCH2); 1.96 (m, 2H, CH2Ge); 5.46
(dd, 1H, CHP, JHH=9.4 Hz, JPH=16.16 Hz); 6.30 (br, 1H, NH);
7.24–7.40 (m, 20H, Ph)
3
2
3h
3i
1.03 (t, 3H, CH2CH3); 1.27 (t, 3H, CH2CH3); 1.85 (m, 2H, CH2Ge); 2.34
(m, 2H, CH2C=O); 2.40 (s, 3H, CH3Ph); 3.60–4.15 (m, 4H, OCH2); 5.52
(dd, 1H, CHP); 6.60 (br, 1H, NH); 7.16–7.34 (m, 17H, Ph)
1.85 (m, 2H, GeCH2); 2.36 (m, 2H, CH2C=O); 3.28 (d, 3H, OMe); 3.69
(d, 3H, OMe); 5.54 (dd, 1H, CHP); 6.50 (br, 1H, NH); 6.7–6.9 (m, 3H,
Ph); 7.24–7.45 (m, 15H, Ph)
3j
1.83 (m, 2H, GeCH2); 2.52 (m, 2H, CH2C=O); 3.28 (d, 3H, OCH3); 3.69
(d, 3H, OCH3); 3.83 (s, 3H, PhOCH3); 5.45 (dd, 1H, CHP); 6.42 (br, 1H,
NH); 6.83 (d, 2H, CH=COMe); 7.24–7.45 (m, 17H, Ph)
3k
3l
1.13 (d, 3H, CH3CH); 1.85 (m, 2H, GeCH2); 2.40 (s, 9H, CH3Ph); 2.74 (m,
1H, CHC=O); 5.66 (dd, 1H, CHP); 6.50 (br, 1H, NH); 7.11–7.42 (m, 26H, Ph)
0.77 (t, 3H, CH3); 0.89 (t, 3H, CH3); 1.13 (d, 3H, CH3CH); 1.50–1.71
(m, 4H, CH2CH3); 1.85 (m, 2H, GeCH2); 2.40 (s, 9H, CH3Ph); 2.74 (m, 1H,
CHC=O); 3.65–4.10 (m, 4H, OCH2); 5.54 (dd, 1H, CHP); 5.91 (s, 2H,
OCH2O);6.50(br,1H,NH);6.7–6.9(m,3H, Ph);7.24–7.45(m,15H, PhMe)

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b-TRIPHENYLGERMANYL PROPIONIC ACID
General Procedure for the Synthesis of 1
2377
A mixture of benzyl carbomate (0.6 g, 4 mmol), the dialkyl phosphi-
te(4 mmol) and AcCl(3 ml) is stirred at ꢁ5ꢀ in an ice/salt bath, the aldehyde
(4 mmol) is added dropwise during a period of 10 min, and stirring is con-
tinued at 0 for 1 h. The cooling bath is removed, the mixture is stirred at
ambient temperature for 5 h, and then the volatile components are removed
under reduced pressure. The remaining product is recrystallized from
EtOAc/hexane. The solids (4 mmol) obtained is dissolved in ethanol
(50 ml) which is added 5% Pd/C catalyst (0.25 g). The solution was stirred
under a hydrogen atmosphere for 12 h at room temperature. The mixture
was then filtered through silica gel and the solvent was removed under
vacuum. Compound 1 were obtained in good yield.
General Procedure for the Synthesis of 3a-l
2.65 mmol compound 1 and 2, 0.6 g DCC (2.92 mmol) were dissolved
in 20 ml of dry dichloromethane under stirring. A solution of 0.06 g
(0.5 mmol) DMAP in 5 ml of dry dichloromethane was dropped slowly
into the reaction mixture. It was stirred at room temperature for five
hours. The solvent was removed under reduced pressure. The crude product
was purified by flash chromatography on a silica gel column using a mixture
of ethyl acetate and petroleum ether (1 : 8) as the eluent, giving white solid
compound in good yield.
IR(cmꢁ1) data of 3b: 3267.0, 3207.0, 3051.0, 2984.2, 2896.0, 1672.7,
155.8, 1484.0, 1429.9, 1389.4, 1227.8, 1148.0, 1090.3, 1033.5, 976.3, 795.9,
739.6, 698.8, 558.7, 464.9.
IR(cmꢁ1) data of 3c: 3271.1, 2968.4, 1677.8, 1533.3, 1487.2, 1430.8,
1363.5, 1249.2, 1091.6, 1006.3, 933.0, 737.4, 700.0, 625.6, 462.8.
IR(cmꢁ1) data of 3d: 3253.1, 3051.0, 2964.5, 2933.0, 1664.7, 1607.0,
1542.0, 1511.5, 1430.1, 1303.0, 1229.1, 1182.2, 1091.4, 1059.0, 1018.8, 843.2,
7337.0, 700.0, 597.0, 55.0, 462.8.
MS data of 3a: 575 (0.86), 498 (60.49), 388 (35.83), 376 (32.65), 305
(100), 227 (25.10), 160 (14.67), 151 (50.99), 132 (11.06), 106 (86.45), 93 (42.75),
79 (18.95), 77 (25.01).
ACKNOWLEDGMENTS
We are thankful to the National Natural Science Found of China (No.
29972024) for the financial support.

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YE, ZENG, AND LIU
REFERENCES
1. Kakimoto Norihiro, et al. Jpn. Kokai Tokkyo Koho, JP 61 1986,
267, 591.
2. Mironov, V.F., et al. Zh. Obshch. Khim. 1986, 56(4), 966.
3. Kakimoto Norihiro, et al. Jpn. Kokai Tokkyo Koho, JP 6200
1987, 092.
4. Atherton, F.R.; Hassal, C.H. and Lambert, R.W. J. Med. Chem. 1987,
30, 1603.
5. Allen, M.C.; Fuhrer, W.; Tuck, B., et al. J. Med. Chem. 1989, 32, 1652.
6. Hassall, C.H. in ‘‘Antibiotics’’; Hahn, F. E. ed., Spring-Verlag, Berlin,
1983. Vol: vi, p. 1–11.
7. Hyun-Joon Ha and Gong-sil Nam. Synth. Commun. 1992, 22, 1143.
8. Chakraborty, S. and Engel, R. Synth. Commun. 1991, 21, 1039.
9. Gajda, T. and Matsiak, M. Synth. Commun. 1992, 22, 2193.
10. Takahashi, K.; Yoshioka, M.; Imai, N., et al. Synthesis 1994, 763.
11. Zheng-Guo Zhu; Guan, Y.D. and Zou, J.W. J. Organomet. Chem.
1994, 479, c1–c5.
Received in the Netherlands November 11, 2000

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