Solvent-free synthesis of α-aminophosphonates from N-heterocycles, activated acetylenes, and diphenyl phosphite

Article abstract of DOI:10.1080/00397910903249598

A three-component, uncatalyzed synthesis of α-aminophosphonates via the reaction of isoquinoline or benzothiazole with activated acetylenes in moderate to good yields under solvent-free conditions is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903249598

This article was downloaded by: [Duke University Libraries]
On: 10 October 2013, At: 02:46
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Solvent-Free Synthesis of α-
Aminophosphonates from N-
Heterocycles, Activated Acetylenes, and
Diphenyl Phosphite
Issa Yavari a , Anvar Mirzaei a & Loghman Moradi a
a Chemistry Department , Tarbiat Modares University , Tehran, Iran
Published online: 26 Jul 2010.
To cite this article: Issa Yavari , Anvar Mirzaei & Loghman Moradi (2010) Solvent-Free Synthesis of α-
Aminophosphonates from N-Heterocycles, Activated Acetylenes, and Diphenyl Phosphite, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:16, 2407-2414, DOI: 10.1080/00397910903249598
To link to this article: http://dx.doi.org/10.1080/00397910903249598
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 40: 2407–2414, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903249598
SOLVENT-FREE SYNTHESIS OF
a-AMINOPHOSPHONATES FROM N-HETEROCYCLES,
ACTIVATED ACETYLENES, AND DIPHENYL PHOSPHITE
Issa Yavari, Anvar Mirzaei, and Loghman Moradi
Chemistry Department, Tarbiat Modares University, Tehran, Iran
A three-component, uncatalyzed synthesis of a-aminophosphonates via the reaction of
isoquinoline or benzothiazole with activated acetylenes in moderate to good yields under
solvent-free conditions is described.
Keywords: Activated acetylene; a-aminophosphon; benzothiazole; diphenyl phosphite; isoquinoline;
a-mercaptophosphonate
INTRODUCTION
Approaches to the synthesis of optically active or racemic a-aminophosphonates
have been intensely investigated over the past few decades.[1,2] Because a-amino-
phosphonates are structural mimics of a-amino acids, some of these compounds
exhibit very high potency in inhibiting enzymes that are involved in the metabolism
of the corresponding amino acids. These compounds have already been found to
act as antibacterial agents, neuroactive compounds, anticancer drugs, and pesti-
cides,[3–6] and some of them have been commercialized.[7]
A number of synthetic methods for a-aminophosphonates have been
developed. Of these, the nucleophilic addition of phosphites to imines, catalyzed
by a base or an acid, is the most convenient. However, these reactions cannot be car-
ried out in a one-pot operation with a carbonyl compound, an amine, and a dialkyl
phosphite because the amine and water present during imine formation can decom-
pose or deactivate the Lewis acid.[8–13]
N-Heterocycles are known to form zwitterions with activated acetylenes such
as dimethyl acetylenedicarboxylate.[14] This type of zwitterion can be trapped by a
variety of electrophiles and proton donors.[15] As part of our current studies on
the development of new routes in heterocyclic synthesis,[16–18] we report a one-pot
synthesis of diphenyl a-aminophosphonates 4.
Received June 29, 2009.
Address correspondence to Issa Yavari, Chemistry Department, Tarbiat Modares University,
P.O. Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir
2407

2408
I. YAVARI, A. MIRZAEI, AND L. MORADI
RESULTS AND DISCUSSION
The reaction of isoquinoline (1) and activated acetylenes 2 in the presence of
diphenyl phosphite (3), proceeded smoothly at rt and was complete within 2 h.
The 1H and 13C NMR spectra of the crude products clearly indicated the formation
of diphenyl a-aminophosphonates 4 in 60–90% yield (Scheme 1).
1
The structures of compounds 4 were deduced from their infrared (IR), H
1
NMR, and 13C NMR spectra. For example, the H NMR spectrum of 4a exhibited
signals for MeO (d 3.70 and 3.97), CH (d 5.65), and vinylic (d 5.47, 5.98, and 6.36)
1
H-atoms, along with multiplets for the aromatic H-atoms. The H-decoupled 13C
NMR spectrum of 4a showed 23 distinct resonances, in agreement with the proposed
=
structure. The IR spectrum of 4a displayed characteristic ester carbonyl and P O
bands. The 1H NMR and 13C NMR spectra of 4b–f are similar to those for 4a except
for the ester moieties, which exhibited characteristic resonances in appropriate
regions of the spectrum.
Although the mechanistic details of the reaction are not known, a plausible
rationalization may be advanced to explain the product formation (see Scheme 2).
Presumably, the zwitterionic intermediate 5 formed from isoquinoline and activated
acetylenes[14] is protonated by 3 to furnish intermediate 6, which is attacked by 7 to
produce 4.
When the reaction was carried out in the presence of benzothiazole (8),
diphenyl phosphonates 9 were obtained in moderate to good yields (Scheme 3).
In summary, we report a synthesis of dialkyl 2-[diphenoxyphosphoryl)-2(1-
H)isoquimolinyl]-2-butendioates under noncatalytic and solvent-free conditions.
Scheme 1. Synthesis of diphenyl a-aminophosphonates 4.
Scheme 2. A plausible mechanism for the formation of diphenyl a-aminophosphonates 4.

SOLVENT-FREE SYNTHESIS OF a-AMINOPHOSPHONATES
2409
Scheme 3. Synthesis of diphenyl phosphonates 9.
Under similar reaction conditions, benzothiazole led to dialkyl 2-[2-(diphenoxypho-
sphoryl)-1,3-benzothiazol-3(2H)-yl]-2-butendioates. The present procedure has
the advantage that the reactants can be mixed without any prior activation or
modification.
EXPERIMENTAL
Compounds 1–3 were obtained from Fluka and were used without further
purification. Melting points were determined on an Electrothermal-9100 apparatus.
1
IR spectra wee measured on a Shimadzu IR-460 spectrometer. H and 13C NMR
spectra were measured on a Bruker DRX-500 Avance instrument in CDCl3 at
500.1 and 125.7 MHz, respectively; d in are stated in parts per million, and J in
are stated in hertz. EI-MS (70 eV) were determined on a Finnigan-MAT-8430 mass
spectrometer, in m=z. Elemental analyses (C, H, N) were performed with a Heraeus
CHN-O-Rapid analyzer.
General Procedure for Synthesis of Compounds 4 and 9
Compound 2 (2 mmol) was added to a stirred solution of 0.47 g of diphenyl
phosphite (2 mmol) and 1 or 8 (2 mmol) at rt. After completion of the reaction
(1–2 h), as indicated by thin-layer chromatography (TLC; AcOEt=hexane, 2:1), the
mixture was separated by column chromatography (SiO2, Merck 230–240 mesh)
using hexane=AcOEt 4:1 as eluent to afford the pure product.
Data
Dimethyl 2-[diphenoxyphosphoryl)-2(1H)isoquinolinyl]-2-butenedioate
(4a). White powder, mp 157–159 ꢀC, yield 0.46 g (90%). IR (KBr) (vmax=cmꢁ1):
l
2925, 1730 (C O), 1693 (C O), 1587, 1480, 1257 (P O), 1149, 929, 764. H
=
=
=
5
NMR: d ¼ 3.70 (3H, s, MeO), 3.97 (3H, s, MeO), 5.47 (1H, d, JPH ¼ 1.9, CH),
5.65 (1H, d, 2JPH ¼ 12.9, CH), 5.98 (1H, d, 3JHH ¼ 7.6, CH), 6.36 (1H, d, 3JHH ¼ 7.6,
3
3
7.6, CH), 6.76 (2H, d, JHH ¼ 8.4, 2 CH), 7.03 (2H, d, JHH ¼ 8.4, 2 CH), 7.06–7.08

2410
I. YAVARI, A. MIRZAEI, AND L. MORADI
(2H, m, 2 CH), 7.14–7.19 (3H, m, 3 CH), 7.24–7.32 (5H, m, 5 CH). 13C NMR:
1
d ¼ 51.3 (MeO), 53.2 (MeO), 57.8 (d, JPC ¼ 155.2, P-CH), 92.8 (CH), 115.5 (CH),
3
3
119.9 (d, JCP ¼ 4.2, 2 CH), 120.3 (d, JCP ¼ 4.2, 2 CH), 123.7 (CH), 125.0 (CH),
3
2
125.1 (CH), 125.2 (d, JCP ¼ 2.8, CH), 125.9 (CH), 127.6 (CH), 127.8 (d, JCP ¼ 6.2,
6.2, C), 129.3 (d, 3JCP ¼ 5.0, C), 129.4 (2 CH), 129.6 (2 CH), 130.9 (d, 3JCP ¼ 3.8, C),
2
2
=
149.6 (CH), 150.1 (d, JCP ¼ 10.5, C), 150.2 (d, JCP ¼ 10.5, C), 164.6 (C O), 164.8
3l
þ
=
(C O). P NMR: d ¼ 10.1. EI-MS: 505 (2, M ), 376 (5), 317 (8), 285 (20), 272 (100),
223 (25), 129 (75), 94 (30), 77 (60), 39 (50). Anal. calc. for C27H24NO7P (505.46): C,
64.16; H, 4.79; N, 2.77. Found: C, 64.31; H, 4.70; N 2.80.
Diethyl 2-[diphenoxyphosphoryl)-2(1H)isoquinolinyl]-2-butenedioate
(4b). White powder, mp 134–136 ꢀC, yield 0.42 g (79%). IR (KBr) (vmax=cmꢁ1):
l
2930, 1733 (C O), 1690 (C O), 1590, 1470, 1260 (P O), 1150, 935, 754. H
=
=
=
3
3
NMR: d ¼ 1.26 (3H, t, JHH ¼ 7.1, Me), 1.38 (3H, t, JHH ¼ 7.1, Me), 3.70 (2H, q,
3JHH ¼ 7.1, CH2O), 3.97 (2H, q, JHH ¼ 7.1, CH2O), 5.45 (1H, d, JPH ¼ 1.8, CH),
5.66 (1H, d, 2JPH ¼ 13.0, CH), 5.96 (1H, d, 3JHH ¼ 7.6, CH), 6.39 (1H, d, 3JHH ¼ 7.6,
7.6, CH), 6.76 (2H, d, 3JHH ¼ 8.4, 2 CH), 7.04–7.08 (4H, m, 4 CH), 7.13–7.19 (3H, m,
3 CH), 7.24–7.31 (5H, m, 5 CH). 13C NMR: d ¼ 13.7 (Me), 14.2 (Me), 57.8 (d,
3
5
1JPC ¼ 155.2, P-C), 59.9 (CH2O), 62.5 (CH2O), 93.2 (d, JCP ¼ 2.9, CH), 111.3
3
3
3
(CH), 119.0 (d, JCP ¼ 4.2, 2 CH), 120.3 (d, JCP ¼ 4.4, 2 CH), 123.7 (CH), 125.0
3
4
(CH), 125.1 (CH), 125.2 (d, JCP ¼ 3.0, CH), 126.0 (CH), 127.6 (d, JCP ¼ 2.6,
2
3
CH), 127.7 (d, JCP ¼ 5.6, C), 129.3 (d, JCP ¼ 3.4, C), 129.3 (2 CH), 129.5 (2 CH),
3
2
2
131.0 (d, JCP ¼ 3.8, C), 149.6 (CH), 150.2 (d, JCP ¼ 11.0, C), 150.3 (d, JCP ¼ 11.0,
11.0, C), 164.1 (C O), 166.3 (C O). 3lP NMR: d ¼ 12.4. EI-MS: 533 (1, Mþ), 404
(6), 331 (9), 285 (22), 300 (100), 237 (27), 129 (73), 94 (29), 77 (62), 39 (49). Anal.
calc. for C29H28NO7P (533.51): C, 65.29; H. 5.29; N, 2.63. Found: C, 65.11; H,
5.23; N, 2.65.
=
=
Di(t-butyl) 2-[diphenoxyphosphoryl)-2(1H)isoquinolinyl]-2-butenedio-
ate (4c). White powder, mp 136–138 ꢀC, yield 0.40 g (68%). IR (KBr) (vmax=cmꢁ1):
l
2932, 1725 (C O), 1690 (C O), 1600, 1490, 1237 (P O), 1135, 923, 746. H NMR:
=
=
=
5
d ¼ 1.45 (9H, s, Me3C), 1.59 (9H, s, Me3C), 5.35 (1H, d, JPH ¼ 1.6, CH), 5.64 (1H,
2
3
3
d, JPH ¼ 12.6, CH), 5.90 (1H, d, JHH ¼ 7.6, CH), 6.46 (1H, d, JHH ¼ 7.60, CH),
3
6.76 (2H, d, JHH ¼ 8.4, 2 CH), 7.13–7.17 (4H, m, 4 CH), 7.19–7.21 (3H, m, 3 CH),
7.25–7.31 (5H, m, 5 CH). 13C NMR: d ¼ 27.9 (Me3C), 28.3 (Me3C), 57.2 (d,
1JPC ¼ 160.0, P-C), 83.7 (OCMe3), 84.0 (OCMe3), 94.9 (CH), 119.4 (CH), 120.0 (d,
3JCP ¼ 4.2, 2 CH), 120.3 (d, JCP ¼ 4.2, 2 CH), 123.7 (CH), 125.0 (CH), 125.2 (CH),
3
3
2
125.3 (d, JCP ¼ 5.6, CH), 126.3 (CH), 127.5 (CH), 127.7 (d, JCP ¼ 5.6, C), 129.2 (2
3
CH), 129.3 (C), 129.4 (2 CH), 131.3 (d, JCP ¼ 3.0, C), 149.4 (CH), 150.0 (d,
JCP ¼ 11.4, C), 150.2 (d, JCP ¼ 11.4, C), 163.0 (C O), 165.6 (C O). 3lP NMR:
2
2
=
=
d ¼ 11.6. EI-MS: 589 (2, Mþ), 460 (7), 359 (11), 285 (26), 356 (100), 265 (24), 129
(72), 94 (31), 77 (62), 39 (53). Anal. calc. for C33H36NO7P (589.62): C, 67.22; H,
6.15; N, 2.38. Found: C, 67.20; H, 6.20; N, 2.45.
Methyl (E)-3-[diphenoxyphosphoryl)-2(1H)isoquinolinyl]-2-propenoate
(4d). White powder, mp 190–192 ꢀC, yield 0.40 g (89%). IR (KBr) (vmax=cmꢁ1):
l
=
=
5
1680 (C O), 1615, 1583, 1257 (P O), 1153, 993, 766. H NMR: d ¼ 3.72 (3H, s,
3
2
MeO), 5.30 (1H, dd, JHH ¼ 13.5, JPH ¼ 1.7, CH), 5.58 (1H, d, JPH ¼ 12.8, CH),

SOLVENT-FREE SYNTHESIS OF a-AMINOPHOSPHONATES
2411
5.88 (1H, d, 3JHH ¼ 7.5, CH), 6.45 (1H, d, 3JHH ¼ 7.5, CH), 6.83 (2H, d, 3JHH ¼ 8.0, 2
3
CH), 6.98 (2H, d, JHH ¼ 8.0, 2 CH), 7.04–7.17 (3H, m, 3 CH), 7.19–7.20 (2H, m, 2
3
CH), 7.23–7.31 (5H, m, 5 CH), 7.53 (1 , d, JHH ¼ 13.5, CH). 13C NMR: d ¼ 51.0
1
3
(MeO), 58.8 (d, JPC ¼ 160.0, P-C), 92.5 (CH), 109.3 (CH), 119.9 (d, JCP ¼ 4.2, 2
3
CH), 120.1 (d, JCP ¼ 4.2, 2 CH), 123.2 (CH), 125.0 (CH), 125.1 (CH), 125.2 (d,
3JCP ¼ 3.0, CH), 127.4 (CH), 127.8 (d, JCP ¼ 5.5, C), 128.5 (CH), 129.3 (d,
2
3JCP ¼ 3.2, C), 129.5 (2 CH), 129.6 (2 CH), 131.4 (d, JCP ¼ 3.6, CH), 147.3 (CH),
3
150.1 (d, JCP ¼ 10.6, C), 150.2 (d, JCP ¼ 10.6, C), 168.5 (C O). 3lP NMR:
d ¼ 11.5. EI-MS: 447 (1, Mþ), 318 (5), 259 (12), 214 (100), 165 (20), 129 (70), 94
(28), 77 (56), 39 (46). Anal. calc. for C25H22NO5P (447.42): C, 67.11; H, 4.96; N,
3.13. Found: C, 67.42; H, 4.87; N 3.05.
2
2
=
Ethyl (E)-3-[diphenoxyphosphoryl)-2(1H)isoquinolinyl]-2-propenoate
(4e). White powder, mp 128–130 ꢀC, yield 0.32 g (70%). IR (KBr) (vmax=cmꢁ1):
l
=
=
1684 (C O), 1613, 1584, 1477, 1258 (P O), 1153, 936, 766. H NMR: d ¼ 1.26
(3H, t, 3JHH ¼ 7.1, Me), 4.15 (2H, q, 3JHH ¼ 7.1, CH2O), 5.27 (1H, dd, 3JHH ¼ 13.5,
5JPH ¼ 2.0, CH), 5.56 (1H, d, JPH ¼ 12.5, CH), 5.85 (1H, d, JHH ¼ 7.5, CH), 6.43
2
3
3
3
3
(1H, d, JHH ¼ 7.5, CH), 6.81 (2H, d, JHH ¼ 8.5, 2 CH), 6.97 (2H, d, JHH ¼ 8.5,
2 CH), 7.01–7.10 (3H, m, 3 CH), 7.14–7.17 (2H, m, 2 CH), 7.20–7.28 (5H, m, 5
CH), 7.50 (1H, d, JHH ¼ 13.5, CH). 13C NMR: d ¼ 14.5 (Me), 58.8 (CH, d,
3
1JPC ¼ 158.0, P-C), 59.7 (CH2O), 93 (CH), 109.2 (CH), 120.0 (d, JCP ¼ 4.2, 2
3
3
CH), 120.2 (d, JCP ¼ 4.2, 2 CH), 123.2 (CH), 125.0 (CH), 125.1 (CH), 125.2 (d,
3JCP ¼ 3.0, CH), 127.4 (CH), 127.9 (d, JCP ¼ 5.5, C), 128.7 (CH), 129.3 (d,
2
3JCP ¼ 3.4, C), 129.5 (2 CH), 129.6 (2 CH), 131.5 (d, JCP ¼ 3.7, CH), 147.1 (CH),
3
150.2 (d, JCP ¼ 11.1, C), 150.3 (d, JCP ¼ 10.5, C), 168.1 (C O). 3lP NMR:
d ¼ 9.3. EI-MS: 461 (2, Mþ), 332 (6), 273 (10), 228 (100), 179 (23), 129 (68), 94
(29), 77 (55), 39 (46). Anal. calc. for C26H24NO5P (461.45): C, 67.67; H, 5.24; N,
3.04. Found: C, 67.72; H, 5.20; N, 2.90.
2
2
=
Diphenyl {2-[(E)-1-(4-methylbenzoyl)-3-(4-metylphenyl)-3-oxo-1-pro-
penyl]-1,2-dihydro-1-isoquinolinyl}phosphonate (4f). White powder, mp
159–161 ꢀC, yield 0.38 g (60%). IR (KBr) (vmax=cmꢁ1): 2923, 1664 (C O), 1593
=
l
=
=
(C O), 1513, 1480, 1268 (P O), 1177, 933, 756. H NMR: d ¼ 2.35 (3H, s, Me),
2
2.37 (3H, s, Me), 5.86 (1H, d, JPH ¼ 7.9, CH), 6.05 (1H, broad, CH), 6.74 (2H, d,
3JHH ¼ 7.8, 2 CH), 6.97–7.08 (4H, m, 4 CH), 7.11–7.19 (6H, m, 6 CH), 7.20–7.27
3
(6H, m, 6 CH), 7.29–7.41 (4H, m, 4 CH), 7.77 (2H, d, JHH ¼ 7.8, 2 CH). 13C
1
NMR: d ¼ 21.2 (Me), 21.8 (Me), 59.0 (d, JPC ¼ 181.0, P-CH), 115.4 (CH), 119.9
3
3
(CH), 120.0 (CH), 120.1 (d, JCP ¼ 3, 2 CH), 120.4 (d, JCP ¼ 3, 2 CH), 120.7
(CH), 125.4 (CH), 125.5 (CH), 126.3 (C), 127.2 (C), 127.8 (CH), 128.2 (2 CH),
128.6 (2 CH), 128.7 (CH), 129.1 (2 CH), 129.4 (2 CH), 129.5 (2 CH), 129.7 (C),
129.8 (2 CH), 129.9 (CH), 130.0 (C), 130.1 (C), 130.2 (C), 133.4 (CH), 142.9 (C),
150.1 (C), 150.2 (C), 156.4 (C O), 187.4 (C O). 3lP NMR: d ¼ 13.2. EI-MS: 625
(1, Mþ), 496 (14), 392 (100), 377 (3), 283 (22), 129 (65), 94 (25), 77 (66), 39 (45). Anal.
calc. for C39H32NO5P (625.66): C, 74.87; H, 5.16; N, 2.24. Found: C, 74.99; H, 5.10;
N, 2.30.
=
=
Dimethyl
2-[2-(diphenoxyphosphoryl)-1,3-benzothiazol-3(2H)-yl]-2-
butenedioate (9a). White powder, mp 150–152 ꢀC, yield 0.41 g (80%). IR (KBr)

2412
I. YAVARI, A. MIRZAEI, AND L. MORADI
l
(vmax=cmꢁ1): 2920, 1730 (C O), 1725 (C O), 1504, 1475, 1258 (P O), 940, 749. H
NMR: d ¼ 3.59 (3H, s, MeO), 3.66 (3H, s, MeO), 5.89 (1H, broad, CH), 6.34 (2H, d,
3JHH ¼ 8, 2 CH), 6.39 (1H, d, 2JPH ¼ 11.4, CH), 6.92–6.95 (2H, m, 2 CH), 7.01–7.04
(2H, m, 2 CH), 7.05–7.10 (3H, m, 3 CH), 7.19–7.24 (5H, m, 5 CH). 13C NMR:
=
=
=
1
d ¼ 52.5 (MeO), 52.9 (MeO), 63.5 (d, JPC ¼ 178.0, P-CH), 99.9 (CH), 110.9 (CH),
3
3
119.8 (d, JCP ¼ 4.4, 2 CH), 119.9 (d, JCP ¼ 4.4, 2 CH), 120.2 (CH), 120.3 (CH),
4
125.5 (d, JCP ¼ 4.0, CH), 125.7 (CH), 129.1 (CH), 129.5 (2 CH), 129.6 (2 CH),
2
2
129.7 (C), 141.4 (C), 143.4 (C), 150.2 (d, JCP ¼ 10.0, C), 150.4 (d, JCP ¼ 9.6, C),
163.7 (C O), 163.8 (C O). 3lP NMR: d ¼ 14.3. EI-MS: 511 (1, Mþ), 509 (7), 452
(12), 278 (100), 192 (22), 160 (23), 135 (16), 94 (28), 77 (32), 39 (21). Anal. calc.
for C25H22NO7PS (511.48): C, 58.71; H, 4.34; N, 2.74. Found: C, 58.80; H, 4.30;
N, 2.68.
=
=
Diethyl
2-[2-(diphenoxyphosphoryl)-1,3-benzothiazol-3(2H)-yl]-2-
butenedioate (9b). White powder, mp 129–131 ꢀC, yield 0.38 g (70%). IR (KBr)
(vmax=cmꢁ1): 2910, 1726 (C O), 1677 (C O), 1514, 1478, 1255 (P O), 933, 751.
=
=
=
lH NMR: d ¼ 1.11 (3H, t, JHH ¼ 9.8, Me), 1.18 (3H, t, JHH ¼ 9.8, Me), 4.10 (2H,
3
3
q,3JHH ¼ 9.8, CH2O), 4.25 (2H, q, JHH ¼ 9.8, CH2O), 6.37 (1H, d, JPH ¼ 7.96,
3
5
2
CH), 6.43 (1H, d, JPH ¼ 11.5, CH), 6.80 (1H, m, CH), 6.93–6.96 (2H, m, 2 CH),
7.04–7.16 (6H, m, 6 CH), 7.23–7.30 (5H, m, 5 CH). 13C NMR: d ¼ 13.7 (Me), 13.8
1
(Me), 61.1 (CH2O), 62.4 (CH2O), 63.5 (d, JPC ¼ 178.5, P-CH), 111.1 (CH), 120.2
3
3
(d, JCP ¼ 1.4, 2 CH), 120.3 (d, JCP ¼ 1.5, 2 CH), 121.5 (CH), 121.8 (CH), 124.6
4
(CH), 125.0 (d, JCP ¼ 2.4, CH), 125.4 (CH), 125.5 (CH), 129.4 (2 CH), 129.5 (2
2
2
CH), 129.7 (C), 139.6 (C), 143.6 (C), 150.2 (d, JCP ¼ 10.5, C), 150.5 (d, þJCP ¼ 9.8,
3l
=
=
9.8, C), 163.2 (C O), 163.3 (C O). P NMR: d ¼ 12.9. EI-MS: 539 (1, M ), 537 (5),
466 (13), 306 (100), 206 (20), 160 (20), 135 (18), 94 (25), 77 (30), 39 (20). Anal. calc.
for C27H26NO7PS (539.54): C, 60.11; H, 4.86; N, 2.60. Found: C, 59.95; H, 4.75;
N, 2.66.
Di(t-butyl)
2-[2-(diphenoxyphosphoryl)-1,3-benzothiazol-3(2H)-yl]-2-
butenedioate (9c). White powder, mp 127–129 ꢀC, yield 0.39 g (65%). IR (KBr)
(vmax=cmꢁ1): 2928, 1724 (C O), 1726 (C O), 1516, 1486, 1253 (P O), 955, 769. H
l
=
=
=
2
NMR: d ¼ 1.40 (9H, s, Me3C), 1.57 (9H, s, Me3C), 6.41 (1H, d, JPH ¼ 14.5, CH),
6.78 (1H, d, 5JPH ¼ 5.0, CH), 7.08 (1H, m, CH), 7.19–7.24 (2H, m, 2 CH), 7.25–7.27
(6H, m, 6 CH), 7.32–7.35 (5H, m, 5 CH). 13C NMR: d ¼ 27.8 (Me3C), 27.9 (Me3C),
1
63.5 (d, JPC ¼ 178.2, P-CH), 82.1 (OCMe3), 83.4 (OCMe3), 111.4 (CH), 120.1 (d,
3JCP ¼ 4.9, 2 CH), 120.7 (d, JCP ¼ 4.5, 2 CH), 121.3 (CH), 121.7 (CH), 123.3 (CH),
3
4
125.0 (CH, d, JCP ¼ 5, CH), 125.5 (CH), 125.6 (CH), 129.7 (2 CH), 129.8 (2 CH),
2
2
126.3 (C), 139.7 (C), 13.9 (C), 149.9 (d, JCP ¼ 7.6, C), 150.5 (d, JCP ¼ 7.4, C),
162.4 (C O), 162.9 (C O). 3lP NMR: d ¼ 12.8. EI-MS: 594 (2, Mþ), 494 (11), 362
(100), 234 (23), 160 (25), 135 (17), 94 (29), 77 (32), 39 (24). Anal. calc. for
C31H34NO7PS (594.64): C, 62.51; H, 5.75; N, 2.35. Found: C, 62.45; H, 5.65; N, 2.41.
=
=
Methyl
(E)-3-[2-(diphenoxyphosphoryl)-1,3-benzothiazol-3(2H)-yl]-2-
propenoate (9d). White powder, mp 145–147 ꢀC, yield 0.34 g (75%). IR (KBr)
(vmax=cmꢁ1): 2900, 1695, (C O), 1577, 1462, 1249 (P O), 1159, 911, 731. H
l
=
=
3
5
NMR: d ¼ 3.72 (3H, s, MeO), 5.59 (1H, dd, JHH ¼ 13.5, JPH ¼ 1.2, CH), 5.88
2
3
(1H, d, JPH ¼ 5.2, CH), 6.95 (2H, d, JHH ¼ 9.8, CH), 6.98–7.02 (4H, m, 4 CH),

SOLVENT-FREE SYNTHESIS OF a-AMINOPHOSPHONATES
2413
7.1–7.15 (4H, m, 4 CH), 7.21–7.26 (4H, m, 4 CH), 7.83 (1H, d, 3JHH ¼ 13.5, CH). 13
C
1
NMR: d ¼ 51.19 (MeO), 61.5 (d, JPC ¼ 181.1, P-CH), 95.9 (CH), 112.4 (CH), 120.0
(d, 3JCP ¼ 4.2, 2 CH), 120.1 (d, 3JCP ¼ 4.4, 2 CH), 122.7 (CH), 124.7 (CH), 125.4 (d,
4JCP ¼ 5.4, CH), 126.5 (CH), 127.3 (CH), 129.5 (C), 129.7 (2 CH), 129.8 (2 CH),
2
2
141.4 (C), 143.4 (CH), 150.2 (d, JCP ¼ 10.5, C), 150.4 (d, JCP ¼ 9.8, C), 168.4
(C O). 3lP NMR: d ¼ 11.4. EI-MS: 453 (1, Mþ), 451 (8), 394 (12), 220 (100), 192
=
(20) 160 (19), 135 (22), 94 (26), 77 (31), 39 (21). Anal. calc. for C23H20NO5PS
(453.45): C, 60.92; H, 4.45; N, 3.09. Found: C, 60.85; H, 4.51; N, 3.12.
REFERENCES
1. Thomas, A. A.; Sharpless, K. B. The catalytic asymmetric aminohydroxylation of
unsaturated phosphonates. J. Org. Chem. 1999, 64, 8379–8385.
2. Albrecht, S.; Defoin, A.; Salomon, E.; Tarnus, C.; Wetterholmb, A.; Haeggstro, J. Z.
Synthesis and structure–activity relationships of novel nonpeptidic metallo aminopepti-
dase inhibitors. Bioorg. Med. Chem. 2006, 14, 7241–7257.
3. Joossens, J.; Veken, P. V.; Surpateanu, G.; Anne, A. M.; El-Sayed, I.; Ali, O. M.;
Augustyns, K.; Haemers, A. Diphenyl phosphonate inhibitors for the urokinase-type
plasminogen activator: Optimization of the P4 position. J. Med. Chem. 2006, 49,
5785–5793.
4. Qi, X.; Lee, S. H.; Kwon, J. Y.; Kim, Y.; Kim, S. J.; Lee, Y. S.; Yoon, J. Aminobromina-
tion of unsaturated phosphonates. J. Org. Chem. 2003, 68, 9140–9143.
5. Ntai, I.; Manier, M. L.; Hachey, D. L.; Bachmann, B. O. Biosynthetic origins of C-P bond
containing tripeptide K-26. Org. Lett. 2005, 7, 2763–2765.
6. Joly, G. D.; Jacobsen, E. N. Thiourea-catalyzed enantioselective hydrophosphonylation
of imines: Practical access to enantiomerically enriched a-amino phosphonic acids.
J. Am. Chem. Soc. 2004, 126, 4102–4103.
7. Berlicki, L.; Kafarski, P. Computer-aided analysis and design of phosphonic and phos-
phinic enzyme inhibitors as potential drugs and agrochemicals. Curr. Org. Chem. 2005,
9, 1829–1950.
8. Azizi, N.; Saidi, M. R. Synthesis of tertiary a-amino phosphonate by one-pot, three-
component coupling mediated by LPDE. Tetrahedron 2003, 59, 5329–5332.
9. Xu, F.; Luo, Y. W. J.; Shen, Q.; Chen, H. Facile one-pot synthesis of phosphonates using
lanthanide chloride as catalyst. Heteroat. Chem. 2006, 17, 389–392.
10. Bioton, L. D.; Villemin, D.; Lohier, J. F.; Sopkova, J.; Jaffr, P. A. Synthesis of triazolyl-
alkylphosphonate starting from x-azidoalkylphosphonates or a-alkynylphosphonates.
Tetrahedron 2007, 63, 9677–9684.
11. Xu, F.; Luo, Y.; Deng, M.; Shen, Q. One-pot synthesis of a-amino phosphonates using
samarium diiodide as a catalyst precursor. Eur. J. Org. Chem. 2003, 24, 4728–4730.
12. Vanderhoydonck, B.; Stevens, C. V. Conjugate addition to 1-phosphono-2-aza-1,3-
butadienes: Synthesis of phosphonylated c-lactams. J. Org. Chem. 2005, 70, 191–198.
13. Atherton, F. R.; Hassal, C. H.; Lambert, R. W. Synthesis and structure–activity relation-
ships of antibacterial phosphonopeptides incorporating (l-aminoethy1)phosphonic acid
and (aminomethy1)phosphonic acid. J. Med. Chem. 1986, 29, 29–40.
14. Dillinger, H. J.; Fengler, G.; Schumann, D.; Winterfeldt, E. Additionen an die dreifach-
bindung—XXII: Das thermodynamisch kontrollierte addukt aus tert.butylisonitril und
acetylendicarbonester. Tetrahedron 1974, 30, 2561–2564.
15. Yavari, I.; Moradi, L.; Mokhtarporiani-Sanandej, A.; Mirzaei, A. Efficient synthesis of
trialkyl 3-phenylbuta-1,3-diene-1,2,4-tricarboxylates by a novel one-pot multicomponent
reaction. Helv. Chim. Acta 2006, 90, 392–394.

2414
I. YAVARI, A. MIRZAEI, AND L. MORADI
16. Yavari, I.; Zabarjad-Shiraz, N.; Partovi, T. Stereoselective synthesis of new phosphory-
lated N,N0-dimethylbarbituric acids. Synth. Commun. 2002, 32, 2763–2769.
17. Yavari, I.; Sabbaghan, M. A synthesis of functionalized pyrroles by reaction of
3,4-diacetylhexane-2,5-dione with primary amines in water. Synth. Commun. 2007, 37,
1791–1800.
18. Yavari, I.; Mirzaei, A.; Moradi, L.; Mokhtarporiani-Sanandej, A. Efficient synthesis of
trialkyl (E)-3-[3-oxo-2–3,4-dihydro-2-(1H)-quinoxalinylidene]-prop-1-ene-1,2,3 tricarbox-
ylates. Synth. Commun. 2007, 37, 1195–1200.