Synthesis and dynamic NMR study of a functionalized sulfonamide phosphonate diester

Article abstract of DOI:10.1080/10426507.2010.515951

Protonation of the highly reactive 1:1 intermediate produced in the reaction between triphenylphosphite and activated acetylene by sulfonamide leads to a phosphonate ylide, which undergoes methanol elimination in the presence of moisture to produce a high

Full text of DOI:10.1080/10426507.2010.515951

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Dynamic NMR Study of a
Functionalized Sulfonamide Phosphonate
Diester
Faramarz Rostami Charati a , Masoumeh Moghimi b , Malek Taher
Maghsoodlou c , Sayyed M. Habibi-Khorassani c , Zinatossadat
Hossaini d , Nariman Maleki c , Brian W. Skelton e & Mohamed Makha
e
a Faculty of Science, Gonbad Higher Education Center, Gonbad, Iran
b Islamic Azad University, Gonbad Branch, Gonbad, Iran
c Department of Chemistry, The University of Sistan & Baluchestan,
Zahedan, Iran
d Chemistry Department, Islamic Azad University, Qaemshahr
Branch, Mazandaran, Iran
e Chemistry School of Biomedical, Biomolecular and Chemical
Science, University of Western Australia, Perth, Australia
Published online: 04 Aug 2011.
To cite this article: Faramarz Rostami Charati , Masoumeh Moghimi , Malek Taher Maghsoodlou ,
Sayyed M. Habibi-Khorassani , Zinatossadat Hossaini , Nariman Maleki , Brian W. Skelton & Mohamed
Makha (2011) Synthesis and Dynamic NMR Study of a Functionalized Sulfonamide Phosphonate
Diester, Phosphorus, Sulfur, and Silicon and the Related Elements, 186:7, 1428-1435, DOI:
10.1080/10426507.2010.515951
To link to this article: http://dx.doi.org/10.1080/10426507.2010.515951
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Phosphorus, Sulfur, and Silicon, 186:1428–1435, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.515951
SYNTHESIS AND DYNAMIC NMR STUDY
OF A FUNCTIONALIZED SULFONAMIDE
PHOSPHONATE DIESTER
Faramarz Rostami Charati,1 Masoumeh Moghimi,2
Malek Taher Maghsoodlou,3 Sayyed M. Habibi-Khorassani,3
Zinatossadat Hossaini,4 Nariman Maleki,3 Brian W. Skelton,5
and Mohamed Makha5
1Faculty of Science, Gonbad Higher Education Center, Gonbad, Iran
2Islamic Azad University, Gonbad Branch, Gonbad, Iran
3Department of Chemistry, The University of Sistan & Baluchestan, Zahedan, Iran
4Chemistry Department, Islamic Azad University, Qaemshahr Branch,
Mazandaran, Iran
5Chemistry School of Biomedical, Biomolecular and Chemical Science,
University of Western Australia, Perth, Australia
GRAPHICAL ABSTRACT
Abstract Protonation of the highly reactive 1:1 intermediate produced in the reaction between
triphenylphosphite and activated acetylene by sulfonamide leads to a phosphonate ylide, which
undergoes methanol elimination in the presence of moisture to produce a highly functionalized
sulfonamide phosphonate diester. A dynamic nuclear magnetic resonance (NMR) effect is
observed in the 1H NMR spectra of this compound as a result of restricted rotation around the
single C N bond. The coalescence temperature was observed at TC = 352.5 K, and the free
energy of activation (ꢀG#) for this process is 75.6 2 kJ.mol−1
.
Keywords Activated acetylenes; dynamic NMR effect; sulfonamide; triphenylphosphite
Received 12 June 2010; accepted 12 August 2010.
The authors thank Dr. Alexandre N. Sobolev for assistance with the crystal structure determination.
Address correspondence to Faramarz Rostami Charati, Faculty of Science, Gonbad Higher Education Center,
P.O. Box 163, Gonbad, Iran. E-mail: frostami@gau.ac.ir
1428

FUNCTIONALIZED SULFONAMIDE PHOSPHONATE DIESTER
1429
INTRODUCTION
Organophosphorus compounds are synthesis targets of interest, because of their
value in a variety of industrial, biological, and chemical synthetic systems.1–5 The physical
properties and chemical reactivity of phosphate esters interlink many areas in chemistry and
biology. Introduction of a phosphate monoester into a molecule such as a drug candidate
enhances the water solubility, hence altering its bioavailability.6–8 As a result, many methods
have appeared describing novel syntheses of organophosphorus compounds.3 There have
been many reports of studies on the reactions between trivalent phosphorus nucleophiles and
α,β-unsaturated carbonyl compounds in the presence of a proton source such as an alcohol
or a phenol.9–11 We report here the reaction of dimethyl acetylenedicarboxylate (DMAD)
with a trivalent phosphorus nucleophile, namely, triphenylphosphite, in the presence of
sulfonamide.
RESULTS AND DISCUSSION
As part of our research on the development of new synthetic methods in organic
synthesis, we describe the reaction of triphenylphosphite 1 and dimethyl acetylenedicar-
boxylate 2 in the presence of sulfonamide 3, which proceeds smoothly in dry diethyl ether at
ambient temperature, in the absence of a catalyst, to produce the sulfonamide phosphonate
diester 5 in good yields (Scheme 1).
CO2Me
Me
Me
Me
PhO
PhO
PhO
MeO2C
SO2
O
O
(PhO)3P
Dry Et2O, r.t.
+
+
S
P
N
N
Ph
Me
H
H
CO2Me
CO2Me
3
1
2
4
Me
SO2
O
PhO
PhO
H2O
- MeOH
H
P
N
H
Me
MeO2C
CO2Me
5
Scheme 1 Synthesis of sulfonamide phosphonate diester 5 from the reaction of triphenylphosphite, dimethyl
acetylenedicarboxylate, and sulfonamide.
The structure of compound 5 as a 1:1:1 adduct was apparent from its mass spectra,
1
which displayed a molecular ion peak at appropriate m/z values. The H and 13C NMR
spectroscopic data, as well as infrared (IR) spectra, are in agreement with the proposed
structure. The structure of compound 5 was also confirmed by X-ray diffraction (Figure 1).

1430
F. R. CHARATI ET AL.
The 1H NMR spectrum of 5 exhibited two singlets readily recognized as arising from
the two diastereotopic methyl groups in the phenyl ring (1.78 and 1.79). The two singlets
at 3.52 and 3.63 belong to the ester methoxy protons. The proton-decoupled 13C NMR
spectrum of 5 showed 32 distinct resonances in agreement with the proposed structure.
3
The observation of JHH = 12 Hz for the vicinal methane protons in 5 indicates
the dominance of the anti arrangement. Because compound 5 possesses two stereogenic
centers, two diastereomers with the anti HCCH arrangement are possible (Scheme 2).
O
(PhO)2P
H
O
(PhO)2P
H
Ar
CO2Me
H
H
CO2Me
Ar
CO2Me
CO2Me
(2S, 3R)-5 or (2R, 3S)-5
(2S, 3S)-5 or (2R, 3R)-5
Scheme 2 Two diastereomers with anti HCCH arrangement for 5.
3
The observation of JCP = 0 for the carbonyl carbon atom of CO2Me group is in
agreement with the (2S, 3S) or (2R, 3R) diastereomer. However, as long as the coupling
constant of at least one other diastereomer is not known, the assignment remains uncertain.
In pursuing our research for synthesis of phosphonate esters by use of triphenyl phosphite
as the reagent in nonpolar solvent media (mixture of n-hexane and diethyl ether), some
classes of phosphonate esters were synthesized.12–14 Herein a new class of sulfonamide
phosphonate ester resulted (compound 5) that has two changeable methyl groups A and B.
Due to the restricted rotation around the C N bond in this molecule, two methyl groups in
the phenyl ring are diastereotopic (Figure 2).
Figure 1 Molecular structure of molecule A of 5. The hydrogen atoms have been omitted for clarity and the
ellipsoids are drawn at the 50% probability level.

FUNCTIONALIZED SULFONAMIDE PHOSPHONATE DIESTER
1431
Figure 2 Dynamic NMR effect of restricted rotation around the C N bond in a molecule of 5.
The dynamic nuclear magnetic resonance (NMR) effect of the following compound is
attributed to a rotational barrier around the C N single bond.15–20 For this phenomenon, the
behavior of the molecule was monitored by 1H NMR techniques at variable temperatures.
From the data, the relevant thermodynamic parameters were calculated. To examine their
behavior, the NMR tube containing compound 5 was placed in the NMR probe and heated
slowly from 298 to 360 K. The coalescence temperature was eventually observed at TC
= 352.5 K, and the activation energy (ꢀG#) of the rotation around C N single bond was
1
calculated as 75.6
2 kJ.mol−1. In the H NMR, the collected spectra relevant to the
dynamic effect are shown in the following variable-temperature (VT) NMR (Figure 3).
In conclusion, the observed dynamic NMR effect of compound 5 arises from the rota-
tional barrier around the C N single bond. The reaction of dialkyl acetylenedicarboxylate
with triphenyl phosphite in the presence of an NH acid such as sulfonamide leads to a facile
synthesis of some functionalized phosphonate ylide and phosphonate esters. The ability to
perform this reaction under neutral conditions using these reagents is an advantage in the
synthesis of a new class of sulfonamide phosphonate esters.
EXPERIMENTAL
Chemicals were purchased from Fluka and used without further purification. Melting
points were measured on an Electrothermal 9100 apparatus (Markham, Ontario, Canada).
Elemental analyses for the C, H, and N were performed using a Heraeus CHN-O rapid
analyzer (Texas City, TX, USA). Mass spectra were recorded on a Finnigan-MAT 8430
spectrometer operating at an ionization potential of 70 eV. IR spectra were measured on
1
a Shimadzu IR-460 spectrometer. H-, 13C, and 31P-NMR spectra were measured with a
Bruker DRX-500 Avance spectrometer at 500.1, 125.8, and 202.4 MHz, respectively.

1432
F. R. CHARATI ET AL.
Figure 3 VT NMR of compound 5.
General Procedure for Preparation of Compound 5
Triphenylphosphite (0.62, 2 mmol) was added slowly to a magnetically stirred so-
lution of dimethyl acetylendicarboxylate 2 (0.284, 2 mmol) and sulfonamide 3 (0.522,
2 mmol) in dry diethyl ether at room temperature. The reaction mixture was then stirred
for 2 h at room temperature. The resultant precipitate was collected and washed with cold
n-hexane and diethyl ether (3 × 5 mL) to yield the phosphonate ylide 4. If a few drops of
distilled water were added to the reaction mixture and then left in an exposed vessel to air
for a week, the phosphonate ester 5 resulted. The workup followed removal of the solvent
under reduced pressure and the resultant yellow residue was collected and crystallized from
ether/n-hexane (4:1).
Dimethyl-N-(1,6-dimethylphenylsulfonamino-N-yl)-
3-(diphenoxyphosphoryl) Butenedioate (5)
Colorless crystals, 0.53 g, yield 70%, m.p. 168–170 ◦C. IR (KBr) (νmax/cm−1): 2951
1
(SO2), 1781 and 1750 (2 C O of esters), 1591 (C C). H NMR (500.1 MHz, CDCl3):
1.78 (3 H, s, CH3), 1.79 (3 H, s, CH3), 3.52 (3 H, s, OCH3), 3.63 (3 H, s, OCH3), 3.75 (1
2
3
3
3
H, dd, JPH = 17 Hz, JHH = 12 Hz, CH), 5.75 (1 H, dd, JPH = 9.6 Hz, JHH = 12 Hz,
CH), 6.9–7.7 (18 H, m, aromatic moiety). 13C NMR (125.7 MHz, CDCl3): δ 18.7 (CH3),
19.7 (CH3), 46.5 (d, 1JCP = 130.9 Hz, CH), 52.6 (OCH3), 52.9 (OCH3), 60.4 (d, 2JCP = 4
Hz, CH), 120.3 (d, 3JCP = 4.9 Hz, 2 CHortho of C6H5), 121.6 (d, 3JCP = 4.3 Hz, 2 CHortho
of C6H5), 125.5 (CHpara of C6H5), 125.6 (CH para of C6H5), 128.4 (2 CH), 129.0 (2 CH),

FUNCTIONALIZED SULFONAMIDE PHOSPHONATE DIESTER
1433
Table 1 Crystal data and structure refinement for compound 5
Empirical formula
Formula weight
Temperature
C32H32NO9PS
637.62
100(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Triclinic
P 1
Unit cell dimensions
a = 8.2746(1) Å
b = 16.2970(2) Å
c = 23.2316(4) Å
A = 80.451(1)◦
B = 89.518(1)◦
γ = 87.915(1)◦
3087.35(8) Å3
4
Volume
Z
Density (calculated)
Absorption coefficient
Crystal size
θ range for data collection
Reflections collected
Independent reflections
Max./min. transmission
Data/restraints/parameters
Goodness of fit on F2 (GOOF) on F2
Final R indices [I > 2σ(I)]
R indices (all data)
1.372 mg/m3
0.213 mm−1
0.33 × 0.23 × 0.11 mm3
2.73 to 30.00◦
91,069
17,954 [R(int) = 0.0516]
1.00/0.92
17,954/0/801
1.002
R1 = 0.0690, wR2 = 0.1781
R1 = 0.1066, wR2 = 0.1914
0.888 and −0.502 e.Å−3
Largest diff. peak and hole
129.2 (CH), 129.4 (C), 129.5 (2 CHmetha of C6H5), 129.8 (2 CHmetha of C6H5), 130.1 (2
CH), 132.9 (CH), 134.2 (2 C), 137.9 (C), 149.9 (d, 2JCP = 7.7 Hz, Cipso of C6H5), 150.5 (d,
3JCP = 9.5 Hz, Cipso of C6H5), 165.3 (d, 2JCP = 5.5 Hz, C O), 169.3 (C O). MS, (m/z,%):
637 (M+, 80), 544 (M+-OPh, 95), 451 (M+-2 Oph, 55). Anal. Calcd. for C32H32NO9PS C,
60.28; H, 5.06; N, 2.20; Found: C, 60.65; H, 5.40; N, 2.18.
X-Ray Crystallography of (5): Crystal/Refinement Details
The X-ray diffracted intensities were measured from a single crystal of 5 on an Oxford
Diffraction Xcalibur or Gemini-R Ultra charge-coupled device (CCD) diffractometer using
monochromatized Mo-Kα radiation (λ = 0.71073 Å). Data were corrected for Lorentz and
polarization effects and absorption correction applied using multiple symmetry equivalent
reflections. The structure was solved by direct method and refined on F2 using the SHELX-
97 crystallographic package. A full-matrix least-squares refinement procedure was used,
minimizing ꢁw(Fo2 − F2c), with w = [σ2(Fo2) + (AP)2 + BP]−1, where P = (Fo2 + 2F2c)/3.
Agreement factors (R1 = ꢁꢁFo| − |Fcꢁ/ꢁ|Fo|, wR2 = {ꢁ[w(F2o − Fc2)2]/ꢁ[w(Fo2)2]}1/2 and
1/2
GOF = {ꢁ[w(F2o − F2c)2]/(n − p)} are cited, where n is the number of reflections and
p is the total number of parameters refined. A = 0.04, B = 4.7). All nonhydrogen atoms
were refined with anisotropic displacement parameters using all reflections. Positions of
hydrogen atoms were localized from difference Fourier synthesis and their atomic param-
eters were constrained to the bonded atoms during refinement. Crystallographic details are
listed in Table 1. Selected bond lengths and angles are provided in Table 2. Crystallographic

1434
F. R. CHARATI ET AL.
Table 2 Selected bond lengths (Å) and angles (◦) for 5
Molecule A
Molecule B
P(1) O(7)
P(1) O(9)
1.461 (2)
1.567 (2)
1.459 (2)
1.569 (2)
P(1) O(8)
1.587 (2)
1.592 (2)
P(1) C(1)
1.821 (3)
1.817 (3)
S(1) O(6)
1.426 (2)
1.433 (2)
S(1) O(5)
1.439 (2)
1.434 (2)
S(1) N(1)
1.650 (2)
1.656 (2)
S(1) C(15)
1.767 (3)
1.763 (3)
O(7) P(1) O(9)
O(7) P(1) O(8)
O(9) P(1) O(8)
O(7) P(1) C(1)
O(9) P(1) C(1)
O(8) P(1) C(1)
O(6) S(1) O(5)
O(6) S(1) N(1)
O(5) S(1) N(1)
O(6) S(1) C(15)
O(5) S(1) C(15)
N(1) S(1) C(15)
119.53 (12)
114.23 (11)
99.61 (11)
112.93 (12)
103.96 (12)
104.72 (12)
120.69 (15)
107.89 (14)
105.39 (13)
105.64 (15)
108.04 (14)
108.82 (13)
119.29 (12)
114.13 (11)
100.30 (11)
112.79 (12)
104.11 (11)
104.43 (12)
119.02 (14)
109.44 (13)
105.58 (12)
105.91 (14)
110.12 (15)
106.14 (13)
data of compound 5 have been deposited at the Cambridge Crystallographic Data Centre
(CCDC number 715537). Copies of the information may be obtained free of charge from
the Director, CCDC, 12 Union Road, Cambridge CB21EZ, UK (Fax: + 44-1223-336033;
e-mail: deposit@ccdc.cam.ac.uk).
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