Synthesis of stable carbamate phosphorus ylides by a four-component reaction and dynamic 1H-NMR study of the energy barriers for the rotation around the carbon-nitrogen single bond and the carbon-carbon double bond

Article abstract of DOI:10.1080/10426507.2014.986267

A stable phosphorus ylide is obtained in high yield by a four-component reaction between triphenylphosphine and dimethyl acetylendicarboxylate in the presence of the intermediate product formed from phenyl isocyanate and substituted phenols in dichloromet

Full text of DOI:10.1080/10426507.2014.986267

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Synthesis of stable carbamate phosphorus ylides by a
four-component reaction, and dynamic 1h nmr study of
the energy barriers for the rotation around the carbon-
nitrogen single bond and the carbon-carbon double
bond
Ghasem Marandia, Malek Taher Maghsoodloub, Hamideh Saravanib, Maryam Shokouhianb &
Eideh Mofarrahb
a Shahid Bakeri High Education Center of Miandoab, Urmia University, Urmia, Iran
b Department of Chemistry, the University of Sistan and Baluchestan, P. O. Box 98135-674,
Zahedan, Iran
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Accepted author version posted online: 31 Dec 2014.
To cite this article: Ghasem Marandi, Malek Taher Maghsoodlou, Hamideh Saravani, Maryam Shokouhian & Eideh Mofarrah
(2014): Synthesis of stable carbamate phosphorus ylides by a four-component reaction, and dynamic 1h nmr study of the
energy barriers for the rotation around the carbon-nitrogen single bond and the carbon-carbon double bond, Phosphorus,
Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2014.986267
To link to this article: http://dx.doi.org/10.1080/10426507.2014.986267
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SYNTHESIS OF STABLE CARBAMATE PHOSPHORUS YLIDES BY A FOUR-
COMPONENT REACTION, AND DYNAMIC 1H NMR STUDY OF THE ENERGY
BARRIERS FOR THE ROTATION AROUND THE CARBON-NITROGEN SINGLE
BOND AND THE CARBON-CARBON DOUBLE BOND
Ghasem Marandi,a,*Malek Taher Maghsoodlou,b Hamideh Saravani,b
Maryam Shokouhian,b Eideh Mofarrahb
a Shahid Bakeri High Education Center of Miandoab, Urmia University, , Iran
b Department of Chemistry, the University of Sistan and Baluchestan, P. O. Box 98135-674,
Zahedan, Iran
*Corresponding Author; E-mail: marandi_gh@yahoo.com
Abstract A stable phosphorus ylide is obtained in high yield by a four component reaction
between triphenylphosphine and dimethyl acetylendicarboxylate in the presence of the
intermediate product formed from phenyl isocyanate and substituted phenols in dichloromethane
at room temperature. This stable phosphorus ylide exists in solution as a mixture of two
geometrical isomers resulting from restricted rotation around the carbon-carbon partial double
bond due to conjugation of the ylide moiety with the adjacent carbonyl group. Dynamic effects
1
are observed in H NMR spectra that are attributed to restricted rotation around the carbon-
carbon double bond and the carbon-nitrogen single bond. These effects are used to calculate the
free activation energy (ΔG‡) and other activation parameters such as ΔH‡, ΔS‡ and Ea.
1
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1
Keywords: Dynamic H NMR; Free activation energy; Phosphorus ylide; Rotational energy
barrier
INTRODUCTION
The design of new synthetic routes and their development for widely used organic
compounds from readily available reagents are the major tasks for an organic chemist.1 Some
reagents such as phosphorus ylides are important in synthetic organic chemistry, especially in the
synthesis of naturally occurring products, compounds with biological and pharmacological
activities.2 Phosphorus ylides are most often prepared by treatment of a phosphonium salts with a
base. The phosphonium salts are usually made from the corresponding phosphine and an alkyl
halide.3-8 In addition, they are also obtained by Michael addition of phosphorus nucleophiles to
activated olefins.3-11 Herein, we describe an efficient synthetic route for the synthesis of stable
phosphorus ylides using triphenylphosphine (4), dimethyl acetylenedicarboxylate (5) and
carbamates (3) in a four-component reaction. The synthesized phosphorus ylide exhibits dynamic
1HNMR effects that afford good information regarding the interchangeable process of rotational
isomers that provide important kinetic data.12-17
RESULTS AND DISCUSSION
Firstly, the work reports the reaction in which phenols (1) and phenyl isocyanate (2) lead to
carbamates (3) that they can be utilized as NH source in the presence of triphenylphosphine (4)
and dimethyl acetylenedicarboxylate
5
for the synthesis of dimethyl 2-[N-(4-
2
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methylphenyl)phenylcarbamate-N-yl]-3-(triphenylphosphoranylidene)butanedioates
(6)
in
excellent yield. No other product could be detected by NMR spectroscopy. (Scheme 1)
<Scheme 1>
1
31
13
The structures of compounds 6a-e were deduced from elemental analyses, IR, H, P, C
NMR and mass spectroscopy. The mass spectra displayed molecular ion peaks at appropriate m/z
values. Any initial fragmentations involve partial or complete loss of the side chains and scission
of the aromatic rings. The 1H, 13C and 31P NMR spectra of the ylides 6a-e are consistent with the
presence of two isomers. The ylide moiety of these compounds is strongly conjugated with the
adjacent carbonyl group and rotation around the partial double bond of the (E)-6 and (Z)-6
geometrical isomers (Scheme 2) is slow on the NMR time scale at ambient temperature. Selected
1H, 13C and 31P NMR chemical shifts and coupling constants in the major and minor geometrical
isomers of compound 6a-e are shown in the experimental section. It must be mentioned that in
compounds (6a-e) the E- and Z- geometrical isomers exist as major and minor isomers.
<Scheme 2>
1
The H NMR spectrum of 6a exhibited sharp singlet lines arising from methyl (δ = 2.28)
and methoxycarbonyl groups (δ = 2.92 and 3.84) and a doublet from a methine proton (δ = 5.04,
3JPH = 20.0 Hz), respectively. All aromatic protons of 6a resonated at δ = 7.03-7.73 for the major
diasteroisomer.
3
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The 13C NMR spectrum of 6a showed signals at δ = 153.86 and 168.62, 3JPC = 13.1 Hz and
δ = 173.24, 2JPC = 15.9 Hz for carbamate and methoxy carbonyl groups, respectively. In addition,
31
the observation of two signals in the P NMR spectrum at δ = 24.06 and 24.78 indicates the
existence of major and minor isomers. Other partial spectroscopic information is reported in the
experimental section for the minor diasteroisomer.
Although the mechanism of this reaction has not been experimentally established, a
proposed mechanism for this reaction is shown on the base of the literature 5-11, 18-23 in Scheme 3.
<Scheme 3>
1
Dynamic effects are observed in the H NMR spectrum of 6a at ambient temperature
which has been attributed to the restricted rotational process around the partial carbon-carbon
double bond, the carbon-carbon and the carbon-nitrogen single bonds12,13 (see Schemes 4 and 5).
Two sharp doublets (δ = 5.04 and 5.06) are observed for the CH protons of the major and
minor isomers of 6a in the 1H NMR spectrum in CDCl3 as solvent at ambient temperature which
appeared as a broad doublet at near to 55°C (328 K). An increasing of the temperature results in
coalescence of the CH resonances. Recently, the free activation energy calculation using the
expression k = πΔ/√2 the first order rate constant (kc) for carbon-carbon double bond rotation has
been reported by Shaabani et al.24 Some spectroscopic data from this article have been extracted
and collected in Table 1. From the coalescence temperature of the proton resonances of the CH
group and by use of the equation for the rate constant, the first-order rate constant k was
4
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calculated for the bond rotation in 6a to 24.53 s−1 at 59°C. For this process, the activation and
kinetic parameters involving kc and ΔG‡, ΔH‡, ΔS‡ and Ea are summarized in Table 1.26,27
<Scheme 4>
<Table 1>
<Table 2>
<Table 3>
<Scheme 5>
<Table 4>
1
1
By further investigations and zooming in to H NMR spectra of 6a another dynamic H
NMR effect was observed which is attributed to the restricted rotational process around the
carbon–nitrogen single bond.
When the temperature was decreased below ambient temperature, the 1H NMR spectrum of
the major 6a-isomer in CDCl3 at +5°C showed a resonance arising from the methoxy protons
which is broadened in comparison to a corresponding doublet measured at ambient temperature.
When the temperature was further increased, the methoxy protons coalesce near 23°C (296 K)
and appear as a sharp symmetrical resonance at 25°C, which is related to a restricted rotation
around the carbon-nitrogen single bond in the major isomer of 6a (see Scheme 2). It must be
mentioned that the methoxy protons of the minor 6a-isomer show coalescence near 20°C (293
K) and appear as a sharp symmetrical resonance at 25°C. These values are collected in Table 2.
5
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The effect of temperature on the rate constant was investigated on the basis of
measurement of different chemical shifts in a series of other separate experiments. The results
were too small so that the changes in first-order rate constant and Gibbs free energy barrier are
negligible in comparison with the results obtained at 23°C (296 K).25
1
The H NMR spectrum of 6a in acetone at 0°C showed a resonance arising from the
methoxycarbonyl protons that is appreciably broadened in comparison with a corresponding
peak measured at ambient temperature (δ = 3.82), whereas the other signals remain unchanged.
The methoxycarbonyl protons coalescence near −3°C and appear as fairly symmetrical resonance
at −10°C, which is relevant to the restricted rotational around the carbon-carbon single bond (see
Scheme 4 and Table 2).
More investigations are made for the restricted rotation around the nitrogen-carbon single
bonds and results are summarized in Tables 3 and 4. An illustrative progress has been shown in
Scheme 5.
CONCLUSION
In conclusion, the novel four-component reaction between triphenylphosphine and
dimethyl acetylenedicarboxylate in the presence of substituted phenols and phenyl isocyanate
provides a simple, one-pot, and efficient route for the synthesis of stable, phosphorus ylides with
probable pharmacological properties. The present procedure carries the advantage which allows
us to calculate free activation energies ΔG‡.
EXPERIMENTAL
6
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Melting points and IR spectra (KBr pellets, ν/cm−1) of all compounds were measured on an
Electrothermal 9100 apparatus and a JASCO FT-IR spectrometer, respectively. The 1H, 13C, and
31P NMR spectra for compounds 6b-e were obtained with a Bruker DRX-400 Avance instrument
using CDCl3 and acetone-d6 as solvents, TMS as internal standard at 400.1, 100.6, 161.9 MHz
except for compound 6a, the spectra of which were obtained on a DRX-500 Avance instrument
using CDCl3 as solvent and TMS as internal standard at 500.1, 125.8, 202.4 MHz. VT NMR
spectra for compound 6a were performed at −17, −10, −5, 0, +5, +10, +15, +20, +25, +30, +50
and +60°C. Elemental analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid
analyzer. Mass spectra were recorded on an Agilent Technologies 5973 mass spectrometer
operating at an ionization potential of 70 eV. Dimethyl acetylenedicarboxylate, phenols, phenyl
isocyanate and triphenylphosphine were purchased from Fluka and were used without further
purification.
General procedure for the preparation of ylide (6a)
Magnetic stirring of a solution of p-cresol (0.108 g, 1 mmol) and phenyl isocyanate (0.119
g, 1 mmol) under solvent-free condition for 6 h led to the formation of carbamate 3. To this
solution, a magnetically stirred solution of triphenylphosphine (0.26 g, 1 mmol) in 10 mL of
CH2Cl2, dimethyl acetylenedicarboxylate (0.14 g, 1 mmol) was added drop-wise over a period of
10 min at room temperature. After approximately 24 h of stirring at room temperature, the
product was filtered off and washed with cold diethyl ether (3×5 mL).
7
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Dimethyl
2-[N-(4-methylphenyl)phenylcarbamate-N-yl]-3-(triphenylphosphoran-
ylidene)butanedioate (6a). Yield: 0.57 g (90%); Orange powder; m.p. 154-157°C; IR: 1745,
1708, 1649 (C=O); MS m/z: 632.5 [M++1, 5], 631.5 [M+, 15], 600.4 [7], 559.4 [3], 405.3 [100],
277.4 [23]; Anal. Calcd. for C38H34NO6P (631.65): C, 72.26; H, 5.43; N, 2.22; Found: C, 72.40;
1
H, 5.54; N, 2.30%. Major isomer (Z)-6a (58%): H NMR (500.1 MHz, CDCl3): δ 2.29 (3H, s,
ArCH3), 2.93 and 3.84 (6H, 2s, 2 OCH3), 5.04 (1H, d, 3JPH = 20.0 Hz, P=C-CH), 7.03-7.73 (24H,
13
1
m, Ph3P, NPh and OAr); C NMR (125.8 MHz, CDCl3): δ 20.83 (s, ArCH3), 40.56 (d, JPC
=
2
134.8 Hz, P=C), 52.32 and 52.61 (2s, 2 OCH3), 62.51 (d, JPC = 14.0 Hz, P=C-CH), 126.36 (d,
3
4
1JPC = 91.5 Hz, Cipso), 128.83 (d, JPC = 12.1 Hz, Cmeta), 132.25 (d, JPC = 2.0 Hz, Cpara), 133.80
2
(d, JPC = 9.1 Hz, Cortho), 118.67, 121.17, 127.17, 127.82, 129.41, 131.16, 134.23 (7s, Carom),
149.39 (s, C, OAr), 153.86 (s, COcarbamat), 168.62 (d, 3JPC =13.1 Hz, C=O), 173.24 (d, 2JPC = 15.9
Hz, P-C=C); 31P NMR (202.4 MHz, CDCl3): δ 24.78 [s, (Ph3P+-C)]. Minor isomer (E)-6a
1
(42%): H NMR (500.1 MHz, CDCl3): δ 1.62 (3H, s, ArCH3), 3.14 and 3.92 (6H, 2s, 2 OCH3),
3
13
5.06 (1H, d, JPH = 17.6 Hz, P=C-CH), 7.03-7.73 (24H, m, Ph3P, NPh and OAr); C NMR
(125.8 MHz, CDCl3): δ 15.34 (s, ArCH3), 41.90 (d, 1JPC = 129.7 Hz, P=C), 48.95 and 49.55 (2s,
1
2 OCH3), 65.90 (d, 2JPC = 12.4 Hz, P=C-CH), 126.97 (d, JPC = 108.7 Hz, Cipso), 128.72 (d, 3JPC
4
2
= 10.1 Hz, Cmeta), 132.13 (d, JPC = 3.0 Hz, Cpara), 133.60 (d, JPC = 10.1 Hz, Cortho), 118.67,
121.66, 126.30, 128.52, 129.39, 129.92, 134.23 (7s, Carom), 148.90 (s, C, ArO), 153.30 (s,
COcarbamat), 170.03 (d, 3JPC = 12.9 Hz, C=O), 173.42 (d, 2JPC =16.0 Hz, P-C=C); 31P NMR (202.4
MHz, CDCl3): δ 24.06 [s, (Ph3P+-C)].
Dimethyl
2-[N-(2-methylphenyl)-N-phenylcarbamate-N-yl]-3-(triphenylphosphor-
anylidene)butanedioate (6b). Yield: 0.60 g (95%); Orange powder; m.p. 157-159°C; IR:
8
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1746, 1714, 1648 (C=O); MS m/z: 632.5 [M++1, 3], 631.5 [M+, 11], 600.4 [3], 559.4 [4], 405.3
[100], 277.4 [55]; Anal. Calcd. for C38H34NO6P (631.65): C, 72.26; H, 5.43; N, 2.22; Found: C,
1
72.33; H, 5.48; N, 2.18%. – Major isomer (Z)-6b (75%): H NMR (400.2 MHz, acetone-d6): δ
3
2.10 (3H, s, ArCH3), 2.91 and 3.91 (6H, 2s, 2 OCH3), 5.01 (1H, d, JPH = 19.6 Hz, P=C-CH),
6.90-7.75 (24H, m, Ph3P, NPh and OAr); 13C NMR (100.6 MHz, acetone-d6): δ 22.11 (s,
ArCH3), 41.29 (d, 1JPC = 136.8 Hz, P=C), 52.38 and 52.63 (2s, 2 OCH3), 62.29 (P=C-CH, 2JPC =
17.0 Hz), 125.71 (d, 1JPC = 90.8 Hz, Cipso), 128.95 (d, 3JPC = 12.8 Hz, Cmeta), 132.29 (d, 4JPC = 2.3
2
Hz, Cpara), 133.81 (d, JPC = 10.0 Hz, Cortho), 118.70, 122.14, 127.15, 127.33, 128.60, 132.00,
3
134.51 (7s, Carom), 145.69 (s, C, OAr), 152.30 (s, COcarbamat), 170.13 (d, JPC =12.8 Hz, C=O),
173.02 (d, 2JPC = 14.1 Hz, P-C=C); 31P NMR (162.0 MHz, acetone-d6): δ 24.11 [ s, (Ph3P+-C)], –
Minor isomer (E)-6b (25%): 1H NMR (400.2 MHz, acetone-d6): δ 2.00 (3H, s, ArCH3), 3.15 and
3
3.82 (6H, 2s, 2 OCH3), 5.11 (1H, d, JPH = 19.4 Hz, P=C-CH), 6.90-7.75 (24H, m, Ph3P, NPh
13
1
and OAr); C NMR (100.6 MHz, acetone-d6): δ 21.78 (s, ArCH3), 43.27 (d, JPC = 134.5 Hz,
P=C), 48.62 and 49.46 (2s, 2 OCH3), 63.27 (P=C-CH, 2JPC = 17.1 Hz), 125.52 (d, 1JPC = 91.0 Hz,
3
4
2
Cipso), 128.84 (d, JPC = 12.1 Hz, Cmeta), 132.18 (d, JPC = 2.1 Hz, Cpara), 133.58 (d, JPC = 10.1
Hz, Cortho), 118.36, 122.43, 127.06, 127.70, 128.48, 132.00, 134.47 (7s, Carom), 145.83 (s, C,
OAr), 153.04 (s, COcarbamat), 168.44 (d, 3JPC = 12.6 Hz, C=O), 171.68 (d, 2JPC = 13.8 Hz, P-C=C);
31P NMR (162.0 MHz, acetone-d6): δ 24.71 [s, (Ph3P+-C)].
Dimethyl
2-[N-(4-formylphenyl)-N-phenylcarbamate-N-yl]-3-(triphenylphosphor-
anylidene)butanedioate (6c). Yield: 0.61 g (95%); Orange powder; m.p. 127-129°C; IR:
1745, 1712, 1644 (C=O); MS m/z: 646.5 [M++1, 4], 645.5 [M+, 13], 614.3 [77], 587.6 [11],
467.5 [100]; Anal. Calcd. for C38H32NO7P (645.64): C, 70.69; H, 5.00; N, 2.17; Found: C, 70.47;
9
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1
H, 5.13; N, 2.22%. – Major isomer (Z)-6c (62%): H NMR (400.2 MHz, CDCl3): δ 2.93 and
3
3.83 (6H, 2s, 2 OCH3), 5.01 (1H, d, JPH = 20.1 Hz, P=C-CH), 7.12-7.81 (24H, m, Ph3P, NPh
13
1
and OAr), 9.94 (1H, s, ArCHO); C NMR (100.6 MHz, CDCl3): δ 41.07 (d, JPC = 135.8 Hz,
2
P=C), 52.43 and 52.71 (2s, 2 OCH3), 61.97 (d, JPC = 16.0 Hz, P=C-CH), 121.87 (s, Carom),
1
3
4
126.23 (d, JPC = 92.6 Hz, Cipso), 128.87 (d, JPC = 12.1 Hz, Cmeta), 132.35 (d, JPC = 1.9 Hz,
2
Cpara), 133.60 (d, JPC = 10.0 Hz, Cortho), 126.92, 127.91, 129.95, 131.07, 133.02 (7s, Carom),
3
2
138.27 (s, OAr), 152.63 (s, COcarbamat), 168.61 (d, JPC = 13.3 Hz, C=O), 172.87 (d, JPC = 14.1
31
Hz, P-C=C), 191.12 (s, ArCHO); P NMR (162.0 MHz, CDCl3): δ 24.87 [s, (Ph3P+-C)]. –
1
Minor isomer (E)-6c (38%): H NMR (400.2 MHz, CDCl3): δ 3.13 and 3.93 (6H, 2s, 2 OCH3),
3
5.02 (1H, d, JPH = 19.5 Hz, P=C-CH), 7.12-7.81 (24H, m, Ph3P, NPh and OAr), 9.94 (1H, s,
13
1
ArCHO); C NMR (100.6 MHz, CDCl3): δ 39.86 (d, JPC = 136.1 Hz, P=C), 49.55 and 48.98
2
1
(2s, 2 OCH3), 62.79 (d, JPC = 17.1 Hz, P=C-CH), 122.19 (s, Carom), 126.69 (d, JPC = 91.3 Hz,
Cipso), 128.72 (d, 3JPC = 12.3 Hz, Cmeta), 132.11 (d, 4JPC = 2.0 Hz, Cpara), 133.78 (d, 2JPC = 9.7 Hz,
Cortho), 127.09, 128.49, 129.42, 131.17, 133.44 (7s, Carom), 138.57 (s, OAr), 151.84 (s, COcarbamat),
169.88 (d, 3JPC =13.1 Hz, C=O), 173.25 (d, 2JPC =14.5 Hz, P-C=C), 191.12 (s, ArCHO);31P NMR
(162.0 MHz, CDCl3): δ 24.13 [s, (Ph3P+-C)].
Dimethyl
2-[N-(2-Nitrophenyl)-N-phenylcarbamate-N-yl]-3-(triphenylphosphor-
anylidene)butanedioate (6d). Yield: 0.62 g (93%); Orange powder; m.p. 128-129°C; IR:
1746, 1714, 1645 (C=O), 1358 (NO2); MS m/z: 663.5 [M++1, 2], 662.5 [M+, 5], 631.5 [2], 407.4
[18], 405.3 [100], 335.3 [14], 277.4 [28]; Anal. Calcd. for C37H31N2O8P (662.62): C, 67.07; H,
1
4.72; N, 4.23; Found: C, 67.16; H, 4.80; N, 4.15%. – Major isomer (E)-6d (76%): H NMR
(400.2 MHz, CDCl3): δ 3.13 and 3.81 (6H, 2s, 2 OCH3), 4.98 (1H, d, 3JPH = 20.0 Hz, P=C-CH),
10
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13
1
7.10-8.10 (23H, m, Ph3P, NPh and OAr); C NMR (100.6 MHz, CDCl3): δ 39.66 (d, JPC
=
2
190.2 Hz, P=C), 52.38 and 52.61 (2s, 2 OCH3), 62.32 (d, JPC = 17.1 Hz, P=C-CH), 126.71 (d,
1JPC = 88.5 Hz, Cipso), 128.91 (d, 3JPC = 13.1 Hz, Cmeta), 132.28 (d, 4JPC = 3.0 Hz, Cpara), 133.8 (d,
2JPC = 10.1 Hz, Cortho), 123.25, 126.60,127.54, 127.87, 130.00, 131.16 and 138.16 (7s, Carom),
3
2
145.01 (s, OAr), 152.30 (s, COcarbamat), 170.01 (d, JPC =18.1 Hz, C=O), 173.01 (d, JPC = 14.1
Hz, C=O); 31P NMR (162.0 MHz, CDCl3): δ 25.45 [s, (Ph3P+-C)]. – Minor isomer (Z)-6d (24%):
1H NMR (400.2 MHz, CDCl3): δ 2.87, 3.89 (6H, 2s, 2 OCH3), 5.01 (1H, d, 3JPH = 16.0 Hz, P=C-
13
1
CH), 7.1-8.1 (23H, m, Ph3P, NPh and OAr); C NMR (100.6 MHz, CDCl3): δ 40.98 (d, JPC
=
2
199.2 Hz, P=C), 48.83 and 49.48 (2s, 2 OCH3), 63.32 (d, JPC = 17.1 Hz, P=C-CH), 126.65 (d,
3
4
1JPC = 90.5 Hz, Cipso), 128.84 (d, JPC = 12.1 Hz, Cmeta), 132.17 (d, JPC = 3.0 Hz, Cpara), 133.58
(d, 2JPC = 10.1 Hz, Cortho), 123.25, 126.60, 127.54, 127.87, 129.95, 138.49 and 142.19 (7s, Carom),
2
3
145.05 (s, OAr), 152.00 (s, COcarbamat), 168.61 (d, JPC =13.1 Hz, C=O), 173.01 (d, JPC = 14.1
Hz, C=O); 31P NMR (162.0 MHz, CDCl3): δ 25.18 [s, (Ph3P+-C)].
Dimethyl
2-[N-(2,6-dimethylphenyl)-N-phenylcarbamate-N-yl]-3-(triphenyl-
phosphoranylidene)butanedioate (6e). Yield: 0.56 g (87%); Orange powder; m.p.: 184-
187°C; IR: 1745, 1713, 1608 (C=O); MS m/z: 646.7 [M++1, 3], 645.6 [M+, 5], 614.7 [8], 539.2
[14], 375.2 [100], 354.4 [19], 265.3 [13]; Anal. Calcd. for C39H36NO6P (645.68): C, 72.55; H,
1
5.62; N, 2.17; Found: C, 72.47; H, 5.64; N, 2.08%. – Major isomer (E)-6e (69%): H NMR
(400.2 MHz, CDCl3): δ 2.10 (6H, 2s, ArMe2), 3.18 and 3.83 (6H, 2s, 2 OCH3), 5.02 (1H, d, 3JPH
= 25.6 Hz, P=C-CH), 6.80-7.90 (23H, m, Ph3P, NPh and OAr); 13C NMR (100.6 MHz, CDCl3):
δ 16. 39 (s, ArMe2), 39.34 (d, 1JPC = 206.3 Hz, P=C), 49.54 and 52.29 (2s, 2 OCH3), 61.50 (d,
1
3
2JPC = 17.1 Hz, P=C-CH), 126.34 (d, JPC = 92.6 Hz, Cipso), 128.87 (d, JPC = 12.1 Hz, Cmeta),
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4
2
132.33 (d, JPC = 3.0 Hz, Cpara), 133.78 (d, JPC = 10.1 Hz, Cortho), 118.62, 125.14, 127.46,
128.14, 128.56, 131.39 and 139.05 (7s, Carom), 148.74 (s, OAr), 152.84 (s, COcarbamat), 170.17 (d,
3JPC = 18.1 Hz, C=O), 173.30 (d, 2JPC = 14.1 Hz, C=O); 31P NMR (162.0 MHz, CDCl3): δ 24.78
1
[s, (Ph3P+-C)]. – Minor isomer (Z)-6e (31%): H NMR (400.2 MHz, CDCl3): δ 2.14 (6H, 2s,
3
ArMe2), 2.90 and 3.89 (6H, 2s, 2 OCH3), 5.00 (1H, d, JPH = 20.1 Hz, P=C-CH), 6.8-7.9 (23H,
13
m, Ph3P, NPh and OAr); C NMR (100.6 MHz, CDCl3): δ 16. 39 (s, ArMe2), 40.65 (d, 1JPC
=
2
215.3 Hz, P=C), 48.92 and 49.53 (2s, 2 OCH3), 62.43 (d, JPC = 17.1 Hz, P=C-CH), 126.89 (d,
3
4
1JPC = 92.6 Hz, Cipso), 128.76 (d, JPC = 12.1 Hz, Cmeta), 132.20 (d, JPC = 2.0 Hz, Cpara), 133.62
2
(d, JPC = 10.1 Hz, Cortho), 121.75, 125.14, 126.85, 127.58, 128.54, 130.33, 139.36 (7s, Carom),
3
2
148.74 (s, OAr), 152.50 (s, COcarbamat), 168.67 (d, JPC = 13.1 Hz, C=O), 173.25 (d, JPC = 15.1
Hz, C=O); 31P NMR (162.0 MHz, CDCl3): δ 24.27 [s, (Ph3P+-C)].
ACKNOWLEDGEMENTS
We gratefully acknowledge the financial support from the Research Council of the
University of Sistan & Baluchestan.
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REFERENCES
1. Laszlo, P. Organic Reactions: Simplicity and Logic. Wiley: New York, 1995.
2. Wittig, G. Science 1980, 210, 600-604.
3. Johanson, A.W. Ylide Chemistry. Academic Press: New York, 1966.
4. Cadogan, J. I. G. Organophosphorus Reagents in Organic Synthesis. Academic Press: New
York, 1979.
5. Engel, R.; Cohen, J. I. Synthesis of Carbon-Phosphorus Bonds. 2nd ed., CRC Press: Boca
Raton, FL, 2004; chapters 1–3.
6. Hudson, H. R. The Chemistry of Compounds. In: Hartley, F. R. (ed.) Primary, Secondary and
Tertiary Phosphorus and Heterocyclic Organophosphorus(III) Compounds, vol. 1. Wiley:
New York, 1990; pp. 382–472.
7. Corbridge, D. E. C. Phosphorus: an Outline of Chemistry, Biochemistry and Uses, Studies in
Inorganic Chemistry, vol. 20. 5th (ed.) Amsterdam, 1995.
8. Ziyaadini, M.; Maghsoodlou, M. T.; Hazeri, N.; Habibi-Khorassani, S. M. Heteratom Chem.
2012, 23, 131-137.
9. Murphy, P. J.; Lee, S. E. J. Chem. Soc. Perkin Trans 1, 1999, 3049-3066.
10. Yavari, I.; Islami, M. R.; J. Chem. Res. 1998, 166-167.
11. Heydari, R.; Hazeri, N.; Maghsoodlou, M. T.; Habibi-Khorasani, S. M.; Marandi, G.; Maleki,
N.; Kabiri, R.; Gholipour-Soleymani, B. Phosphorus Sulfur Silicon Relat. Elem. 2010, 185,
2135-2141.
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12. Kabiri, R.; Hazeri, N.; Habibi-Khorasani, S. M.; Maghsoodlou, M. T.; Ebrahimi, A.;
Saghatforoush, L.; Marandi, G.; Razmjoob, Z. Arkivoc 2008, xvii, 12-19.
13. Habibi-Khorasani, S. M.; Maghsoodlou, M. T.; Ebrahimi, A.; Farahani Vasheghani, F.;
Mosaddeg, E.; Kazemain, M. A. Tetrahedron Lett. 2009, 50, 3621-3624.
14. Cervinka, O. In: Roppoport, Z. Eds., The Chemistry of Enamines, Wiley: New York, 1994,
Part 1, P. 219.
15. Anet, F. A. L.; Anet, R.; Cotton, F. A.; Jackman, L. M. Eds., in Dynamic Nuclear Magnetic
Resonance Spectroscopy, Academic Press: New York, 1975, Chapter 8.
16. Oki, M. In: Application of Dynamic NMR Spectroscopy to Organic Chemistry, Eds., VCH:
Weinheim, 1985.
17. Kolodiazhnyi, O. I. Phosphorus Ylides. Wiley-VCH, Weinheim: Germany, 1999.
18. Habibi-Khorasani, S. M.; Maghsoodlou, M. T.; Ebrahimi, A. Kazemain, M. A.; Zakarianejad,
M. Phosphorus Sulfur Silicon Relat. Elem. 2009, 184, 2959-2961.
19. Maghsoodlou, M. T.; Habibi-Khorasani, S. M.; Heydari, R.; Hassankhani, A.; Marandi, G.;
Nassiri, M.; Mosaddeg, E. Mol Divers. 2007, 11, 87-91.
20. Saghatforoush, L.; Maghsoodlou, M. T.; Aminkhani, A.; Marandi, G.; Kabiri, R. J. Sulfur
Chem. 2006, 27, 583-588.
21. Marandi, G.; Maghsoodlou, M. T.; Hazeri, N.; Heydari, R.; Habibi-Khorasani, S. M.;
Ebrahimi, A.; Mollaee Poor, S.; Hosseini Mahdiabad, H.; Nassiri, M.; Kabiri, R. Hetroatom
Chem. 2010, 21, 228-235.
22. Hazeri, N; Habibi-Khorasani, S. M.; Maghsoodlou, M. T.; Marandi, G.; Nassiri, M.;
Shahzadeh, A.G. J. Chem. Res. (S). 2006, 215-217.
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23. Marandi, G.; Akbarzadeh Torbati, N.; Heydari, R.; Hazeri, N.; Habibi-Khorassani, S. M.;
Maghsoodlou, M. T.; Adrom, B.; Skelton, B. W.; Makha, M. Phosphorus Sulfur Silicon
Relat. Elem. 2012, 187, 1450-1461.
24. Shaabani, A.; Safaei, H. R.; Hemyari, K.; Moghimi, A. J. Chem. Res. (S). 2001, 192-194.
25. Habibi-Khorassani, S. M.; Ebrahimi, A. Maghsoodlou, M. T.; Same-Salari, S.; Nasiri, S.;
Ghasempour, H. Magn. Reson. Chem. 2011, 49, 213-220.
26. Habibi-Khorassani, S. M.; Maghsoodlou, M. T.; Ebrahimi, A. Marzyeh Mohammadi,;
Shahraki, M.; Aghdaei, E. J. Phys. Org. Chem. 2012, 25, 1328-1335.
27. Ziyaadini, M.; Maghsoodlou, M. T.; Hazeri, N.; Habibi-Khorassani, S. M. Heteroatom. Chem.
2012, 23, 131-137.
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Table 1. Selected 1H NMR chemical shifts δ/ppm of 6a and 4a (500 MHz) along with activation parameters in CDCl3 for the
restricted rotational process around the carbon-carbon double bond.
kc/s−1
Temp./°C
Tc/K
Compound
6a
δ/ppm
∆ν/Hz
11.052
19.155
∆G‡
∆H‡
∆S‡
kJmol−1
kJmol−1
kJmol−1K−1
20
5.0198
5.0419
5.06
6.7608
6.7991
6.78
24.53
42.53
332
330
72.76±1
70.79±1
60
20
59.241
–0.0407
60
25
4.83, 4.85
5.0
177.6
312
65.5[a]
4a
4a
Major rotamer
1H
3.19 and 3.77 (6H, 2s, 2 OCH3), 4.83 (1H, d, 3JHP 16.1 Hz, P-C-CH), 7.47–7.85 (19H, m, 3 C6H5 and C6H4).
37.35 (d, 1JCP 126.3 Hz, P=C), 49.78 and 53.56 (2s, 2 OMe), 55.76 (d, 2JPC 17.3 Hz P-C-CH), 123.37 (s, 2 CH, C
13C
1JPC 92.0 Hz, Cipso), 129.21 (d, JPC 12.3 Hz, Cmeta), 132.44 (d, JPC 1 Hz, Cpara), 132.75 (s, 2C, C6H4), 133.89
3
4
134.09 (d, 2JPC 10.0 Hz, Cortho), 167.97 (2 C=O, phthalimide), 169.81 (d, 3JPC 14.0 Hz, C=O ester), 171.7 (d, 3JP
ester).
23.84 (s, Ph3P=C).
31P
4a
Major rotamer
1H
3.66 and 3.73 (6H, 2s, 2 OCH3). 4.85 (1H, d, 3JHP 17.5 Hz, P-C-CH), 7.47–7.85 (19H, m, 3 C6H5 and C6H4).
39.51 (d, 1JCP 131.0 Hz, P=C), 51.18 and 53.28 (2s, 2 OMe), 55.13 (d, 2JPC 17.3 Hz, P-C-CH), 123.36 (s, 2CH,
13C
3
4
1JPC 92.3 Hz, Cipso); 129.11 (d, JPC 12.3 Hz, Cmeta), 132.45 (d, JPC 1.0 Hz, Cpara), 132.65 (s, 2C, C6H4), 133.99
2
3
3
134.07 (d, JPC 6.5 Hz, Cortho), 167.96 (2 C=O, phthalimide), 169.64 (d, JPC 13.7 Hz, C=O ester), 171.8 (d, JP
ester).
24.00 (s, Ph3P=C).
31P
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[a] Selected spectroscopic data and free activation energy for 4a from ref. [24] are presented here.
1
Table 2. Selected H NMR chemical shifts δ/ppm of 6a (500 MHz) along with activation parameters in CDCl3 for the
restricted rotational process around the carbon-carbon single bond in mode A and B (see Scheme 4).
kc/s−1
Temp.
°C
Tc/K
296
Compound
6a-(major)
δ/ppm
∆ν/Hz
∆G‡
∆H‡
∆S‡
kJmol−1
kJmol−1
kJmol−1K−1
20
50
20
50
20
50
20
50
3.0947
3.2161
3.14
60.712
134.81
62.48±1
60.44±1
48.12
–0.044
6.6595
6.7896
6.79
65.067
23.606
25.956
144.47
297
3.8881
3.9351
3.92
52.19
293
61.83±1
6a-(minor)
33.188
–0.0985
4
2.8904
2.9423
6.79
57.63
295
62.27±1
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Table 3. Selected 1H NMR chemical shifts δ/ppm of 6a (500 MHz, Me4Si) along with activation
parameters ΔG‡/kJmol−1 in CDCl3 for the restricted rotational process around the carbon-
nitrogen single bonds in mode C and D (see Scheme 5).
kc/s−1
33.32
33.32
ΔG‡/kJmol−1
58.00±2
Temp/°C
Tc/K
Compound
δ/ppm
CO2CH3
3.81, 3.84
3.84
Δν/Hz
15.00
15.00
15
35
15
35
270
254
6a-(major)
6a-(minor)
3.82, 3.85
3.85
54.43±2
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Table 4. Selected 1H NMR chemical shifts δ/ppm of 6a (500 MHz, Me4Si) along with activation
parameters in CDCl3 for the restricted rotational process around the carbon-nitrogen single bonds
in mode E and F (see Scheme 5).
kc/s−1
ΔG‡/kJmol−1
Temp./°C
Tc/K
Compound
δ/ppm
Δν/Hz
CO2CH3
2.84, 2.85
3.86
5.00
11.10
21.81
294
296
64.11±2
62.88±2
6a-(major)
6a-(minor)
–15
60
–15
60
3.16, 3.18
3.18
10.00
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CO2Me
X1
O
X2
C
C
O
Ph3P
+
X2
OH
NCO
H
CO2Me
N
O
4
5
N H
CO2Me
solvent-free
r. t., 6h
X2
+
O
Ph3P
r. t., CH2Cl2
X1
X1
CO2Me
6
3
2
1
X1
X2
1,3,6
a
% Yield
90
4-Me
H
H
2-Me
b
c
93
88
4-CHO
2-NO2
2-Me
H
H
d
e
93
87
6-Me
Scheme 1: Synthesis of carbamate containing phosphorus ylides.
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CH3
CH3
O
O
O
O
N H
N H
Ph3P
CO2Me
Ph3P
MeO
CO2Me
OMe
O
O
(E)-6a Minor isomer
(Z)-6a Major isomer
Scheme 2: E and Z geometrical isomers of phosphorus ylides as major and minor isomers.
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O
H3C
H3C
O
C
O
N
OH
O
H
N
O
N
CO2Me
C
H
3a
Ph3P
C
2
4
1a
CH3
CO2Me
H3C
O
H
5
PPh3
O
N
6a
MeO2C
CO2Me
PPh3
MeO2C
CO2Me
Scheme 3: A proposed mechanism for the synthesis of phosphorus ylides.
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CH3
CO2Me
O
H
O
N
O
Ph3P
Tc = 293 °K
O
H
N
OMe
Ph3P
CO2Me
O
CH3
OMe
O
(B)
CH3
CH3
O
O
O
O
Tc = 332°K
N H
N H
Ph3P
CO2Me
Ph3P
CO2Me
OMe
O
O
MeO
(E)-6a Minor isomer
(Z)-6a Major isomer
CH3
(A)
O
CO2Me
O
Tc = 296 °K
H
Ph3P
MeO
N
O
H
N
O
Ph3P
CO2Me
O
O
MeO
CH3
Scheme 4: Conformational interchanges around the C-C single bonds in the major and minor
compounds.
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CH3
CH3
CH3
CH3
O
O
O
O
Tc = 270 °K
Tc = 254 °K
O
O
O
O
N H
N H
CO2Me
N H
N H
CO2Me
Ph3P
MeO
CO2Me
Ph3P
Ph3P
MeO
CO2Me
Ph3P
O
OMe
O
O
(D)
OMe
O
(C)
CH3
CH3
O
O
O
O
Tc = 332 °K
N H
CO2Me
N H
O
Ph3P
Ph3P
CO2Me
OMe
O
MeO
(E)-6a Minor isomer
(Z)-6a Major isomer
CH3
(F)
CH3
(E)
CH3
CH3
O
O
O
O
O
Tc = 294 °K
O
O
N H
CO2Me
Tc = 296 °K
O
N H
Ph3P
N H
Ph3P
CO2Me
N H
CO2Me
Ph3P
MeO
O
Ph3P
CO2Me
MeO
OMe
O
O
OMe
O
Scheme 5: Conformational interchanges around the C-N single bond in the major and the minor
diastereoisomers.
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CO2Me
C
X1
O
X2
C
O
Ph3P
+
X2
OH
NCO
H
CO2Me
N
O
N H
CO2Me
solvent-free
r. t., 6h
X2
+
Ph3P
O
r. t., CH2Cl2
X1
X1
CO2Me
X1: 2-Me, 4-Me, 4-CHO, 2-NO2
X2: H, 6-Me
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