Synthesis and study of dynamic 1H NMR of carbon-carbon double bond rotation energy barrier in stable phenothiazine phosphorus ylides

Article abstract of DOI:10.1080/10426500601047149

The 1:1 intermediates generated by the addition of triphenylphosphine to dialkyl acetylenedicarboxylates were trapped by an NH-acidic compound such as phenothiazine to give dialkyl-2-(phenothiazino)-3-(triphenylphosphoranylidene)- butanedioates in high yields. The ylide moiety of these compounds was strongly conjugated with the adjacent carbonyl group, and rotation around the partial double bond in the (E) and (Z) geometrical isomers was slow on the NMR time scale. The dynamic effects in the ylide moiety were investigated by ¹H NMR. They are attributed to a restricted rotation around the carbon-carbon double bond. Copyright Taylor & Francis Group, LLC.

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Synthesis and Study of Dynamic
1H NMR of Carbon–Carbon
Double Bond Rotation Energy
Barrier in Stable Phenothiazine
Phosphorus Ylides
Malek Taher Maghsoodlou a , Sayyed Mostafa Habibi
Khorassani a , Uranous Niroumand a , Faramarz
Rostami Charati a & Maryam Khosrosharodi a
a Department of Chemistry, The University of Sistan
and Balouchestan, Zahedan, Iran
Published online: 30 Jan 2007.
To cite this article: Malek Taher Maghsoodlou , Sayyed Mostafa Habibi Khorassani ,
Uranous Niroumand , Faramarz Rostami Charati & Maryam Khosrosharodi (2007):
Synthesis and Study of Dynamic 1H NMR of Carbon–Carbon Double Bond Rotation
Energy Barrier in Stable Phenothiazine Phosphorus Ylides, Phosphorus, Sulfur, and
Silicon and the Related Elements, 182:3, 647-655
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Phosphorus, Sulfur, and Silicon, 182:647–655, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500601047149
Synthesis and Study of Dynamic 1H NMR
of Carbon–Carbon Double Bond Rotation Energy
Barrier in Stable Phenothiazine Phosphorus Ylides
Malek Taher Maghsoodlou
Sayyed Mostafa Habibi Khorassani
Uranous Niroumand
Faramarz Rostami Charati
Maryam Khosrosharodi
Department of Chemistry, The University of Sistan and Balouchestan,
Zahedan, Iran
The 1:1 intermediates generated by the addition of triphenylphosphine to di-
alkyl acetylenedicarboxylates were trapped by an NH-acidic compound such as
phenothiazine to give dialkyl-2-(phenothiazino)-3-(triphenylphosphoranylidene)-
butanedioates in high yields. The ylide moiety of these compounds was strongly
conjugated with the adjacent carbonyl group, and rotation around the partial dou-
ble bond in the (E) and (Z) geometrical isomers was slow on the NMR time scale.
The dynamic effects in the ylide moiety were investigated by 1H NMR. They are
attributed to a restricted rotation around the carbon–carbon double bond.
Keywords Rotational energy; phenothiazine; triphenylphosphine; phosphorus ylides;
dynamic NMR
INTRODUCTION
Phenothiazines have proven to be a pharmaceutically important class
of heterocycles. Due to their pharmacological efficacy, they are applied
as sedatives, tranquilizers, antiepilectica, antipyretica, and antitumor
agents, as well as bactericides and pesticides.1,2 Interestingly, phenoth-
iazines are able to cleave DNA upon photochemical induction.3 It was
recognized quite early that the low oxidation potential of this class of
Received August 2, 2005; accepted August 23, 2006.
The authors gratefully acknowledge financial support from the Research Council of
The University of Sistan and Balouchestan, Zahedan, Iran.
Address correspondence to Malek Taher Maghsoodlou, Department of Chemistry,
The University of Sistan and Balouchestan, P.O. Box 98135-674, Zahedan, Iran. E-mail:
MT maghsoodlou@yahoo.com
647

648
M. T. Maghsoodlou
tricyclic nitrogen-sulfur heterocycles and their propensity to form sta-
ble radical cations play a key role in their physiological activities.4
With respect to the importance of heterocycles, the development
of simple synthetic routes for widely used organic materials, and
especially for organophosphorus compounds, from readily available
reagents is one of the major tasks in organic synthesis. Organophos-
phorous compounds are of particular interest as synthetic targets due
to their importance in industrial, biological, and chemical syntheses.5
Many strategies have appeared describing novel syntheses of
organophosphorus compounds, including our previous report.13 Here
we report an efficient synthetic route to sterically congested nitrogen-
containing phosphorus ylides 4 using triphenylphosphine, dialkyl
acetylenedicarboxylates 1, and phenothiazine 2 (Scheme 1).
SCHEME 1
RESULTS AND DISCUSSION
On the basis of well-established chemistry of trivalent phosphorus
nucleophiles,13−17 it is reasonable to assume that the first step in the for-
mation of phosphorus ylides 4 is performed by the nucleophilic reaction
of triphenylphosphine with dialkyl acetylenedicarboxylates 1. Subse-
quent protonation of the highly reactive 1:1 adduct by phenothiazine
2 leads to the vinyl triphenylphosphonium salts 3. The nucleophilic
attack of the phenothiazine anion on the vinyl triphenylphosphonium
cation finally yields phosphoranes 4 as mixtures of the E and Z isomers
(Scheme 2).
All of the compounds 4a–c are stable solid powders whose structures
are supported by 1H, 13C, and 31P NMR as well as the IR spectral data.
The mass spectra of these compounds display the molecular ion peak
at m/z = 405, 457, and 489 (M+-phenothiazine) for 4a, 4b, and 4c,

Dynamic 1H NMR of Phenothiazine Phosphorus Ylides
649
SCHEME 2
respectively. 1H NMR data of compounds 4a and 4b show the presence
of the Z and E rotamers, while phosphorane 4c is found only as one
1
rotamer. The H NMR spectrum of 4a displays sharp signals at 2.99
and 3.93 ppm for the major rotamer and 3.65 and 3.79 ppm for the
minor rotamer arising from the methyl protons of the methoxy groups.
The signal at δ = 3.65 for the methyl group of the minor rotamer appears
at a higher field because of the anisotropic effect of phenyl groups of the
triphenylphosphine moiety.18 The 1H NMR spectrum of 4a also displays
two doublets at δ = 4.22 (3 J = 14.6 Hz) and δ = 4.25 (3 J = 15.9 Hz)
PH
PH
for the methine protons of the major and minor rotamer, respectively
(Table I).
The 1H NMR spectrum of 4b is similar to that of 4a except for
the ethyl group, which exhibits characteristic signals with appropriate
chemical shifts. The 1H NMR spectrum of 4c shows a different pattern
from those of 4a and 4b. It shows one doublet and two sharp singlets
for the methine and the methyl protons, repectively. This indicates the
presence of only one rotamer. Evidence for the presence of two rotamers
in the case of 4a and 4b and of only one rotamer in the case of 4c indi-
cated by 1H NMR data is further confirmed by 13C and 31P NMR spectra.
In each 31P NMR spectrum of 4a and 4b, two signals were observed
at δ = 25.3 and 24.7 and δ = 25.1 and 24.8 ppm, respectively, which
were attributed to the E and Z rotamers (Table I and Scheme 3). These
shifts are similar to those observed for other phosphorus ylides.19,20
√
The first-order rate constant (k = πꢀυ/ 2) in the interconversion

650

Dynamic 1H NMR of Phenothiazine Phosphorus Ylides
651
SCHEME 3
between the two rotamers was studied by variable temperature 1H
NMR spectroscopy for compound 4a in CDCl3 as a solvent.
1
The H NMR spectrum of 4a in CDCl3 solution at an ambient tem-
perature displayed two doublets for the CH proton at δ = 4.22 and 4.28
ppm. Increasing the temperature to 65◦C resulted in coalescence. The
1
same was observed in the variable temperature H NMR spectrum of
4b. From the colescence temperature of the proton resonances of the
CH group and using the equation for the rate constant,18 we calculated
the first-order rate constant (k) for the bond rotation in 4a to 66.6 s−1
at 25◦C (Table II).
Application of absolute-rate theory equation with a transmission co-
efficient of 1 gave a free-energy of activation (ꢀG =) for 4a of 62.5
2 kJ mol−1, for which all known sources of errors were estimated and
included (Table II).6,21
The experimental data available are not suitable for obtaining mean-
ingful values of ꢀH= and ꢀS=, although the errors in ꢀG=should not
1
be large.8 In summary, dynamic NMR effects were observed in the H
NMR spectra of compounds 4, which are attributed to a restricted ro-
tation around the carbon–carbon double bond.
TABLE II Selected 1H Chemical Shifts (ppm) and Activation
Parameters (kJ mol−1) for 4a,b in CDCl3
Resonance
Compound Temp. (◦C) (CH of Ylide) ꢀυ K (S−1
) )
TC(K) ꢀG#(KJ mol−1
4a
4b
25
65
25
60
4.22, 4.28
4.22
4.11, 4.24
4.17
30.0
—
65
66.6
—
144.4
—
298
—
298
—
62.5
—
60.6
—
—

652
M. T. Maghsoodlou
In conclusion, we have prepared novel phenothiazine-containing
phosphorus ylides via a one-pot reaction between triphenylphosphine
and dialkyl acetylenedicarboxylates in the presence of a NH-acid such
as phenothiazine. The present method has the advantage that the re-
action is performed under neutral conditions. The substances can be
mixed without any activation or modification (without using support
or a catalyst). The phosphoranes 4a–c may be considered potentially
useful synthetic intermediates.
EXPERIMENTAL
Melting points and IR spectra were measured on an Electrotermal 9100
apparatus and a Shimadzu IR 470 spectrophotometer, respectively. 1H,
13C, and 31P NMR spectra were recorded with a BRUKER DRX-500
AVANCE instrument in CDCl3 as a solvent at 500.1, 125.8, and 202.4
MHz, respectively. Mass spectra were obtained with a Finigan-Matt
8430 mass spectrometer operating at an ionization potential of 70 eV.
Dialkyl acetylenedicarboxylates 1, triphenylphosphine, and phenoth-
iazine 2 were purchased from Fluka (Buchs, Switzerland) and were
used without further purification.
General Procedure for Preparation of Ylides (4)
To a magnetically stirred solution of triphenylphosphine (0.262 g,
1 mmol) and phenothiazine (0.199 g, 1 mmol) in 5 mL of acetone
was added dropwise a mixture of the dialkyl acetylenedicarboxylate
(1 mmol) in 1 mL of acetone at −5◦C over 10 min. The reaction mix-
ture was then allowed to warm up to r.t. and stirred for 4 h. The
solid product was filtered and washed with (3 × 10 mL) cold di-
ethyl ether to give ylides 4a–c. Characteristic analytical and spectro-
scopic data of dialkyl-2-(phenothiazine-N-yl)-3-(triphenylphosphorani-
lidene)butandioates 4a–c follow.
Dimethyl-2-(phenothiazino)-3-(triphenylphosphoranylidene)-
butanedioate (4a)
Yellow solid, yield 95%, m.p. 186–188◦C IR (KBr), υmax (cm−1): 1730
(C O), 1600 (C C), MS (m/z, %): 405 (M+-phenothiazine, 100), 262.2
(Ph3P, 60), 199.2 (phenothiazine, 65), 183 ((CH3)3CO2CCHCO2H,60),
167.2 (phenothiazine-S, 35), 77.1 (Ph, 18); major isomer 4a-(E) (52%),
1H NMR (CDCl3): δ 2.9 (s, 3H, OCH3) and 3.9 (s, 3H, OCH3), 4.2 (d,
3 J = 14.6 Hz, 1H, P C CH), 6.6–7.9 (m, 23H, arom-H). 13C NMR
PH

Dynamic 1H NMR of Phenothiazine Phosphorus Ylides
653
1
(CDCl3): δ 42.5 (d, JPC = 123.7 Hz, P C), 49.0 (s, OCH3), 52.4 (s,
OCH3), 65.3 (d, 2 J = 14.6 Hz, P C CH), 115.3 (s, C S), 121.8 (s,
PH
1
CH) 122.3 (s, CH), 122.6 (s, CH), 125.7 (s, CH), 126.1 (d, JPC = 92.8
3
4
Hz, Cipso), 128.4 (d, JPC = 12.3 Hz, Cmeta), 131.7 (d, JPC = 2.8 Hz,
C
para), 133.5 (d, 2 JPC = 9.7 Hz, Cortho), 146.6 (s, C N), 169.2 (d, 2 JPC
=
12.8 Hz, C O), 174.2 (d, JPC = 17.2 Hz, C O). 31P NMR (CDCl3): δ
3
25.3; minor isomer 4a-(Z) (48%), 1H NMR (CDCl3): δ 3.7 (s, 3H, OCH3),
3.9 (s, 3H, OCH3), 4.3 (d, 3 J = 15.9 Hz, 1H, P-C-CH), 6.6–8.0 (m, 23H,
PH
arom-H). 13C NMR (CDCl3): δ 43.8 (d, JPC = 125.7 Hz, P=C), 50.3 (s,
1
2
OCH3), 52.2 (s, OCH3), 64.8 (d, JPC = 14.9 Hz, P C CH), 114.8 (s,
C S), 121.6 (s, CH), 122.5 (s, CH), 122.7 (s, CH), 125.4 (s, CH), 126.2
1
3
(d, JPC = 92.8 Hz, Cipso), 128.5 (d, JPC = 15.6 Hz, Cmeta), 131.9 (d,
4 JPC = 2.8 Hz, Cpara), 133.6 (d, JPC = 9.8 Hz, Cortho), 146.5 (s, C N),
2
169.1 (d, JPC = 12.4 Hz, C O), 174.1 (d, JPC = 17.2 Hz, C O). 31P
2
3
NMR (CDCl3): δ 24.7.
Diethyl-2-(phenothiazino)-3-(triphenylphosphoranylidene)-
butanedioate (4b)
Yellow solid, yield 85%, m.p. 180–182◦C, IR (KBr), υmax, (cm−1): 1720
(C O), 1630 (C C), MS (m/z, %): 457 (M-2CO2Et, 8), 359.3 (M-
phenothiazine-CH2CH3,18), 262.2 (PPh3, 90), 199.2 (phenothiazine,
90), 183.1 (t-EtO2CCCHCO2H, 95); major isomer 4b-(E) (56%), 1H NMR
3
3
(CDCl3): δ 0.4 (t, JHH = 7.0 Hz, 3H, CH3), 1.3 (t, JHH = 7.0 Hz, 3H,
3
CH3), 3.4 (m, 2H, CH2), 4.1 (d, 1H, J = 18.5 Hz, P C CH), 4.3 (m,
PH
2H, CH2), 6.5–8.0 (m, 23H, arom-H). 13C NMR (CDCl3): δ 13.9 (s, CH3),
14.4 (s, CH3), 42.2 (d,1 JPC = 123.3 Hz, P C), 57.5 (s, CH2), 61.4 (s, CH2),
65.5 (d, 2 JPC = 15.2 Hz, P C CH), 117.9 (s, C S), 121.8 (s, CH) 122.3
1
(s, CH), 122.6 (s, CH), 125.7 (s, CH), 127.1 (d, JPC = 85.0 Hz, Cipso),
128.3 (d, 3 JPC = 12.2 Hz, Cmeta), 131.6 (d, 4 JPC = 2.8 Hz, Cpara), 133.6 (d,
2 JPC = 9.7 Hz, Cortho), 146.7 (s, C N), 168.6 (d, 2 JPC = 12.8 Hz, C O),
173.67 (d, JPC = 14.6 Hz, C O). 31P NMR (CDCl3): δ 25.1; minor iso-
3
mer 4b-(Z) (44%), 1H NMR (CDCl3): δ 0.5 (t, 3 JHH = 6.9 Hz, 3H, CH3),
3
3
1.4 (t, JHH = 6.9 Hz, 3H, CH3), 3.8 (m, 2H, CH2), 4.2 (d, J = 14.9
PH
Hz, 1H P C CH), 4.4 (m, 2H, CH2), 6.5–8.0 (m, 23H, arom-H). 13C
1
NMR (CDCl3): δ 14.0 (s, CH3), 14.1 (s, CH3), 44.5 (d, JPC = 124.4 Hz,
2
P C), 58.6 (s, CH2), 61.2 (s, CH2) 64.8 (d, JPC = 13.6 Hz, P C CH),
117.9 (s, C S), 121.6 (s, CH), 122.1 (s, CH), 122.5 (s, CH), 125.7 (s, CH),
126.3 (d, 1 JPC = 74.8 Hz, Cipso), 128.5 (d, 3JPC = 12.2 Hz, Cmeta), 131.5
4
2
(d, JPC = 2.5 Hz, Cpara), 133.7 (d, JPC = 8.7 Hz, Cortho), 146.8 (C N),
168.6 (d, JPC = 12.6 Hz, C O), 173.7 (d, JPC = 14.6 Hz, C O). 31P
2
3
NMR (CDCl3): δ 24.8.

654
M. T. Maghsoodlou
Di-tert-butyl-2-(phenothiazino)-3-
(triphenylphosphoranylidene)-butanedioate (4c)
Yellow crystals, yield 90%, m.p. 198–199◦C, IR (KBr), υmax, (cm−1):
1720 (C O), 1620 (C C), MS (m/z, %): 488.9 (M-phenothiazine-H, 18),
433 (M-phenothiazine-tBu, 18), 377.3 (M-phenothiazine-CO2-tBu, 100),
262.1 (Ph3P, 38), 199.4 (phenothiazine, 90), 183.1 (tBuO2CCCHCO2H,
1
35). H NMR (CDCl3): δ 0.9 (s, 18H, CH3), 1.7 (s, 9H, CH3), 4.1 (d,
3 J = 16.5 Hz, 1H, P C CH), 6.0–8.0 (m, 23H, arom-H). 13C NMR
PH
(CDCl3): δ 28.3 (s, CH3), 28.4 (s, CH3), 41.6 (d, 1 JPC = 123.7 Hz, P C),
66.3 (d, 2 JPC = 14.7 Hz, P C CH), 76.8 (s, CMe3), 80.2 (s, CMe3), 115.2
(s, C S), 121.1 (s, CH), 122.2 (s, CH), 122.6 (s, CH), 125.8 (s, CH), 127.0
3
3
(d, JPC = 94.0 Hz, Cipso), 128.1 (d, JPC = 12.2 Hz, Cmeta), 131.4 (s,
Cpara), 133.6 (d, 2 JPC = 10.6 Hz, Cortho), 146.9 (s, C N), 147.0 (s, C N),
167.7 (d, JPC = 12.2 Hz, C O), 172.1 (d, JPC = 17.6 Hz, C O). 31P
2
3
NMR (CDCl3): δ 24.6.
REFERENCES
[1] M. Sainsbury, In Comperehensive Heterocyclic Chemistry, A. Katritzky and C. W.
Rees, eds., 3rd. ed., pp. 995, (Pergamon Press, Oxford, 1984).
[2] (a) F. Mietzsch, Angew.Chem., 66, 363 (1954); (b) M. Ionescu and H. Mantsch, Adv.
Heterocycl.Chem., 8, 83 (1967); (c) C. Bodea and I. Silberg, Adv. Heterocycl. Chem.,
9, 321 (1968); (d) L. Valzelli and S. Garattini, In Principles of Psychopharmacology,
W. G. Clark ed., p. 255, (Academic Press, 1970); (e) C. O. Okafor, Heterocycl. Chem.,
23, 1 (1978); (f) J. Szabo, Chem. Heterocycl. Compd., 15, 239 (1979); (g) W. J. Albery,
A. W. Foulds, K. J. Hall, A. R. Hillman, R. G. Edgell, and A. F. Orchard, Nature, 282,
792–794 (1979).
[3] (a) E. Nishwaki, H. Nakagawa, M. Takasaki, T. Matsumoto, H. Sakurai, and M.
Shibuy, Heterocycles, 31, 1763 (1990); (b) J. Decuyper, J. Piette, M. Lopez, M. P.
Merville, and A. Vorst, Biochem. Pharmacol., 33, 4025 (1984); (c) A.G. Motten, G. R.
Buettner, and C. F. Chignell, Photochem. Photobiol., 42, 9 (1985); (d) H. Fuitta and
C. Matsuo, Chem. Biol. Interac., 66, 27 (1988).
[4] (a) I. Forrest and F. Forrest, Biochem. Biophys. Acta, 29, 441 (1985); (b) Y. Lia, Bull.
Chem. Soc. Jpn., 44, 663 (1971); (c) J. C. Moutet and G. Reverdy, Nouv. J. Chim., 7,
105 (1983).
[5] P. Laszelo, Organic Reaction: Simplicity and Logic, (Wiley, New York, 1995).
[6] H. R. Hudson, The Chemistry of Organophosphorus Compounds: Primary, Sec-
ondary, and Tertiary Phosphines and Heterocyclic Organophosphorus(III) Com-
pounds, 1, pp. 386–472, (Wiley, New York, 1990).
[7] R. Engel, Synthesis of Carbon-Phosphorus Bonds (CRC Press, Boca Raton, FL,
1998).
[8] D. E. C. Corbridge, Phosphorus: An Outline of its Chemistry, Biochemistry, and
Technology, 5th ed. (Elsevier, Amsterdam, 1995).
[9] J. I. G. Cadogan, Organophosphorus Reagents in Organic Synthesis (Academic Press,
New York, 1977).
[10] R. A. Cherkasov and M. A. Pudovik, Russ. Chem. Rev., 63, 1019 (1994).
[11] K. M. Pitrusiewiz and M. Zabloka, Chem. Rev., 94, 1375 (1994).

Dynamic 1H NMR of Phenothiazine Phosphorus Ylides
655
[12] H. J. Bestmann and O. Vostrowsky, Top. Curr. Chem., 109, 86 (1983).
[13] I. Yavari and M. T. Maghsoodlou, Tetrahedron Lett., 39, 4579 (1998).
[14] I. Yavari and A. Ramazani, Phosphorus, Sulfur, and Silicon, 130, 73 (1997).
[15] I. Yavari, H. Mosslemin, and A. R. Montahaei, J. Chem. Res. (S), 9, 576 (1998).
[16] I. Yavari and M. R. Islami, Phosphorus, Sulfur, and Silicon, 130, 22 (1978).
[17] A. Shaabani and F. Negat Sadeghi, J. Chem. Res. (S), 9, 584 (1998).
[18] A. Shaabani, H. R. Safaei, K. Hemyari, and A. Moghimi, J. Chem. Res (S), 5, 192
(2001).
[19] J. C. Tebby, In Phosphorus 31 NMR Spectroscopy in Stereochemical Analysis, J. G.
Verkade and L. D. Quin, eds., pp. 1–60, (VCH, Weinheim, 1987).
[20] (a) E. Vedeje and K. A. J. Snoble, J. Am. Chem. Soc., 95, 5778 (1973); (b) E. Vedeje,
K. A. J. Snoble, and P. L. Fuchs, J. Org. Chem., 38, 1178 (1973).
[21] H. Gu¨nther,NMR Spectroscopy, 2nd ed., p. 9, (Wiley, New York, 1995).