One-pot synthesis of Alkyl 3-(Diphenylphosphoryl)-3-(10H-phenothiazin-10- yl)propanoates from Alkyl acetylenecarboxylates, phenothiazine, and triphenylphosphine

Article abstract of DOI:10.1080/10426500802704845

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and alkyl acetylenecarboxylates by phenothiazine, leads to vinyltriphenylphosphonium salts, which undergo a Michael addition reaction with conjugate

Full text of DOI:10.1080/10426500802704845

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One-Pot Synthesis of Alkyl
3-(Diphenylphosphoryl)-3-
(10H-phenothiazin-10-
yl)propanoates from Alkyl
Acetylenecarboxylates,
Phenothiazine, and
Triphenylphosphine
Ali Ramazani a & Fariba Sadri b
a Department of Chemistry, Islamic Azad
University–Zanjan Branch, Zanjan, Iran
b Chemistry Department, Payam Noor University
(PNU), Abhar, Zanjan, Iran
Published online: 18 Nov 2009.
To cite this article: Ali Ramazani & Fariba Sadri (2009): One-Pot Synthesis of
Alkyl 3-(Diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)propanoates from Alkyl
Acetylenecarboxylates, Phenothiazine, and Triphenylphosphine, Phosphorus, Sulfur,
and Silicon and the Related Elements, 184:12, 3126-3133
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Phosphorus, Sulfur, and Silicon, 184:3126–3133, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802704845
One-Pot Synthesis of Alkyl 3-(Diphenylphosphoryl)-3-
(10H-phenothiazin-10-yl)propanoates from Alkyl
Acetylenecarboxylates, Phenothiazine, and
Triphenylphosphine
Ali Ramazani1 and Fariba Sadri2
1Department of Chemistry, Islamic Azad University–Zanjan Branch,
Zanjan, Iran
2Chemistry Department, Payam Noor University (PNU), Abhar, Zanjan,
Iran
Protonation of the highly reactive 1:1 intermediates, produced in the reaction be-
tween triphenylphosphine and alkyl acetylenecarboxylates by phenothiazine, leads
to vinyltriphenylphosphonium salts, which undergo a Michael addition reaction
with conjugate bases to produce the corresponding phosphorus ylides. The phospho-
rus ylides react with water forming phenothiazine containing diphenylphosphine
oxide derivatives in moderate yields.
Keywords Acetylenic ester; DEPT-135 experiment; phenothiazine; phenothiazine con-
taining diphenylphosphine oxide derivatives; phosphorus ylide; triphenylphosphine;
vinyltriphenylphosphonium salts
INTRODUCTION
The phosphorus ylides represent an outstanding achievement of the
chemistry of the twentieth century.1–16 They have found use in a wide
variety of reactions of interest to synthetic chemists.1–16 Phosphorus
ylides are important reagents in synthetic organic chemistry,1–16 espe-
cially in the synthesis of naturally occurring products, and compounds
with biological and pharmacological activity.6 The development of the
modern chemistry of natural and physiologically active compounds
would have been impossible without the phosphorus ylides.1–16 These
compounds have attained great significance as widely used reagents for
Received 25 August 2008; accepted 14 December 2008.
The authors are thankful to the Islamic Azad University–Zanjan Branch and Payam
Noor University (PNU), Abhar Center for partial support of this work.
Address correspondence to Ali Ramazani, Department of Chemistry, Islamic Azad
University–Zanjan Branch, P O Box 49195-467, Zanjan, Iran. E-mail: aliramazani@
gmail.com
3126

One-Pot Synthesis of Phenothiazines
3127
linking synthetic building blocks with the formation of carbon–carbon
double bonds, and this has aroused much interest in the study of
the synthesis, structure, and properties of P-ylides and their deriva-
tives.1–16 Several methods have been developed for preparation of phos-
phorus ylides.1–16 These ylides are most often prepared by the treat-
ment of a phosphonium salt with a base. Most of the phosphonium salts
are usually made from phosphine and an alkyl halide,1–16 and they are
also obtained by the Michael addition of phosphorus nucleophiles to
activated olefins.1–16
β-Additions of nucleophiles to the vinyl group of vinylic phospho-
nium salts leading to the formation of new alkylidenephosphoranes
has attracted much attention as a very convenient and synthetically
useful method in organic synthesis.18−30 Phosphorus ylides are a class
of special type of zwitterions, which bear strongly nucleophilic, electron-
rich carbanions. The electron distribution around the P+–C− bond
and its consequent chemical implications had been probed and as-
sessed through theoretical, spectroscopic, and crystallographic investi-
gations.30 The proton affinity of these ylides can be used as a molecular
guide to assess their utility as synthetic reagents and their function as
ligands in coordination and organometallic chemistry.17,30
Previously we have established a convenient, one-pot method for
preparing stabilized phosphorus ylides utilizing in situ generation
of the phosphonium salts.18−28 Stabilized phosphorus ylides, versa-
tile intermediates in synthetic organic chemistry, can be prepared by
the novel reaction of dialkyl acetylenedicarboxylates (DAAD), triph-
enylphosphine (TPP), and acids such as phenols, imides, amides, enols,
oximes, and alcohols.18–28 The reaction31 involves an intermediate
formed by the 1:1 conjugate addition reaction of the TPP to DAAD,
and concomitant protonation of the intermediate by an acid leads to
vinyltriphenylphosphonium salts.18−28 The salts are unstable interme-
diates and are converted to stabilized phosphorus ylides via a Michael
addition reaction.18−28 The stabilized phosphorus ylides are able to
take part in the normal intramolecular Wittig reactions, but they are
not generally able to participate in the normal intermolecular Wit-
tig reactions.18−28 Intermolecular Wittig reactions of the ylides are ob-
served only with highly electron-poor carbonyl groups such as indane-
1,2,3-trione.31 The ylides are converted to electron-poor alkenes via
elimination of TPP in solvent-free conditions.31 Almost all of the final
products are valuable families of compounds.31 In this article, we wish
to describe a simple one-pot method for the preparation of alkyl 3-
(diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)propanoates 10 from
alkyl acetylenecarboxylates, phenothiazine, and triphenylphosphine
(Scheme 1).

3128
A. Ramazani and F. Sadri
SCHEME 1 Synthesis of phenothiazine containing diphenylphosphine oxide
derivatives (10).
RESULTS AND DISCUSSION
Triphenylphosphine 1, alkyl acetylenecarboxylates 2, and phenoth-
iazine 3 were reacted in a 1:1:1 ratio in acetone at room temper-
ature to give alkyl 3-(diphenylphosphoryl)-3-(10H-phenothiazin-10-
yl)propanoates 10 and benzene 11 (Scheme 1). The reactions were mon-
itored with using of TLC technique. The reaction proceeded smoothly
and cleanly under mild conditions, and no side reactions were observed.
Reactions are known in which an organophosphorus compound is pro-
duced from an acid (CH, NH, OH, and SH-acids), a acetylenic ester, and
a phosphine such as a tributylphosphine or triphenylphosphine.19–21
Thus, compounds 10 may be regarded as the product of an addition-
elimination reaction. Such addition-elimination products may result
from an initial addition of triphenylphosphine 1 to the acetylenic ester
2 and concomitant protonation of the 1:1 adduct 4, followed by attack
of the anion of phenothiazine 5 on the vinylphosphonium cation 5 to
form intermediates 6 and 7. Hydrolysis of the intermediates 6 and
7 via intermediates 8 and 9, along with loss of benzene 11 leads to

One-Pot Synthesis of Phenothiazines
3129
SCHEME 2 Proposed mechanism for the formation of alkyl 3-
(diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)propanoates (10).
formation of alkyl 3-(diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)
propanoates 10 (Scheme 2).
The mechanism of the reaction outlined above has not been estab-
lished experimentally. However, a possible explanation19 is proposed in
Scheme 2.
The structure of products 10 was proven by their 1H NMR and
1
13C NMR spectral data (see the Experimental section). The H NMR
spectrum of compound 10b exhibited six signals readily recognized
3
as arising from its appropriate functional groups [1.02 (3 H, t, JHH

3130
A. Ramazani and F. Sadri
SCHEME 3 Synthesis of phenothiazine-containing stabilized phosphorus
ylides (13).
= 7.1 Hz, CH3); 2.81–2.99 and 3.06–3.19 (2 H, 2 m, CH2); 3.88 (2 H,
3
q, JHH = 7.1 Hz, OCH2); 4.00–4.10 (1 H, m, CH-P); 7.10–7.99 (m, 18
H, aromatic)]. The 13C NMR spectrum of the compound 10b showed
four distinct resonances in the aliphatic region, as was expected. The
functionality of CH2-CH-P of compound 10b was established by a
DEPT-135 experiment [δ = 34.89 (s, CH2, negative signal) and δ =
1
42.93 (d, JPC = 67.93 Hz, CH, positive signal)]. Partial assignment
of these resonances is given in the Experimental section. The 1H
and 13C NMR of compound 10a are similar to those of the compound
10b, except in the alkyl moiety of ester group that appears in an
appropriate chemical shift (see the Spectral Analysis section).28,32
The 31P NMR spectra of the compounds 10 exhibited signals readily
recognized as arising from their Ph2P=O functional group (δ =
33.34 for the compound 10a and δ = 33.12 for the compound 10b).
Synthesis of phenothiazine containing stabilized phosphorus ylides 13
from from dialkyl acetylenedicarboxylates 12, phenothiazine 3, and
triphenylphosphine 1 have been reported (Scheme 3).33
CONCLUSION
In summary, we have found a new and efficient method for the
synthesis of alkyl 3-(diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)

One-Pot Synthesis of Phenothiazines
3131
propanoates (10) from triphenylphosphine (1), alkyl acetylenecarboxy-
lates (2), and phenothiazine (3) (Scheme 1). We believe the reported
method offers a simple and efficient route for the preparation of
the phenothiazine-containing diphenylphosphine oxide derivatives 10
(Scheme 1 and Scheme 2). Its easy work-up and acceptable yields make
it a useful method. Possible extensions are under investigation.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus
and are uncorrected. IR spectra were recorded on a Mattson 1000 FT-IR
1
spectrometer. H and 13C NMR spectra were measured with a Bruker
Spectrospin spectrometer at 250 and 62.5 MHz, respectively.
General Procedure for the Preparation of Alkyl 3-(Diphenyl-
phosphoryl)-3-(10H-phenothiazin-10-yl)propanoates 10a–b
To a magnetically stirred solution of triphenylphosphine 1 (0.262 g,
1.00 mmol) and phenothiazine 3 (0.199 g, 1.0 mmol) in acetone (4 mL), a
mixture of alkyl acetylenecarboxylate 2 (0.10 mL, 1.0 mmol) in acetone
(1 mL) at −10◦C was added dropwise over 15 min, and the mixture
was stirred for 35 min at −10◦C. The mixture was allowed to warm
up to room temperature and stirred for 3 h. The product precipitated
as white crystals. The crystals were separated from acetone by simple
filtration and washed with cold diethyl ether (3 × 15 mL). The product
was dried at room temperature.
Methyl 3-(Diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)
propanoate (10a)
White crystals; mp: 185–186◦C; Yield: 43.2%. IR (KBr) (vmax, cm−1):
3062 (C–H, aromatic); 2954 (C–H, aliph); 1739 (C=O, ester); 1443
(arom.); 1200 (P=O and C-O). 1H NMR (CDCl3) δ: 2.85–3.00 and
3.05–3.20 (2 H, 2 m, CH2); 3.45 (3 H, s, OCH3); 4.02–4.15 (1 H, m,
CH-P); 7.12–8.00 (18 H, m, aromatic). 13C NMR (CDCl3) δ: 34.72 (s,
CH2); 43.32 (d, 1JPC = 68.37 Hz, CHP); 51.89 (s, OCH3); 127.25–135.90
3
(fairly complex, arom.); 161.72 (d, JPC = 3.15 Hz, CO of ester). 31P
NMR (CDCl3) δ: 33.34.
Ethyl 3-(Diphenylphosphoryl)-3-(10H-phenothiazin-10-yl)
propanoate (10b)
White crystals; mp: 190–191◦C; Yield: 51.4%. IR (KBr) (vmax, cm−1):
3046 (C–H, aromatic); 2985 and 2915 (C–H, aliph.); 1739 (C=O, ester);

3132
A. Ramazani and F. Sadri
1
1439 (arom.); 1185 (P=O and C-O). H NMR (CDCl3) δ: 1.02 (3 H, t,
3JHH = 7.1 Hz, CH3); 2.81–2.99 and 3.06–3.19 (2 H, 2 m, CH2); 3.88
3
(2 H, q, JHH = 7.1 Hz, OCH2); 4.00–4.10 (1 H, m, CH-P); 7.10–7.99
(m, 18 H, aromatic). 13C NMR (CDCl3) δ: 13.91 (s, CH3); 34.89 (s, CH2);
42.93 (d, 1JPC = 67.93 Hz, CH); 60.74 (s, OCH2); 127.20–135.10 (fairly
3
complex, arom.); 171.31 (d, JPC = 16.98 Hz, CO of ester). 31P NMR
(CDCl3) δ: 33.12.
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