On the PPh3 catalyzed reaction between dibenzoylacetylene and vicinal -OH and -SH acids. One-pot synthesis of 1,3-dioxolane derivative

Article abstract of DOI:10.2478/s11532-009-0106-z

The efficient conjugate addition of vicinal - OH and - SH acids such as ethylene glycol and 1,2-ethanedithiol to dibenzoylacetylene in the presence of PPh3 leads to different products depending on the reaction conditions. Ab initio calculations at HF/6-31

Full text of DOI:10.2478/s11532-009-0106-z

Cent. Eur. J. Chem. • 8(1) • 2010 • 188–193
DOI: 10.2478/s11532-009-0106-z
Central European Journal of Chemistry
On the PPh3 catalyzed reaction between
dibenzoylacetylene and vicinal –OH and –SH
acids. One-pot synthesis of 1,3-dioxolane
derivative
Research Article
Rahebeh Amiri1*, Mina Haghdadi2, Maedeh Nozari1
1 Chemistry Department, Islamic Azad University, Central Tehran Branch,
P.O.Box 14515-871 Tehran, Iran
2 Chemistry Department, Islamic Azad University, Babol Branch,
Babol 1465613111, Iran
Received 16 June 2009; Accepted 23 August 2009
Abstract: The efficient conjugate addition of vicinal – OH and - SH acids such as ethylene glycol and 1,2-ethanedithiol to dibenzoylacetylene
in the presence of PPh3 leads to different products depending on the reaction conditions. Ab initio calculations at HF/6-31G* level
shows that the unsymmetrical envelope conformation of 2,2-disubstituted 1,3-dioxolane 1 is more stable than the half-chair and Cs
symmetric envelope forms.
Keywords: 1,3-Dioxolane • Dibenzoylacetylene • Triphenylphosphine • 1,2-Ethanedithiol
© Versita Warsaw and Springer-Verlag Berlin Heidelberg.
1. Introduction
and versatile method to generate sulfur-containing
compounds [5,6].
The addition of stabilized nucleophilescarbon-based or
Continuing from out earlier results in this field
heteronucleophiles, to activated alkynes has been used [7-9], we here report that both ethylene glycol and
far less often in organic synthesis than electrophilic ethanedithiol undergo smooth addition reactions
addition to these systems. These nucleophilic reactions with dibenzoylacetylene in the presence of
can be highly stereoselective or nearly stereorandom, triphenylphosphine at ambient and reflux temperatures,
depending on reaction conditions [1]. One particularly leading to the production of 2-(2-hydroxy-ethoxy)-1-
useful intramolecular trapping involves the condensation phenyl-3-(2-phenyl-[1,3]-dioxolan-2-yl)-propan-1-one
of bi-functionalized groups with activated alkynes to 1,
produce heterocyclic compounds in one or two steps in
good yields [2,3]. On the other hand, different products
2-{2-[1-Benzoyl-
phosphanylidene)-propoxy]-ethoxy}-1,4- diphenyl-but-
2-ene-1,4- dione 2 and 2-(2-mercapto-ethylsulfanyl)-
3-oxo-3-phenyl-2-(triphenyl-λ5
-
areobtainedfromthereactionbetweenactivatedalkynes
and trivalent phosphorus nucleophiles in the presence
of a proton source such as an alcohol or thiol [4]. The
dithiol addition chemistry provides a useful general
1,4-diphenyl-butane-1,4-dione
3 (see Scheme 1).
The results of ab initio calculations at the HF/6-31G*
level are reported for the different conformations of
2,2-disubstituted 1,3-dioxolane 1.
* E-mail: rahebeha@hotmail.com
188

R. Amiri, M. Haghdadi, M. Nozari
Ph
O
COPh
PPh3
PhOC
COPh
+ HOCH2CH2OH
O
OCH2CH2OH
room temperature
1
COPh
Ph3P
COPh
PPh3
O
COPh
PhOC
PhOC
COPh
+ HOCH2CH2OH
O
reflux
COPh
2
PhOC
PPh3
COPh
+ HSCH2CH2SH
COPh
room temperature
or reflux
SCH2CH2SH
3
Scheme 1. The synthesis of compounds 1-3
mixture of dibenzoylacetylene (0.45g, 2 mmol) in CHCl3
(5 mL) was added dropwise for 2 min at –5°C. The
reaction mixture was then allowed to warm up to room
temperature and stirred for 24 h. The solvent was
removed under reduced pressure and the viscous residue
was purified by column chromatography using n-hexane
– EtOAc (3:1) and preparative TLC on silica gel (Merck
silica gel DC- Fertigplatten 60/Kieselgur HF254+366) 20×20 cm
plates using n-hexane – EtOAc (6:1) as eluent. Zones
were detected by quenching of indicator fluorescence
upon exposure to 366 nm UV light. The product was
obtained by extraction of silica gel with acetone to
produce compound 1 as white powder, yield: 0.25 g
(73%), TLC-Rf = 0.28, m.p. 110-112°C. IR(KBr) νmax/ cm-1:
2. Experimental procedure
Triphenylphosphine,1,2-ethanedioland1,2-ethanedithiol
were obtained from Fluka and were used without further
purification. Dibenzoylacetylene was prepared by a
known method [10,11]. Melting points were measured on
an Electrothermal 9100 apparatus. Elemental analyses
for C and H were performed using a Leco 600 instrument.
The NMR spectra were recorded at 300 (1H) and 75.5
(13C) MHz on a Bruker 300-AVANCE FT-NMR instrument
with CDCl3 as solvent. Chemical shifts (δ) are reported
relative to TMS as the internal standard. IR spectra
were recorded on a Bomem MB-100 IR spectrometer.
Mass spectra were recorded on a Finnigan-Matt TSQ-
70 spectrometer. Analytical thin layer chromatography
was performed on glass plates prepared with silica gel.
Column chromatography was performed using 230-400
mesh Merck silica gel with mixtures of hexane, CH2Cl2
and EtOAc used as eluents.
1
3439 (OH) and 1683 (C=O); H NMR (CDCl3) δ/ ppm:
2
3
2.63 and 3.30 ( dd, 2 H, JHH = 15.8 Hz, Jgauche= 4.7 Hz
and 3Janti = 8.9 Hz, CH2 ), 3.15 and 3.37 ( dd, 2 H, CH2 ),
3.48 and 3.73 ( dd, 2 H, CH2 ), 3.65 and 4.06 ( dd, 2 H,
CH2 ), 4.07 and 4.28 (dd, 2 H, CH2-OH), 4.58 ( dd, 1 H,
3Jgauche= 4.7 Hz and 3Janti = 8.9 Hz, CH ), 7.27-7.75 ( m, 10
H, 2 C6H5 ); 13C NMR (CDCl3) δ/ ppm: 37.73 (CH2), 58.32,
59.88, 61.25, 63.91 ( 4 OCH2 ), 74.61 (CH), 99.11 (C),
127.09, 128.22, 128.39, 128.65, 128.86, 133.20 (6 CH),
137.29, 139.27 (2 C), 197.07 (C ═ O).
2.1. Preparation of 2-(2-hydroxy-ethoxy)-
1-phenyl-3-(2-phenyl-[1,3]-dioxolan-2-yl)-
propan-1-one (1)
Anal. Calcd. For C20H22O5 (Mr = 342.1): C 70.15, H
6.43%; found: C 70.19, H 6.45%. MS (EI, 70 eV): m/z
= 343 (M+ +1)
To a magnetically stirred solution of Ph3P (0.52 g, 2 mmol)
and 1,2-ethanediol (0.12 g, 2 mmol) in CHCl3 (10 mL), a
189
189

On the PPh3 catalyzed reaction between dibenzoylacetylene
and vicinal –OH and –SH acids. One-pot synthesis
of 1,3-dioxolane derivative
removing the solvent, the products were purified by thin
layer chromatography using n-hexane – EtOAc (3:1) as
eluent. In each case the same product was obtained.
Extraction of silica gel with acetone produced compound
3 as a light yellow powder, yield: 0.45 g (68%), TLC-Rf
= 0.57, m.p. 125-127°C. IR(KBr) νmax/ cm-1: 2371 (S-H),
2.2. Preparation of 2-{2-[1-Benzoyl-3-oxo-
3-phenyl-2-(triphenyl-λ5-phosphanylidene)-
propoxy]-ethoxy}-1,4-diphenyl-but-2-ene-
1,4-dione (2)
Compound 2 was prepared in a manner similar to 1,
except that the reaction mixture was then heated to
boiling temperature and refluxed for 72 h. After removing
the solvent, the residue was purified by thin layer
chromatography using CH2Cl2– n-hexane– EtOAc
(6:0.5:0.5) as eluent. The product was obtained by
extractionofsilica gelwithacetonetoproduce compound
2 as light yellow powder, yield: 0.55 g (70%), TLC-Rf =
0.79, m.p. 157-159°C. IR(KBr) νmax/ cm-1: 1708 and 1745
1
1731 and 1774 (C=O), 688 (C-S); H NMR (CDCl3) δ/
ppm: 2.62- 2.94 ( m, 4 H, 2 S-CH2 ), 3.47 and 4.12 ( ABX
system, 2 H, CH2 ), 4.88- 4.90 ( dd, H, S-CH ), 7.48- 8.09
( m, 10 H, 2 C6H5 ); 13C NMR (CDCl3) δ/ ppm: 29.35,
29.86 (2 SCH2), 38.47 (SCH) 41.87 (CH2), 128.59,
129.12, 129.16, 129.17, 133.68, 133.98, 135.98, 136.43
(8 CH), 195.41, 197.82 (2 C ═ O).
Anal. Calcd. For C18H18S2O2 (Mr = 330.3): C 65.40, H
5.45; found: C 65.43. H 5.48. MS (EI, 70 eV): m/z = 331
(M+ +1)
1
(C=O), 1055 (C-O); H NMR (CDCl3) δ/ ppm: 3.96 and
4.48 ( t, 4 H, 3JHH = 4 Hz, 2 CH2 ), 4.51 ( s, H, CH ), 6.07
( s, H, C=CH ), 7.37-8.11 ( m, 35 H, 7 C6H5 ); 13C NMR
(CDCl3) δ/ ppm: 42.90 (P=C), 64.86, 65.63 (2 OCH2),
67.14 (OCH), 99.27 (CH), 125.93, 127.41, 128.18,
128.48, 128.65,128.66, 128.67, 128.68, 129.19, 129.70,
130.16, 133.17 (12 CH), 133.62 (C), 197.07, 199.01,
204.89, 207.23 (4 C ═ O).
3. Results and discussion
The reaction of dibenzoylacetylene with 1,2-ethanediol
and 1,2-ethanedithiol in presence of PPh3 was carried
out in CHCl3 at ambient and reflux temperatures.
Compounds 1, 2 and 3 were obtained in overall yields
of 60-75%. Their structures were deduced from their
elemental analyses and their 1H NMR, 13C NMR and IR
spectral data.
Anal. Calcd. For C52H41O6P (Mr = 792.2): C 78.77, H
5.17 %; found: C 78.80, H 5.21%. MS (EI, 70 eV): m/z
= 793 (M+ +1)
1
2.3. Preparation of 2-(2-Mercapto-ethylsulfanyl)-
1,4-diphenyl-butane-1,4-dione (3)
The H NMR spectrum of 1 exhibited one methyne
proton ( δ = 4.56-4.60 ppm ) and two methylene protons
at δ = 2.63 and 3.30 ppm as double doublets with Jgauche
and Janti values of 4.74 and 8.92 Hz for the adjacent
methyne proton.
Compound 3 was prepared in a manner similar to 1,
but using 1,2-ethanedithiol (0.19 g, 2 mmol) instead
of ethyleneglycol. Reactions were carried out both
at ambient and reflux temperatures for 24 h. After
1
Also, the H decoupled 13C NMR spectrum of 1
showed that the phenyl groups are diastereotopic. They
O
PPh3
COPh
OH
PhOCHC
Ph
HO
OH
_
Ph
PPh3
O
O
O
HO
1a
1b
Ph3P
O
O
O
Ph
O
Ph
Ph
OH
_ Ph3PO
Ph
OH
O
1
O
O
HO
HO
1c
Scheme 2. The mechanism of the formation of compound 1
190

R. Amiri, M. Haghdadi, M. Nozari
exhibited 8 signals and distinct resonances in agreement the unsymmetrical envelope, CS symmetric envelope
with the remainder of the proposed structure.
and half-chair forms. The lowest energy conformation of
The structural assignment of compound 1 performed 1 is the unsymmetrical envelope form. This conformation
on the basis of 1H and 13C NMR spectra was supported is more stable than the CS symmetric envelope and half-
by the IR spectra. A single distinctive absorption band chair by 14.2 and 27.3 kJ mol-1, respectively.
1
appeared in the carbonyl region (see Experimental). The
The H NMR spectra of 2 show the characteristic
OH absorption band of compound 1 appears at about signals in corresponding regions of the spectrum.
3439 cm-1.
For example, there are two singlets for the methyne
We propose a plausible mechanism for the formation proton (δ = 4.51 ppm) and vinylic proton (δ = 6.07 ppm)
of the 1,3-dioxolane derivative 1, which is indicated in respectively. Also, the phenyl protons appear as
Scheme 2. The functionalized compound 1a apparently multiplets at δ = 7.37-8.11 ppm.
results from the initial addition of triphenylphosphine
The 13C NMR spectrum of 2 showed resonances in
to dibenzoylacetylene and subsequent protonation of agreement with the proposed structure but the number
the 1:1 adduct by ethylene glycol. Then the positively of signals is reduced because the presence of the 31P
1
charged ion is attacked by the conjugate base of ethylene nucleus complicates both the H and 13C NMR spectra
glycol to produce ylide 1b, which, in turn, is protonated. of 2. The carbonyl band in the IR spectrum is expected
Such an addition product may be attacked by another at 1708-1745 cm-1 for this compound, but conjugation
ethylenglycol molecule on the carbonyl group adjacent with the carbon-carbon double bond appears to be a
to triphenylphosphonium. Subsequent elimination of plausible factor which might lead to the reduction of
triphenylphosphine oxide produces 1c. Then the ring these absorption frequencies. The strong stretching
closure is followed by protonation to give compound 1.
vibration of C-O groups is observed around 1055 cm-1.
1,3-Dioxolane heterocycles can be used as
When the reaction was carried out at reflux
monomers in polymerization reactions [12]. They may temperature, the uncyclized structure was the main
also find other uses as chemical intermediates [13], product. As shown in Scheme 3, the intermediate 1b,
process solvents, and as odorants structurally related when treated with a second mole of dibenzoylacetylene,
to dioxolane [14]. One of the most important factors successfully underwent a conjugate addition to give
influencing the properties of a particular compound is product 2.
the stereochemistry of the ring dioxolane. We therefore
The structure of compound 3 was deduced from 1H
considered and compared the different conformations of NMR spectra that showed two characteristic signals
compound 1 from both structural and energetic points of identified as methyne (δ = 4.88-4.90 ppm) and methylene
view. The results of ab initio calculations at HF/6-31G* protons (δ = 3.47 and 4.12 ppm), along with multiplets
level for the different conformations of 1,3-dioxolane (δ = 2.62-2.94 ppm) for the two –S-CH2 fragments in
derivative 1 are shown in Table 1 and Fig. 1. They the structure. The phenyl residues gave rise to some
indicate that there are three major conformers, namely, signals in the aromatic region (δ = 7.48-8.09 ppm). The
COPh
Ph
OCH2CH2OH
COPh
HOCH2CH2O
3
O
OCH2CH2OH
O
1
5
O
O
2
O
Ph
COPh
4
Ph
O
Envelop-1 (C )
Half-chair 1 (C )
1
Envelop-1 (C )
1
s
-1
-1
-1
0.0 kJ.mol
14.23 kJ.mol
27.27 kJ.mol
Figure 1. Energy of the different conformations of 2,2- disubstituted 1,3-dioxolane 1 from HF/6-31G* calculations.
191
191

On the PPh3 catalyzed reaction between dibenzoylacetylene
and vicinal –OH and –SH acids. One-pot synthesis
of 1,3-dioxolane derivative
1H decoupled 13C NMR spectrum of 3 displayed fourteen Table 1. Calculated heats of formation, total and zero-point
vibrational energies(a) relative energy(b) for the conformations of
2,2-disubstituted-1,3-dioxolane (1).
distinct resonances, which is in agreement with the
structure. The structural assignments were supported
by IR spectra, which exhibited two absorption bands in
the carbonyl region (see Experimental procedure). Of
special interest is the S-H absorption at 2371 cm-1 and
the C-S stretching frequency at 688 cm-1.
When the reaction was run at reflux temperature,
the same product 3 was obtained in the same yield.
Envelop- 1
(C1)
Half-chair -1
(C1)
Envelop- 1
(CS)
HF/6-31G*/
-1144.459790
0.418215
0.0
-1144.454319
0.418162
14.23
-1144.449132
0.417920
27.27
hartree
ZPE / hartree
Erel / kJ mol –1
Bond lengths
/ Å
A
possible explanation for the formation of
mercapto-ethylsulfanyl derivative is proposed
3
O1-C2
1.41
1.40
1.40
1.53
1.41
1.40
1.40
1.53
1.40
1.40
1.40
1.54
in Scheme 4. The compound 3b, obtained via the
same mechanism as 1b, underwent a subsequent
elimination of triphenylphosphine oxide to produce
compound 3.
C2-O3
O3-C4
C4-C5
C4- O1
1.41
1.41
1.41
Bond angles
/ deg
O1-C2-O3
104.9
107.0
102.7
103.7
105.5
107.1
102.2
103.3
104.3
107.8
103.6
103.9
4. Conclusion
C2-O3-C4
O3-C4-C5
C4-C5-O1
The reaction between dibenzoylacetylene and ethylene
glycol in the presence of PPh3 produced compounds 1
and 2 at ambient and reflux temperature respectively.
The uncyclized product 3 was also formed in the
same reaction conditions with ethylenedithiol. The
one-pot synthesis of 2,2-disubstituted-1,3-dioxolane
1 under neutral conditions without any modification is
a significant achievement in the present procedure.
Moreover, according to the ab initio calculations
at HF/6-31G* level, the chiral envelope geometry
of 1,3-dioxolane derivative 1 is the most stable
conformer.
C5-O1-C2
109.6
109.9
108.5
Dihedral
angles / deg
O1-C2-O3-C4
C2-O3-C4-C5
O3-C4-C5-O1
C4-C5-O1-C2
C5-O1-C2-O3
34.6
-33.5
19.9
0.3
31.4
-34.9
25.4
-7.2
34.8
23.3
3.5
17.6
-32.4
-20.8
-13.9
(a)Zero-point vibrational energy is scaled by a factor of 0.9135
to eliminate known systematic errors in calculations.
(b)Including zero-point energy.
COPh
O
PPh3
PhOC
COPh
H
O
1b
COPh
COPh
COPh
2
Scheme 3. The mechanism of the formation of compound 2
192

R. Amiri, M. Haghdadi, M. Nozari
O
PPh3
Ph
SH
_
1a
+
Ph
S
S
O
HS
3b
O
Ph
H2O
Ph
- Ph3PO
S
O
HS
3
Scheme 4. The mechanism of the formation of compound 3
5. Calculations
with no geometrical constraints [16]. The restricted
Hartree-Fock calculations with the split-valence 6-31G*
Ab initio molecular orbital calculations were carried out basis set, which include a set of d-type polarization
using the GAUSSIAN 98 program [15]. Geometries functions on all non-hydrogen atoms, were used in the
for all structures were fully optimized by means of calculations [17].
analytical energy gradients using the Berny optimizer
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