Reaction between 5-isopropylidene-2,2-dimethyl-1,3-dioxane-4,6-dione and trialkyl(aryl) phosphites in the presence of alcohols

Article abstract of DOI:10.3184/174751911X13073888700333

5-Isopropylidene-2,2-dimethyl-1,3-dioxane-4,6-dione (the condensation product of Meldrum's acid and acetone) reacts with trialkyl(aryl) phosphites in the presence of alcohols to produce dialkyl 2-[1-(dialkoxyphosphoryl)-1- methylethyl]malonate in good yie

Full text of DOI:10.3184/174751911X13073888700333

336 RESEARCH PAPER
JUNE, 336–338
JOURNAL OF CHEMICAL RESEARCH 2011
Reaction between 5-isopropylidene-2,2-dimethyl-1,3-dioxane-4,6-dione
and trialkyl(aryl) phosphites in the presence of alcohols
Mohammad R. Hosseini-Tabatabaei*a, Alireza Hassanabadia, Dadkhoda Ghazanfarib and
Adel Mirib
aDepartment of Chemistry, Islamic Azad University, Zahedan Branch, PO Box 98135-978, Zahedan, Iran
bDepartment of Chemistry, Islamic Azad University, Kerman Branch, Kerman, Iran
5-Isopropylidene-2,2-dimethyl-1,3-dioxane-4,6-dione (the condensation product of Meldrum’s acid and acetone)
reacts with trialkyl(aryl) phosphites in the presence of alcohols to produce dialkyl 2-[1-(dialkoxyphosphoryl)-1-
methylethyl]malonate in good yields.
Keywords: Meldrum’s acid, isopropylidene malonate, trialkyl(aryl) phosphites, alcohols
As versatile reagents and important intermediates, Meldrum’s
acid (isopropylidene malonate) and its derivatives have been
widely used in organic synthesis.1–3 The successful attack by
nucleophilic trivalent phosphorus on a carbon atom is facili-
tated when the later is conjugated with a carbonyl group or
when it is part of an unsaturated bond otherwise activated.4–11
There have been many studies on the reactions between triva-
lent phosphorus nucleophiles and unsaturated carbonyl com-
pounds in the presence of a proton source such as an alcohol.3
The reaction of trimethyl phosphite and dimethyl acetylenedi-
carboxylate (DMAD) in the presence of alcohols is reported to
produce phosphite ylide derivatives which are stable at low
temperatures, but are converted to phosphonate derivatives by
warming or by treatment with water.12 There are some other
recent reports on the reaction between phosphites and acetyle-
nic esters in the presence of an acidic organic compound, all of
which proceed to products through a phosphite ylide interme-
diate.13–15 However, this intermediate has not been isolated or
characterized in any of these reports as it is usually hydrolysed
or rearranged to the corresponding phosphonates. In the con-
text of our recent studies16,17 on the reactivity of isopropylidene
Meldrum’s acid, we studied the reaction between 5-isopropyli-
dene-2,2-dimethyl-1,3-dioxane-4,6-dione 1, and trialkyl(aryl)
phosphites 3 in the presence of an alcohol 2. This reaction led
to dialkyl 2-[1-(dialkoxyphosphoryl)-1-methylethyl]malonate
4 in good yields (Scheme 1). Here we report the results of our
study on the reaction between isopropylidene Meldrum’s acid
and trialkyl(aryl) phosphites in the presence of alcohols.
Results and discussion
The reaction of isopropylidene Meldrum’s acid 1 with
trialkyl(aryl) phosphites 3 in the presence of alcohols 2 led to
dialkyl 2-[1-(dialkoxyphosphoryl)-1-methyl-ethyl]malonates
4 in high yields (Scheme 1).
Compound 4a was known and its structure was deduced
by comparison of its spectral data with those of an authentic
sample.18 Compounds 4b–f were new and their structures were
deduced from their elemental analyses and spectral data. The
mass spectrum of compound 4b showed the molecular ion
1
peak at m/z 282 whilst its H NMR spectrum displayed two
doublets (JHP = 9.8 Hz) at 3.75 and 3.80 ppm for two POCH3
groups and two singlets at 3.71 and 3.73 ppm for two methoxy-
carbonyl groups and a doublet for the methine proton at
3.67 ppm (3JHP = 5.1 Hz). Two sharp signals were observed at
1.42 and 1.48 ppm attributed to the protons of two methyl
groups. The 13C NMR spectrum of compound 4b showed ten
Scheme 1 Synthesis of dialkyl 2-[1-(dialkoxyphosphoryl)-1-methylethyl]malonate by reaction between isopropylidene Meldrum’s
acid and trialkyl(aryl) phosphites in the presence of alcohols.
* Correspondent. E-mail: dr_hosseini_tabatabaei@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2011 337
Scheme 2 Suggested mechanism for formation of compound 4.
(2 CH3), 37.97 (d, 1Jcp= 143.9 Hz, P-C), 52.84 and 52. 86 (2 OCH3),
53.45 and 53.97 (m, 2 POCH3), 55.16 (d, 2JCP = 12.3 Hz, CH), 167.75
(d, 2JCP = 12.9 Hz, C=O), 171.15 (d, 3JCP = 20.3 Hz, C=O). 31P NMR
(121.5 MHz, CDCl3): δ 35.07.
distinct resonances in agreement with the proposed structure.
The structural assignments made on the basis of the NMR
spectra of compound 4b were supported by its IR spectrum,
the ester carbonyl groups exhibited strong absorption bands
at 1755 and 1742 cm−1. The 31P NMR spectrum of compound
4b displayed a signal at 35.07 ppm. A reasonable mechanism
for the formation of compound 4 is presented in Scheme 2. The
initial addition of trialkyl(aryl) phosphite on isopropylidene
Meldrum’s acid leads to a diionic intermediate 5. Cyclisation
of this zwitterionic intermediate produces the oxaphosphorane
6. The attack of the alcohol on 6 is initiated by conjugate addi-
tion to the double bond and cleavage of the phosphorus–oxygen
bond by the nucleophile leads to an intermediate 7, this
intermediate first losses acetone to give ketene 8 and then the
alcohol may attack 8 to produce 4.
Dimethyl 2-[1-(diethoxyphosphoryl)-1-methylethyl]malonate (4c):
Yield: 92%; Yellow oil. IR (KBr) νmax/cm−1: 1760 and 1735 (C=O),
Anal. Calcd for C12H23O7P: C, 46.45; H, 7.47%. Found: C, 46.63; H,
7.34%. MS (m/z, %): 310 (M+, 7).1H NMR (300 MHz, CDCl3): δ 1.28
and 1.34 (6 H, 2 t, 3JHH = 7.3 Hz, 2 CH3), 1.38 and 1.41 (6H, 2s, 2CH3),
3
3.67 (1 H, d, JHP = 5.1 Hz, CH), 3.69 and 3.86 (6 H, s, 2OCH3),
4.04–4.29 (4H, m, 2 OCH2). 13C NMR (75.47 MHz, CDCl3): δ 15.83
and 16.02 (2 CH3), 20.14 and 21.55 (2 CH3), 34.09 (d, 1Jcp= 143.9 Hz,
2
P-C), 52.98 and 53.16 (2 OCH3), 55.33 (d, JCP = 12.3 Hz, CH),
66.55–67.50 (m, 2 POCH2), 167.49 (d, 2JCP = 12.9 Hz, C=O), 171.32
(d, 3JCP = 20.3 Hz, C=O). 31P NMR (121.5 MHz, CDCl3): δ 35.10.
Di-iso-propyl2-[1-(dimethoxyphosphoryl)-1-methylethyl]malonate
(4d): Yield: 92%; Yellow oil. IR (KBr) νmax/cm−1: 1751 and 1729
(C=O), Anal. Calcd for C14H27O7P: C, 49.70; H, 8.04%. Found: C,
In summary, we report here that reaction between 5-isopro-
pylidene-2,2-dimethyl-1,3-dioxane-4,6-dioneandtrialkyl(aryl)
phosphites in the presence of alcohols provides a simple
and efficient one pot route for the synthesis of dialkyl 2-
[1-(dialkoxyphosphoryl)-1-methylethyl]malonate in excellent
yields.
1
49.79; H, 8.09%. MS (m/z, %): 338 (M+, 5). H NMR (300 MHz,
CDCl3): δ 1.23 (12 H, d, 3JHH = 6.5 Hz, 2 CHMe2), 1.35 and 1.40 (6H,
3
2s, 2CH3), 3.61 (1 H, d, JHP = 5.1 Hz, CH), 3.70 - 3.77 (6 H, m,
2POCH3), 5.01 (2H, sept, 3JHH = 6.5 Hz, 2 CHMe2). 13C NMR (75.47
MHz, CDCl3): δ 20.14 and 21.67 (2 CH3), 21.85 and 22.04 (2 CHMe2),
1
2
35.26 (d, Jcp= 143.9 Hz, P-C), 57.22 (d, JCP = 12.3 Hz, CH), 61.53
2
and 62.89 (2 d, JCP 6.9 Hz, 2 POCH3), 69.05 (2 CHMe2), 167.73
Experimental
(d, 2JCP = 12.9 Hz, C=O), 170.92 (d, 3JCP = 20.3 Hz, C=O). 31P NMR
(121.5 MHz, CDCl3): δ 35.28.
Elemental analyses were performed using a Costech ECS 4010
CHNS-O analyser. Mass spectra were recorded on a FINNIGAN-
MAT 8430 mass spectrometer operating at an ionisation potential of
70eV.IRspectrawererecordedonaShimadzuIR-470spectrometer.1H,
13C and 31P NMR spectra were recorded on Bruker DRX-300 Avance
spectrometer in CDCl3 using TMS as internal standard or 85% H3PO4
as external standard. The chemicals used in this work were purchased
from Fluka (Buchs, Switzerland) and were used without further
purification. Compound 1 was prepared as previously described in the
literature.19
Di-tert-butyl 2-[1-(diphenoxyphosphoryl)-1-methylethyl]malonate
(4e): Yield: 87%; Yellow oil. IR (KBr) νmax/cm−1: 1756 and 1733
(C=O), Anal. Calcd for C26H35O7P: C, 63.66; H, 7.19%. Found: C,
1
63.49; H, 7.28%. MS (m/z, %): 490 (M+, 3). H NMR (300 MHz,
CDCl3): δ 1.42 and 2.51 (18 H, 2s, 2 CMe3), 1.49 and 1.63 (6H, 2s,
2CH3), 3.57 (1 H, d, 3JHP = 5.1 Hz, CH), 7.16–7.55 (10 H, m, aroma-
tic). 13C NMR (75.47 MHz, CDCl3): δ 20.37 and 21.80 (2 CH3),
1
28.15 and 28.73 (2 CMe3), 39.06 (d, JCP = 143.9 Hz, P-C), 58.02
2
3
(d, JCP = 12.3 Hz, CH), 83.41 (OCMe3), 120.61 (d, JCP = 5.1 Hz,
4
4 CHortho), 126.79 (s, 2 CHpara), 130.07 (d, JCP = 7.8 Hz, 4 CHmeta),
Preparation of compounds (4b–f); general procedure
149.94 (d, 2Jcp = 10.3 Hz, Cipso), 150.66 (d, 2Jcp = 10.3 Hz, Cipso), 167.90
(d, 2JCP = 12.9 Hz, C=O), 171.66 (d, 3JCP = 20.3 Hz, C=O). 31P NMR
(121.5 MHz, CDCl3): δ 34.87.
To a magnetically stirred solution of isopropylidene Meldrum’s acid
(2 mmol) and an appropriate alcohol (4 mmol) in dichloromethane
(15 mL) was added dropwise a mixture of trialkyl(aryl) phosphite
(2 mmol) at room temperature over 2 min. The reaction mixture was
then stirred for 24 h at room temperature. The solvent was removed
under reduced pressure and the residue was purified by column
chromatography on silica gel (60, 230–400 mesh) using ethyl acetate–
hexane (3:1) mixture as eluent.
Dibenzyl 2-[1-(dimethoxyphosphoryl)-1-methylethyl]malonate
(4f): Yield: 90%; Yellow oil. IR (KBr) νmax/cm−1: 1753 and 1730
(C=O), Anal. Calcd for C22H27O7P: C, 60.82; H, 6.26%. Found: C,
1
60.94; H, 6.14%. MS (m/z, %): 434 (M+, 7). H NMR (300 MHz,
3
CDCl3): δ 1.30 and 1.44 (6H, 2s, 2CH3), 3.57 (1H, d, JHP = 5.1 Hz,
Dimethyl 2-[1-(dimethoxyphosphoryl)-1-methylethyl]malonate
(4b): Yield: 90%; Yellow oil. IR (KBr) νmax/cm−1: 1755 and 1742
(C=O), Anal. Calcd for C10H19O7P: C, 42.56; H, 6.79%. Found:
C, 42.43; H, 6.91%. MS (m/z, %): 282 (M+, 5). 1H NMR (300 MHz,
CDCl3): δ 1.42 and 1.48 (2s, 6H, 2CH3), 3.67 (1 H, d, 3JHP = 5.1 Hz,
CH), 3.71 and 3.73 (6 H, 2 s, 2 OCH3), 3.75 and 3.80 (6 H, d, 3JPH = 9.8
Hz, 2POCH3). 13C NMR (75.47 MHz, CDCl3): δ 20.17 and 20.23
CH), 3.78–3.89 (6H, m, 2POCH3), 5.11 (4H, s, 2 OCH2), 7.28–7.58
(10 H, m, aromatic).13C NMR (75.47 MHz, CDCl3): δ 21.03 and 21.89
1
2
(2 CH3), 36.06 (d, Jcp = 143.9 Hz, P-C), 57.08 (d, JCP = 12.3 Hz,
2
CH), 61.77 and 62.61 (2 d, JCP 6.9 Hz, 2 POCH3), 66.75 (2 OCH2),
128.03, 128.55, 128.71, 128.82, 129.03, 135.72 (aromatic), 168.35 (d,
3
2JCP = 12.9 Hz, C=O), 172.01 (d, JCP = 20.3 Hz, C=O). 31P NMR
(121.5 MHz, CDCl3): δ 35.19.

338 JOURNAL OF CHEMICAL RESEARCH 2011
9
B.E. Maryano and A.B. Reits, Chem. Rev., 1989, 89, 863.
We gratefully acknowledge financial support from the Research
Council of Islamic Azad University of Zahedan of Iran.
10 J.C. Tebby in Phosphorus-31 NMR spectroscopy in stereochemical
analysis, eds J. C. Verkade and L. D. Quin, VCH, Weinheim, 1987; chap. 1,
pp. 1–60.
Received 4 December 2010; accepted 10 May 2011
Paper 1000462 doi: 10.3184/174751911X13073888700333
Published online: 11 July 2011
11 M.V. George, S.K. Khetan and R.K. Gupta, Adv. Heterocycl. Chem., 1976,
19, 354.
12 A.W. Johnson, W.C. Kaska, K.A.O. Starzewski and D.A. Dixon, Ylides
and imines of phosphorus, John Wiley and Sons, New York, 1993,
pp. 386–387.
13 I. Yavari and M. Anary-Abbasinejad, Org. Biomol. Chem., 2003, 3, 560.
14 M.T. Maghsoodlou, S.M. Habibi Khorassani, R. Heydari and F. Roastami
Charati, J. Chem. Res., 2006, 5, 364.
15 M.T. Maghsoodlou, S.M. Habibi Khorassani, M.K. Rofouei, S.R.
Adhamdoust and M. Nassiri, Arkivoc, 2006, 143.
16 I.Yavari, A. Habibi, and M.R. Hosseini-Tabatabaei, Monatsh. Chem., 2003,
134, 1651.
References
1
2
3
4
H. McNab, Chem. Soc. Rev., 1978, 7, 345.
B.C. Chen, Heterocycles, 1991, 32, 529.
A.S. Ivanov, Chem. Soc. Rev., 2008, 37, 789.
Corbridge, D.E.C., Phosphorus an outline of the chemistry, biochemistry
and uses, 5th edn, Elsevier, Amsterdam, 1995.
Engel, R., Synthesis of carbon-phosphorus bonds, CRC Press, Boca Raton,
1988.
J.I.G. Cadogan, Organophosphorus reagents in organic synthesis,
Academic Press, New York, 1979.
5
6
17 I. Yavari, M.R. Hosseini-Tabatabaei and A. Habibi, Synth. Commun., 2003,
33, 2709.
18 B.N. Dolgov, N.P. Kharitonov and M.G. Voronkov, Zh. Obshch. Khim.,
1954, 24, 1193.
19 D. Davidson and S.A. Bernhard, J. Am. Chem. Soc.,1948, 70, 3426.
7
8
O.I. Kolodiazhnyi, Russ. Chem. Rev., 1997, 66, 225.
H.J. Bestmann and R. Zimmermann, Top. Curr. Chem., 1983, 109, 85.

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