Efficient one-pot synthesis of alkyl 2-(bromomethyl)-2-(4-aryl)-4-alkoxy-5- oxo-2,5-dihydrofuran-3-carboxylate

Article abstract of DOI:10.1080/00397911.2010.540694

One-pot, three-component reaction of different phenacyl bromides and dialkylacetylenedicarboxilates was carried out with triphenylphosphine and functionalized oxodihydrofuran derivatives in excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.540694

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Efficient One-Pot Synthesis of Alkyl 2-
(Bromomethyl)-2-(4-aryl)-4-alkoxy-5-
oxo-2,5-dihydrofuran-3-carboxylate
Mohammad Anary-Abbasinejad a , Alireza Hassanabadi b & Maedeh
Abbasi Gavarti a
a Department of Chemistry , Islamic Azad University , Yazd Branch ,
Yazd , Iran
b Department of Chemistry , Islamic Azad University , Zahedan
Branch , Zahedan , Iran
Accepted author version posted online: 21 Oct 2011.Published
online: 25 Jan 2012.
To cite this article: Mohammad Anary-Abbasinejad , Alireza Hassanabadi & Maedeh
Abbasi Gavarti (2012) Efficient One-Pot Synthesis of Alkyl 2-(Bromomethyl)-2-(4-aryl)-4-
alkoxy-5-oxo-2,5-dihydrofuran-3-carboxylate, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 42:10, 1426-1431, DOI:
10.1080/00397911.2010.540694
To link to this article: http://dx.doi.org/10.1080/00397911.2010.540694
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Synthetic Communications1, 42: 1426–1431, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.540694
EFFICIENT ONE-POT SYNTHESIS OF ALKYL
2-(BROMOMETHYL)-2-(4-ARYL)-4-ALKOXY-
5-OXO-2,5-DIHYDROFURAN-3-CARBOXYLATE
Mohammad Anary-Abbasinejad,1 Alireza Hassanabadi,2 and
Maedeh Abbasi Gavarti1
1Department of Chemistry, Islamic Azad University, Yazd Branch, Yazd,
Iran
2Department of Chemistry, Islamic Azad University, Zahedan Branch,
Zahedan, Iran
GRAPHICAL ABSTRACT
Abstract One-pot, three-component reaction of different phenacyl bromides and dialkyl-
acetylenedicarboxilates was carried out with triphenylphosphine and functionalized oxodi-
hydrofuran derivatives in excellent yields.
Keywords Acetylenic esters; oxodihydrofurans; phenacyl bromides; triphenylphosphine
Multicomponent condensation reactions (MCRs), because of atom economy, sim-
plicity, and amenability to automated synthesis, have advantages over other organic
synthesis methods. The development of new MCRs is an interestingly research topic
in applied sciences.[1–3] Dihydrofurans are the most important heterocycles com-
monly found in a large variety of naturally occurring substances.[4,5] The develop-
ment of new and efficient methods for their synthesis remains an area of current
interest, and a whole series of new synthetic methods have appeared in the litera-
ture.[6–19] Among synthetic methodologies for dihydrofurans, nonionic as well as
ionic procedures have been exploited. Radical[5] or carbenoid[10–12] additions to ole-
fins have been utilized as non-ionic procedures. Among ionic reaction conditions,
dihydrofuran syntheses via tandem nucleophilic reaction of 1,3-dicarbonyl com-
pounds[13–15] or ylides[16–20] with enones have been reported. Nucleophilic addition
of triphenylphosphine to activated acetylene is well known to produce a reactive
zwitterionin intermediate,[21–23] which may be trapped by acidic organic compounds
Received July 16, 2010.
Address correspondence to Alireza Hassanabadi, Department of Chemsitry, Islamic Azad
University, Zahedan Branch, P.O. Box 98135-978, Zahedan, Iran. E-mail: ar_hasanabadi@yahoo.com
1426

5-OXO-2,5-DIHYDROFURAN
1427
Scheme 1. Condensation of acetylenic esters and arylphenacyl bromides in the presence of triphenyl-
phosphine.
such an alcohols. Reaction between dimethyl acetylenedicarboxylate and triphenyl-
phosphine in the presence of alcohols has been reported to produce phosphorus ylide
as an intermediate or final product. When a-hydroxy carbonyl compounds were
used, the intramolecular Wittig reaction of the ylide intermediate afforded oxygen
heterocycles.[24,25] Similar reactions have been developed for the synthesis of a var-
iety of carbocycles and heterocycles, using N-H,[25,26] O-H, S-H[27] and C-H[28] acidic
compounds to trap the zwitterionic DMAD-PPh3 intermediate in condition of our
precision studies on the reaction of PPh3-DMAD zwitterions with organic acidic
compounds.[29]
Here we report that the reaction of different phenacyl bromides, dialkyl acetyle-
nedicarboxylates, and triphenylphosphine afforded oxodihydrofuran derivatives in
good yields. Treatment of dimethyl acetylenedicarboxylate (DMAD) with triphenyl-
phosphine and 4-chlorophenacyl bromide in dichloromethane at room temperature
after 24 h afforded methyl 2-(bromomethyl)2-(4-chlorophenyl)4-methoxy-5-oxo-2,5-
dihydrofuran-3-carboxylate (3a) in 88% yield (Scheme 1).
The mass spectrum of 3a displayed a molecular ion peak at m=z ¼ 374. The 1H
NMR spectrum of 3a exhibits two sharp lines at d ¼ 3.83 and 4.32 ppm for the pro-
tons of two methoxy groups. The methylene protons resonate at 4.34 ppm as an AB
2
quartet (d1 ¼ 4.12, d2 ¼ 4.56, JHH ¼ 11 Hz). The aromatic protons resonated
between 7.27 and 7.50 ppm. 13C NMR spectrum of compound 3a shows 12 distinct
signals, which is consistent with the proposed structure. This assignment was sup-
ported by the infrared (IR) spectrum of compound 3a, which exhibited absorption
bonds at 1781 and 1711 cmꢀ1 due to carbonyl groups. Although the mechanistic
details of the reaction are not known, a plausible mechanism may be advanced to
rationalize product formation (Scheme 2).[30] The initial addition of triphenyl-
phosphine on DAAD (2) led to a diionic intermediate 4, followed by addition of

1428
M. ANARY-ABBASINEJAD, A. HASSANABADI, AND M. A. GAVARTI
Scheme 2. Suggested mechanism for formation of compound 3.
the anion 4 to the carbonyl group of arylphenacyl bromide (1) to form intermediate
5. This then loosed an alkoxide ion and cyclized to intermediate 6. The elimination
of triphenylphosphine by the alkoxide ion led to oxodihydrofuran derivatives 3.
In summary, the reaction of different arylphenacyl bromides and dialkyl
acetylenedicarboxilates was carried out with triphenylphosphine, and functionalized
oxodihydrofuran derivatives 3a–f were obtained in good yields.
The present procedure has the advantages that not only is the reaction per-
formed under neutral conditions but also the starting materials and reagents can
be mixed without any activation or modification. The procedure described here pro-
vides an acceptable one-pot method for the preparation of alkyl 2-(bromomethyl)-2-
(4-aryl)-4-alkoxy-5-oxo-2,5-dihydrofuran-3-carboxylate.
EXPERIMENTAL
Melting points were determined with an Electrothermal 9100 apparatus.
Elemental analyses were performed using a Costech ECS 4010 CHNS-O analyzer
at the analytical laboratory of the Islamic Azad University, Yazd branch. Mass spec-
tra were recorded on a Finnigan-MAT 8430 mass spectrometer operating at an ioni-
zation potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470
spectrometer. 1H and13C NMR spectra were recorded on a Bruker DRX-500 Avance
spectrometer at solution in CDCl3 using tetramethylsilane (TMS) as internal
standard. The chemicals used in this work were purchased from Fluka (Buchs,
Switzerland) and were used without further purification.
Preparation of Compounds 3a–f
A mixture of triphenylphosphine (1 mmol) in 2 mL dichloromethane was added
to a magnetically stirred solution of phenacyl bromides 1 (1 mmol) in 20 mL dichlor-
omethane and dialkyl acetylenedicarboxylate 2 (1 mmol) in 10 mL dichloromethane
at room temperature. The reaction mixture was then allowed to stir for 24 h.
The solvent was evaporated at reduced pressure, and the residue was purified by

5-OXO-2,5-DIHYDROFURAN
1429
silica-gel column chromatography using hexane–ethyl acetate (3:1) as eluent. The
solvent was removed under reduced pressure to afford the product.
Methyl 2-(Bromomethyl)-2-(4-chlorophenyl)-4-methoxy-
5-oxo-2,5-dihydrofuran-3-carboxylate (3a)
Yield: 88%; yellow oil. IR (KBr) (nmax, cmꢀ1): 1781 and 1711 (C O). Analyses:
=
Calcd. for C14H12BrClO5, C, 44.77; H, 3.22%. Found: C, 44.82, H, 3.16%. MS (m=z,
%): 374 (7). 1H NMR (500 MHz, CDCl3): d 3.83 and 4.32 (6 H, 2 s, 2 OCH3), 4.34 (2
H, AB quartet, 2JHH ¼ 11 Hz, CH2), 7.27–7.50 (4 H, m, aromatic). 13C NMR (125.8
MHz, CDCl3): d 36.93 (CH2), 52.45 and 60.05 (2 OCH3), 84.26 (C-O), 123.46, 134.65
=
(olefinic carbons), 127.39, 129.04, 135.42, 149.50 (aromatic), 161.75, 164.72 (2 C O
ester).
Ethyl 2-(Bromomethyl)-2-(4-chlorophenyl)-4-ethoxy-
5-oxo-2,5-dihydrofuran-3-carboxylate (3b)
Yield: 86%; yellow oil. IR(KBr) (nmax, cmꢀ1): 1779, 1719 (C O). Analyses:
Calcd. for C16H16BrClO5, C, 47.61; H, 4.00%. Found: C, 47.54, H, 4.08%. MS
=
(m=z, %): 402 (11). 1H NMR (500 MHz, CDCl3): d 1.26 and 1.37 (6 H, 2 t,
2
3JHH ¼ 7 Hz, 2 CH3), 4.25 (2 H, AB quartet, JHH ¼ 11 Hz, CH2), 4.26 and 4.64 (4
3
H, 2 q, JHH ¼ 7 Hz, 2 OCH2), 7.29–7.43 (4 H, m, aromatic). 13C NMR (125.8
MHz, CDCl3): d 14.41 and 15.94 (2CH3), 37.53 (CH2), 61.99 and 69.11 (2OCH2),
84.75 (C-O), 124.92, 135.72 (olefinic carbons), 127.86, 129.42, 135.25, 149.60 (aro-
=
matic), 161.76, 165.42 (2 C O ester).
t-Butyl 2-(Bromomethyl)-2-(4-chlorophenyl)-4-t-butoxy-
5-oxo-2,5-dihydrofuran-3-carboxylate (3c)
Yield: 92%; yellow oil. IR (KBr) (nmax, cmꢀ1): 1775, 1720 (C O). Analyses:
Calcd. for C20H24BrClO5, C, 52.25; H, 5.26%. Found: C, 52.31, H, 5.40%. MS
=
1
(m=z, %): 458 (7). H NMR (500 MHz, CDCl3): d 1.33 and 152 (18 H, 2 s, 2 t-
2
Bu), 4.22 (2 H, AB quartet, JHH ¼ 11 Hz, CH2), 7.11–7.54 (4 H, m, aromatic).
13C NMR (125.8 MHz, CDCl3): d 30.12 and 30.62 (6 CH3 of 2 t-Bu), 38.26
(CH2), 82.68 and 83.07 (2 C of 2 t-Bu), 84.93 (C-O), 124.80, 135.61 (olefinic carbons),
=
128.88, 129.75, 135.14, 149.53 (aromatic), 161.82, 165.57 (2 C O ester).
Methyl 2-(Bromomethyl)-2-(4-bromophenyl)-4-methoxy-
5-oxo-2,5-dihydrofuran-3-carboxylate (3d)
Yield: 85%; yellow oil. IR (KBr) (nmax, cmꢀ1): 1778, 1708 (C O). Analyses:
=
Calcd. for C14H12Br2O5, C, 40.03; H, 2.88%. Found: C, 40.15, H, 2.95%. MS (m=z,
%): 418 (9). 1H NMR (500 MHz, CDCl3): d 3.82 and 4.30 (6 H, 2 s, 2 OCH3), 4.37 (2
H, AB quartet, 2JHH ¼ 11 Hz, CH2), 7.25–7.71 (4 H, m, aromatic). 13C NMR (125.8
MHz, CDCl3): d 36.85 (CH2), 52.45 and 60.12 (2 OCH3), 84.19 (C-O), 123.40, 134.68
=
(olefinic carbons), 127.22, 129.00, 135.51, 149.42 (aromatic), 161.60, 165.39 (2 C O
ester).

1430
M. ANARY-ABBASINEJAD, A. HASSANABADI, AND M. A. GAVARTI
Ethyl 2-(Bromomethyl)-2-(4-bromophenyl)-4-ethoxy-
5-oxo-2,5-dihydrofuran-3-carboxylate (3e)
Yield: 80%, yellow oil. IR (KBr) (nmax, cmꢀ1): 1773, 1705 (C O). Analyses:
Calcd. for C16H16Br2O5, C, 42.89; H, 3.60%. Found: C, 42.75, H, 3.68%. MS
=
(m=z, %): 446 (10). 1H NMR (500 MHz, CDCl3): d 1.28 and 1.42 (6 H, 2 t, 3JHH ¼ 7
2
7 Hz, 2 CH3), 4.30 (2 H, AB quartet, JHH ¼ 11 Hz, CH2), 4.25 and 4.69 (4 H, 2 q,
3JHH ¼ 7 Hz, 2 OCH2), 7.25–7.77 (4 H, m, aromatic). 13C NMR (125.8 MHz,
CDCl3): d 14.38 and 15.96 (2CH3), 37.54 (CH2), 61.92 and 69.08 (2OCH2), 84.72
(C-O), 124.90, 135.76 (olefinic carbons), 127.88, 130.21, 135.19, 149.67 (aromatic),
=
161.71, 165.32 (2 C O ester).
t-Butyl 2-(Bromomethyl)-2-(4-bromophenyl)-4-t-butoxy-
5-oxo-2,5-dihydrofuran-3-carboxylate (3f)
Yield: 90%, yellow oil, IR(KBr) (nmax, cmꢀ1): 1779, 1705 (C O). Analyses:
Calcd. for C20H24Br2O5, C, 47.64; H, 4.80%. Found: C, 47.77, H, 4.71%. MS
=
1
(m=z, %): 502 (5). H NMR (500 MHz, CDCl3): d 1.30 and 157 (18 H, 2 s, 2
2
t-Bu), 4.17 (2 H, AB quartet, JHH ¼ 11 Hz, CH2), 7.28–7.69 (4 H, m, aromatic).
13C NMR (125.8 MHz, CDCl3): d 30.05 and 30.71 (6 CH3 of 2 t-Bu), 38.12
(CH2), 82.60 and 83.14 (2 C of 2 t-Bu), 84.98 (C-O), 124.76, 135.52 (olefinic carbons),
=
128.83, 129.70, 135.08, 149.61 (aromatic), 161.84, 165.69 (2C O ester).
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