Reaction of methyl 1-(2-bromo-4-methoxy-1,4-dioxobutyl)- cyclohexanecarboxylate with zinc and aromatic aldehydes

Full text of DOI:10.1016/j.mencom.2014.04.019

Mendeleev
Communications
Mendeleev Commun., 2014, 24, 178–179
Reaction of methyl 1-(2-bromo-4-methoxy-1,4-dioxobutyl)-
cyclohexanecarboxylate with zinc and aromatic aldehydes
Nikolay F. Kirillov,*a Pavel A. Slepukhin,b Elena A. Nikiforova,a
Aleksandr N. Vasyanin,a Sergey N. Shurova and Pavel M. Kashkina
a Department of Chemistry, Perm State University, 614990 Perm, Russian Federation.
Fax: +7 342 237 1611; e-mail: kirillov@psu.ru
b I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
624090 Ekaterinburg, Russian Federation
DOI: 10.1016/j.mencom.2014.04.019
Treatment of methyl 1-(2-bromo-4-methoxy-1,4-dioxobutyl)cyclohexanecarboxylate with zinc followed by aromatic aldehydes affords
methyl 1-(2-aryl-5-oxotetrahydrofuran-3-carbonyl)cyclohexanecarboxylates.
O
The Reformatsky reagents, derived from b-bromo g-oxo esters
Cl
MeO
and zinc, react with aromatic aldehydes to give tetrahydropyran-
2,4-diones.1–4 In continuation of these studies aiming to prepare
O
Br
ZnBr
3
Zn
analogous compounds containing an ester group (see Schemes 1
and 2), we converted methyl 1-(2-bromo-4-methoxy-1,4-dioxo-
butyl)cyclohexanecarboxylate 5 into the corresponding organo-
zinc Reformatsky reagent 6, and coupled the latter with aromatic
aldehydes. Compound 5 was obtained by the Reformatsky
protocol using methyl 1-bromocyclohexanecarboxylate 1 and
methyl 4-chloro-4-oxobutanoate 3 as the reactants followed by
bromination of the intermediate methyl 1-(4-methoxy-1,4-dioxo-
butyl)cyclohexanecarboxylate 4 (Scheme 1).†
– ZnBrCl
CO2Me
CO2Me
1
2
O
O
Br
OMe
O
OMe
Br2
– HBr
CO2Me
CO2Me
O
4
5
In fact, the Reformatsky reagent 6 added to the carbonyl group
of aromatic aldehydes 7a,b giving zinc bromide alkoxides 8a,b.
In the course of the reaction, the latter underwent cyclization into
terahydrofuran derivatives 9a,b upon elimination of zinc bromide
Scheme 1
methoxide. The IR spectra of these compounds have the absorp-
tion bands of the carbonyl groups at 1700, 1735, 1780–1785 cm–1.
Appearance of the carbonyl group absorption band at 1780–1785
cm–1 is typical of five-membered furanone moiety rather than six-
membered pyranone one in 10a,b, whose oscillation should be in
a region of 1735 cm–1 (see ref. 5). The products 9a,b have
structures of methyl 1-(2-aryl-5-oxotetrahydrofuran-3-carbonyl)
cyclohexanecarboxylates (Scheme 2).‡
† The IR spectra of compounds 4, 5 in a thin layer and 9a,b from mulls
in mineral oil were measured on a Spectrum Two PerkinElmer Fourier
spectrometer. The 1H NMR spectra were recorded at 300 MHz on a Varian
Mercury Plus-300 instrument in CDCl3 with TMS as an internal standard.
Quantum-chemical calculations were carried out using the program package
‘Firefly’6 on the PSU-Tesla supercomputer of Scientific-educational
Center of Parallel and Distributive Calculations of Perm State University.
Methyl 1-(4-methoxy-1,4-dioxobutyl)cyclohexanecarboxylate 4. A mix-
ture of methyl 4-chloro-4-oxobutanoate 3 (15 g, 0.1 mol) and methyl
1-bromocyclohexanecarboxylate 1 (24.3 g, 0.11 mol) in anhydrous ethyl
acetate (50 ml) was added dropwise to zinc powder (9.8 g) in anhydrous
ethyl acetate (10 ml). The mixture was refluxed for 1 h, cooled and treated
with water and 10% hydrochloric acid. The organic layer was separated,
the water layer was twice extracted with ethyl acetate. The combined
extracts were washed with water and dried with anhydrous Na2SO4. The
solvent was removed and the product was distilled in vacuo. Yield 14.4 g
(56%), bp 160–163°C (10 Torr), nD20 1.4688, d420 1.1219. IR (n/cm–1):
1739, 1726, 1715 (C=O). 1H NMR, d: 1.20–2.28 [m, 10H, (CH2)5], 2.52
(t, 2H, C3H2, J 6.8 Hz), 2.77 (t, 2H, C2H2, J 6.8 Hz), 3.62 (s, 3H, MeO),
3.69 (s, 3H, MeO). Found (%): C, 61.11; H, 7.74. Calc. for C13H20O5 (%):
C, 60.92; H, 7.87.
Methyl 1-(2-bromo-4-methoxy-1,4-dioxobutyl)cyclohexanecarboxylate
5. Bromine (6.7 g, 2.2 ml, 0.042 mol) was added to a solution of com-
pound 4 (10.3 g, 0.04 mol) in anhydrous acetic acid (30 ml). The mixture
was heated for 1 h, and after removing the solvent and the excess of bromine
the product was distilled in vacuo. Yield 9.0 g (67%), bp 176–179°C
(8 Torr), nD20 1.4944, d420 1.3668. IR (n/cm–1): 1746, 1730, 1721 (C=O).
1H NMR, d: 1.02–2.34 [m, 10H, (CH2)5], 2.61 and 3.05 (2m, 2H, CH2), 3.62
(s, 3H, MeO), 3.69 (s, 3H, MeO), 4.91 (m, 1H, CH). Found (%): C, 46.75;
H, 5.54; Br, 23.59. Calc. for C13H19BrO5 (%): C, 46.58; H, 5.71; Br, 23.84.
‡
Methyl 1-(2-aryl-5-oxotetrahydrofuran-3-carbonyl)cyclohexanecar-
boxylates 9a,b. A mixture of zinc powder (1 g), catalytic amount of
mercuric chloride, methyl 1-(2-bromo-4-methoxy-1,4-dioxobutyl)cyclo-
hexanecarboxylate 5 (3.7 g, 11 mmol), aromatic aldehyde 7 (10 mmol),
anhydrous ethyl acetate (10 ml) and anhydrous benzene (10 ml) was
heated for 2 h, cooled and treated with water and 10% hydrochloric acid.
The organic layer was separated, the water layer was twice extracted with
ethyl acetate. The combined extracts were washed with water and dried
with anhydrous sodium sulfate. Then the solvent was removed and the
product was recrystallized from methanol.
Methyl 1-[2-(4-bromophenyl)-5-oxotetrahydrofuran-3-carbonyl)]cyclo-
hexanecarboxylate 9a. Yield 2.17 g (53%), mp 110–111°C. IR (n/cm–1):
1700, 1735, 1780 (C=O). 1H NMR, d: 1.06–2.23 [m, 10H, (CH2)5], 2.72
(t, 2H, C4H2, J 7.5 Hz), 3.35 (s, 3H, MeO), 3.59 (m, 1H, C3H), 5.51 (d, 1H,
C2H, J 5.0 Hz), 7.07 (d, 2H, HAr, J 8.7 Hz), 7.29 (d, 2H, HAr, J 8.7 Hz).
Found (%): C, 55.93; H, 5.03; Br, 19.38. Calc. for C19H21BrO5 (%): C,
55.76; H, 5.17; Br, 19.52.
Methyl 1-[2-(4-chlorophenyl)-5-oxotetrahydrofuran-3-carbonyl)]cyclo-
hexanecarboxylate 9b.Yield 1.75 g (48%), mp 90–91°C. IR (n/cm–1): 1700,
1735, 1785 (C=O). 1H NMR, d: 1.02–2.20 [m, 10H, (CH2)5], 2.72 (t, 2H,
C4H2, J 7.5 Hz), 3.34 (s, 3H, MeO), 3.61 (m, 1H, C3H), 5.51 (d, 1H, C2H,
J 5.0 Hz), 7.06 (d, 2H, HAr, J 8.4 Hz), 7.29 (d, 2H, HAr, J 8.4 Hz). Found (%):
C, 62.71; H, 5.87; Cl, 9.61. Calc. for C19H21ClO5 (%): C, 62.55; H, 5.80; Cl, 9.72
.
© 2014 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2014, 24, 178–179
5
Br(1)
C(9)
Zn
MeO
MeO
O
O
O
C(8)
C(7)
C(10)
C(11)
Zn Br
O
C(1)
O(4)
O
Br
Zn
O(5)
C(6)
C(2)
C(19)
C(13)
O
C(18)
O(1)
O(2)
C(12)
OMe
C(17)
C(3)
C(4)
OMe
6'
6''
O(3)
C(14)
C(16)
C(5)
C(15)
E = –5233.9444 a.u.
E = –5233.9465 a.u.
ArCHO
7a,b
Figure 1 General view of the molecule 9a based on the X-ray data with
50% probability thermal ellipsoids.
MeO
O
O
space group. Bond lengths and bond angles are within deviations
from the standard values. Both carbonyl bonds of the COOR
moieties are 1.192(3) Å long, the lengths of the ketone C=O
and C–Br bonds are 1.211(3) and 1.900(2) Å, respectively. The
cyclohexyl fragment acquires a chair conformation with axial
position of the COOMe group, the tetrahydrofuran cycle exists
in an envelope conformation with deviation from the plane of
the C(3) atom and trans-location of substituents at C(2) and C(3)
atoms. There are not essential short-cut intermolecular contacts
in the crystal packing.
To explain the regioselectivity of the process, we performed
the non-empirical calculations of geometric and electronic char-
acteristics of possible intermediates (Ar = 4-BrC6H4) by the
B3LYP/6-31(d) method. The calculated values of total energies
E (a.u.) of possible intermediates and reaction products are shown
in Scheme 2. The Reformatsky reagent 6 very likely exists in the
form of zinc-enolate and is stabilized by coordination of zinc
with the ester carbonyl oxygen (intermediates 6' and 6'', while
intermediate 6'' is 5.5 kJ mol–1 more stable).
The addition of an aromatic aldehyde to the Reformatsky
reagent affords intermediate 8a stabilized by coordination of
zinc at the ketone carbonyl oxygen. Further on, intermediate 8a
turns into intermediate 8'a as far as furan ring closure should
be promoted by coordination of zinc at the ester carbonyl oxygen.
Elimination of MeOZnBr from intermediate 8'a leads ultimately
to furanone 9a. Intermediate 8''a, a precursor of pyrandione 10a,
is 6.3 kJ mol–1 less stable than 8'a. Moreover, pyrandione 10a is
also 9.7 kJ mol–1 less stable than furanone 9a.
Zn Br
MeO2C
O
Ar
8a,b
E(8a) = –8150.6795 a.u.
Br
MeO
CO2Me
Ar
O
Zn
O
O
Br
Zn
O
O
Ar
CO2Me
O
OMe
8'a,b
8''a,b
E(8'a) = –8150.6797 a.u.
E(8''a) = –8150.6774 a.u.
– MeOZnBr
– MeOZnBr
O
CO2Me
Ar
O
Ar
O
O
O
CO2Me
O
9a,b
10a,b
E(10a) = –3684.5602 a.u.
E(9a) = –3684.5639 a.u.
a Ar = 4-BrC6H4
b Ar = 4-ClC6H4
This work was supported by the Ministry of Education and
Science of the Russian Federation (project no. 3.3925.2011) and
Russian Foundation for Basic Research (grant no. 13-03-96010).
Scheme 2
The structure of compounds obtained was ultimately estab-
lished by the X-ray study of a single crystal of compound 9a
(Figure 1).§ This compound crystallizes in the centrosymmetric
References
1 N. F. Kirillov, V. V. Shchepin and D. N. Litvinov, Russ. J. Org. Chem.,
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§
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2007, 43, 1628 (Zh. Org. Khim., 2007, 43, 1633).
The X-ray diffraction analysis of compound 9a was performed at
295(2) K on an Xcalibur S (Oxford diffraction) automatic single crystal
diffractometer with graphite monochromated MoKa (l = 0.71073 Å)
radiation. The extinction correction was introduced by multi-scanning
method (m = 2.328 mm–1).
Crystal data. The colourless single crystals (C19H21BrO5, M = 409.27),
triclinic, a = 7.81270(10), b = 10.7584(18) and c = 11.670(2) Å; a =
= 85.04(3)°, b = 77.46(3)°, g = 68.860(9)°, V = 893.0(2) Å3, Z = 2, space
group P1, 3564 independent reflections collected (Rint = 0.0268), including
2123 with I > 2s(I). The solution and refinement of the structure were
carried out using the SHELXTL software package.7 The final refinement
converged to R1 = 0.0346 [I > 2s(I)].
5 E. Pretsch, P. Bulmann and K.Affolter, Structure Determination of Organic
Compounds. Tables of Spectral Data, Springer-Verlag, Berlin, 2000, p. 293.
6 A. A. Granovsky, Firefly version 8.0.0, http//classic.chem.msu.su/gran/
firefly/index.html.
7 G. M. Sheldrick, Acta Crystallogr., 2008, A64, 112.
CCDC 995474 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via http://www.ccdc.cam.ac.uk. For details,
see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2014.
Received: 17th September 2013; Com. 13/4204
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