Intermolecular disproportionation between dimethyl (2-furylmethylidene)malonate and 4-methoxybenzylamine

Article abstract of DOI:10.1016/j.mencom.2016.09.022

Sodium hydride-promoted disproportionation of the title compounds affords tetramethyl 2-(2-furyl)propane-1,1,3,3-tetracarboxylate and furfural N-(4-methoxybenzyl)imine.

Full text of DOI:10.1016/j.mencom.2016.09.022

Mendeleev
Communications
Mendeleev Commun., 2016, 26, 429–430
Intermolecular disproportionation between
dimethyl (2-furylmethylidene)malonate and 4-methoxybenzylamine
Seda A. Torosyan,a Yulia N. Biglova,b Fanusa A. Gimalovaa and Mansur S. Miftakhov*a
a Ufa Institute of Chemistry, Russian Academy of Sciences, 450054 Ufa, Russian Federation.
Fax: +7 347 235 6066; e-mail: bioreg@anrb.ru
b Department of Chemistry, Bashkir State University, 450076 Ufa, Russian Federation
DOI: 10.1016/j.mencom.2016.09.022
CO2Me
CO2Me
H2N
NaH
OMe
+
THF, room
temperature
O
Sodium hydride-promoted disproportionation of the title
compounds affords tetramethyl 2-(2-furyl)propane-1,1,3,3-
tetracarboxylate and furfural N-(4-methoxybenzyl)imine.
OMe
CO2Me
CO2Me
CO2Me
+
O
O
N
MeO2C
In a study of NaH-promoted aza-Michael reaction of equimolar
amounts of unsaturated malonate 11 with 4-methoxybenzylamine 2
with incomplete consumption of the reactants, we observed that
two unexpected products were formed, namely, tetraester 3 and
imine 4 (Scheme 1). Obviously, compounds 3 and 4 are the
products of intermolecular disproportionation of the starting com-
pounds 1 and 2.
prototropic shift to produce a more stable anion B. Fragmentation
of the latter by β-elimination with release of malonate anion C
leads to imine 4. The resulting anion C reacts with diester 1
available in the solution to give tetraester 3.
Ar
Fur
NH
a
NaH
1 + 2
THF, room
CO2Me
CO2Me
H2N
temperature, 24 h
MeO2C
CO2Me
NaH
OMe
+
A
THF, room
temperature
O
2
1
Ar
N
Fur
OMe
1
4 + MeO2C
CO2Me
3
CO2Me
CO2Me
CO2Me
C
MeO2C
+
O
B
Fur = 2-furyl
Ar = 4-MeOC6H4
O
N
MeO2C
CO2Me
3
4
Scheme 1
Scheme 2
Formally, this reaction starting from 2 moles of malonate 1
and 1 mole of amine 2 should have given 1 mole of tetraester 3
and 1 mole of imine 4. However, the reaction of 1 and 2 in 2:1
molar ratio and with 1.67 equiv. NaH afforded a reaction mixture
containing not only 3 and 4 but also the original compounds 1
and 2. Each of the components 1, 2, 3, and 4 was isolated in pure
form in 35, 36, 7, and 56% yields, respectively, by column
chromatography on SiO2.†
We assume the following stage-by-stage routes of formation
of compounds 3 and 4 (Schemes 2 and 3). Carbanion A generated
after addition of amine 2 to the activated double bond of 1 can be
consumed in two ways. In pathway a, carbanion A undergoes a
Reaction of malonate 1 with 4-methoxybenzylamine. A solution of
4-methoxybenzylamine 2 (78 mg, 0.57 mmol) in THF (3 ml) was added
dropwise under argon to a suspension of NaH (40 mg, 1.67 mmol) in
anhydrous THF (30 ml) stirred at room temperature. The mixture was
stirred for 15 min, then malonate 1 (240 mg, 1.14 mmol) in THF (3 ml)
was added and the mixture was stirred for 24 h. The solution was then
concentrated and the residue was separated on a column with SiO2 using
light petroleum–ethyl acetate (4:1) as the eluent to give 80 mg of the starting
malonate 1, 40 mg of a 1:3:4 mixture in the ratio 1:1:4 (1H NMR),
30 mg of tetraester 3, 50 mg of imine 4, and 30 mg of 4-methoxybenzyl-
amine 2. Repeated chromatography of the mixed fraction gave 20 mg of
imine 4, 5 mg of tetraester 3, and 5 mg of malonate 1. Eventually, taking
the components of the mixed fraction into account, starting from 240 mg
(1.14 mmol) of 1 and 78 mg (0.57 mmol) of 2, we obtained 35 mg (7%)
of tetraester 3, 85 mg (35%) of diester 1, 70 mg (56%) of imine 4, and
30 mg (36%) of amine 2.
†
IR spectra of samples were obtained in thin layer using an IR
Prestige-21 Shimadzu spectrometer. H and 13C spectra were recorded
1
on Bruker AM-300 (300.13 and 75.47 MHz, respectively) and Bruker
AVANCE-500 (500.13 and 125.77 MHz, respectively) spectrometers
using Me4Si as the internal standard. The reaction was monitored by TLC
on Sorbfil plates (Russia). Compounds were visualized by wetting the
plates with a solution of anisic aldehyde and sulfuric acid in ethanol
followed by heating at 120–150°C. The products were isolated by column
chromatography on silica gel (30–60 g of the adsorbent per 1 g of the
compound).
Dimethyl (2-furylmethylidene)malonate 1. IR (n/cm–1): 2954, 1728, 1713,
1634, 1475, 1438, 1367, 1356, 1257, 1224, 1207, 1084, 1064, 1021, 757,
1
593. H NMR (300 MHz, CDCl3) d: 3.83 (s, 3H, OMe), 3.91 (s, 3H,
OMe), 6.50 (dd, 1H, H4fur, J 1.8 and 3.5 Hz), 6.77 (d, 1H, H3fur, J 3.5 Hz),
7.48 (d, 1H, CH=), 7.52 (d, 1H, H5fur, J 1.4 Hz). 13C NMR (75 MHz,
CDCl3) d: 52.58 (OMe), 112.67 (C3fur), 118.28 (C4fur), 121.18 (=C2),
128.22 (=CH), 146.37 (Cf5ur), 148.88 (C2fur), 164.55 and 166.74 (CO2Me).
Found (%): C, 57.42; H, 4.52. Calc. for C10H10O5 (%): C, 57.14; H, 4.80.
© 2016 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 429 –

Mendeleev Commun., 2016, 26, 429–430
of tetraester 3 in the mixture is noticeably lower than that of
Ar
NH
Fur
imine 4, which is explained by its easy retro-Michael decomposi-
tion under the conditions of our experiment. The resulting com-
pound 1 is consumed in the formation of both A and 3. The chain
of reactions involving compound 3 recurs and its content in the
mixture decreases in symbate way. As expected, model tests have
shown that on treatment with NaH in THF, tetraester 3 comes
into equilibrium with 1. In this regard, a publication2 should be
noted, in which zinc- and indium-promoted reactions of ethene-
tricarboxylates with N-propargylamines to afford methylenepyrro-
lidines are considered.
NaH
b
1 + 2
1 + 2
THF, room
temperature, 24 h
MeO2C
CO2Me
A
Fur = 2-furyl
Ar = 4-MeOC6H4
Fur
CO2Me
+
NaH
3
MeO2C
CO2Me
THF, room
temperature
CO2Me
1
C
In total, the transfomation herein described is particularly
interesting from a mechanistic standpoint, since products 3 and 4
are readily available using standard techniques. It should be also
emphasized that this reaction is unusual and unprecedented among
the numerous examples of inter- and intramolecular dispropor-
tionations (for selected publications, see refs. 3–7).
[A]
1 + 2 + 3
Scheme 3
In the alternative pathway b (Scheme 3), the ‘primary’ carb-
anion A undergoes a prototropic shift into B along with decom-
position into the original compounds 1 and 2 by the retro-Michael
scheme. As a result, the observed ‘mutation’is caused by parallel
reactions of formation of 3 and 4 (pathway a) and ‘recovery’ of
1, 2 (pathway b) occurring via carbanion A. Note that the content
This study was supported by the Russian Science Foundation
(project no. 15-13-00039).
References
Tetramethyl 2-(2-furyl)propane-1,1,3,3-tetracarboxylate 3. Mp 64–66°C.
IR (n/cm–1): 2997, 1757, 1737, 1717, 1462, 1455, 1334, 1297, 1288,
1262, 1239, 1217, 1189, 1174, 1142, 165. 1H NMR (500 MHz, CDCl3)
d: 3.59 (s, 6H, OMe), 3.72 (s, 6H, OMe), 4.08 (d, 2H, H3, H1, J 8.2 Hz),
1 R. E. Beyler and L. H. Sarett, J. Am. Chem. Soc., 1952, 74, 1397.
2 S. Morikawa, S.Yamazaki,Y. Furusaki, N. Amano, K. Zenke and K. Kakiuchi,
J. Org. Chem., 2006, 71, 3540.
3 M. Jereb and D. Vrazic, Org. Biomol. Chem., 2013, 11, 1978.
4 C. Stuekler, T. C. Reiter, N. Bandendistel and K. Faber, Tetrahedron, 2010,
66, 663.
5 M. M. Mojtahedi, E. Akbarsadeh, R. Sharifi and M. Abaee, Org. Lett.,
2007, 9, 2791.
6 Y. Ikushima, K. Hatakeda, O. Sato, T. Yokoyama and M. Arai, Angew.
Chem. Int. Ed., 2001, 40, 210.
4.35 (t, 1H, H2, J 8.1 Hz), 6.23 (m, 2H, H4fur, H3fur), 7.27 (d, 1H, H5fur
,
J 0.8 Hz). 13C NMR (125 MHz, CDCl3) d: 37.85 (C2), 52.62 and 52.74
(OMe), 52.90 (C1, C3), 108.87 (Cf3ur), 110.39 (C4fur), 142.05 (C5fur), 150.59
(C2fur), 167.68 and 167.99 (CO2Me). Found (%): C, 52.88; H, 5.18. Calc.
for C15H18O9 (%): C, 52.63; H, 5.30.
N-[(1E)-2-Furylmethylidene]-N-(4-methoxybenzyl)amine 4. Rf 0.22
(light petroleum–ethyl acetate, 4:1). IR (n/cm–1): 1645, 1610, 1511, 1247,
7 N. Furukawa, S. Ogawa, K. Matsumura and H. Fujihara, J. Org. Chem.,
1991, 56, 6341.
1
1175, 1034, 822, 751. H NMR (500 MHz, acetone-d6) d: 3.76 (s, 3H,
OMe), 4.67 (s, 2H, CH2), 6.55 (q, 1H, H3fur, J 1.7 Hz), 6.87–6.88 (m, 1H,
H4fur), 6.89 (d, 2H, HAr, J 8.7 Hz), 7.25 (d, 2H, HAr, J 8.7 Hz), 7.67 (d,
1H, H5fur, J 0.9 Hz), 8.25 (s, 1H, CH=N). 13C NMR (125 MHz, acetone-d6)
d: 54.57 (OMe), 64.17 (CH2), 111.65 (C3fur), 113.13 (C4fur), 113.65 (CHAr),
129.18 (CHAr), 131.62 (CAr), 144.72 (Cf5ur), 149.89 (CH=N), 152.35
(C2fur), 158.77 (CAr). Found (%): C, 72.41; H, 6.15; N, 6.61. Calc. for
C13H13NO2 (%): C, 72.54; H, 6.09; N, 6.51.
Received: 21st March 2016; Com. 16/4880
– 430 –