Synthesis of amines of the di- and trifurylmethane series

Article abstract of DOI:10.1007/s10593-007-0058-1

Methods are proposed for the synthesis of amines of the di-and trifurylmethane series-prospective compounds for the production of polymers and macrocyclic molecules-on the basis of 2-(2-furylmethyl)-1,3-isoindolinedione.

Full text of DOI:10.1007/s10593-007-0058-1

Chemistry of Heterocyclic Compounds, Vol. 43, No. 4, 2007
SYNTHESIS OF AMINES OF THE DI- AND TRIFURYLMETHANE SERIES
T. A. Nevolina, T. A. Stroganova, M. V. Shevlyakov, and A. V. Butin
Methods are proposed for the synthesis of amines of the di- and trifurylmethane series – prospective
compounds for the production of polymers and macrocyclic molecules – on the basis of 2-(2-furyl-
methyl)-1,3-isoindolinedione.
Keywords: di- and trifurylmethanes, 2-(2-furylmethyl)-1,3-isoindolinedione, carbonyl compounds,
hydrazinolysis, acid-catalyzed condensation.
On account of the unique properties of the furan ring furan compounds have found application in many fields
of chemistry – for the production of various carbo- and heterocyclic systems, in the synthesis of polymeric materials
and macromolecules. Difurylmethanes occupy a significant place among furan derivatives. Difurylmethane structures
have attracted the attention of investigators engaged in the chemistry of polymeric compounds since they are readily
obtainable replacements for the diphenylmethanes employed in the synthesis of polymers [1-4]. Diamines of the
difurylmethane series have found use in the production of epoxide resins [5], while the difurfuryl diisocyanates
synthesized from them are used in the production of polyurethane systems [6-8].
A traditional method for the synthesis of difurylmethane structures is the acid-catalyzed condensation of
carbonyl compounds with furan derivatives; the use of concentrated sulfuric acid [9, 10], ion-exchange resins [11,
12], acidic zeolites [13], phosphoric acid [14], and concentrated perchloric acid [15] has been described. However,
the ease of reaction of the amino group in furfurylamine with carbonyl compounds presupposes certain features of the
condensation. In order to prevent side transformations it is necessary to protect the amino function.
The original method for the synthesis of diamines of the difurylmethane series, which makes it possible
to avoid the introduction of a protecting group, involves condensation of furfurylamine and carbonyl compounds
in hydrochloric acid [16-19]. The latter in this case acts as catalyst and solvent and also deactivates the amino
group, thereby preventing the occurrence of undesirable side reactions at the amino group. A significant
disadvantage of this method is the fact that the process takes place without a solvent, which prevents the use of
crystalline substances in the reaction.
O
O
O
AcOH
N
+
O
O
O
∆
NH2
O
1
__________________________________________________________________________________________
Department of Organic Chemistry and Scientific-Research Institute of the Chemistry of Heterocyclic
Compounds, Kuban State Technological University. Krasnodar 350072, Russia; e-mail: stroganova@kubstu.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 505-512, April, 2007. Original article
submitted June 19, 2006.
408
0009-3122/07/4304-0408©2007 Springer Science+Business Media, Inc.

409

410

Thus, the acid-catalyzed condensation of carbonyl compounds with N-substituted furfurylamine
provides the most convenient and universal method for the synthesis of diamines of the difurylmethane series
since any reagents can be used irrespective of their state of aggregation.
For the synthesis of difurylarylmethanes based on furfurylamine we used 2-(2-furylmethyl)-1,3-
isoindolinedione – the product from reaction of furfurylamine with phthalic anhydride.
This compound enters readily into reaction with various aromatic aldehydes in dioxane at 40-50°C in the
presence of catalytic amounts of 70% perchloric acid (Tables 1 and 2).
R
R
HClO4
Ar
+
O
2
dioxane
O
O
O
R
Ar
2a–g
O
N
R =
O
2 a Ar = Ph, b Ar = 4-BrC6H4, c Ar = 4-ClC6H4, d Ar = 4-O2NC6H4,
e Ar = 4-Me2NC6H4, f Ar = 3-O2NC6H4, g Ar = 3,4-(МеО)2C6H3
Since the aim of the difurylmethane synthesis was to produce the diamines, we removed the protecting
groups by reaction of the methanes 2a-d with hydrazine hydrate.
R
NH2
R
H2N
.
NH2NH2 H2O
O
O
O
O
Ar
Ar
3a–d
2a–d
The synthesized amines 3a-d were viscous oily liquids (Tables 3 and 4).
For the synthesis of the symmetrical triamine the furfural 4 was prepared by the formylation of 2-(2-furyl-
methyl)-1,3-isoindolinedione (1).
O
O
N
N
POCl3
DMF
O
O
O
O
O
4
1
Condensation of the obtained aldehyde with the furan 1 in dioxane in the presence of perchloric acid as
catalyst leads to the trifluoromethane 5 with a yield of 49%.
We developed [20] a convenient single-stage method for the production of symmetrical
trifluoromethanes by the reaction of 5-R-furfural with ethylene glycol in the presence of the ion-exchange resin
Amberlyst 15. By the reaction of the aldehyde 4 with ethylene glycol in benzene, catalyzed by Amberlyst 15
(50% of the mass of the furfural), it is possible to synthesize the symmetrical trifluoromethane 5 with a yield of
80%. When boiled with hydrazine hydrate compound 5 gives the triamine 6.
411

412

We have thus proposed methods for the synthesis of difurylmethane diamines and a symmetrical
trifurylmethane triamine – prospective compounds for use in the chemistry of polymeric materials and
macrocycles.
HO
OH
4
+
Amberlyst 15
R
R
O
O
.
HClO4
NH2NH2 H2O
2
4
+
O
1
O
R
5
R
NH2
H2N
O
O
O
O
R =
N
O
6
H2N
EXPERIMENTAL
1
The H NMR spectra were recorded in DMSO on a Bruker AC-200 spectrometer (200 MHz) with
HMDS as internal standard (δ 0.055 ppm). Thin-layer chromatography was performed on Silufol and SORBFIL
plates with iodine, bromine, and a solution of 2,4-DNPH as developers.
Synthesis of 2-(5-{Aryl[5-(2,3-dioxo-2,3-dihydro-1H-2-isoindolylmethyl)-2-furyl]methyl}-1,3-iso-
indolinediones 2a-d, f, g. To a suspension of (10 mmol) of compound 1 in 5 ml of dioxane we added
(5.5 mmol) of the respective benzaldehyde and (0.7 ml) of 70% perchloric acid. The reaction mixture was stirred
at 40-50°C. After 20-40 min the initial substances had completely dissolved. The reaction mixture was stirred
until the product had separated as a precipitate and was left at room temperature for 3-4 h. The precipitate was
separated by filtration, washed with cold dioxane, dried, and crystallized from a mixture of methylene chloride
and petroleum ether.
Synthesis of 2-(5-{4-N,N-Dimethylaminophenyl[5-(1,3-dioxo-2,3-dihydro-1H-2-isoindolylmethyl)-
2-furyl]methyl}-2-furylmethyl)-1,3-isoindolinedione 2e. The reaction was carried out by the general procedure
for the synthesis of compounds 2 with a 4-ml excess of perchloric acid. The crystalline precipitate was washed
with dioxane and was then washed thoroughly with a solution of NaHCO3. The subsequent treatment was similar
to the previous method.
Hydrazinolysis of Compounds 2a-d (General Procedure). Synthesis of Aryldi(5-aminomethyl-
2-furyl)methanes 3a-d. To a solution of (5 mmol) of the compound 2a-d in 40 ml of ethanol we added (1 ml) of
hydrazine hydrate. The mixture was boiled until the initial imide had completely disappeared (TLC). The
reaction mixture was poured into water, the precipitated hydrazide was filtered off, and the amines 3a-d were
extracted from the filtrate with hot ethyl acetate. Evaporation of the solvent at reduced pressure gave the
diamines (3a-d) in the form of oils.
413

5-(1,3-Dioxo-2,3-dihydro-1H-2-isoindolylmethyl)-2-furaldehyde (4). To a suspension of compound 1
(2.27 g, 10 mmol) in (3 ml) of DMFA while stirring and cooling with iced water we added dropwise (10 ml)
(100 mmol) of phosphorus oxychloride. At the end of the addition the mixture was kept at room temperature for
10 min and then at 50°C until the imide (1) had been completely consumed (TLC). The cooled reaction mixture
was poured onto crushed ice and neutralized to pH 8 by the successive addition of a solution of sodium
hydroxide and solid sodium bicarbonate. The crystalline precipitate was filtered off, washed with water, and
dried. After recrystallization from ethanol with active carbon we obtained 2.11 g (83%) of the aldehyde 4 in the
1
form of cream-colored crystals; mp 136-138°C (from ethanol). H NMR spectrum, δ, ppm (J, Hz): 4.96 (2H, s,
CH2); 6.17 (1Н, d, J = 3.2, HFur-4); 7.22 (1Н, d, J = 3.2, HFur-3); 7.88-8.05 (4H, m, HPhth); 9.40 (1H, s, CHO).
Found, %: C 65.91; H 3.52; N 5.53. C14H9NO4. Calculated, %: C 65.88; H 3.55; N 5.49.
Tris[(1,3-dioxo-2,3-dihydro-1H-2-isoindolylmethyl)-2-furyl]methane (5). A mixture of (1.27 g,
5 mmol) of furfural 4, (0.33 ml) (6 mmol) of ethylene glycol, and 0.64 g of ion-exchange resin Amberlyst 15
(50% on the weight of the furfural) in 70 ml of benzene was boiled with azeotropic distillation of the water until
the furfural had been completely converted. The resin was filtered off, (20 ml) of petroleum ether was added, and
the hot solution was filtered through a thin layer of silica gel. After crystallization the trifurylmethane 5 (0.94 g,
80%) was obtained in the form of a white powder; mp 168-169°C (from petroleum ether). 1H NMR spectrum, δ,
ppm (J, Hz): 4.68 (6Н, s, СН2), 5.56 (1Н, s, СН), 5.99 (3Н, d, J = 3.1, НFur-3); 6.21 (3Н, d, J = 3.1, НFur-4);
7.79-7.89 (12H, m, HPhth). Found, %: C 69.43; H 3.67; N 6.12. C40H25N3O9. Calculated, %: C 69.46; H 3.64; N
6.08.
Tris(5-aminomethyl-2-furyl)methane (6). The hydrazinolysis of compound 5 was conducted by the
method described for compounds 2a-e, and the triamine 6 was obtained in the form of a yellow oil with a yield
of 54%. The oxalate of the amine 6 is a white powder; mp 156-157°C (from ethyl acetate). 1H NMR spectrum,
δ, ppm (J, Hz): 4.42 (6Н, s, СН2); 5.56 (1Н, s, СН); 6.17 (3Н, d, J = 3.1, НFur-3); 6.44 (3Н, d, J = 3.1, НFur-4);
7.22 (12H, br. s, NH3 + HOOCCOO–). Found, %: C 63.83; H 6.30; N 13.99. C16H19N3O3. Calculated, %: C 63.77;
+
H 6.36; N 13.94.
REFERENCES
1.
2.
3.
S. Gharbi and A. Gandini, J. Soc. Chim.Tunisie, 6, 17 (2004).
S. Abid, R. El Gharbi, and A. Gandini, Polymer, 45, 6469 (2004).
M. Abid, S. Gharbi, R. El Gharbi, and A. Gandini, in: Abstracts of 11th International Conference
''Recent Advances in Environmentally Compatible Polymers'', Tsukuba, Japan (2001), p. 27.
A. Afli, S. Gharbi, R. El Gharbi, Y. Le Bigot, and A. Gandini, Eur. Polym. J., 38, 667 (2002).
X. He, A. H. Canner, and J. A. Koutsky, J. Polym. Sci., Polym. Chem. Ed., 30, 533 (1992).
J. L. Cawse, J. L. Stanford, and R. H. Still, Makromol. Chem., 185, 697 (1984).
J. L. Cawse, J. L. Stanford, and R. H. Still, Makromol. Chem., 185, 709 (1984).
S. Boufi, A. Gandini, and M. N. Belgacem, Polymer, 36, 1689 (1995).
4.
5.
6.
7.
8.
9.
S. Pennanen and G. Nyman, Acta Chem. Scand., 26, 1018 (1972).
10.
Yu. Shapiro and V. G. Kul'nevich, in: Chemistry and Technology of Furan Compounds [in Russian],
Mezhvuz. Sb. Nauch. Tr. Krasnodar. Politekhn. In-ta, Krasnodar (1975), p. 75.
I. Iovel, Y. Goldberg, and M. Shymanska, J. Mol. Catal., 57, 97 (1989).
I. Iovel, Y. Goldberg, and M. Shimanskaya, Khim. Geterotsikl. Soedin., 746 (1989). [Chem. Heterocycl.
Comp., 25, 613 (1989)].
11.
12.
13.
14.
F. Algarra, A. Corma, H. Garcia, and J. Primo, Appl. Catal. A: General, 128, 119 (1995).
R. H. Sieber and P. Hornig, Liebigs Ann. Chem., 743, 144 (1971).
414

15.
16.
S. V. Zhuravlev and V. G. Kul’nevich, Khim. Geterotsikl. Soedin., 597 (1983). [Chem. Heterocycl.
Comp., 19, 478 (1983)].
A. Lesimple, Y. Le Bigot, M. Delmas, A. Gaset, and G. Roux, Fr. Pat. 9302072; Chem. Abstr., 118,
254738 (1993).
17.
18.
M. S. Holfinger, A. H. Conner, D. R. Holm, and C. G. Hill, Jr., J. Org. Chem., 60, 1595 (1995).
A. Lesimple, Y. Le Bigot, M. Delmas, A. Gaset, and G. Roux, Fr. Pat. 9302071 (1993); Chem. Abstr.,
118, 254737 (1993).
19.
20.
M. Skouta, A. Lesimple, Y. Le Bigot, and M. Delmas, Synth. Commun., 24, 2571 (1994).
A. V. Butin, T. A. Stroganova, L. N. Sorotskaya, and V. G. Kul’nevich, Arkivoc, 1, 641 (2000).
415