Synthesis of new N-heteroaryl derivatives of 4-pyrones from kojic acid based Baylis-Hillman acetates

Article abstract of DOI:10.1007/s10593-013-1188-2

A series of kojic acid benzyl ether derivatives possesing imidazole, benzimidazole, and pyrazole rings were synthesized by S_N2'- substitution of these heterocycles using prepared Baylis-Hillman acetates.

Full text of DOI:10.1007/s10593-013-1188-2

Chemistry of Heterocyclic Compounds, Vol. 48, No. 11, February, 2013 (Russian Original Vol. 48, No. 11, November, 2012)
SYNTHESIS OF NEW N-HETEROARYL DERIVATIVES OF
4-PYRONES FROM KOJIC ACID BASED BAYLIS–HILLMAN
ACETATES
Z. Ghasemi1*, M. Eshtad1, and F. Poorhossain Mejarshin1
A series of kojic acid benzyl ether derivatives possesing imidazole, benzimidazole, and pyrazole rings
were synthesized by SN2'-substitution of these heterocycles using prepared Baylis–Hillman acetates.
Keywords: N-alkylbenzimidazoles, N-alkylimidazoles, N-alkylpyrazoles, kojic acid, Baylis–Hillman
reaction.
Nucleophilic displacement of Baylis–Hillman acetates to obtain a variety of multifunctional allylic
derivatives is one of the most straightforward reactions in organic synthesis [1, 2]. These derivatives, which are
accessible by two possible mechanisms (SN2 or SN2'), depending on the reaction conditions, can be used for
various further transformations [3-8]. Arylation and heteroarylation of Baylis–Hillman acetates by the above
two mechanisms or by cross-coupling reactions make them valuable candidates for construction of polycyclic
natural, synthetic, and bioactive molecules [9-14].
Kojic acid (5-hydroxy-2-hydroxymethyl-4-pyrone), a natural antioxidant and potent tyrosine
inhibitor, has been the subject of several synthetic studies owing to their various biological properties
[15-19]. Benzimidazole, imidazole, and pyrazole are also frequently found in diverse compounds, including
biologically and therapeutically active agents, natural products, and functional materials [20-25]. Following
our recent work on the synthesis of new functional 4-pyrones based on Baylis–Hillman chemistry [26] or
cross-coupling reactions [27], we report here the synthesis of imidazolyl, benzimidazolyl, and pyrazolyl
derivatives of kojic acid by N-substitution of these heterocycles with the corresponding Baylis–Hillman
acetates with the hope that combining the structural properties of these azaaryls with the kojic acid
backbone will result in new products with interesting properties.
O
O
O
O
R1
R1
H2C
R2
R1
CH2
AcCl, Py
CH2Cl2
R2
CH2
H
R2
DABCO, room temp.
R
O
R
O
R
O
O
O
OH
1a (R = H, R1 = OBn)
1b (R = Ph, R1 = H)
2a–f
O
OAc
3a–d
_______
*To whom correspondence should be addressed, e-mail: z.ghasemi@tabrizu.ac.ir.
1Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz 5166616471,
Iran.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1767-1773, November, 2012.
Original article submitted March 4, 2012.
1652
0009-3122/13/4811-1652©2013 Springer Science+Business Media New York

TABLE 1. Synthesis of Baylis–Hillman Alcohols 2a-f and Acetates 3a-d
Alcohols 2*
Acetates 3*2
Entry
R
R1
R2
(yield, %)
(yield, %)
1
2
3
4
5
6
7
8
H
OBn
H
Me
2a (70)
3a (61)
Ph
H
Me
2b (69)
OBn
H
Et
2c (72)
Ph
H
Et
2d (74)
OBn
H
OBu
OBu
OMe
OEt
2e (80)
3b (56)
Ph
H
2f (78)
OBn
OBn
2g (75) [26]
2h (85) [26]
3c (67) [26]
3d (55)
H
_______
*Conditions of entries 1-4: aldehyde 1a or 1b (2 mmol), alkyl vinyl ketone
(4 mmol), DABCO (2 mmol), THF (20 ml), room temp., 1 h; conditions of
entries 5-6: aldehyde 1a or 1b (2 mmol), butyl acrylate (6 mmol), DABCO
(2 mmol), H2O–dioxane (1:1, 10 ml), room temp., 45 min.
*2Conditions: Baylis–Hillman alcohol (2 mmol), acetyl chloride (0.6 ml),
pyridine (0.12 ml), abs. CH2Cl2 (6 ml), room temp., 4 h.
N
O
N
BnO
N
N
H
H2O–THF
room temp., 5 h
O
O
COR2
4a–c
N
N
H
N
BnO
BnO
N
3a–d
H2O–THF
60°C, 3 h
Me
O
O
COR2
5a–c
6a,b
N
Me
N
N
N
H
O
COR2
H2O–THF
60°C, 3 h
TABLE 2. Synthesis of N-Substituted Azaaryls 4a-c, 5a-c, and 6a,b
Entry*
R2
Products (yield, %)
4a (73)
1
2
3
4
5
6
7
8
OMe
OEt
OBu
OMe
OEt
OBu
Me
4b (75)
4c (80)
5a (85)
5b (79)
5c (88)
6a (77)
OEt
6b (76)
_______
* Conditions: acetate 3a-d (1 mmol), hetarene (1.2 mmol), H2O (2 ml), THF
(10 ml), room temp., 5 h (entries 1-3) or 60°C, 3 h (entries 4-8).
1653

In this work, we firstly report the new Baylis–Hillman reactions of 2-formyl-4-pyrones 1a,b. Reactions
of aldehydes 1a,b with alkyl vinyl ketones such as methyl vinyl ketone and ethyl vinyl ketone in THF in the
presence of a stoichiometric amount of DABCO at room temperature for 1 h afforded the adducts 2a-d in good
yields (Table 1). In contrast to similar reactions with alkyl acrylates that were carried out in aqueous media [26],
reactions of these vinylic ketones were optimized in absolute THF. Treatment of aldehydes 1a,b with butyl
acrylate in 1,4-dioxane−water (1:1, v/v) medium gave the alcohols 2e,f in excellent yields (Table 1), as already
reported for methyl and ethyl acrylates [26]. Alcohol 2a, obtained from kojic acid derived aldehyde 1a, was
acetylated with acetyl chloride in dry CH2Cl2 in the presence of pyridine to afford acetate 3a. This product, as
well as the acetates 3b-d, resulting from reactions of compound 1a with alkyl acrylates (Table 1), was treated
with imidazole, benzimidazole, and 3-methylpyrazole in H2O–THF to give N-allylated compounds containing
imidazole 4a-c, benzimidazole 5a-c, and pyrazole 6a,b moieties (Table 2). The nucleophilic attack of imidazole
were completed in milder conditions than in the case of benzimidazole and pyrazole rings. Furthermore, the
reactivity of 3-methylpyrazole at the N-1 position has been observed in other similar conjugative reactions of
this reagent [28]. Moreover, all the reactions exhibit excellent E/Z selectivity, because no isomeric vinyl and
allylic methylene protons in the 1H NMR spectra of the products were observed. The obtained compounds 4a-c,
5a-c, and 6a,b have E configuration, as it could be expected for N-functionalized azaaryls [14].
In summary, some new Baylis–Hillman derivatives of 2-carboxaldehyde-4-pyrones were synthesized.
Modification of some Baylis–Hillman acetates containing the kojic acid scaffold by reactions with imidazole,
benzimidazole, and 3-methylpyrazole afforded the N-allylated compounds in good yields. The biological
activity studies of these compounds are in progress.
EXPERIMENTAL
1
FT-IR spectra were obtained on a Bruker Tensor 27 spectrometer. H and 13C NMR spectra were
recorded on a Bruker Spectrospin Avance 400 spectrometer (400 and 100 MHz respectively) in CDCl3; residual
1
solvent peaks were used as standard (7.26 ppm for H, 76.0 ppm for 13C). Elemental analyses were performed
on a Vario EL ΙΙΙ apparatus (Elementar Co.). Melting points were determined on an Electrothermal MEL-TEMP
apparatus (model 1202D) and are uncorrected. Preparative thin layer chromatographies were done with prepared
glass-backed plates (20 × 20 cm, 500 µm) using silica gel (Merck Kieselgel 60 PF254+366). All reagents were
purchased from Merck organics. The solvents were purified and dried according to the literature [29].
Synthesis of Baylis–Hillman Adducts 2a-d (General Method). To a solution of aldehyde 1a,b
(2 mmol) and DABCO (0.224 g, 2 mmol) in THF (20 ml), alkyl vinyl ketones (4 mmol) are added, and the
solution is stirred at room temperature for 1 h. The mixture is concentrated by a rotary evaporator, and the crude
residue is purified by preparative TLC (CH2Cl2–MeOH, 30:1) to give pure products 2a-d.
5-Benzyloxy-2-[(1-hydroxy-2-methylidene-3-oxo)butyl]-4H-pyran-4-one (2a). Yield 0.42 g (70%).
1
White solid; mp 99-100°C. IR spectrum, ν, cm-1: 3321 (br., OH), 3095, 3012, 2930, 1698, 1642, 1205. H NMR
spectrum, δ, ppm (J, Hz): 2.48 (3H, s, CH3); 4.54 (1H, d, J = 6.7, OH); 5.46 (1H, d, J = 6.7, CHOH); 5.13 (2H, s,
PhCH2O); 6.33 (1H, s) and 6.44 (1H, s, =CH2); 6.62 (1H, s, H-3); 7.40–7.51 (5H, m, H Ph); 7.61 (1H, s, H-6).
13C NMR spectrum, δ, ppm: 25.1; 68.9; 70.9; 111.8; 126.7; 127.4; 127.7; 128.2; 134.6; 140.2; 144.5; 146.1; 165.6;
173.7; 198.4. Found, %: C 67.71; H 5.62. C17H16O5. Calculated, %: C 67.99; H 5.37.
2-[(1-Hydroxy-2-methylidene-3-oxo)butyl]-6-phenyl-4H-pyran-4-one (2b). Yield 0.37 g (69%).
1
White solid; mp 94-96°C. IR spectrum, ν, cm-1: 3244 (br., OH), 3094, 2925, 1697, 1653, 1403. H NMR
spectrum, δ, ppm (J, Hz): 2.40 (3H, s, CH3); 4.54 (1H, d, J = 6.7, OH); 5.50 (1H, d, J = 6.7, CHOH); 6.34 (1H,
d, J = 0.6) and 6.39 (1H, s, =CH2); 6.48 (1H, d, J = 1.9, H-5); 6.65 (1H, d, J = 1.9, H-3); 7.41-7.49 (3H, m,
H Ph); 7.65-7.67 (2H, m, H Ph). 13C NMR spectrum, δ, ppm: 25.2; 68.6; 109.9; 111.7; 124.8; 127.9; 128.0;
129.9; 130.5; 145.1; 162.5; 166.8; 179.5; 198.1. Found, %: C 71.38; H 5.43. C16H14O4. Calculated, %: C 71.10;
H 5.22.
1654

5-Benzyloxy-2-[(1-hydroxy-2-methylidene-3-oxo)pentyl]-4H-pyran-4-one (2c). Yield 0.45 g (72%).
White solid; mp 58-60°C. IR spectrum, ν, cm-1: 3328 (br., OH), 3096, 3012, 2980, 1689, 1642, 1452, 1253.
1H NMR spectrum, δ, ppm (J, Hz): 1.03 (3H, t, J = 7.2, CH2CH3); 2.73 (2H, q, J = 7.2, CH2CH3); 4.31 (1H, br.
s, OH); 4.99 (2H, s, PhCH2O); 5.30 (1H, d, J = 5.8, CHOH); 6.13 (1H, s) and 6.28 (1H, s, =CH2); 6.48 (1H, s,
H-3); 7.29-7.35 (5H, m, H Ph); 7.47 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 6.8; 30.1; 68.8; 70.8; 111.6;
126.6; 126.7; 127.3; 127.6; 134.6; 140.2; 144.1; 146.0; 166.2; 173.9; 200.9. Found, %: C 68.57; H 6.05.
C18H18O5. Calculated, %: C 68.78; H 5.77.
2-[(1-Hydroxy-2-methylidene-3-oxo)pentyl]-6-phenyl-4H-pyran-4-one (2d). Yield 0.42 g (74%).
1
White solid; mp 70-72°C. IR spectrum, ν, cm-1: 3338 (br., OH), 3033, 2960, 1699, 1644, 1202. H NMR
spectrum, δ, ppm (J, Hz): 1.09 (3H, t, J = 7.2, CH2CH3); 2.78 (2H, q, J = 7.2, CH2CH3); 4.32 (1H, br. s, OH);
5.50 (1H, s, CHOH); 6.26 (1H, d, J = 0.4) and 6.37 (1H, s, =CH2); 6.50 (1H, d, J = 1.9, H-5); 6.68 (1H, d,
13
J = 1.9, H-3); 7.44-7.49 (3H, m, H Ph); 7.65-7.68 (2H, m, H Ph). C NMR spectrum, δ, ppm: 6.9; 30.3; 69.3;
110.1; 111.7; 124.8; 126.7; 128.0; 129.9; 130.5; 144.4, 162.4; 166.7; 179.4; 201.1. Found, %: C 71.59; H 5.38.
C17H16O4. Calculated, %: C 71.82; H 5.67.
Synthesis of Baylis–Hillman Adducts 2e,f (General Method). To a solution of aldehydes 1a,b
(2 mmol) and DABCO (0.224 g, 2 mmol) in dioxane–H2O (1:1, 10 ml), butyl acrylate (6 mmol) is added and
the solution is stirred at room temperature for 45 min. After adding water (100 ml), the mixture is extracted with
EtOAc (4×30 ml). The combined organic extract is washed with H2O (100 ml), dried over Na2SO4, and concen-
trated to dryness. The crude residue is purified by preparative TLC (acetone–CHCl3– n-hexane, 1:1:2) to give
products 2e,f.
2-[(5-Benzyloxy-4-oxo-4H-pyran-2-yl)hydroxymethyl]acrylic Acid Butyl Ester (2e). Yield 0.57 g
(80%). White solid; mp 80-84°C. IR spectrum, ν, cm-1: 3415 (br., OH), 3093, 2959, 1715 (ester C=O), 1643
1
(pyrone C=O), 1202. H NMR spectrum, δ, ppm (J, Hz): 0.91 (3H, t, J = 7.1, (CH2)3CH3); 1.31-1.40 (2H, m,
CH2CH2CH2CH3); 1.58-1.65 (2H, m, CH2CH2CH2CH3); 3.92 (1H, d, J = 7.3, OH); 4.16 (2H, t, J = 6.6,
COOCH2); 5.03 (2H, s, PhCH2O); 5.25 (1H, d, J = 7.3, CHOH); 5.97 (1H, s, H-3); 6.43 (1H, s) and 6.54 (1H, s,
=CH2); 7.31-7.38 (5H, m, H Ph); 7.49 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 12.6; 18.1; 29.4; 64.3; 69.5;
70.8; 111.8; 126.7; 127.4; 127.6; 127.7; 134.6; 136.7; 140.2; 146.12, 164.5; 165.4; 173.7. Found, %: C 67.14;
H 6.13. C20H22O6. Calculated, %: C 67.03; H 6.19.
2-[Hydroxy(4-oxo-6-phenyl-4H-pyran-2-yl)methyl]acrylic Acid Butyl Ester (2f). Yield 0.51 g
(78%). White solid; mp 92-94°C. IR spectrum, ν, cm-1: 3296 (br., OH), 2960, 1715 (ester C=O), 1655 (pyrone
1
C=O), 1452, 1329, 1219. H NMR spectrum, δ, ppm (J, Hz): 0.85 (3H, t, J = 7.3, (CH2)3CH3); 1.30-1.39 (2H,
m, CH2CH2CH2CH3); 1.57-1.54 (2H, m, CH2CH2CH2CH3); 4.14 (2H, t, J = 6.6, COOCH2); 5.13 (1H, br. s,
OH); 5.47 (1H, s, CHOH); 6.15 (1H, s, H-5); 6.51 (2H, s, =CH2); 6.64 (1H, d, J = 2.1, H-3); 7.39-7.47 (3H, m,
13
H Ph); 7.64-7.66 (2H, m, H Ph). C NMR spectrum, δ, ppm: 12.5; 18.0; 29.4; 64.1; 68.8; 109.8; 111.7; 124.8;
126.3; 127.9; 129.7; 130.4; 137.5; 162.7; 164.5; 167.0; 179.6. Found, %: C 69.25; H 6.26. C19H20O5.
Calculated, %: C 69.50; H 6.14.
Synthesis of Baylis–Hillman Acetates 3a-d (General Method). The crude alcohols 2a,e,g,h
(2.0 mmol) are dissolved in dry CH2Cl2 (6 ml). Acetyl chloride (0.6 ml, 8.4 mmol) and pyridine (0.12 ml,
1.5 mmol) are added, and the solution is stirred at room temperature for 4 h. The mixture is concentrated by a
rotary evaporator, and the residue is purified by preparative TLC (acetone–n-hexane, 1:3) to give acetates 3a-d.
1-(5-Benzyloxy-4-oxo-4H-pyran-2-yl)-2-methylidene-3-oxobutyl acetate (3a) obtained from alcohol
1
2a. Yield 0.42 g (61%). Colorless liquid. IR spectrum, ν, cm-1: 3090, 2928, 1752, 1679, 1652, 1594. H NMR
spectrum, δ, ppm: 2.11 (3H, s, CH3); 2.35 (3H, s, CH3); 5.01 (2H, s, PhCH2O); 6.13 (1H, s, CHOAc); 6.34
(1H, s) and 6.39 (1H, s, =CH2); 6.46 (1H, s, H-3); 7.29-7.37 (5H, m, H Ph); 7.50 (1H, s, H-6). 13C NMR
spectrum, δ, ppm: 19.6; 24.6; 67.1; 70.8; 112.9; 126.6; 126.7; 127.3; 127.6; 134.5; 140.1; 142.3; 146.2; 161.8;
167.7; 173.2; 195.4. Found, %: C 66.34; H 5.41. C19H18O6. Calculated, %: C 66.66; H 5.30.
1655

2-[Acetyloxy(5-benzyloxy-4-oxo-4H-pyran-2-yl)methyl]acrylic acid butyl ester (3b) obtained from
alcohol 2e. Yield 0.45 g (56%). White solid; mp 110-112°C. IR spectrum, ν, cm-1: 3088, 2915, 1748, 1720,
1
1649, 1570. H NMR spectrum, δ, ppm (J, Hz): 0.87 (3H, t, J = 7.1, (CH2)3CH3); 1.27-1.38 (2H, m,
CH2CH2CH2CH3); 1.52-1.64 (2H, m, CH2CH2CH2CH3); 2.12 (3H, s, OCOCH3); 4.18 (2H, t, J = 6.6, COOCH2);
5.04 (2H, s, PhCH2O); 5.78 (1H, s, CHOAc); 6.39 (1H, s) and 6.45 (1H, s, =CH2); 6.53 (1H, s, H-3); 7.28-7.36
(5H, m, H Ph); 7.49 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 12.5; 18.1; 19.6; 29.3; 64.4; 69.5; 70.8; 112.8;
126.6; 126.7; 127.4; 127.6; 134.5; 140.1; 142.3; 146.2; 161.5; 162.5; 168.4; 173.7. Found, %: C 65.65; H 6.13.
C22H24O7. Calculated, %: C 65.99; H 6.04.
2-[Acetyloxy(5-benzyloxy-4-oxo-4H-pyran-2-yl)methyl]acrylic acid ethyl ester (3d) obtained from
alcohol 2h. Yield 0.41 g (55%). Colorless liquid. IR spectrum, ν, cm-1: 3084, 2982, 1752, 1722, 1650, 1445,
1
1219. H NMR spectrum, δ, ppm (J, Hz): 1.23 (3H, t, J = 7.1, CH2CH3); 2.12 (3H, s, OCOCH3); 4.18 (2H, q,
J = 7.1, CH2CH3); 5.02 (2H, s, PhCH2O); 5.91 (1H, s, CHOAc); 6.39 (1H, s) and 6.44 (1H, s, =CH2); 6.50 (1H,
s, H-3); 7.29-7.37 (5H, m, H Ph); 7.51 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 12.9; 19.5; 60.4; 67.9; 70.7;
113.0; 126.6; 127.3; 127.5; 127.6; 134.3; 134.4; 140.1; 146.2; 161.5; 162.9; 167.7; 173.2. Found, %: C 64.25; H
5.13. C20H20O7. Calculated, %: C 64.51; H 5.41.
Synthesis of compounds 4a-c, 5a-c, 6a,b (General Method). To a solution of Baylis–Hillman acetate
3a-d (1 mmol) in THF–H2O (5:1, 12 ml), imidazole, benzimidazole, or 3-methylpyrazole (1.2 mmol) are added.
The resulting mixture is stirred (5 h at room temperature for imidazole and 3 h at 60°C for benzimidazole and
3-methylpyrazole). After concentration by removal of the THF, the reaction mixture is extracted with EtOAc
(3×10 ml). The organic phase is washed with brine (10 ml) and dried over Na2SO4. The solvents are removed
under reduced pressure to give the crude product, which is purified by preparative TLC using n-hexane–acetone
(2:1) as eluent.
(E)-3-[5-Benzyloxy-4-oxo-4H-pyran-2-yl]-2-[(imidazol-1-yl)methyl]acrylic Acid Methyl Ester (4a).
Yield 0.27 g (73%). White solid; mp 116-118°C. IR spectrum, ν, cm-1: 3070, 2926, 1720, 1641, 1443, 1091.
1H NMR spectrum, δ, ppm: 3.84 (3H, s, CH3); 5.12 (2H, s, PhCH2O); 5.20 (2H, s, CH2N); 6.58 (1H, s, H-3);
6.93 (1H, br. s, H-4 Im); 7.06 (1H, br. s, H-5 Im); 7.27 (1H, s, –CH=CCOOMe); 7.29–7.37 (5H, m, H Ph); 7.53
(1H, s, H-2 Im); 7.75 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 41.7; 52.2; 70.9; 118.2; 119.7; 126.8; 127.2;
127.5; 127.8; 129.9; 130.9; 131.6; 134.1; 139.6; 146.9; 156.9; 164.6; 172.8. Found, %: C 65.32; H 4.80; N 7.49.
C20H18N2O5. Calculated, %: C 65.57; H 4.95; N 7.65.
(E)-3-[5-Benzyloxy-4-oxo-4H-pyran-2-yl]-2-[(imidazol-1-yl)methyl]acrylic Acid Ethyl Eter (4b). Yield
0.29 g (75%). White solid; mp 107-109°C. IR spectrum, ν, cm-1: 3072, 2930, 1722, 1644, 1450, 1089. 1H NMR
spectrum, δ, ppm (J, Hz): 1.25 (3H, t, J = 7.1, CH2CH3); 4.23 (2H, q, J = 7.1, CH2CH3); 5.09 (2H, s, PhCH2O); 5.23
(2H, s, CH2N); 6.64 (1H, s, H-3); 6.92 (1H, br. s, H-4 Im); 7.03 (1H, s, H-5 Im); 7.25 (1H, s, –CH=CCOOEt);
7.28-7.37 (5H, m, H Ph); 7.54 (1H, s, H-2 Im); 7.76 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 12.7; 40.3; 61.6;
70.8; 118.3; 119.6; 126.7; 127.0; 127.4; 127.9; 129.9; 130.9; 131.5; 134.0; 139.5; 146.8; 156.7; 164.7; 172.8.
Found, %: C 66.02; H 5.13; N 7.09. C21H20N2O5. Calculated, %: C 66.31; H 5.30; N 7.36.
(E)-3-[(5-Benzyloxy-4-oxo-4H-pyran-2-yl)]-2-[(imidazol-1-yl)methyl]acrylic Acid Butyl Ester (4c).
Yield 0.33 g (80%). White solid; mp 123-124°C. IR spectrum, ν, cm-1: 3068, 2927, 2862, 1715, 1645, 1456,
1
1261, 1091. H NMR spectrum, δ, ppm (J, Hz): 0.87 (3H, t, J = 7.4, (CH2)3CH3); 1.26-1.32 (2H, m,
CH2CH2CH2CH3); 1.56-1.63 (2H, m, CH2CH2CH2CH3); 4.15 (2H, t, J = 6.7, COOCH2); 5.04 (2H, s, PhCH2O); 5.11
(2H, s, CH2N); 6.51 (1H, s, H-3); 6.85 (1H, br. s, H-4 Im); 6.98 (1H, br. s, H-5 Im); 7.20 (1H, s, –CH=CCOOBu);
7.26-7.38 (5H, m, H Ph); 7.60 (1H, s, H-2 Im); 7.65 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 12.6; 18.0; 29.4;
41.6; 65.4; 70.9; 118.3; 119.6; 126.8; 127.1; 127.6; 127.8; 129.8; 131.3; 131.4; 134.1; 139.5; 146.9; 157.0;
164.2; 172.8. Found, %: C 67.29; H 5.63; N 6.77. C23H24N2O5. Calculated, %: C 67.63; H 5.92; N 6.86.
(E)-2-[(Benzimidazol-1-yl)methyl]-3-[(5-benzyloxy-4-oxo-4H-pyran-2-yl)]acrylic Acid Methyl Ester
(5a). Yield 0.35 g (85%). White solid; mp 120-122°C. IR spectrum, ν, cm-1: 3070, 2859, 1719, 1640, 1444,
1264. 1H NMR spectrum, δ, ppm: 3.78 (3H, s, COOCH3); 5.09 (2H, s, PhCH2O); 5.43 (2H, s, CH2N); 6.61 (1H,
s, H-3); 7.29-7.34 (4H, m, H Ar); 7.35-7.41 (5H, m, H Ph); 7.60 (1H, s, H-6); 7.80 (1H, s, –CH=CCOOMe);
1656

8.10 (1H, br. s, H-2'). 13C NMR spectrum, δ, ppm: 40.1; 52.2; 70.9; 108.6; 119.2; 119.8; 121.7; 122.5; 126.8;
127.3; 127.6; 127.8; 130.8; 131.6; 132.9; 134.1; 139.5; 142.5; 146.9; 156.9; 164.6; 172.9. Found, %: C 68.98; H
4.53; N 6.97. C24H20N2O5. Calculated, %: C 69.22; H 4.84; N 6.73.
(E)-2-[(Benzimidazol-1-yl)methyl]-3-[(5-benzyloxy-4-oxo-4H-pyran-2-yl)]acrylic Acid Ethyl Ester
(5b). Yield 0.34 g (79%). White solid; mp 118-120°C. IR spectrum, ν, cm-1: 3063, 2963, 1714, 1644, 1454,
1251, 1204. 1H NMR spectrum, δ, ppm (J, Hz): 1.26 (3H, t, J = 7.1, CH2CH3); 4.22 (2H, q, J = 7.1, CH2CH3);
5.09 (2H, s, PhCH2O); 5.44 (2H, s, CH2N); 6.62 (1H, s, H-3); 7.26-7.28 (4H, m, H Ar); 7.32-7.39 (5H, m,
H Ph); 7.62 (1H, s, H-6); 7.80 (1H, s, –CH=CCOOEt); 8.07 (1H, br. s, H-2'). 13C NMR spectrum, δ, ppm: 12.9;
40.2; 61.5; 70.9; 108.7; 119.2; 119.7; 121.7; 122.5; 126.8; 127.2; 127.6; 127.8; 131.4; 131.6; 132.8; 134.1;
139.5; 142.4; 146.9; 156.0, 164.1; 172.9. Found, %: C 69.49; H 5.01; N 6.69. C25H22N2O5. Calculated, %:
C 69.76; H 5.15; N 6.51.
(E)-2-[(Benzimidazol-1-yl)methyl]-3-[(5-benzyloxy-4-oxo-4H-pyran-2-yl)]acrylic Acid Butyl Ester
(5c). Yield 0.40 g (88%). White solid; mp 126-128°C. IR spectrum, ν, cm-1: 3065, 2958, 1714, 1644, 1455,
1
1252, 1204. H NMR spectrum, δ, ppm (J, Hz): 0.78 (3H, t, J = 7.3, (CH2)3CH3); 1.12-1.21 (2H, m,
CH2CH2CH2CH3); 1.45-1.52 (2H, m, CH2CH2CH2CH3); 4.07 (2H, t, J = 6.7, COOCH2); 4.99 (2H, s, PhCH2O);
5.32 (2H, s, CH2N); 6.51 (1H, s, H-3); 7.17-7.21 (4H, m, H Ar); 7.28-7.32 (5H, m, H Ph); 7.58 (1H, s, H-6);
7.82 (1H, s, –CH=CCOOBu); 7.98 (1H, br. s, H-2'). 13C NMR spectrum, δ, ppm: 12.5; 17.9; 29.3; 39.9; 65.2;
70.8; 108.5; 119.3; 119.5; 121.3; 122.2; 126.7; 127.2; 127.5; 127.7; 131.1; 131.3; 132.6; 134.0; 139.4; 142.2;
146.7; 157.0; 164.1; 172.8. Found, %: C 70.38; H 5.89; N 6.45. C27H26N2O5. Calculated, %: C 70.73; H 5.72;
N 6.11.
(E)-5-Benzyloxy-2-{2-[(3-methylpyrazol-1-yl)methyl]-3-oxobut-1-enyl}-4H-pyran-4-one
(6a).
White solid. Yield 0.28 g (77%); mp 110-112°C. IR spectrum, ν, cm-1: 3033, 2955, 1692, 1654, 1202. 1H NMR,
δ, ppm: 2.24 (3H, s, ArCH3); 2.40 (3H, s, COCH3); 5.09 (2H, s, PhCH2O); 5.25 (2H, s, CH2N); 5.96 (1H, br. s,
H Ar); 6.72 (1H, s, H-3); 7.28-7.32 (2H, m, –CH=CCOMe, H Ar); 7.33-7.39 (5H, m, H Ph); 7.62 (1H, s, H-6).
13C NMR spectrum, δ, ppm: 25.3; 42.5; 46.5; 70.7; 103.9; 118.1; 118.5; 126.6; 127.7; 127.9; 129.4; 130.6;
131.2; 137.5; 139.7; 146.4; 157.4; 164.5; 173.5. Found, %: C 68.86; H 5.66; N 7.53. C21H20N2O4. Calculated,
%: C 69.22; H 5.53; N 7.69.
(E)-3-[(5-Benzyloxy-4-oxo-4H-pyran-2-yl)]-2-[(3-methylpyrazol-1-yl)methyl]acrylic Acid Ethyl Ester
(6b). Yield 0.30 g (76%). White solid; mp 113-115°C. IR spectrum, ν, cm-1: 3065, 2923, 1720, 1640, 1444, 1092.
1H NMR spectrum, δ, ppm (J, Hz): 1.28 (3H, t, J = 7.1, CH2CH3); 2.22 (3H, s, ArCH3); 4.24 (2H, q, J = 7.1,
CH2CH3); 5.09 (2H, s, PhCH2O); 5.27 (2H, s, CH2N); 5.97 (1H, br. s, H Ar); 6.74 (1H, s, H-3); 7.26-7.30 (2H,
m, –CH=CCOMe, H Ar); 7.31-7.39 (5H, m, H Ph); 7.60 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 13.0; 43.5;
46.4; 60.9; 70.9; 104.2; 118.3; 118.7; 126.7; 127.5; 127.7; 129.3; 130.4; 134.9; 137.9; 140.2; 146.6; 157.6;
164.5; 173.2. Found, %: C 66.76; H 5.76; N 7.33. C22H22N2O5. Calculated, %: C 66.99; H 5.62; N 7.10.
This paper reports a part of a research project entitled "Synthesis of new heterocyclic derivatives of
4-pyrones via nucleophilic substitution reactions". We thank the research affair of the University of Tabriz for
financial support.
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