Synthesis and fungicidal activities of 1-[(2,2-diaryl-1,3-dioxolan-4-yl) methyl]-1H-azoles

Article abstract of DOI:10.1007/s11172-007-0147-4

Ketalization of benzophenones with epichlorohydrin or 3-chloropropane-1,2- diol gave 2,2-diaryl-4-chloromethyl-1,3-dioxolanes, which were used to alkylate sodium salts of imid-azole or 1,2,4-triazole. The resulting 1-[(2,2-diaryl-1,3- dioxolan-4-yl)methyl

Full text of DOI:10.1007/s11172-007-0147-4

Russian Chemical Bulletin, International Edition, Vol. 56, No. 5, pp. 975—979, May, 2007
975
Synthesis and fungicidal activities
of 1ꢀ[(2,2ꢀdiarylꢀ1,3ꢀdioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles
V. S. Talismanov and S. V. Popkovꢀ
D. I. Mendeleyev University of Chemical Technology of Russia,
9 Miusskaya pl., 125047 Moscow, Russian Federation.
Fax: +7 (495) 496 6058. Eꢀmail: popkovsv@rctu.ru
Ketalization of benzophenones with epichlorohydrin or 3ꢀchloropropaneꢀ1,2ꢀdiol gave
2,2ꢀdiarylꢀ4ꢀchloromethylꢀ1,3ꢀdioxolanes, which were used to alkylate sodium salts of imidꢀ
azole or 1,2,4ꢀtriazole. The resulting 1ꢀ[(2,2ꢀdiarylꢀ1,3ꢀdioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles exꢀ
hibit high fungicidal activities.
Key words: imidazoles, 1,2,4ꢀtriazoles, alkylation, 1,3ꢀdioxolanes, epichlorohydrin,
1ꢀ[(1,3ꢀdioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles, fungicides.
A considerable part of current fungicides are 1,2,4ꢀtriꢀ
azole or imidazole derivatives. Azole fungicides exhibit
system properties, have low consumption rates and a broad
range of action, and are slightly toxic; in this respect, they
are superior to many other classes of fungicidal preparaꢀ
tions.1 According to their mechanism of action, 1ꢀsubstiꢀ
tuted azoles are inhibitors of the biosynthesis of steroids.2,3
The best known and widely used dioxolaneꢀcontaining
azole fungicides include propiconazole and difenoconꢀ
azole with an azolylmethyl group in position 2 of the
dioxolane ring.
Novel substituted 1ꢀ[(2,2ꢀdiarylꢀ1,3ꢀdioxolanꢀ4ꢀ
yl)methyl]ꢀ1Hꢀazoles 3 and 4 were obtained in two steps.
Ketalization of benzophenones 1 with epichlorohydrin in
CCl4 in the presence of BF3•Et2O as a catalyst4—6
(method A) or with 3ꢀchloropropaneꢀ1,2ꢀdiol with
azeotropic removal of water in benzene in the presence of
pꢀtoluenesulfonic acid as a catalyst7,8 (method B) gave
2,2ꢀdiarylꢀ4ꢀchloromethylꢀ1,3ꢀdioxolanes 2, which then
were used to alkylate sodium salts of 1,2,4ꢀtriazole or
imidazole9,10 (Scheme 1).
To reduce the amount of a byꢀproduct of epichloroꢀ
hydrin polymerization, we employed an excess of benꢀ
zophenones in the synthesis of 2,2ꢀdiarylꢀ4ꢀchloromethylꢀ
1,3ꢀdioxolanes 2 according to method A. However,
method B is preferred because the use of a double excess
of comparatively inexpensive 3ꢀchloropropaneꢀ1,2ꢀdiol
allows a higher degree of conversion of the benzopheꢀ
nones and the diol can be easily removed by washing of
the reaction mixture with water. The yields of 2,2ꢀdiarylꢀ
4ꢀchloromethylꢀ1,3ꢀdioxolanes were 78% (2a, A),
80% (2b, A), and 93—96% (2a—e, B). The compounds
obtained are yellowish oily liquids that are soluble in most
1
organic solvents. The H NMR spectra of derivatives 2
show characteristic signals for the 2,2,4ꢀtrisubstituted
dioxolane: two doublets of doublets at δ 3.48—3.49 and
3.64—3.67 for the chloromethyl protons, usually two douꢀ
blets of doublets at δ 4.02—4.04 and 4.11—4.12 for the
methylene protons of the dioxolane ring, and a quintet at
δ 4.43—4.45 for the methine proton of the dioxolane ring.
The IR spectra of chloromethyldioxolanes 2 contain no
signal for the carbonyl group of the starting ketone; inꢀ
stead, five characteristic bands of the dioxolane ring11
With the aim to obtain novel fungicides in the series of
1ꢀsubstituted azoles, we synthesized 1ꢀ[(2,2ꢀdiarylꢀ1,3ꢀ
dioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles and studied their funꢀ
gicidal activities. The above compounds are structurally
similar to propiconazole and difenoconazole but contain
an azolylmethyl group in a different position (Scheme 1).
appear at 1085—1250 cm–1
.
Alkylation of sodium salts of 1,2,4ꢀtriazole and imidꢀ
azole was carried out in boiling DMF for 16—18 h.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 940—944, May, 2007.
1066ꢀ5285/07/5605ꢀ0975 © 2007 Springer Science+Business Media, Inc.

976
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 5, May, 2007
Talismanov and Popkov
Scheme 1
i.
, BF3•Et2O, CCl4 or HOCH2CH(OH)CH2Cl, TsOH, PhH, ∆.
a
But
4ꢀCl
b
Cl
4ꢀCl
c
Cl
2,4ꢀCl2
d
Cl
4ꢀBr
e
Br
4ꢀBr
R1
R2
In lowerꢀboiling solvents such as acetonitrile and dioxane,
the reaction did not yield the desired products. Nor were
derivatives 3 and 4 obtained in an alternative way using
reactions of 3ꢀ(1Hꢀazolꢀ1ꢀyl)propaneꢀ1,2ꢀdiols with benꢀ
zophenones both under azeotropic removal of water in an
aromatic solvent (benzene, toluene, and pꢀxylene) in the
presence of pꢀtoluenesulfonic acid as a catalyst and over
molecular sieves (3 Å) in dehydrated polar solvents (THF,
DMSO, and EtOH) in the presence of pꢀtoluenesulfonic
acid or H2SO4 as a catalyst.
It is known that alkylation of 1,2,4ꢀtriazole with alkyl
halides produces 1ꢀ and 4ꢀsubstituted derivatives.12 In the
synthesis of triazoles 3, the percentage of the 4ꢀsubstituted
isomer in the reaction products was 2—9% (HPLCꢀMS
data). Individual 1ꢀsubstituted 1,2,4ꢀtriazoles and imidꢀ
azoles were isolated by flash chromatography as white
crystals (3d,e) or yellowish oily liquids (3a—c, 4a—e) and
converted into crystalline oxalates that are stable in
storage. The 1H NMR spectra of 1ꢀ[(2,2ꢀdiarylꢀ1,3ꢀ
dioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles show quintets for the
methine proton of the dioxolane ring at δ 4.54—4.59 (3)
and 4.47—4.54 (4), two doublets of doublets for the meꢀ
thylene protons of the dioxolane ring at δ 3.87—4.16 (3)
and 3.82—4.05 (4), and two doublets of doublets for
the methylene protons of the azolylmethyl fragment at
δ 4.33—4.44 (3) and 4.14—4.43 (4). The double set of
doublet signals in the 1H NMR spectra of dioxolaneꢀ
containing azoles 3c and 4c indicates the formation of
mixtures of the diastereomers in the ratios 1 : 4.56 and
1 : 3.76, respectively. The 2D 1H—1H NMR spectrum
(NOE) of a diastereomeric pair of compound 3c shows a
cross peak due to a coupling of the H(5) proton of triazole
with the H(2) and H(6) protons of the 4ꢀchlorophenyl
substituent in the major stereoisomers; therefore, they
have Eꢀconfiguration.
The compounds obtained were tested in vitro for funꢀ
gicidal activity according to a very common procedure13
with five phytopathogenic fungi: Fusarium oxysporum
(F.o.), Fusarium moniliforme (F.m.), Bipolaris sorokiniana
(B.s.), Rhizoctonia solani (R.s.), and Venturia inaequalis
(V.i.). We studied the effects of the test compounds (c =
30 mg L–1) on the radial growth of mycelium in potato
saccharose agar with the widely used fungicide triadimefon
as a reference compound (Table 1). The compounds obꢀ
tained proved to be mostly superior in fungicidal activity
Table 1. Growth inhibition of the mycelium of the
pathogenic fungi by 1ꢀ[(2,2ꢀdiarylꢀ1,3ꢀdioxolanꢀ4ꢀ
yl)methyl]ꢀ1Hꢀazoles 3 and 4 in vitro (c = 30 mg L–1
)
Compound
Mycelium growth inhibition (%)
V.i.
R.s.
F.o.
F.m.
B.s.
3a
3b
3c
3d
3e
4a
4b
4c
30
65
39
47
47
51
67
59
74
56
53
63
94
99
95
94
75
81
92
95
85
54
54
77
72
73
62
64
74
78
73
57
72
59
72
70
72
71
79
60
93
99
94
90
66
71
70
78
75
71
67
93
85
100
45
4d
4e
Triadimefon

1ꢀ[(1,3ꢀDioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 5, May, 2007
977
4ꢀChloromethylꢀ2ꢀ(4ꢀchlorophenyl)ꢀ2ꢀ(2,4ꢀdichlorophenyl)ꢀ
to triadimefon. Imidazole derivatives 4 were more effiꢀ
cient than 1,2,4ꢀtriazole derivatives 3. The best inhibitor
was compound 4d derived from imidazole and 4ꢀbromoꢀ
4´ꢀchlorobenzophenone.
1,3ꢀdioxolane (2c). The yield was 96% (B), b.p. 205—207 °C
20
(0.5 Torr), nD = 1.5960. Found (%): C, 50.46; H, 3.34.
C16H12Cl4O2. Calculated (%): C, 50.83; H, 3.20. A mixture of
diastereomers A and B. 1H NMR (DMSOꢀd6), δ: 3.48 (dd,
3
2
0.43 HB, CH2Cl, J = 8.0 Hz, J = 8.8 Hz); 3.64 (dd, 0.57 HA,
CH2Cl, 3J = 5.8 Hz, 2J = 8.8 Hz); 3.75—3.80 (m, 1.43 H,
CH2Cl; CH2O); 4.02 (d, 1 H, CH2O, 3J = 8.8 Hz); 4.25 (dd,
0.57 HA, CH2O, 3J = 6.2 Hz, 2J = 8.8 Hz); 4.45 (q, 0.57 HA,
CHO, 3J = 5.6 Hz); 4.55 (q, 0.43 HB, CHO, 3J = 5.6 Hz);
7.32—7.46 (m, 4 H, Ar); 7.51—7.69 (m, 2 H, Ar); 7.75 (d,
Experimental
1
H NMR spectra were recorded on a Bruker AMꢀ300 inꢀ
strument (300.13 MHz). 13C NMR spectra were recorded on a
Bruker WMꢀ250 instrument (62.9 MHz) with Me4Si as the inꢀ
ternal standard. IR spectra were recorded on a Specord Mꢀ80
instrument (thin films for liquids and Nujol for solids). The
course of the reaction was monitored and the purity of the
compounds was checked by TLC (Sorbfil AꢀUF). Substituted
benzophenones were prepared according to a known procedure.14
2,2ꢀDiarylꢀ4ꢀchloromethylꢀ1,3ꢀdioxolanes 2a,b. Method A
(general procedure). Boron trifluoride etherate (0.28 g, 0.25 mL,
0.002 mol) was added to a stirred solution of benzophenone 1a,b
(0.1 mol) in CCl4 (250 mL). The mixture was stirred at room
temperature for 20 min. Then epichlorohydrin (7.40 g, 6.27 mL,
0.08 mol) was added at 25—30 °C and stirring was continued at
room temperature for 2 h. The reaction mixture was washed
with 3% NaOH (100 mL) and water (100 mL) and dried over
anhydrous MgSO4. The solvent was removed and the residue
was fractionated in vacuo.
4
4
0.57 HA, Ar, J = 4.2 Hz); 7.81 (d, 0.43 HB, Ar, J = 4.2 Hz).
13C NMR (DMSOꢀd6), δ: 45.1 (CH2Cl); 67.1 (CH2O); 75.2
(CHO); 109.1 (OCO); 127.0, 128.0, 128.8, 129.9, 130.5, 130.7,
132.5, 132.7, 133.1, 133.3, 134.2, 134.3, 137.4, 138.4, 139.2
(Ar). IR (thin film, ν/cm–1): 1248, 1225, 1175, 1117, 1085
(COCOC); 736 (C—Cl).
2ꢀ(4ꢀBromophenyl)ꢀ4ꢀchloromethylꢀ2ꢀ(4ꢀchlorophenyl)ꢀ1,3ꢀ
dioxolane (2d). The yield was 93% (B), b.p. 183—185 °C
20
(0.5 Torr), nD = 1.5953. Found (%): C, 49.19; H, 3.47.
C
16H13BrCl2O2. Calculated (%): C, 49.52; H, 3.38. 1H NMR
(DMSOꢀd6), δ: 3.48 (dd, 1 H, CH2Cl, 3J = 8.1 Hz, 2J = 11.0 Hz);
3.66 (dd, 1 H, CH2Cl, 3J = 4.4 Hz, 2J = 11.0 Hz); 4.02 (dd, 1 H,
CH2O, 3J = 5.2 Hz, 2J = 7.4 Hz); 4.11 (dd, 1 H, CH2O, 3J =
7.0 Hz, 2J = 7.4 Hz); 4.43 (q, 1 H, CHO, 3J = 5.9 Hz); 7.25—7.53
(m, 8 H, Ar). 13C NMR (DMSOꢀd6), δ: 45.1 (CH2Cl); 67.1
(CH2O); 75.1 (CHO); 109.0 (OCO); 121.8, 127.9, 128.0, 128.3,
128.5, 131.2, 131.4, 133.1, 140.5, 140.9 (Ar). IR (thin film,
ν/cm–1): 1245, 1225, 1175, 1115, 1085 (COCOC); 736 (C—Cl);
625 (C—Br).
2,2ꢀDiarylꢀ4ꢀchloromethylꢀ1,3ꢀdioxolanes 2a—e. Method B
(general procedure).
A mixture of benzophenone 1a—e
(0.05 mol), 3ꢀchloropropaneꢀ1,2ꢀdiol (11.05 g, 0.1 mol), and
pꢀtoluenesulfonic acid monohydrate (0.48 g, 0.0025 mol) was
refluxed in benzene for ~24 h with azeotropic removal of water.
The reaction mixture was neutralized with 2% NaOH (100 mL)
and washed with water (200 mL). The solvent was removed and
the residue was fractionated in vacuo.
2,2ꢀBis(4ꢀbromophenyl)ꢀ4ꢀchloromethylꢀ1,3ꢀdioxolane (2e).
The yield was 95% (B), b.p. 194—196 °C (0.5 Torr),
20
nD = 1.6022. Found (%): C, 44.11; H, 3.21. C16H13Br2ClO2.
Calculated (%): C, 44.43; H, 3.03. 1H NMR (DMSOꢀd6), δ:
3.46 (dd, 1 H, CH2Cl, 3J = 8.1 Hz, 2J = 11.0 Hz); 3.64 (dd, 1 H,
3
2
3
2ꢀ(4ꢀtertꢀButylphenyl)ꢀ4ꢀchloromethylꢀ2ꢀ(4ꢀchlorophenyl)ꢀ
1,3ꢀdioxolane (2a). The yield was 78% (method A) and 95% (B),
b.p. 189—191 °C (0.5 Torr), nD20 = 1.5670. Found (%): C, 65.59;
H, 6.16. C20H22Cl2O2. Calculated (%): C, 65.76; H, 6.07.
1H NMR (DMSOꢀd6), δ: 1.33 (s, 9 H, CMe3); 3.49 (dd, 1 H,
CH2Cl, 3J = 8.8 Hz, 2J = 11.0 Hz); 3.67 (dd, 1 H, CH2Cl, 3J =
CH2Cl, J = 4.4 Hz, J = 11.0 Hz); 4.04 (dd, 1 H, CH2O, J =
5.2 Hz, 2J = 7.4 Hz); 4.12 (dd, 1 H, CH2O, 3J = 7.0 Hz, J =
2
7.4 Hz); 4.45 (q, 1 H, CHO, 3J = 5.9 Hz); 7.34, 7.48 (both d,
4 H each, Ar, 3J = 8.6 Hz). 13C NMR (DMSOꢀd6), δ: 44.9
(CH2Cl); 66.9 (CH2O); 75.0 (CHO); 109.1 (OCO); 121.3, 125.4,
127.7, 127.9, 139.8, 130.0, 140.5, 141.0 (Ar). IR (thin film,
ν/cm–1): 1245, 1225, 1175, 1115, 1085 (COCOC); 736 (C—Cl);
635 (C—Br).
2
3
2
5.2 Hz, J = 11.0 Hz); 4.02 (dd, 1 H, CH2O, J = 5.2 Hz, J =
8.0 Hz); 4.11 (dd, 1 H, CH2O, J = 6.7 Hz, 2J = 8.0 Hz); 4.44
3
(q, 1 H, CHO, 3J = 5.9 Hz); 7.18—7.54 (m, 8 H, Ar). 13C NMR
(DMSOꢀd6), δ: 30.7 (CMe3); 34.1 (CMe3); 44.9 (CH2Cl); 67.2
(CH2O); 75.7 (CHO); 109.1 (OCO); 125.3, 125.4, 125.6, 125.7,
127.3, 127.6, 127.7,128.0, 128.2, 131.3, 132.8, 138.5, 141.1,
150.6, 150.7 (Ar). IR (thin film, ν/cm–1): 1248, 1222, 1170,
1115, 1085 (COCOC); 735 (C—Cl).
1ꢀ[(2,2ꢀDiarylꢀ1,3ꢀdioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles 3a—e
and 4a—e (general procedure). A mixture of a chloromethyldiꢀ
oxolane 2 (0.03 mol) and a sodium salt of 1,2,4ꢀtriazole or
imidazole (0.03 mol) was refluxed in DMF (50 mL) for 16—20 h,
filtered, and evaporated. The residue was chromatographed on
silica gel in acetone—hexane with a concentration gradient of
acetone from 10 to 40%. Noncrystallized products were disꢀ
solved in acetone (20 mL) and treated with an equimolar amount
of oxalic acid dissolved in acetone (20 mL). The resulting crysꢀ
tals of oxalates of azoles 3a—c and 4a—e were filtered off, washed
with acetone (10 mL) and hexane (50 mL), and dried in air.
1ꢀ{[2ꢀ(4ꢀtertꢀButylphenyl)ꢀ2ꢀ(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolanꢀ
4ꢀyl]methyl}ꢀ1Hꢀ1,2,4ꢀtriazole (3a), oxalate. The yield was 59%,
m.p. 162—163 °C. Found (%): C, 59.31; H, 5.58; N, 8.40.
4ꢀChloromethylꢀ2,2ꢀbis(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolane (2b).
The yield was 80% (A) and 92% (B), b.p. 168—170 °C (0.4 Torr),
20
nD = 1.5953. Found (%): C, 55.65; H, 3.98. C16H13Cl3O2.
Calculated (%): C, 55.92; H, 3.81. 1H NMR (DMSOꢀd6), δ:
3.49 (dd, 1 H, CH2Cl, 3J = 8.2 Hz, 2J = 11.0 Hz); 3.64 (dd, 1 H,
3
2
3
CH2Cl, J = 5.6 Hz, J = 11.0 Hz); 4.03 (dd, 1 H, CH2O, J =
5.8 Hz, 2J = 7.6 Hz); 4.12 (dd, 1 H, CH2O, 3J = 7.0 Hz, J =
2
7.6 Hz); 4.45 (q, 1 H, CHO, 3J = 5.8 Hz); 7.35, 7.46 (both d,
4 H each, Ar, 3J = 8.8 Hz). 13C NMR (DMSOꢀd6), δ: 44.9
(CH2Cl); 66.9 (CH2O); 75.0 (CHO); 109.2 (OCO); 127.8, 128.4,
133.3, 140.5, 144.7 (Ar). IR (thin film, ν/cm–1): 1250, 1225,
1170, 1115, 1087 (COCOC); 732 (C—Cl).
C
22H24ClN3O2·H2C2O4. Calculated (%): C, 59.08; H, 5.37;
N, 8.61. 1H NMR (DMSOꢀd6), δ: 1.29 (s, 9 H, CMe3);
3.94—4.18 (m, 2 H, CH2O); 4.35 (d, 2 H, CH2N, 3J = 5.9 Hz);
4.59 (q, 1 H, CHO, 3J = 5.8 Hz); 7.25—7.47 (m, 8 H, Ar); 7.97

978
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 5, May, 2007
Talismanov and Popkov
(s, 1 H, H(3) triaz.); 8.09 (s, 1 H, H(5) triaz.). 13C NMR
(DMSOꢀd6), δ: 30.8 (CMe3); 34.2 (CMe3); 50.7, 50.8 (CH2N);
66.9 (CH2O); 74.4, 74.5 (CHO); 109.1 (OCO); 124.9, 125.0,
125.3, 125.5, 127.6, 127.7, 128.0, 128.2, 131.3, 132.8, 138.5,
138.6, 141.1 (arom.); 144.7 (C(3) triaz.); 150.7 (Ar); 151.4 (C(5)
triaz.); 160.9 (oxalate). IR (Nujol, ν/cm–1): 1247, 1220, 1172,
1115, 1087 (COCOC); 720 (C—Cl).
(CH2O); 74.5 (CHO); 108.6, 109.0 (OCO); 121.4, 125.6, 127.9,
128.1, 131.0, 131.2, 140.7, 141.2 (Ar); 144.7 (C(3) triaz.), 151.4
(C(5) triaz.). IR (Nujol, ν/cm–1): 1247, 1212, 1177, 1117, 1087
(COCOC); 625 (C—Br).
1ꢀ{[2ꢀ(4ꢀtertꢀButylphenyl)ꢀ2ꢀ(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolanꢀ
4ꢀyl]methyl}ꢀ1Hꢀimidazole (4a), oxalate. The yield was 63%,
m.p. 177—178 °C. Found (%): C, 61.97; H, 5.69; N, 5.44.
C23H25ClN2O2·H2C2O4. Calculated (%): C, 61.66; H, 5.59;
N, 5.75. 1H NMR (DMSOꢀd6), δ: 1.28 (s, 9 H, CMe3); 3.87
(dd, 1 H, CH2O, 3J = 5.6 Hz, 2J = 8.6 Hz); 4.02 (dd, 1 H,
CH2O, 3J = 7.2 Hz, 2J = 8.6 Hz); 4.18 (dd, 1 H, CH2N, 3J =
1ꢀ{[2,2ꢀBis(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolanꢀ4ꢀyl]methyl}ꢀ1Hꢀ
1,2,4ꢀtriazole (3b), oxalate. The yield was 74%, m.p.
173—174 °C. Found (%): C, 51.84; H, 3.77; N, 9.17.
C18H15Cl2N3O2•H2C2O4. Calculated (%): C, 51.52; H, 3.67;
N, 9.01. 1H NMR (DMSOꢀd6), δ: 3.97 (dd, 1 H, CH2O, 3J =
2
3
2
7.0 Hz, J = 14.0 Hz); 4.35 (dd, 1 H, CH2N, J = 3.5 Hz, J =
2
3
5.5 Hz, 2J = 8.8 Hz); 4.05 (dd, 1 H, CH2O, 3J = 6.8 Hz, J =
14.0 Hz); 4.48 (q, 1 H, CHO, J = 5.8 Hz); 7.12 (s, 1 H, H(5)
8.8 Hz); 4.38 (dd, 1 H, CH2N, 3J = 6.6 Hz, 2J = 13.9 Hz); 4.44
(dd, 1 H, CH2N, 3J = 5.2 Hz, 2J = 13.9 Hz); 4.54 (q, 1 H, CHO,
3J = 5.9 Hz); 7.35, 7.42 (both d, 4 H each, Ar, 3J = 8.8 Hz); 7.98
(s, 1 H, H(3) triaz.); 8.45 (s, 1 H, H(5) triaz.). 13C NMR
(DMSOꢀd6), δ: 50.7 (CH2N); 67.0 (CH2O); 74.7 (CHO);
108.6 (OCO); 127.6, 128.2, 133.1, 140.4, 144.7 (Ar); 144.7
(C(3) triaz.); 151.4 (C(5) triaz.); 160.9 (oxalate). IR (Nujol,
ν/cm–1): 1245, 1215, 1175, 1115, 1085 (COCOC); 725 (C—Cl).
1ꢀ{[2ꢀ(4ꢀChlorophenyl)ꢀ2ꢀ(2,4ꢀdichlorophenyl)ꢀ1,3ꢀdiꢀ
oxolanꢀ4ꢀyl]methyl}ꢀ1Hꢀ1,2,4ꢀtriazole (3c), oxalate. The yield
was 65%, m.p. 193—195 °C. Found (%): C, 48.16; H, 3.36;
N, 8.18. C18H14Cl3N3O2·H2C2O4. Calculated (%): C, 47.97;
H, 3.22; N, 8.39. A mixture of diastereomers A and B. 1H NMR
(DMSOꢀd6), δ: 3.87 (dd, 0.18 HB, CH2O, 3J = 5.6 Hz, 2J =
imidaz.); 7.28—7.45 (m, 9 H, Ar + H(4) imidaz.); 8.17 (s, 1 H,
H(2) imidaz.). 13C NMR (DMSOꢀd6), δ: 31.0 (CMe3); 34.2
(CMe3); 49.5 (CH2N); 66.6 (CH2O); 74.9 (CHO); 109.2 (OCO);
121.5, 121.9 (C(5) imidaz.); 123.3 (C(4) imidaz.); 124.9, 125.2,
125.4, 125.6, 127.5, 127.6, 127.7, 128.1, 128.3, 132.8 (Ar); 136.7
(C(2) imidaz.); 138.5, 141.0, 150.7 (Ar); 163.4 (oxalate).
IR (Nujol, ν/cm–1): 1247, 1220, 1172, 1115, 1087 (COCOC);
720 (C—Cl).
1ꢀ{[2,2ꢀBis(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolanꢀ4ꢀyl]methyl}ꢀ1Hꢀ
imidazole (4b), oxalate. The yield was 42%, m.p. 192—193 °C.
Found (%): C, 54.54; H, 3.81; N, 6.11. C19H16Cl2N2O2·H2C2O4.
Calculated (%): C, 54.21; H, 3.90; N, 6.02. 1H NMR (CDCl3),
δ: 3.87 (dd, 2 H, CH2O, 3J = 5.4 Hz, 2J = 8.8 Hz); 4.05 (dd, 1 H,
3
2
3
CH2N, J = 6.8 Hz, J = 13.2 Hz); 4.14 (dd, 1 H, CH2N, J =
4.8 Hz, 2J = 13.2 Hz); 4.47 (q, 1 H, CHO, 3J = 5.4 Hz); 6.97 (s,
1 H, H(5) imidaz.); 7.29 (s, 1 H, H(4) imidaz.); 7.34, 7.41
(both d, 4 H each, Ar, 3J = 8.8 Hz); 7.67 (s, 1 H, H(2) imidaz.).
13C NMR (DMSOꢀd6), δ: 49.3 (CH2N); 66.6 (CH2O); 75.0
(CHO); 108.8 (OCO); 121.5 (C(5) imidaz.); 123.3 (C(4)
imidaz.);127.5, 128.1, 133.0 (Ar); 136.7 (C(2) imidaz.); 140.3,
144.6 (Ar); 163.4 (oxalate). IR (Nujol, ν/cm–1): 1247, 1220,
1170, 1115, 1085 (COCOC); 720 (C—Cl).
2
8.8 Hz); 4.02 (dd, 0.82 HA, CH2O, 3J = 5.6 Hz, J = 8.8 Hz);
3
4.08 (dd, 0.82 HA, CH2O, J = 6.8 Hz, 2J = 8.8 Hz); 4.24 (dd,
2
0.18 HB, CH2O, 3J = 6.8 Hz, J = 8.8 Hz); 4.33 (dd, 0.18 HB,
CH2N, 3J = 6.6 Hz, 2J = 14.0 Hz); 4.42—4.58 (m, 2.64 H,
CH2N + CHO); 4.54 (q, 0.18 HB, CHO, 3J = 5.6 Hz); 7.24,
3
7.47 (both d, 2 H each, Ar, J = 8.0 Hz); 7.53 (d, 2 H, Ar, 3J =
8.2 Hz); 7.79 (s, 1 H, Ar); 7.98 (s, 1 H, H(3) triaz.); 8.45 (s, 1 H,
H(5) triaz.). 13C NMR (DMSOꢀd6), δ: 50.1, 50.6 (CH2N); 67.0
(CH2O); 74.6, 75.2 (CHO); 108.3 (COC); 127.0, 128.0, 128.9,
129.7, 130.5, 130.7, 132.8, 133.3, 134.3, 136.7, 138.6 (Ar); 144.7
(C(3) triaz.); 151.5 (C(5) triaz.); 161.0 (oxalate). IR (Nujol,
ν/cm–1): 1247, 1220, 1172, 1115, 1087 (COCOC); 727 (C—Cl).
1ꢀ{[2ꢀ(4ꢀBromophenyl)ꢀ2ꢀ(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolanꢀ4ꢀ
yl]methyl}ꢀ1Hꢀ1,2,4ꢀtriazole (3d). The yield was 72%, m.p.
128—129 °C. Found (%): C, 51.52; H, 3.74; N, 9.83.
C18H15BrClN3O2. Calculated (%): C, 51.39; H, 3.59; N, 9.99.
1H NMR (DMSOꢀd6), δ: 4.04 (dd, 1 H, CH2O, 3J = 5.2 Hz,
1ꢀ{[2ꢀ(4ꢀChlorophenyl)ꢀ2ꢀ(2,4ꢀdichlorophenyl)ꢀ1,3ꢀdiꢀ
oxolanꢀ4ꢀyl]methyl}ꢀ1Hꢀimidazole (4c), oxalate. The yield
was 66%, m.p. 179—181 °C. Found (%): C, 50.76; H, 3.54;
N, 5.77. C19H15Cl3N2O2•H2C2O4. Calculated (%): C, 50.47;
H, 3.43; N, 5.61. A mixture of diastereomers A and B. 1H NMR
(DMSOꢀd6), δ: 3.82 (dd, 0.21 HB, CH2O, 3J = 5.8 Hz, 2J =
8.6 Hz); 4.01 (d, 0.79 H, CH2O, 3J = 5.4 Hz); 4.12—4.32 (m,
0.21 HB + 0.79 HA, CH2O); 4.40 (dd, 1 H, CH2N, 3J = 6.2 Hz,
2J = 14.1 Hz); 4.43—4.50 (m, 1.79 H, CH2N + CHO); 4.54 (q,
0.21 HB, CHO, 3J = 5.4 Hz); 7.07 (s, 0.21 HB, H(5) imidaz.);
7.12 (s, 0.79 HA, H(5) imidaz.); 7.26—7.43 (m, 4 H, Ar); 7.51
(d, 2 H, Ar, 3J = 8.6 Hz); 7.77 (s, 1 H, Ar); 7.82 (s, 0.79 HA,
H(4) imidaz.); 7.87 (s, 0.21 HB, H(4) imidaz.); 8.42 (s, 0.21 HB,
H(2) imidaz.); 8.45 (s, 0.79 HA, H(2) imidaz.). 13C NMR
(DMSOꢀd6), δ: 48.9, 49.3 (CH2N); 66.7 (CH2O); 74.9, 75.7
(CHO); 108.3, 108.5 (OCO); 121.4, 121.6 (C(5) imidaz.); 123.2
(C(4) imidaz.); 127.0, 128.0, 128.8, 129.9, 130.5, 130.7, 132.5,
132.7, 133.1, 133.3, 134.2, 134.3 (Ar); 136.6, 136.7 (C(2)
imidaz.); 137.4, 138.4, 139.2 (Ar); 163.4 (oxalate). IR (Nujol,
ν/cm–1): 1247, 1220, 1172, 1115, 1087 (COCOC); 727 (C—Cl).
1ꢀ{[2ꢀ(4ꢀBromophenyl)ꢀ2ꢀ(4ꢀchlorophenyl)ꢀ1,3ꢀdioxolanꢀ4ꢀ
yl]methyl}ꢀ1Hꢀimidazole (4d), oxalate. The yield was 60%,
m.p. 221—222 °C. Found (%): C, 49.79; H, 3.63; N, 5.38.
3
2
2J = 8.8 Hz); 4.09 (dd, 1 H, CH2O, J = 6.6 Hz, J = 8.8 Hz);
4.33 (d, 2 H, CH2N, 3J = 5.2 Hz); 4.58 (q, 1 H, CHO, 3J =
5.2 Hz); 7.23—7.42 (m, 6 H, Ar); 7.47 (d, 2 H, Ar, J = 8.8 Hz);
7.94 (s, 1 H, H(3) triaz.); 8.01 (s, 1 H, H(5) triaz.). 13C NMR
(DMSOꢀd6), δ: 50.6 (CH2N); 66.9 (CH2O); 74.6 (CHO); 108.6
(OCO); 121.7, 127.6, 127.9, 128.2, 128.4, 131.1, 131.3, 133.0,
140.4, 140.8 (Ar); 144.7 (C(3) triaz.); 151.4 (C(5) triaz.).
IR (Nujol, ν/cm–1): 1245, 1215, 1177, 1115, 1080 (COCOC);
715 (C—Cl); 625 (C—Br).
1ꢀ{[2,2ꢀBis(4ꢀbromophenyl)ꢀ1,3ꢀdioxolanꢀ4ꢀyl]methyl}ꢀ1Hꢀ
1,2,4ꢀtriazole (3e). The yield was 67%, m.p. 116—117 °C.
Found (%): C, 46.73; H, 3.33; N, 9.19. C18H15Br2N3O2. Calcuꢀ
lated (%): C, 46.48; H, 3.25; N, 9.03. 1H NMR (DMSOꢀd6), δ:
3.93—4.16 (m, 2 H, CH2O); 4.33 (d, 2 H, CH2N, 3J = 5.4 Hz);
4.59 (q, 1 H, CHO, 3J = 5.4 Hz); 7.31 (d, 4 H, Ar, 3J = 8.3 Hz);
7.47 (d, 4 H, Ar, 3J = 8.8 Hz); 7.95 (s, 1 H, H(3) triaz.); 8.02 (s,
1 H, H(5) triaz.). 13C NMR (DMSOꢀd6), δ: 50.6 (CH2N); 66.9
C
19H16BrClN2O2·H2C2O4. Calculated (%): C, 49.48; H, 3.56;
N, 5.50. 1H NMR (DMSOꢀd6), δ: 3.89 (dd, 1 H, CH2O,
3J = 5.9 Hz, 2J = 8.8 Hz); 4.04 (dd, 1 H, CH2O, 3J = 7.4 Hz,

1ꢀ[(1,3ꢀDioxolanꢀ4ꢀyl)methyl]ꢀ1Hꢀazoles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 5, May, 2007
979
2J = 8.8 Hz); 4.20 (dd, 1 H, CH2N, 3J = 6.6 Hz, 2J = 14.0 Hz);
3. B. A. Khaskin, Zh. Vses. Khim. Oꢀva im. D.I. Mendeleeva,
1988, 33, 698 [Mendeleev Chem. J., 1988, 33 (Engl. Transl.)].
4. A. A. Petrov, Zh. Obshch. Khim. [J. Gen. Chem. USSR], 1940,
11, 981 (in Russian).
5. A. A. Gevorkyan, P. I. Kazaryan, O. V. Avakyan, and R. A.
Vardanyan, Khim. Geterotsikl. Soedin., 1991, 27, 33 [Chem.
Heterocycl. Compd., 1991, 27, 27 (Engl. Transl.)].
6. P. I. Kazaryan, O. V. Avakyan, A. A. Gevorkyan, R. G.
Kulinkovich, and G. A. Panosyan, Khim. Geterotsikl. Soedin.,
1983, 19, 1607 [Chem. Heterocycl. Compd., 1983, 19, 1267
(Engl. Transl.)].
7. J. Wolinski and A. Czerwinska, Acta Pol. Pharm., 1976,
33, 695.
8. Y. Hiraguri and T. Endo, J. Am. Chem. Soc., 1987, 109, 3779.
9. DE Pat. 3 305 769; Chem. Abstrs., 1984, 100, 191859c.
10. M. Bergtrap and P. Larsen, Acta Chem. Scand., 1990,
44, 1050.
11. Physical Methods in Heterocyclic Chemistry, Ed. A. R.
Katritzky, Academic Press, New York—London, 1963,
660 pp.
12. T. W. Bently, L. M. Howle, and P. J. Wareham, Tetraꢀ
hedron, 1992, 48, 7869.
13. Metodicheskie rekomendatsii po opredeleniyu fungitsidnoi
aktivnosti novykh soedinenii [Methodological Recommendaꢀ
tions for Estimation of the Fungicidal Activities of Novel Comꢀ
pounds], NIITEKhIM, Cherkassy, 1984, 32 pp. (in Russian).
14. F. Smeets and J. Verhulst, Bull. Soc. Chim. Belg., 1952,
61, 694.
3
4.37 (dd, 1 H, CH2N, J = 3.7 Hz, 2J = 14.0 Hz); 4.51 (q, 1 H,
CHO, 3J = 5.9 Hz); 7.17 (s, 1 H, H(5) imidaz.); 7.28—7.47 (m,
7 H, Ar + H(4) imidaz.); 7.56 (d, 2 H, Ar, 3J = 8.1 Hz); 8.17 (s,
1 H, H(2) imidaz.). 13C NMR (DMSOꢀd6), δ: 49.4 (CH2N);
66.7 (CH2O); 75.1 (CHO); 108.8 (OCO); 119.6 (Ar); 121.5,
121.8 (C(5) imidaz.); 123.3 (C(4) imidaz.); 127.5, 127.6, 127.8,
128.0, 128.2, 128.5, 131.2, 131.4 (Ar); 136.7 (C(2) imidaz.);
140.2, 140.7 (Ar); 163.5 (oxalate). IR (Nujol, ν/cm–1): 1245,
1215, 1175, 1115, 1085 (COCOC); 720 (C—Cl); 630 (C—Br).
1ꢀ{[2,2ꢀBis(4ꢀbromophenyl)ꢀ1,3ꢀdioxolanꢀ4ꢀyl]methyl}ꢀ1Hꢀ
imidazole (4e), oxalate. The yield was 59%, m.p. 210—212 °C.
Found (%): C, 45.82; H, 3.31; N, 5.20. C19H16Br2N2O2 H2C2O4.
Calculated (%): C, 45.51; H, 3.27; N, 5.05. 1H NMR
(DMSOꢀd6), δ: 3.87 (dd, 1 H, CH2O, 3J = 5.9 Hz, 2J = 8.8 Hz);
3
2
4.04 (dd, 1 H, CH2O, J = 6.6 Hz, J = 8.8 Hz); 4.18 (dd, 1 H,
3
2
3
CH2N, J = 6.6 Hz, J = 13.9 Hz); 4.35 (dd, 1 H, CH2N, J =
3.7 Hz, 2J = 13.9 Hz); 4.48 (q, 1 H, CHO, 3J = 5.9 Hz); 7.12 (s,
1 H, H(5) imidaz.); 7.25—7.41 (m, 5 H, Ar + H(4) imidaz.);
7.48 (d, 4 H, Ar, 3J = 8.8 Hz); 8.05 (s, 1 H, H(2) imidaz.).
13C NMR (DMSOꢀd6), δ: 49.3 (CH2N); 66.6 (CH2O); 74.9
(CHO); 108.8, 109.2 (OCO); 121.4, 121.7 (C(5) imidaz.); 123.4
(Ar); 125.5 (C(4) imidaz.); 127.8, 128.1, 131.0, 131.2, (Ar);
136.7 (C(2) imidaz.); 140.7, 141.2 (Ar), 163 (oxalate). IR (Nujol,
ν/cm–1): 1245, 1210, 1175, 1115, 1085 (COCOC); 625 (C—Br).
References
1. N. N. Mel´nikov, Agrokhimiya [Agrochemistry], 1993, 10, 80
(in Russian).
2. S. L. Kelly, D. C. Lamb, and M. Cannieux, Biochem. Soc.
Trans., 2001, 29, 122.
Received February 8, 2007;
in revised form March 21, 2007