WO2014051445A1 - Pyrrole-3,4-dicarboxamides - Google Patents

Pyrrole-3,4-dicarboxamides Download PDF

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WO2014051445A1
WO2014051445A1 PCT/PL2013/000119 PL2013000119W WO2014051445A1 WO 2014051445 A1 WO2014051445 A1 WO 2014051445A1 PL 2013000119 W PL2013000119 W PL 2013000119W WO 2014051445 A1 WO2014051445 A1 WO 2014051445A1
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vanadium
compound
reaction
formula
solution
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French (fr)
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Patrycja PACIOREK
Janusz SZKLARZEWICZ
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Uniwersytet Jagielloński
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Definitions

  • the invention relates to new chemical compounds from the group of pyrrole and the method of their preparation.
  • Pyrrole and their derivatives are one of the most important classes of heterocyclic compounds.
  • the syntheses of the compounds are attractive due to the fact, that the pyrrole group is a major, basic, repeatable unit of macrocyclic compouds, for example porphiryns [K. M. Smith, Porphyrins and Mettalloporphirins, Ed. Elsevier: Amsterdam (1975); B. Franek, A. Norm, Angew. Chem. Int. Ed. Engl, 34 (1995) 1795-1811 ; J. L. Sessler, S. J. Weghorn, Expanded, contracted and Isomeric Porphyrins; Pergamon: Oxford (1997)].
  • the methods of pyrrole derivatives synthesis with the use of the compounds type 1,3-diketone are known.
  • One of these methods is characterized in that 4 components are needed to the synthesis, i.e. 1,3-diketone, amine, aromatic aldehyde and nitroalkane.
  • the reaction runs using iron(III) compound as catalyst. After the reaction ends, evaporation in vacuum as well as purification with chromatography column are used in order to get rid of solvent excess [S. Maiti, S. Biswas, U. Jana, J. Org. Chem. 75 (2010) 1674-1683].
  • Ri is alkyl group C ⁇ - C 10 , straight or branched
  • R 2 is -H, -CI, -OH, -NH 2 or -OCH 3 .
  • R 2 is -H, -CI, -OH, -NH 2 or -OCH 3 group, and if R ⁇ is alkyl group: -CH 2 -CH 2 -CH 2 -CH 2 -CH 3 , then R 2 is -H.
  • vanadium compounds can be used as a reaction promoter, however simple salts of vanadium(IV) are used preferably, including vanadium acetylacetonate and vanadium oxides for example vanadium(IV) oxide and vanadium(V) oxide.
  • the reaction may be carried out in aerobic or anaerobic conditions.
  • the reaction may be carried out in an inert atmosphere, for example argon.
  • Alcohols, alcohol-water mixtures may be used as organic solvents, however ethanol or the mixture of ethanol-water (EtOH:H 2 0 1 : 1 - 4: 1 v/v) is used preferably.
  • the key role in the method of synthesis according to the invention plays the use of vanadium compounds as reaction promoters.
  • the synthesis method maybe based on the dimerization reaction of the transiently formed Schiff bases, and then cyclization of dimer to pyrrole structure.
  • the imine formed in the process is complexed by vanadium, what changes the charge distribution at carbon atoms allowing for dehydrogenation of one of the carbon atoms with simultaneous C-C bond formation and cyclization to form pyrrole.
  • the method according to the invention allows obtaining novel compounds, with the use of substrates with complex structures, in one-step process, in relatively simple manner.
  • the compounds according to the invention due to the presence of pyrrole unit, may exhibit valuable pharmacological, optical, electrical properties also as sensor elements.
  • the resulting compounds have functional groups that allow the potential use of these substances as antibacterial and antifungal compounds.
  • Acetoacetanilide (1771.1 mg, 9.99 mmol) and benzhydrazide (680.2 mg, 4.99 mmol) were dissolved in 100 cm of ethanol.
  • the solution was heated to reflux under argon atmosphere for 15 min.
  • Vanadyl sulphate monohydrate (1810.3 mg, 10.00 mmol) and 25 cm 3 of water were added to the solution.
  • the solution was heated to reflux under argon atmosphere for further 20 min. Then, the solution was allowed to crystallize at room temperature. After several days the product was precipitated.
  • the resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 1255.9 mg.
  • Elemental analysis data calculated for C 27 H 24 N 4 0 3 C - 71.67%, H - 5.35%, N - 12.38%.
  • Elemental analysis data calculated for C 27 H2 4 N 4 0 3 C - 71.67%, H - 5.35%, N - 12.20%.
  • Elemental analysis data calculated for C 27 H 24 N 4 0 3 C - 71.67%, H - 5.35%, N - 12.20%.
  • Acetoacetanilide (1772.0 mg, 10.00 mmol) and 4-chlorobenzhydrazide (852.4 mg, 5.00 mmol) were dissolved in 100 cm of ethanol.
  • the solution was heated to reflux under argon atmosphere for 10 min.
  • Vanadyl sulphate monohydrate (906.1 mg, 5.00 mmol) was added to the solution.
  • the solution was heated to reflux under argon atmosphere for further 30 min. Then, the solution was allowed to crystallize at room temperature. After several days the crystals of product were precipitated.
  • the resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 1450.0 mg.
  • Elemental analysis data calculated for C 2 7H 23 C1N 4 0 3 C - 66.60%, H - 4.76%, N - 11.51%.
  • a single crystal was selected from the resulting material for the rentgenostructural analysis. Diffraction data obtained for single crystal allowed for the spatial structure determination. Crystallographic data for the compound are presented in Table 2.
  • Elemental analysis data calculated for C 35 H 40 N 4 O 3 C - 74.44%, H - 7.14%, N - 9.92%.
  • Elemental analysis data calculated for C 27 H 25 N 5 0 3 C - 69.36%, H - 5.39%, N - 14.98%.
  • Experimental data derived by elemental analysis C - 68.57%, H - 5.48%, N - 14.64%). Mp. 310.0 - 313.0°C.
  • Acetoacetanilide (355.1 mg, 2.00 mmol) and 4-methoxybenzhydrazide (338.0 mg, 2.03 mmol) were dissolved in 50 cm of ethanol.
  • the solution was heated to reflux under argon atmosphere for 20 min.
  • Vanadyl acetylacetonate (526.0 mg, 2.00 mmol) was added to the solution.
  • the solution was heated to reflux under argon atmosphere for further 20 min. Then, the solution was allowed to crystallize at room temperature. After several days the product was precipitated.
  • the resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 130.0 mg.
  • a single crystal was selected from the resulting material for the rentgenostructural analysis. Diffraction data obtained for single crystal allowed for the spatial structure determination. Crystallographic data for the compound are presented in Table 3.
  • Acetoacetanilide (1772.3 mg, 10.00 mmol) and 4-hydroxybenzhydrazide (761.0 mg, 5.00 mmol) were dissolved in 100 cm 3 of ethanol.
  • the solution was heated to reflux under argon atmosphere for 15 min.
  • Vanadyl sulphate monohydrate (904.8 mg, 5.00 mmol) was added to the solution.
  • the solution was heated to reflux under argon atmosphere for further 20 min. Then, was filtered and the filtrate was allowed to crystallize at room temperature. After several days the crystals of product were precipitated.
  • the resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 900.0 mg.
  • Elemental analysis data calculated for C 27 H 24 N 4 0 4 C - 69.22%, H - 5.16%, N - 11.96%.
  • Experimental data derived by elemental analysis C - 68.42%, H - 5.33%, N - 10.68%. Mp. 311.0 - 313.0°C.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

The invention relates to the pyrrole derivatives with the general formula in which R1 is alkyl group C1 - C10, straight or branched, R2 is -H, -C1, -OH, -NH2 or -OCH3. The invention includes also the method of the synthesis of pyrrole derivatives in the reaction of ketoanilide with hydrazide, with the use of vanadium compound as a reaction promoter.

Description

PYRROLE-3,4-OICARBOXAMIDES
The invention relates to new chemical compounds from the group of pyrrole and the method of their preparation.
Pyrrole and their derivatives are one of the most important classes of heterocyclic compounds. The syntheses of the compounds are attractive due to the fact, that the pyrrole group is a major, basic, repeatable unit of macrocyclic compouds, for example porphiryns [K. M. Smith, Porphyrins and Mettalloporphirins, Ed. Elsevier: Amsterdam (1975); B. Franek, A. Norm, Angew. Chem. Int. Ed. Engl, 34 (1995) 1795-1811 ; J. L. Sessler, S. J. Weghorn, Expanded, contracted and Isomeric Porphyrins; Pergamon: Oxford (1997)]. These systems are presented, inter alia, in hemoglobin and chlorophyll. The group is also presented in the structure of indole, vitamin B12 and tryptamine. These compounds and their derivatives exhibit both, biological and pharmacological properties [E. Bellur, I. Freifeld, P. Langer, Tetrahedron Lett. , 47 (2005) 2151-2154].
Pyrrole derivatives, which exhibit biological properties: antibacterial [G. Daidone. B. Maggio, D. Schillaci, Pharmazie 45 (1990) 441-442], antidiabetic [G. F. Holland, U.S. Patent 4,282,242, 1981 ; Chem. Abstr. 95 (1981) 187068e], anti -inflammatory [T. Kimura, A. Kawara, A. Nakao, S-. Ushiyama, T. Shimozato, K. Zusuki, PCT Int Appl. CODEN:PIXXD2 WO 2000001688 Al, 200001132000, p. 173], antioxidative, antifungal [H. M. Meshram. B. R. V. Prasad, D. Davis, K. Bowen, H. Xu, V. Velvadapu, C. Ballard, Tetrahedron 64 (2008) 4174-4182], as well as pharmacological properties such as, for example, atorvastatin used as a medicine for cholesterol lowering [P. Mathew, C. V. Asokan, Tetrahedron 62 (2006) 1708-1716] are known in the literature.
These compounds may be used as ligands in modern magnetic materials, as bridging units in the synthesis of mesoporous compounds type MOF and modern polymeric materials [E. Shadpour, M. and B. Sheikholeslami, Irian Polymer Journal 7 (1998) 121-128].
A great progress has been achieved in recent years in organic synthesis of pyrrole derivatives. Several methods for preparation of these compounds have been developed. One of these methods is the application of metals as catalysts. The syntheses of pyrrole derivatives with the use of such metals as: iron(III), copper(I), titanium(IV), palladium(II), silver(I), gold(I), manganese(III), indium(III), platinum(II) and zinc(II) are known. However, the synthesis of pyrrole derivatives with the use of vanadium compounds is not known.
The methods of pyrrole derivatives synthesis with the use of the compounds type 1,3-diketone are known. One of these methods is characterized in that 4 components are needed to the synthesis, i.e. 1,3-diketone, amine, aromatic aldehyde and nitroalkane. The reaction runs using iron(III) compound as catalyst. After the reaction ends, evaporation in vacuum as well as purification with chromatography column are used in order to get rid of solvent excess [S. Maiti, S. Biswas, U. Jana, J. Org. Chem. 75 (2010) 1674-1683].
The pyrrole derivatives with formula 1 are known,
Figure imgf000003_0001
Formula 1 in which: ¾ is -Me or -Et group, R2 is C02Et, 4-Cl-PhS02, 4-N02-Ph, -Ph, thiophen-3-yl or indol-3-yl group, R3 - is -NHPh or -ME group. It is possible to obtain the abovementioned pyrrole derivatives in the reaction of suitable alkyl derivative, 2-chloroacetylacetonate, with proper hydrazide, which leads to hydrazine. Afterwards hydrazine reacts with 1,3-diketone in the presence of sodium carbonate and forms pyrrole derivative. The whole process runs in tetrahydrofurane at room temperature. After the reaction, the solvent is removed under reduced pressure, then the residue is extracted using ethyl acetate. Obtained 1-aminopyrrole is crystallized from properly selected solvent or is cleaned at chromatographic column with silicagel, eluting with cyclohexane and ethyl acetate [O. A. Attanasi, P. Filippone, F. R. Perrulli, S. Santeusanio, Tetrahedron 57 (2001) 1387-1394]. The invention relates to novel derivatives of pyrrole with the general formula 2:
Figure imgf000004_0001
Formula 2 in which: Ri is alkyl group C\ - C10, straight or branched, R2 is -H, -CI, -OH, -NH2 or -OCH3.
If Ri is -CH3 then R2 is -H, -CI, -OH, -NH2 or -OCH3 group, and if R\ is alkyl group: -CH2-CH2-CH2-CH2-CH3, then R2 is -H.
The method of pyrrole derivatives preparation with the general formula 2 according to the invention is characterized in that the compound type ketoanilide with the general formula 3:
Figure imgf000004_0002
Formula 3 which Ri is as defined above, is reacted with hydrazide with the general formula
Figure imgf000004_0003
Formula 4 in which R2 is as defined above, using a vanadium compound as a reaction promoter. The reaction according to the invention is carried out in organic or aqueous-organic solvent, at temperature range from 20°C up to boiling point of the mixture. 0.5 mole - 1 mole of hydrazide and 0.5 - 4 mole of vanadium compound are used per 1 mole of ketoanilide.
Any of vanadium compounds can be used as a reaction promoter, however simple salts of vanadium(IV) are used preferably, including vanadium acetylacetonate and vanadium oxides for example vanadium(IV) oxide and vanadium(V) oxide.
The reaction may be carried out in aerobic or anaerobic conditions. The reaction may be carried out in an inert atmosphere, for example argon.
Alcohols, alcohol-water mixtures may be used as organic solvents, however ethanol or the mixture of ethanol-water (EtOH:H20 1 : 1 - 4: 1 v/v) is used preferably.
The key role in the method of synthesis according to the invention plays the use of vanadium compounds as reaction promoters. The synthesis method maybe based on the dimerization reaction of the transiently formed Schiff bases, and then cyclization of dimer to pyrrole structure. Presumably, the imine formed in the process is complexed by vanadium, what changes the charge distribution at carbon atoms allowing for dehydrogenation of one of the carbon atoms with simultaneous C-C bond formation and cyclization to form pyrrole.
The method according to the invention allows obtaining novel compounds, with the use of substrates with complex structures, in one-step process, in relatively simple manner.
The compounds according to the invention, due to the presence of pyrrole unit, may exhibit valuable pharmacological, optical, electrical properties also as sensor elements. The resulting compounds have functional groups that allow the potential use of these substances as antibacterial and antifungal compounds.
The method of the synthesis according to the invention is further illustrated in the examples.
Example 1
The compound with formula 2, in which R\ is a alkyl group: -CH3 and R2 is -H. Acetoacetanilide (354.2 mg, 1.99 mmol) and benzhydrazide (136.8 mg, 1.00 mmol) were dissolved in 30 cm of ethanol. The solution was heated to reflux under argon atmosphere for 10 min. Vanadyl acetylacetonate (256.6 mg, 1.00 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 20 min. The solution was then allowed to crystallize at room temperature. After several days crystals of the product were precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 123.3 mg. Elemental analysis data calculated for C27H24N403: C - 71.67%, H - 5.35%, N - 12.38%. Experimental data derived by elemental analysis: C - 71.32%, H - 5.46%, N - 12.32%. Mp. 280.0 - 282.0°C. Experimental data derived by IR (cm"1): 3337, 3144, 3061, 2928, 1669, 1653, 1632, 1621, 1612, 1597, 1568, 1556, 1521, 1498, 1437, 1388, 1339, 1310, 1278, 1248, 1194, 1103, 1076, 909, 899, 752, 688.
A single crystal was selected from the resulting material for the rentgenostructural analysis. Diffraction data obtained for single crystal allowed for the spatial structure determination. The compound with the chemical molecular formula C27H24N403 was obtained. Crystallographic data for the compound are presented in Table 1.
Table 1 empirical formula C27H24N403
molecular weight 452.50
crystal size (mm) 0.25 0.14 x 0.04
crystallographic system triclinic
space group P T
a (A) 7.180(5)
b (A) 12.397(5)
c (A) 13.460(5)
a (°) 99.964(5)
β (°) 100.535(5)
γ (°) 100.205(5)
V (A3) 1 132.8(10)
z 2
T (K) 1 10(2)
Dc (Mg/m3) 1.327
μ (mm"1) 0.089
measured reflections 14699
symmetry independent reflections 4676
observed reflections [Ι>2σ(Ι)] 3267
R factors [Ι>2σ(Ι)] R = 0.0455
wR2 = 0.1008
S 1.021 Example 2
The compound with formula 2, in which
Figure imgf000007_0001
is a alkyl group: -CH3 and R2 is -H.
Acetoacetanilide (1771.1 mg, 9.99 mmol) and benzhydrazide (680.2 mg, 4.99 mmol) were dissolved in 100 cm of ethanol. The solution was heated to reflux under argon atmosphere for 15 min. Vanadyl sulphate monohydrate (1810.3 mg, 10.00 mmol) and 25 cm3 of water were added to the solution. The solution was heated to reflux under argon atmosphere for further 20 min. Then, the solution was allowed to crystallize at room temperature. After several days the product was precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 1255.9 mg. Elemental analysis data calculated for C27H24N403: C - 71.67%, H - 5.35%, N - 12.38%. Experimental data derived by elemental analysis: C - 71.19%, H - 5.44%, N - 12.30%. Mp. 280.0 - 282.0°C. Experimental data derived by IR (cm"1): 3337, 3144, 3061, 2928, 1669, 1653, 1632, 1621, 1612, 1597, 1568, 1556, 1521, 1498, 1437, 1388, 1339, 1310, 1278, 1248, 1 194, 1 103, 1076, 909, 899, 752, 688.
Example 3
The compound with formula 2, in which Ri is a alkyl group: -CH3 and R2 is -H.
Acetoacetanilide (354.8 mg, 2.00 mmol) and benzhydrazide (136.5 mg, 1.00 mmol) were dissolved in 40 cm3 of ethanol. The solution was heated to reflux under argon atmosphere for 10 min. Vanadium(IV) oxide (664.6mg, 4.00 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 20 min. Then, the vanadium(IV) oxide was filtered and the filtrate was allowed to crystallize at room temperature. After several days the product was precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 30.5 mg. Elemental analysis data calculated for C27H24N403: C - 71.67%, H - 5.35%, N - 12.20%. Experimental data derived by elemental analysis: C - 71.00%, H - 5.40%, N - 12.30%. Mp. 280.0 - 282.0°C. Experimental data derived by IR (cm"1): 3337, 3144, 3061, 2928, 1669, 1653, 1632, 1621, 1612, 1597, 1568, 1556, 1521, 1498, 1437, 1388, 1339, 1310, 1278, 1248, 1 194, 1103, 1076, 909, 899, 752, 688. Example 4
The compound with formula 2, in which R\ is a alkyl group: -CH3 and R2 is -H.
Acetoacetanilide (354.2 mg, 2.00 mmol) and benzhydrazide (136.1 mg, 1.00 mmol) were dissolved in 40 cm of ethanol. The solution was heated to reflux under argon atmosphere for 15 min. Vanadium(V) oxide (1486.0 mg, 8.16 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 30 min. Then, the vanadium(V) oxide was filtered and the filtrate was allowed to crystallize at room temperature. After several days the product was precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 108.6 mg. Elemental analysis data calculated for C27H24N403: C - 71.67%, H - 5.35%, N - 12.20%. Experimental data derived by elemental analysis: C - 71.43%, H - 5.40%, N - 12.36%. Mp. 280.0 - 282.0°C. Experimental data derived by IR (cm"1): 3337, 3144, 3061, 2928, 1669, 1653, 1632, 1621, 1612, 1597, 1568, 1556, 1521, 1498, 1437, 1388, 1339, 1310, 1278, 1248, 1194, 1103, 1076, 909, 899, 752, 688.
Example 5
The compound with formula 2, in which R\ is a alkyl group: -CH3 and R2 is -CI.
Acetoacetanilide (1772.0 mg, 10.00 mmol) and 4-chlorobenzhydrazide (852.4 mg, 5.00 mmol) were dissolved in 100 cm of ethanol. The solution was heated to reflux under argon atmosphere for 10 min. Vanadyl sulphate monohydrate (906.1 mg, 5.00 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 30 min. Then, the solution was allowed to crystallize at room temperature. After several days the crystals of product were precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 1450.0 mg. Elemental analysis data calculated for C27H23C1N403: C - 66.60%, H - 4.76%, N - 11.51%. Experimental data derived by elemental analysis: C - 66.09%, H - 4.97%, N - 11.30%. Mp. 264.8 - 266.8°C. Experimental data derived by IR (cm"1): 3334, 3138, 2916, 1657, 1635, 1611, 1596, 1569, 1557, 1524, 1497, 1488, 1439, 1387, 1342, 1295, 1279, 1247, 1 193, 1 107, 1074, 1016, 911, 900, 847, 755, 697, 686, 667. A single crystal was selected from the resulting material for the rentgenostructural analysis. Diffraction data obtained for single crystal allowed for the spatial structure determination. Crystallographic data for the compound are presented in Table 2.
Table 2 empirical formula C27H23C1N403
molecular weight 486.94
crystal size (mm) 0.39 x 0.20 x 0.08
crystallographic system triclinic
space group P T
a (A) 7.257(5)
b (A) 12.602(5)
c (A) 13.243(5)
a (°) 101.341(5)
β (°) 101.240(5)
γ (°) 97.537(5)
V (A3) 1 146.5(10)
z 2
T (K) 110(2)
Dc (Mg/m3) 1.41 1
μ (mm"1) 0.206
measured reflections 15045
symmetry independent reflections 4744
observed reflections [Ι>2σ(Ι)] 4191
R factors [Ι>2σ(Ι)] R = 0.0361
wR2 = 0.0857
S 1.021
Example 6
The compound with formula 2, in which Ri is a alkyl group: -CH2-CH2-CH2-CH2-CH3 and R2 is -H.
3-oxo-N-phenyl-octanamide (466.7 mg, 2.00 mmol) and benzhydrazide (136.4 mg, 1.00 mmol) were dissolved in 40 cm of ethanol. The solution was heated to reflux under argon atmosphere for 20 min. Vanadium(V) oxide (741.6 mg, 4.076 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 40 min. Then, the vanadium(V) oxide was filtered and the filtrate was allowed to crystallize at room temperature. After several days the crystals of product were precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 106.2 mg. Elemental analysis data calculated for C35H40N4O3: C - 74.44%, H - 7.14%, N - 9.92%. Experimental data derived by elemental analysis: C - 74.02%, H - 7.07%, N - 10.12%. Mp. 295.7 - 297.0°C. Experimental data derived by IR (cm"1): 3238, 3059, 2958, 2928, 2856, 1667, 1633, 1598, 1538, 1499, 1439, 1380, 1303, 1287, 1254, 1 117, 1074, 914, 897, 749, 690, 631.
Example 7
The compound with formula 2, in which Ry is a alkyl group: -CH3 and R2 is -NH2.
Acetoacetanilide (1773.1 mg, 10.00 mmol) and 4-aminobenzhydrazide (755.1 mg, 5.00 mmol) were dissolved in 100 cm of ethanol. The solution was heated to reflux under argon atmosphere for 20 min. Vanadyl sulphate monohydrate (905.6 mg, 5.00 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 40 min. Then, VOS04-H20 was filtered and the filtrate was allowed to crystallize at room temperature. After several days the crystals of product were precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 625.0 mg. Elemental analysis data calculated for C27H25N503: C - 69.36%, H - 5.39%, N - 14.98%. Experimental data derived by elemental analysis: C - 68.57%, H - 5.48%, N - 14.64%). Mp. 310.0 - 313.0°C. Experimental data derived by IR (cm"1): 3374, 3354, 3303, 3222, 3149, 3051, 2969, 1657, 1629, 1599, 1568, 1555, 1526, 1498, 1440, 1391, 1340, 1312, 1286, 1251 , 1 184, 1 135, 1 106, 1075, 912, 841, 751 , 696, 627.
Example 8
The compound with formula 2, in which R\ is a alkyl group: -CH3 and R2 is -OCH3.
Acetoacetanilide (355.1 mg, 2.00 mmol) and 4-methoxybenzhydrazide (338.0 mg, 2.03 mmol) were dissolved in 50 cm of ethanol. The solution was heated to reflux under argon atmosphere for 20 min. Vanadyl acetylacetonate (526.0 mg, 2.00 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 20 min. Then, the solution was allowed to crystallize at room temperature. After several days the product was precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 130.0 mg. Elemental analysis data calculated for C28H26N404: C - 69.70%), H - 5.43%), N - 1 1.61%. Experimental data derived by elemental analysis: C - 68.88%, H - 5.42%, N - 10.96%. Mp. 240.9 - 242.4°C. Experimental data derived by IR (cm"1): 3328, 3140, 3055, 2930, 2840, 1670, 1652, 1638, 1607, 1597, 1554, 1528, 1511, 1497, 1441, 1420, 1387, 1312, 1291, 1263, 1 175, 1032, 912, 898, 842, 751, 687.
A single crystal was selected from the resulting material for the rentgenostructural analysis. Diffraction data obtained for single crystal allowed for the spatial structure determination. Crystallographic data for the compound are presented in Table 3.
Table 3 empirical formula C28H26N404
molecular weight 482.53
crystal size (mm) 0.73 x 0.55 x 0.24
crystallographic system triclinic
space group P T
a (A) 7.438(5)
b (A) 12.618(5)
c (A) 13.321(5)
(°) 102.105(5)
β (°) 101.383(5)
γ (°) 94.903(5)
V (A3) 1 187.8(10)
z 2
T (K) 1 10(2)
Dc (Mg m3) 1.349
μ (mm"1) 0.0926
measured reflections 15495
symmetry independent reflections 4938
observed reflections [Ι>2σ(Ι)] 3834
R factors [Ι>2σ(Ι)] R = 0.0423
wR2 = 0.0913
S 1.033
Example 9
The compound with formula 2, in which R\ is a alkyl group: -C¾ and R2 is -OH.
Acetoacetanilide (1772.3 mg, 10.00 mmol) and 4-hydroxybenzhydrazide (761.0 mg, 5.00 mmol) were dissolved in 100 cm3 of ethanol. The solution was heated to reflux under argon atmosphere for 15 min. Vanadyl sulphate monohydrate (904.8 mg, 5.00 mmol) was added to the solution. The solution was heated to reflux under argon atmosphere for further 20 min. Then,
Figure imgf000011_0001
was filtered and the filtrate was allowed to crystallize at room temperature. After several days the crystals of product were precipitated. The resulting compound was filtered, washed with ethanol and allowed to air dry. Weight of the obtained compound was 900.0 mg. Elemental analysis data calculated for C27H24N404: C - 69.22%, H - 5.16%, N - 11.96%. Experimental data derived by elemental analysis: C - 68.42%, H - 5.33%, N - 10.68%. Mp. 311.0 - 313.0°C. Experimental data derived by IR (cm"1): 3308, 3152, 2981, 1662, 1638, 1629, 1609, 1598, 1586, 1568, 1554, 1526, 1500, 1443, 1391, 1338, 1314, 1280, 1253, 1219, 1 195, 1176, 1100, 1076, 915, 902, 850, 754, 695, 624.

Claims

12 i—C„'<J I JI J J J' 1 1 -J Claims
1. Pyrrole derivatives with the general formula 2:
Figure imgf000013_0001
Formula 2 in which: Ri is alkyl group C\ - C10, straight or branched, R2 is -H, -CI, -OH, -NH2 or -OCH3.
2. A method of pyrrole derivatives preparation with the general formula 2 with the use of ketoanilide and metal compound as catalyst, characterized in that the ketoanilide with the general formula 3:
Figure imgf000013_0002
Formula 3 in which Ri is alkyl group Q - C10, straight or branched, is reacted with hydrazide with the general formula 4:
Formula 4
Figure imgf000013_0003
in which R2 is -H, -CI, -OH, -NH2 or -OCH3, using a vanadium compound as a reaction promoter, wherein. 0.5 mole - 1 mole of hydrazide and 0.5 - 4 mole of vanadium compound are used per 1 mole of ketoanilide.
3. The method according to claim 2, characterized in that simple vanadium salt, vanadium complexes or vanadium oxides are used as a vanadium compound.
4. The method according to claim 3, characterized in that, vanadyl sulphate is used as a vanadium salt.
5. The method according to claim 3, characterized in that vanadyl acetylacetonate is used as a vanadium salt.
6. The method according to claim 2 or 3, characterized in that V204 and V205 are used as vanadium oxides.
7. The method according to claim 2, characterized in that the reaction is carried out n organic or aqueous-organic solvent.
8. The method according to claim 7, characterized in that, alcohol is used as an organic solvent.
9. The method according to claim 2 or 7, characterized in that the reaction is carried out at temperatures from 20°C up to the boiling point of the reaction mixture.
10. The method according to claim 2, characterized in that the reaction is carried out in aerobic or anaerobic conditions.
11. The method according to claim 10, characterized in that the reaction is carried out in inert atmosphere.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4282242A (en) 1980-03-07 1981-08-04 Pfizer Inc. Antidiabetic pyrrolecarboxylic acids
EP0300688A1 (en) * 1987-07-21 1989-01-25 FISONS plc Pyrrole derivatives, process for their preparation and pharmaceutical compositions containing them
WO2000001688A1 (en) 1998-07-02 2000-01-13 Sankyo Company, Limited Five-membered heteroaryl compounds

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4282242A (en) 1980-03-07 1981-08-04 Pfizer Inc. Antidiabetic pyrrolecarboxylic acids
EP0300688A1 (en) * 1987-07-21 1989-01-25 FISONS plc Pyrrole derivatives, process for their preparation and pharmaceutical compositions containing them
WO2000001688A1 (en) 1998-07-02 2000-01-13 Sankyo Company, Limited Five-membered heteroaryl compounds

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
0. A. ATTANASI; P. FILIPPONE; F. R. PERRULLI; S. SANTEUSANIO, TETRAHEDRON, vol. 57, 2001, pages 1387 - 1394
ATTANASI ET AL: "Effect of Metal Ions in Organic Synthesis", ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL: THE NEW JOURNAL FOR ORGANIC SYNTHESIS, ORGANIC PREPARATION AND PROCEDURES CO., NEWTON HIGHLANDS, MA, US, vol. 18, no. 1, 1986, pages 1 - 5, XP009174675, ISSN: 0030-4948 *
B. FRANEK; A. NONN, ANGEW. CHEM. INT. ED. ENGL., vol. 34, 1995, pages 1795 - 1811
CHEM. ABSTR., vol. 95, 1981, pages 187068E
E. BELLUR; 1. FREIFELD; P. LANGER, TETRAHEDRON LETT., vol. 47, 2005, pages 2151 - 2154
E. SHADPOUR, M.; B. SHEIKHOLESLAMI, IRIAN POLYMER JOURNAL, vol. 7, 1998, pages 121 - 128
G. DAIDONE.; B. MAGGIO; D. SCHILLACI, PHARMAZIE, vol. 45, 1990, pages 441 - 442
H. M. MESHRAM.; B. R. V. PRASAD; D. DAVIS; K. BOWEN; H. XU; V. VELVADAPU; C. BALLARD, TETRAHEDRON, vol. 64, 2008, pages 4174 - 4182
J. L. SESSLER; S. J. WEGHOM: "Expanded, contracted and Isomeric Porphyrins", 1997, PERGAMON
K. M. SMITH: "Porphyrins and Mettalloporphirins", 1975, ELSEVIER
O. A. ATTANASI ET AL.: "Regioselective Synthesis of Stable 2-(Trifluoromethyl)-2,3-dihydro-1H-pyrrol-2-ols and Derived Fluorinated Heterocycles", SYNTHESIS, no. 12, 25 September 2001 (2001-09-25), pages 1837 - 1845, XP002717280 *
O. A. ATTANASI ET AL.: "Solid-phase synthesis of 4-triphenylphosphoranylidene-4,5- dihydropyrazol-5-ones, 4-aminocarbonyl-pyrroles, 4-methoxy-1H-pyrazol-5(2H)-ones and 2-thiazolin-4-ones from polymer-bound 1,2-diaza-1,3-butadienes", TETRAHEDRON, vol. 57, no. 27, 2001, pages 5855 - 5863, XP002717279, ISSN: 0040-4020 *
O. ATTANASI ET AL.: "Effect of metal ions in organic synthesis; part XXIII. Easy and high-yield direct synthesis of 3-(aminocarbonyl)-1-ureidopyrroles by the copper(II) chloride-catalyzed reaction of aminocarbonylazoalkenes with 3-oxoalkanamides", SYNTHESIS, no. 8, 1984, pages 671 - 672, XP002717278, ISSN: 0039-7881 *
P. MATHEW; C. V. ASOKAN, TETRAHEDRON, vol. 62, 2006, pages 1708 - 1716
S. MAITI; S. BISWAS; U. JANA, J ORG. CHEM., vol. 75, 2010, pages 1674 - 1683

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