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Synthesis and antibacterial activity of novel 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide derivatives.

Kethireddy S, Eppakayala L, Maringanti TC - Chem Cent J (2015)

Bottom Line: The structures of the synthesized compounds were confirmed by (1)H, (13)C NMR, Mass and IR spectral data.These compounds also exhibited excellent antibacterial activity with zone of inhibition 22-25 mm against P. aeruginosa (Gram negative bacteria) and S. pyogenes (Gram positive bacteria).Synthesized and recorded antibacterial activity of some new 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives.Graphical abstract:Synthesis of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide derivatives.

View Article: PubMed Central - PubMed

Affiliation: Geethanjali College of Engineering and Technology, Keesara, Rangareddy, 501301 Telangana India ; Mahatma Gandhi Institute of Technology, Gandipet, Hyderabad, 500 075 Telangana India.

ABSTRACT

Background: The intensely increasing multi-drug resistant microbial infections have encouraged the search for new antimicrobial agents. Hydrazone derivatives are known to exhibit a wide variety of biological activities including anti-microbial. In heterocyclic moiety, imidazo[1,2-a]pyrimidines are the subject of immense interest for their antimicrobial activity and also for their analgesic, antipyretic and anti-inflammatory properties.

Results: Condensation of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 7 with aromatic aldehydes a-k in ethanol at reflux led to the generation of hydrazone derivatives 8a-k in 80-92% yield. The synthesis of carbohydrazide 7 was accomplished in six steps from commercially available 2-amino pyrimidine. The structures of the synthesized compounds were confirmed by (1)H, (13)C NMR, Mass and IR spectral data. All the synthesized hydrazone derivatives 8a-k were tested in vitro for their antibacterial activity. Compounds 8d, 8e and 8f exhibited excellent antibacterial activity with zone of inhibition 30-33 mm against E. coli (Gram negative bacteria) and S. aureus (Gram positive bacteria). These compounds also exhibited excellent antibacterial activity with zone of inhibition 22-25 mm against P. aeruginosa (Gram negative bacteria) and S. pyogenes (Gram positive bacteria).

Conclusion: Synthesized and recorded antibacterial activity of some new 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives.Graphical abstract:Synthesis of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide derivatives.

No MeSH data available.


Related in: MedlinePlus

Synthesis of 5,6,7,8-tetrahydro-imidazo [1,2-a]pyrimidine-hydrazone derivatives 8a–k. Reagents and conditions: a 1,1,3-trichloro acetone, NaHCO3, EtOH, reflux, 10 h; b CaCO3, water, reflux, 1 h; c oxone, DMF, 5°C, 2 h; d Conc; H2SO4, ethanol, reflux, 16 h; e 10% Pd–C, Ethanol, H2, 30 psi, 3 h; f hydrazine hydrate, Ethanol, reflux, 6 h; g benzaldehydes a–k, ethanol, reflux, 6 h.
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Sch1: Synthesis of 5,6,7,8-tetrahydro-imidazo [1,2-a]pyrimidine-hydrazone derivatives 8a–k. Reagents and conditions: a 1,1,3-trichloro acetone, NaHCO3, EtOH, reflux, 10 h; b CaCO3, water, reflux, 1 h; c oxone, DMF, 5°C, 2 h; d Conc; H2SO4, ethanol, reflux, 16 h; e 10% Pd–C, Ethanol, H2, 30 psi, 3 h; f hydrazine hydrate, Ethanol, reflux, 6 h; g benzaldehydes a–k, ethanol, reflux, 6 h.

Mentions: The synthesis of 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives 8a–k described in this paper were prepared according to the synthetic Scheme 1. The cyclo condensation reactions of 1,1,3-trichloro acetone with 2-aminopyrimidine 1 to 2-(dichloromethyl)imidazo[1,2-a]pyrimidine 2 was carried out in ethanol at reflux temperature for 10 h. Dichloromethyl imidazo[1,2-a]pyrimidine 2 was treated with CaCO3 in water at reflux for 1 h to produce imidazo[1,2-a]pyrimidine-2-carbaldehyde 3. The oxidation of aldehyde 3 was carried out in presence of oxone to obtain the desired imidazo[1,2-a]pyrimidine-2-carboxylic acid 4. Esterification of carboxylic acid 3 followed by the hydrogenation in presence of PtO2 at 30 psi resulted in the formation of ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxylate 6. Treatment of compound 6 with hydrazine-hydrate in ethanol at reflux temperature enabled in forming the key intermediate 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 7. Condensation of carbohydrazide 7 with various aromatic aldehydes a–k in ethanol at reflux led to the generation of hydrazone derivatives 8a–k in 80–92% yield (Scheme 1). The structures of the synthesized compounds were confirmed by 1H NMR, Mass and IR spectral data. As a representative example, the 1H NMR spectra of (E-N′-(4-(trifluoromethyl)benzylidene)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 8d is characterized as follows: the four singlets at 11.26, 8.52, 7.36 and 6.32 ppm with one proton integration corresponds to –CO–NH–N–, –N=HC–Ar, Imidazo-HC=C– and –CH2–NH– groups, respectively. The doublet signals at 7.85 and 7.78 ppm with two proton integration represents to 4-CF3 aromatic ring. The broad singlets with two proton integrations at 3.94, 3.35 and 1.95 ppm corresponds to the cyclic 5,6,7,8-tetrahydroimidazo ring. The mass spectra of the synthesized compounds showed (M+H) peaks, in agreement with their molecular formula. The IR data provided functional group evidence for the formation of the expected structures.Scheme 1


Synthesis and antibacterial activity of novel 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide derivatives.

Kethireddy S, Eppakayala L, Maringanti TC - Chem Cent J (2015)

Synthesis of 5,6,7,8-tetrahydro-imidazo [1,2-a]pyrimidine-hydrazone derivatives 8a–k. Reagents and conditions: a 1,1,3-trichloro acetone, NaHCO3, EtOH, reflux, 10 h; b CaCO3, water, reflux, 1 h; c oxone, DMF, 5°C, 2 h; d Conc; H2SO4, ethanol, reflux, 16 h; e 10% Pd–C, Ethanol, H2, 30 psi, 3 h; f hydrazine hydrate, Ethanol, reflux, 6 h; g benzaldehydes a–k, ethanol, reflux, 6 h.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4582076&req=5

Sch1: Synthesis of 5,6,7,8-tetrahydro-imidazo [1,2-a]pyrimidine-hydrazone derivatives 8a–k. Reagents and conditions: a 1,1,3-trichloro acetone, NaHCO3, EtOH, reflux, 10 h; b CaCO3, water, reflux, 1 h; c oxone, DMF, 5°C, 2 h; d Conc; H2SO4, ethanol, reflux, 16 h; e 10% Pd–C, Ethanol, H2, 30 psi, 3 h; f hydrazine hydrate, Ethanol, reflux, 6 h; g benzaldehydes a–k, ethanol, reflux, 6 h.
Mentions: The synthesis of 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives 8a–k described in this paper were prepared according to the synthetic Scheme 1. The cyclo condensation reactions of 1,1,3-trichloro acetone with 2-aminopyrimidine 1 to 2-(dichloromethyl)imidazo[1,2-a]pyrimidine 2 was carried out in ethanol at reflux temperature for 10 h. Dichloromethyl imidazo[1,2-a]pyrimidine 2 was treated with CaCO3 in water at reflux for 1 h to produce imidazo[1,2-a]pyrimidine-2-carbaldehyde 3. The oxidation of aldehyde 3 was carried out in presence of oxone to obtain the desired imidazo[1,2-a]pyrimidine-2-carboxylic acid 4. Esterification of carboxylic acid 3 followed by the hydrogenation in presence of PtO2 at 30 psi resulted in the formation of ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxylate 6. Treatment of compound 6 with hydrazine-hydrate in ethanol at reflux temperature enabled in forming the key intermediate 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 7. Condensation of carbohydrazide 7 with various aromatic aldehydes a–k in ethanol at reflux led to the generation of hydrazone derivatives 8a–k in 80–92% yield (Scheme 1). The structures of the synthesized compounds were confirmed by 1H NMR, Mass and IR spectral data. As a representative example, the 1H NMR spectra of (E-N′-(4-(trifluoromethyl)benzylidene)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 8d is characterized as follows: the four singlets at 11.26, 8.52, 7.36 and 6.32 ppm with one proton integration corresponds to –CO–NH–N–, –N=HC–Ar, Imidazo-HC=C– and –CH2–NH– groups, respectively. The doublet signals at 7.85 and 7.78 ppm with two proton integration represents to 4-CF3 aromatic ring. The broad singlets with two proton integrations at 3.94, 3.35 and 1.95 ppm corresponds to the cyclic 5,6,7,8-tetrahydroimidazo ring. The mass spectra of the synthesized compounds showed (M+H) peaks, in agreement with their molecular formula. The IR data provided functional group evidence for the formation of the expected structures.Scheme 1

Bottom Line: The structures of the synthesized compounds were confirmed by (1)H, (13)C NMR, Mass and IR spectral data.These compounds also exhibited excellent antibacterial activity with zone of inhibition 22-25 mm against P. aeruginosa (Gram negative bacteria) and S. pyogenes (Gram positive bacteria).Synthesized and recorded antibacterial activity of some new 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives.Graphical abstract:Synthesis of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide derivatives.

View Article: PubMed Central - PubMed

Affiliation: Geethanjali College of Engineering and Technology, Keesara, Rangareddy, 501301 Telangana India ; Mahatma Gandhi Institute of Technology, Gandipet, Hyderabad, 500 075 Telangana India.

ABSTRACT

Background: The intensely increasing multi-drug resistant microbial infections have encouraged the search for new antimicrobial agents. Hydrazone derivatives are known to exhibit a wide variety of biological activities including anti-microbial. In heterocyclic moiety, imidazo[1,2-a]pyrimidines are the subject of immense interest for their antimicrobial activity and also for their analgesic, antipyretic and anti-inflammatory properties.

Results: Condensation of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 7 with aromatic aldehydes a-k in ethanol at reflux led to the generation of hydrazone derivatives 8a-k in 80-92% yield. The synthesis of carbohydrazide 7 was accomplished in six steps from commercially available 2-amino pyrimidine. The structures of the synthesized compounds were confirmed by (1)H, (13)C NMR, Mass and IR spectral data. All the synthesized hydrazone derivatives 8a-k were tested in vitro for their antibacterial activity. Compounds 8d, 8e and 8f exhibited excellent antibacterial activity with zone of inhibition 30-33 mm against E. coli (Gram negative bacteria) and S. aureus (Gram positive bacteria). These compounds also exhibited excellent antibacterial activity with zone of inhibition 22-25 mm against P. aeruginosa (Gram negative bacteria) and S. pyogenes (Gram positive bacteria).

Conclusion: Synthesized and recorded antibacterial activity of some new 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives.Graphical abstract:Synthesis of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide derivatives.

No MeSH data available.


Related in: MedlinePlus