Abstract: A facile synthesis of title compounds has been carried out under ultrasound irradiation. The main advantages of the present procedure are shorter reaction time and higher yield. Products have been characterized by IR, PMR, CMR, GCMS study and screened for their antimicrobial activity

Bhausaheb Karale

Charnshing Gill

Mahendra Sonawane

Sharad Shelke

English

Nature Precedings

 1 
 
Ultrasonicated synthesis of 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-ones and their 
antimicrobial screening 
 
Sharad N. Shelkea*, Mahendra P. Sonawanea, Bhausaheb K. Karalea and  
Charnshing H. Gillb 
a P.G. Department of Chemistry, S.S.G.M. College, Kopargaon (M.H.), 423 601, India.   E-mail: 
snshelke@yahoo.co.in 
b Department of chemistry, Dr. B. A. M. University, Aurangabad, India. 
 
Abstract: A facile synthesis of title compounds has been carried out under ultrasound irradiation. 
The main advantages of the present procedure are shorter reaction time and higher yield. Products 
have been characterized by IR, PMR, CMR, GCMS study and screened for their antimicrobial 
activity.  
Keywords: Ultrasonication, 3-formylchromone, enaminiketone, bioactivity.    
 
Among the different functionalized chromones, 3-formylchromones occupy a unique 
position because they can be transformed into various heterocycles by interesting reactions with 
different nucleophiles.[1] 3-Formylchromone when treated with phenyl hydrazine gives 1-phenyl-
4-(2-hydroxy benzoyl) pyrazoles,[2] whereas substituted 3-formylchromone when treated with 
pyrrolidine[3] under reflux gives 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-one. The 
enaminoketones[4] constitute an important class of synthon, which can be elaborated to a wide 
variety of heterocyclic compounds. The titled compound 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-
prop-2-en-1-ones was utilized for the synthesis of pyrazoles[3]. 
Pyrrolidine containing compounds are versatile antidiabetic, antiobesity,[5] 
anticonvulsant[6] and antibacterial agents.[7] 
The chemical applications of ultrasound, now called sonochemistry, have become an 
exciting new field of research during the last few decades.[8] The use of ultrasound irradiation 
technique for activating various reactions is well documented in the literature such as synthesis of 
azoles and diazines,[9] Reformatsky reaction,[10] oxidation of substrates like hydroquinones,[11] 
conversion of nitro compounds to carbamates,[12] Pinacol coupling,[13] Ullmann condensation,[14] 
Suzuki cross-coupling[15] and various other transformations in synthetic organic chemistry.16] 
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Result and Discussion  
In view of advantages of ultrasound irradiation in organic synthesis and utility of the titled 
compound, we aimed the synthesis of 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-ones 3 
by the reaction of pyrrolidine 2 on 3-formylchromones 1 under the influence of ultrasound 
irradiation. In earlier report[3] 2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-ones have been 
prepared by time consuming conventional method require 5 hours and yield obtained was pour. 
In this communication, a number of 3-formylchromone 1 are treated with pyrrolidine 2 in dry 
ethanol under influence of ultrasound irradiation. By this method, the time required for 
completion of the reaction is less and yields are better at room temperature, hence no vigorous 
heating is required.  In general, the reactions using ultrasonication technique is very clean and 
required shorter time for completion. 
Compounds 3c and 3i were obtained in good yield within 30-35 min under ultrasonication 
Each experiment using ultrasonication technique was repeated three times to confirm the 
consistency of the results. Comparative results obtained are tabulated in the Table-I. 
Scheme:  
O
O
CHO
R1
R2
R3
OH
O
R1
R2
R3
N
Ethanol
N
H
))))))))
1 2 3  
Pyrrolidine reacts with 3-formylchromones by attacking the electron-deficient center of 
the C2 carbon, and the probable mechanism may be as follows. 
 
The required 4-oxo-4H-chromone-3-carbaldehydes 1 was prepared by Vilsmeir-Haack 
reaction from variously substituted o-hydroxyacetophenones.  
Experimental: 
All experiments under ultrasonication were carried out in bath type ultrasonicator model EN-
20U-S manufactured by Enertech Electronica Pvt., Ltd., Mumbai, India having maximum power 
output of 100W and 33 KHz operating frequency. 
 All the recorded melting points were determined in open capillary tubes and are 
uncorrected. I.R. spectra were recorded on Perkin-Elmer FTIR spectrophotometer in KBr disc. 
The 1H NMR and 13C NMR spectra were scanned on Bruker 300 MHz and 400 MHz FT 
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spectrophotometer respectively using DMSO-d6 or CDCl3 as a solvent and TMS as an internal 
standard, while mass spectra were recorded on Finnigan mass spectrometer. 
General procedure:  
1-(2-Hydroxy-phenyl)-3-pyrrolidin-1-yl-propenone 3a 
To a 100 mL RBF was added 6-chloro-4-oxo-4H-chromone-3-carbaldehyde 1a (2.08 gm, 
0.01 mol) and pyrrolidine 2 (1.42 gm, 0.02 mol) and dry ethanol (10 mL). The reaction vessel 
was then lowered into a sonication bath and sonicated for 25-40 minutes till a clear solution was 
obtained. Progress of the reaction was monitored with the help of TLC. After completion of the 
reaction the contents were poured into crushed ice and the product obtained was separated by 
filtration. The product was crystallized from alcohol. This typical experimental procedure was 
followed to prepare the compounds 3 b-i. The compounds synthesized by above procedures are 
listed in Table-I with their characterization data. IR, PMR, CMR and GC-MS data have 
confirmed their structures and agreement with those obtained for the products synthesized by 
earlier method.[3] 
 
 
Table-I: Characterization data of synthesized compounds 3 a-i. 
 
Comp. 
No. 
R1 R2 R3 Time 
(min) 
Yield 
(%) 
Melting 
Points 
(oC) 
Lit. 
Yield[3] 
(%) 
3a H H Cl 25 82 148 79 
3b H H F 28 82 170 80 
3c H H Me 30 87 174 75 
3d H Me Cl 40 80 172 70 
3e H Me H 28 79 140 65 
3f Cl H Cl 35 81 166 76 
3g Me H Me 30 80 158 75 
3h H H  H 25 82 142 74 
3i H H Et 35 84 100 80 
 
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Spectral data of representative example 3c: 
Entry 3c: 1H NMR (CDCl3, 300 MHz) δ: 1.99 (m, 4H), 2.30 (s, 3H), 3.34 (t, 2H), 3.59 (t, 
2H), 5.70 (d, 1H, J=18 Hz), 6.82 to 7.47 (m, 3H), 8.05 (d, 1H, J=18 Hz), 13.83 (s, 1H); 13H NMR 
(DMSO, 400 MHz) δ: 189.85, 160.05, 150.21, 117.02-134.10, 90.03, 52.49, 46.58, 24.59, 24.49, 
20.05; IR (KBr) cm-1: 3122, 1623, 1585 & 1544; GC-MS (70 eV) m/z: 231 (M+), 161, 70.  
Antimicrobial Screening: 
Compounds listed in Table-II were screened (doses of 100 μg) for their antibacterial activity 
against gram-ve bacteria E. coli and gram+ve bacteria S. albus using filter paper disc method. 
Plates inoculated with E. coli were incubated for 48 hr and plates inoculated with S. albus for 24 
hr respectively at RT. Streptomycin sulphate were used as a standard. Inhibition zones were 
measured in mm and results obtained are shown in Table-II. 
All these compounds were also screened (doses of 100 μg) for their antifungal activity against 
A. niger using greseofulvin as a standard. The results are shown in Table-II. 
 
Table-II:  Antimicrobial Activities of 1-(2-hydroxy-phenyl)-3-pyrrolidin-1-yl-  
                   propenones 3. 
    
Compound Inhibition zone in mm (diameter) 
 E. coli S. albus A.niger 
3a 08 12 04 
3b 08 06 04 
3c 08 06 - 
3d 06 10 - 
3f 08 10 4 
Streptomycin 
sulphate 
18 22 Not 
tested 
Griseofulvin 
 
Not tested 
 
Not 
tested 
12 
 
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Acknowledgement: 
Authors are thankful to the Principal G. T. Sangle, S.S.G.M. College, Kopargaon, 
Ahmednagar for providing necessary facilities and constant encouragement. One of the authors 
(SNS) thanks UGC, New Delhi for the award of Teacher Fellowship. 
 
References:  
 
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Chem., 20, 1437 (1983). 
2. Ghosh, C. K.; Mukhopadhyay, K. K. REACTION of 4-oxo-4H-[1]benzopyran-3-
carboxaldehyde with phenyl hydrazine and formation of 1-phenyl-4-(2-hydroxybenzoyl) 
pyrazoles. J. Indian Chem. Soc., LV, 52 (1978). 
3. Shelke, S. N.; Dalvi, N. R.; Shingare, M. S., Gill, C. H.; Karale, B. K. SYNTHESIS of 2-
(1H-pyrazol-3-yl)-phenols,  Indian J. Heterocycl. Chem., 15, 403 (2006). 
4. Mousawi, S. A.; John, E.; Kandery, N. A. SYNTHESIS and chemical reactivity of 2-(4-
dimethylamino-2-oxobut-3-enyl)-isoindole-1,3-dione and of 4-(4-dimethylamino-2-oxobut-
3-enyloxy)-2H-phthalazin-1-one. J. Heterocycl. Chem., 41 (3), 381 (2004). 
5. Cheng, T. W.; Chen, S.; Devasthale, P.; Ding, C. Z.; Herpin, T. F.; Wu, S.; Zhang, H.; 
Wang, W; Ye, X. PREPARATION of substituted heterocyclic derivatives as antidiabetic 
and antiobesity. PCT Int. Appl. WO 2004004665 A2, 543 (2004).  
6. Kwon, T.; Kwon, P.; Song, S.; Park, M.; Choi, J. SYNTHESIS and anticonvulsant 
evalution of 5-vinyl-pyrrolidin-2-ones:a potential GABA-AT inhibitor. Bull. Korean. 
Chem. Soc., 23(6), 917 (2002).  
7. Hattori, K.; Yamada, A.; Kuroda, S.; Chiba, T.; Murata, M.; Sakane, K. SYNTHESIS and 
antibacterial evalution of noval 2[N-lmidoylpyrrolidinyl] carbapenems. , Bioorg. Med. 
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9. Kidwai, M.; Venkataramanan, R.; Dave, B. POTASSIUM carbonate, a support for the 
green synthesis of azoles and diazines. J. Heterocycl. Chem., 39, 1045 (2002). 
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hydroquinones to quinones catalysed by ceric ammonium nitrate doped on metal exchange 
K-10 clay. Synthesis, 2, 198 (2003). 
11. Ross, N. A.; Bartsch, R. A. SONOCHEMICAL Reformatsky reactions of a-bromoester 
with sym-(keto)dibenzo-16-crown-5. J. Heterocycl. Chem., 38, 1255 (2001). 
12. Chandrashekhar, S.; Narsihmulu, C.; Jagadeshwar, V. ULTRASOUND promoted “onepot” 
conversion of nitro compounds to carbamates. Synlett., 5, 771 (2002). 
13. Li, J.-T.; Bian, Y.-J.; Zang, H.-J.; Li, T.-S. Pinacol coupling of aromatic aldehydes and 
ketones using magnesium in aq. ammonium chloride under ultrasound. Synth. Commun., 32 
(4), 542 (2002). 
14. Robin, M.; Pique, V.; Faure, R.; Glay, J. ULTRASONIC irradiation of the Ullmann 
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anthranilic acid derivatives. J. Heterocycl. Chem., 39, 1083 (2002). 
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coupling reactions in ionic liquid at ambient conditions. Chem. Commun., 61, 616 (2002). 
16. Shelke, S. N.; Dalvi, N. R.; Kale, S. B.; More, M. S.; Gill, C.H. and Karale, B. K. 
ENVIRONMENTALLY benign synthesis of fluorinated pyrazolone derivatives and their 
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Graphical abstract: 
 
Ultrasonicated synthesis of 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-ones and their 
antimicrobial screening 
 
Sharad N. Shelke*, Mahendra P. Sonawane, Bhausaheb K. Karale and  
Charnshing H. Gill. 
O
O
CHO
R1
R2
R3
OH
O
R1
R2
R3
N
Pyrrolidine/ethanol
))))))))
 
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a support for the green synthesis of azoles and diazines.

CHEMISTRY of 4-oxo-4H-[1]benopyran-3-carboxaldehyde.

ENVIRONMENTALLY benign synthesis of fluorinated pyrazolone derivatives and their antimicrobial activity.

Pinacol coupling of aromatic aldehydes and ketones using magnesium in aq. ammonium chloride under ultrasound.

PREPARATION of substituted heterocyclic derivatives as antidiabetic and antiobesity.

REACTION of 4-oxo-4H-[1]benzopyran-3-carboxaldehyde with phenyl hydrazine and formation of 1-phenyl-4-(2-hydroxybenzoyl) pyrazoles.

SONOCHEMICAL Reformatsky reactions of a-bromoester with sym-(keto)dibenzo-16-crown-5.

SYNTHESIS and antibacterial evalution of noval 2[N-lmidoylpyrrolidinyl] carbapenems.

SYNTHESIS and chemical reactivity of 2-(4-dimethylamino-2-oxobut-3-enyl)-isoindole-1,3-dione and of 4-(4-dimethylamino-2-oxobut3-enyloxy)-2H-phthalazin-1-one.

SYNTHESIS of 2-(1H-pyrazol-3-yl)-phenols,

ULTRASONIC irradiation of the Ullmann condensation: Application to the preparation of dioxolo, dioxino, cyclopent, and imidazolo anthranilic acid derivatives.

ULTRASOUND promoted “onepot” conversion of nitro compounds to carbamates.

ULTRASOUND-promoted Suzuki crosscoupling reactions in ionic liquid at ambient conditions.

USE of Sonication for the coupling of Sterically Hindered Substrates in the phenolic Mitsunobu Reaction.

Ultrasonicated synthesis of 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-ones and their antimicrobial screening

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Ultrasonicated synthesis of 1-(2-hydroxyaryl)-3-(pyrrolidin-1-yl)-prop-2-en-1-ones and their antimicrobial screening

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