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PhCOCl-Py/Basic Alumina as a Versatile Reagent for Benzoylation in Solvent-Free Conditions

Department of Chemistry, University of Jammu, Jammu-180 006, India
Author to whom correspondence should be addressed.
Molecules 2003, 8(4), 374-380;
Received: 9 December 2002 / Revised: 13 January 2003 / Accepted: 31 March 2003 / Published: 30 April 2003


A solvent-free procedure using PhCOCl-Py/basic alumina under microwave irradiation has been developed for N-, O- and S-benzoylation.


Benzoylation is an important transformation in Organic Synthesis [1]. A number of reagents can be used for carrying out this reaction, such as benzoyl chloride [1], benzoic anhydride [2], benzoyltetrazole [3], 2-benzoyl-1-methylpyridinium chloride [4], S-benzoic-O,O-diethylphosphoro-dithoic anhydride [5], benzoyl cyanide [6], etc. Though benzoyl chloride may be a health hazard due to its toxicity, nevertheless it is widely used because of its ready availability and low cost. The reaction is usually catalyzed by bases like pyridine, triethylamine and sodium hydroxide [7].
Recently, organic reactions on solid supports [8], and those assisted by microwaves, especially under solvent-free conditions [9], have attracted much attention because of their enhanced selectivity, milder reaction conditions and associated ease of manipulation. Recently, we have reported an acetylation using Ac2O-py/basic alumina [10a]. Acetyl chloride did not work under these conditions, consequently development of a solvent-free protocol, meeting Green Chemistry principles is desirable.

Results and Discussion

For the aforementioned reasons, and in light of our general interest in using microwaves for the development of environmentally friendlier synthetic alternatives [10], we became interested in an expeditious synthesis of these compounds. We now report a simple procedure for the benzoylation of amino, hydroxy and thiol groups under solvent-free conditions using PhCOCl-Py/basic alumina.
Benzoylation of aniline using benzoyl chloride over different solid supports in presence of various catalysts was studied in order to select the most efficient combination (Table 1). In order to optimize the results, we also carried out benzoylation of aniline under different conditions by testing various molar ratios and amounts of support. From the results it is clear that PhCOCl-Py/basic alumina was the most efficient reagent and that a ratio of 1 mmole of the substrate, 2 mmole of PhCOCl, 0.6 mmole of pyridine and 2 gm of support gave optimum results, hence we have extended the use of this reagent and conditions for the benzoylation of –NH2, -OH and –SH groups (Table 2).
Table 1. Preparation of benzanilide from aniline using various reagents (power=300 W)
Table 1. Preparation of benzanilide from aniline using various reagents (power=300 W)
Reaction Tempb
PhCOCl/Acidic Al2O3852-5464
PhCOCl-Py/Basic Al2O3192-94100
Notes: a Time at which maximum yield was obtained.b Final temperature was measured by immersing a glass thermometer into the reaction mixture at the end of exposure to microwave irradiation and gives the approximate temperature range.c Yield of isolated products.
Further, the support can be reused several times without loss of activity. The method is environmentally friendly as hydrochloric acid (the by-product) remains adsorbed on the basic alumina and does not escape into the atmosphere. The method can be used for selective mono and dibenzoylation (cf. Table 2, entries 19, 20, 21, 22 and 33, 34).
Table 2. Microwave-assisted N-, O- and S-benzoylations using PhCOCl-Py/basic alumina (power = 300W).
Table 2. Microwave-assisted N-, O- and S-benzoylations using PhCOCl-Py/basic alumina (power = 300W).
EntryReactantProductTemperaturea (°C)Time (min)Yieldb (%)m.p./Lit. m.p. (°C)
1AnilineBenzanilide92-941100162-3/164-6 [11]
22-Nitroaniline2-Nitrobenzanilide85-8728796-7/98 [12]
33-Nitroaniline3-Nitrobenzanilide94-96560155-6/157 [12]
44-Nitroaniline4-Nitrobenzanilide99-100692198-9/199 [12]
52-Anisidine2-Methoxybenzanilide134-3636058-59/60 [12]
64-Anisidine4-Methoxybenzanilide100-02265153-54/154 [12]
73-Toluidine3-Methylbenzanilide84-86194124-5/125 [12]
84-Toluidine4-Methylbenzanilide84-86255156-7/158 [12]
9PiperazineN-Benzoylpiperazine94-96155194-5/196 [12]
10PiperidineN-Benzoylpiperidine91-931.570317/320-21 [13]c
11MorpholineN-Benzoylmorpholine103-0526473-4/74-5 [13]
12BenzylamineN-Benzoylbenzylamine104-06193104-5/105-6 [13]
13CyclohexylamineN-Benzoylcyclohexyl-amine96-98179145-6/147 [12]
14PhenolPhenylbenzoate109-1147468-9/69-72 [11]
153-Cresol3-Methylphenyl-benzoate128-3067052-53/55 [11]
164-Cresol4-Methylphenylbenzoate98-10057170-71/71 [11]
174-Hydroxybenzoic acid4-Benzoyloxybenzoic acid81-83369220-21/221-23 [13]
18Vanillin4-Benzoyloxy-3-methoxy benzaldehyde97-9946477-78/78 [12]
19Resorcinol3-Hydroxyphenyl-benzoate41-43965134/135-7 [13]
20Resorcinol1,3-Dibenzoyloxy-benzene92-94955115-17/117 [13]
21Resacetophenone4-Benzoyloxy-2-Hydroxy-acetopheneone74-76759105-6/106-7 [13]
22Resacetophenone2,4-Dibenzoyloxyaceto phenone78-8086578-9/80-1 [13]
232-Nitrophenol2-Nitrophenylbenzoate98-10076049-50/50 [12]
244-Nitrophenol4-Nitrophenylbenzoate74-76665139-40/142 [12]
251-Naphthol1-Benzoyloxy-naphthalene108-1046254-5/56 [12]
262-Naphthol2-Benzoyloxy-naphthalene104-06260105-06/107 [12]
27EthylenediamineN,N-Dibenzoylethylene-diamine112-14239242-43/244 [13]
292-Amino-4-(4-bromo-phenyl)thiazole 2-(N-Benzoylamino)-4-(4-bromophenyl)thiazole81-83299115-16
332-Aminobenzene-thiol1-Thiobenzoyloxy-2-N-benzoylaminobenzene98-100260153-4/154-5 [13]
Notes: a Final temperature was measured by immersing a glass thermometer in the reaction mixture at the end of the exposure to microwave irradiation and gives an approximate temperature range.b Yield of isolated productsc Boiling point
Figure 1. Effect of microwave power on the benzoylation of aniline and 2-nitroaniline
Figure 1. Effect of microwave power on the benzoylation of aniline and 2-nitroaniline
Molecules 08 00374 g001
Further, the reaction has been carried out at different power levels from 80-800 watts in the cases of aniline and 2-nitroaniline in order to select the more appropriate power level. The results are shown graphically in Figure 1. It is clear that power level of 300 W gave the maximum yield.


A rapid, economic and environmentally friendly method has been developed for benzoylation of -NH2, -OH and –SH groups using PhCOCl-Py/basic alumina. The reagent system described here may be a good alternative to well known methods since the benzoylation proceeds expeditiously with high yields under solvent-free conditions.



Melting points were recorded on a Toshniwal melting point apparatus and are uncorrected. All reactions were carried out in a commercially available BPL BMO 800T domestic microwave oven having a maximum power output of 800 W operating at 2450 MHz. IR spectra were obtained on a Hitachi 270-30 spectrophotometer using KBr discs. 1H-NMR spectra were recorded using a JNM-PMX 60 NMR Spectrometer (60 MHz). Mass spectra were recorded using JEOL D-300 spectrometer.

General Synthetic Procedure

Substrate (2 mmole), benzoyl chloride (4 mmole), pyridine (0.6 mmole) and basic alumina (2 g) were added in a 50 mL beaker. The mixture was stirred to obtain a free flowing powder, which was irradiated in a microwave oven at 300 W for an appropriate time (Table 2, as monitored by TLC). After cooling to room temperature, the product was extracted with methylene chloride (3 x15 mL). The combined extracts were washed with water and dried over sodium sulfate. The product obtained after removal of solvent under reduced pressure was crystallized from a suitable solvent (EtOAc-pet. ether; EtOH). The structure of the products was confirmed by 1H-NMR, IR and mass spectral data and comparison with authentic samples prepared according to literature methods.

Spectral and Analytical Data of Selected Compounds

2-(N-Benzoylamino)-4-phenylthiazole (entry 28): IR cm-1: 1586 (C=N), 1720 (COPh); 1H-NMR (CDCl3+ DMSO-d6): δ 5.06 (bs, 1H, NH, exchangeable with D2O), 7.1-7.8 (m, 11H, Harom); m/z(%): M+ 280 (77.5); Anal. calcd. for C16H12N2OS: C, 68.57; H, 4.28; N, 10.00. Found: C, 68.53; H, 4.25; N, 9.98.
2-(N-Benzoylamino)-4-(4-bromophenyl)thiazole (entry 29): IR cm-1: 1590 (C=N), 1722 (COPh); 1H-NMR (CDCl3+ DMSO-d6): δ 4.95 (bs, 1H, NH, exchangeable with D2O), 7.06-8.0 (m, 10H, Harom); m/z(%): M+ 359 (40.2); Anal. calcd. for C16H11BrN2OS: C, 53.48; H, 3.06; N, 7.79. Found: C, 53.43; H, 3.02; N, 7.75.
2-(N-Benzoylamino)-4-(4-chlorophenyl)thiazole (entry 30): IR cm-1: 1582 (C=N), 1720 (COPh); 1H-NMR (CDCl3+ DMSO-d6): δ 4.89 (bs, 1H, NH, exchangeable with D2O), 7.26-8.5 (m, 10H, Harom); m/z(%): M+ 314 (37.5); Anal. calcd. for C16H11ClN2OS: C, 61.04; H, 3.49; N, 8.90. Found: C, 61.07; H, 3.43; N, 8.95.
2-(N-Benzoylamino)-4-(4-fluorophenyl)thiazole (entry 31): IR cm-1: 1596 (C=N), 1730 (COPh); 1H-NMR (CDCl3+ DMSO-d6): δ 5.41 (bs, 1H, NH, exchangeable with D2O), 7.1-8.6 (m, 10H, Harom); m/z(%): M+ 298 (53.1); Anal. calcd. for C16H11FN2OS: C, 64.42; H, 3.69; N, 9.39. Found: C, 64.39; H, 3.75; N, 9.33.
1-Thiobenzoyloxy-2-aminobenzene (entry 32): IR cm-1: 3300, 3469 (NH2), 1730 (COPh); 1H-NMR (CDCl3+ DMSO-d6): δ 7.1-8.5 (m, 9H, Harom), 9.16 (bs, 2H, NH2, exchangeable with D2O); m/z (%): M+ 229 (53.1); Anal. calcd. for C13H11NOS: C, 68.12; H, 4.80; N, 6.11. Found: C, 68.09; H, 4.75; N, 6.08.


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Paul, S.; Nanda, P.; Gupta, R. PhCOCl-Py/Basic Alumina as a Versatile Reagent for Benzoylation in Solvent-Free Conditions. Molecules 2003, 8, 374-380.

AMA Style

Paul S, Nanda P, Gupta R. PhCOCl-Py/Basic Alumina as a Versatile Reagent for Benzoylation in Solvent-Free Conditions. Molecules. 2003; 8(4):374-380.

Chicago/Turabian Style

Paul, Satya, Puja Nanda, and Rajive Gupta. 2003. "PhCOCl-Py/Basic Alumina as a Versatile Reagent for Benzoylation in Solvent-Free Conditions" Molecules 8, no. 4: 374-380.

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