Liu Xiuying, Qie Lujiang, Ma Zhiguang, Shan Jinhuan, Shen Shigang
(College of Chemistry & Environmental Science, Hebei University, Baoding 071002, China)
Received Apr. 8, 2002.
AbstractIn this paper, N-benzylphthalimide was firstly synthesized under microwave irradiation. The influence of some factors to the product yield, such as the proportion of reaction reagents, the irradiation time and alkaline reagents KCO-Al was investigated and the optimum experimental conditions were found. The yield of the product could attain 98% in 420s, which not only increased the yield ,but also took much shorter time than that reaction time reported by the predecessors.
The compounds of N-alkylating phthalimides are important intermediate of synthesizing the fatty primary amine and a -amino acid. The classical method is to make salt with the reaction of phthalimide and KOH, then the N-alkylating phthalimides is produced with the reaction of halogenated compound and the salt in the presence of N,N-dimethylformamide (DMF). At present some methods are reported as: the phase transfer catalytic effects of polyethylene glycols in N-alkylation; convenient synthesis of N-substituted phthalimide; the reaction of N-alkylation of phthalimide by the inorganic supported reagent[3,4]. The above reported reaction time is longer. Take the synthesis of N-benzylphthalimide as an example: the reaction time usually takes about 10h, the fastest reaction time takes 4 h and the highest yield is 94%.
In recent years, it is reported that the speed of chemical reaction by heating chemicals with microwave is times or even thousands times faster than that of general chemical reactions. Since Canadian chemist Richard Gedye and others reported to make chemical reactions with microwave oven in 1986, the studies on synthetic chemistry of using microwave technology become more and more common.This paper is reported on the study of the conditions to synthesize N-benzylphthalimide with microwave irradiation to raise the yield and speed up the reaction. It has got the better results.
2.1 Reagents and instruments
Benzyl chloride, N,N-dimethylformamide, Potassium carbonate and Aluminium oxide are all of analytical grades and Phthalimide is chemical grade. All the reagents are used without further treatment.
Microwave oven (WD75, 750W, 2450Mhz) is from Galanz Electric Limited Company of Shunde, the Infrared spectrophotometer (FTS-40) is from BIO-RAD of America, and the extractor is made by ourselves.
Melting point is tested by capillary method.
2.2 Reaction procedure
N-benzylphthalimide was synthesized with phthalimide and benzyl chloride as reaction reagents, KCO-Al used as catalyst and DMF as solvent. Under microwave irradiation, the whole process could be seen from the following equation
2.3 Preparation of supported alkaline reagent KCO-Al
30g neutral Al was added into 100ml water in which 20g KCO was dissolved and the solution was stirred continuously for 1h. at 60-65. After the water was evaporated, the product obtained was put into the oven (130) and dried for 2h. then the supported catalyst KCO-Al was got (KCO content 3mmol in each gram of catalyst).
2.4 Preparation of N-benzylphthalimide
After 1.90g phthalimide (12.5mmol) and 5g KCO-Al (15mmol) were grinded evenly, they were put into 50ml beaker containing 3.2g benzyl chloride (25mmol) and 2g DMF which were well stirred. The above mixture was put into microwave oven and irradiated continuously for 420s, then it was taken out and extracted with 70ml absolute ethanol for 1h.. The extracting solution was concentrated to about 10ml and mixed with 150ml water in a 500ml beaker. Immediately, the white crystal could be seen, then 10ml 5% aqueous NaOH was added into it and stirred for 10min to dissolve phthalimide which had not reacted. Under the reduced pressure, the white crystal was filtered and washed repeatedly with water until the pH value of it was neutral. The sample obtained was put into oven (105) for 2h and the product was obtained. The experimental results showed that the average yield could attain 98% and its mp. was 113-114, which was the same as the reference value  ,meanwhile, the infrared spectrum of the product obtained was just the same as that reported in Sadtler Spectrum Collection
3 RESULTS AND DISCUSSION
3.1 Influence of the proportion of reaction reagents to yield
The relationship between the proportion of reaction reagents and yield was shown in Table 1. When phthalimide: benzyl chloride =1:1 (molar ratio), the yield was very low; when phthalimide: benzyl chloride =1:2 (molar ratio), the maximum yield (98%) could be obtained. But when benzyl chloride was increased further, the yield did not change.
Table 1.Relationship between the proportion of reaction reagents and the yield
|No.||phthalimide: benzyl chloride (molar ratio)||average yield (%)|
5g KCO-Al and suitable DMF were added and irradiated continuously for 420s under microwave oven.
3.2 Influence of the irradiation time to the product yield
The influence of irradiating time, power and temperature to the yield were investigated in our experiments, the results showed that when the microwave oven was at 600W (the temperature reached 120), and the reaction reagents were irradiated continuously, the yield was less than 5%. When the microwave oven was at 750W (the temperature reached 150), and the reaction reagents were irradiated discontinuously, it took longer time. In this section, the influence of time to the yield in 750W microwave oven with continuous irradiation was mainly discussed and the results were given in Table 2.
Table 2. Relationship between the irradiated time and the yield
|No.||power (W)||time of irradiation (s)||average yield (%)|
5g KCO-Al and 2g DMF were added and irradiated continuously under 750W microwave oven.
As could be seen in it, the yield was 80% when the continuous irradiation time was 330s,and that was 98% when it was 420s. It should be noted that the yield decreased as the products obtained changed color or became coked if the reaction time was longer once more.
3.3 Influence of the supported alkaline reagents KCO-Al to the yield
The reagent Al was selected from Huamao Plant of Shanghai (referred as A) and No.3 Chemical Reagent Plant of Tianjin (referred as B). The two kinds of supported alkaline reagents KCO-Al (A) and KCO-Al (B) were made by the same method described above and the experiments had been separately carried out with these two kinds of alkaline reagents. The results were shown in the Table 3.
Table 3. Relationship between KCO-Al and the yield
|No.||Producer of Al||Quantity of KCO-Al (g)||Average yield (%)|
* 3.2g benzyl chloride and 2g DMF were added and irradiated continuously under 750W microwave oven for 420s
As it could be seen in Table3, the product yield could attain 98% when 5g KCO-Al (A) was used; When it was less than 5g , the yield was lower; and when it was more than 5g, the color of products would become yellow and the yield was much lower. When 5g KCO-Al (B) was added, the products would be coked. This would be caused by the larger surface of Al (B), which absorbed too much microwave energy. When KCO-Al (B) added was less than 5g, the yield was not high. The results described above showed that it was suitable to use 5g KCO-Al (A) as supported carrier in the experiment.
In the paper, N-benzylphthalimide was successfully synthesized under microwave irradiation and the optimum conditions were obtained (Phthalimide: Benzyl Chloride: KCO-Al=1:2:1.2 under continuous irradiation for 420s in 750W microwave oven with suitable amount DMF as solvent). The yield could attain 98%, it was the highest value, and the reaction time needed was only 420s, which was much shorter than the fastest time (4h) reported by others. In addition, the method was easy to operate, the inorganic supported reagent could be recovered, and the pollution could be reduced as well.