Synthesis of 5-Nitrofurfural Diacetate and 5-Nitrofurfural Semicarbazone An Undergraduate Laboratory Experiment Xiaorong Li and Qianguang Liu Shaanxi Teachers University, Xian, Shaanxi 710062, People's Republic of China
James C. Chang University of Northern Iowa, Cedar Falls. iA 50614 Nitration of aromatic compounds is a typical electrophilic substitution reaction that is discussed in all organic textbooks. Now we introduce an experiment of the nitration of furfural, which is very suitable for the undergraduate organic laboratory. This experiment demonstrates how to nitrate an aromatic compound having a n aldehyde group that can be oxidized by nitrating agents. Proton NMR is also used in this experiment to identify the important intermediate, 5nitrofurfural diacetate.
Preparation of 5-Nitrofurfural Semicarbazone About 2 g of 5-nitrofurfuraldiacetate,prepared above, is placed in 20 mL of 50%HzSOa, and the mixture is boiled gently for 1-2 min. A solution of 5-nitrofurfuralis formed. This solution is added slowly to a solution containing 1.5 g of semicarhazide hydrochloride in 100 mL of water. The mixture is stirred far -20 min, and the yellow precipitated produced is filtered, washed with water and 95% ethanol, and air-dried. The yield is 90%(mp 238-240 "C).
Preparation of 5-Nitrofurfural Dlacetate A mixture containing 4.3 mL of concentrated HNOs and 0.03 mL of concentrated HlS04 is added dropwise, with stirring, into 45 mL of acetic anhydride, cooled by an ice-salt mixture (-5 to 5 "C).Then 5.2 mL of freshly distilled furfural is added dropwise into the acid mixture, with stirring, maintaining the temperature at -5 to 5 'C during the addition. The mixture is stirred for 1h, still keeping the temperature between -5 and 5 'C. Then 40 mL of water is added to the mixture, and the mixture is stirred at room temperature for 30 min. A white precipitate fonns at this point. Then 10% NaOH solution is added to the mixture until the pH of the mixture reaches 2.5 to 2.1, and the mixture is warmed on a water bath at-55 "C for 1 h. The mixture is allowed to stand at room temperature overnight, and the white precipitate formed is filtered, washed with water, recrystallized from 95%ethanol,and air-dried. The yield is 80%(mp 88-90 "C).The proton NMR of this compound, 5-furfural diacetate, is determined.
Since the aldehyde group is easily oxidized, i t is necessary to orotect it when a n aromatic aldehvde is beine nitrated. o n e method of protection is by preparing the dyacetate of the aldehvde before nitration (1-3). In this exoerimenr. the diacetatekethod along with the use of low tekperature'and a moderate nitrating aeent, nitric acid-acetic anhvdrate mixture, is used, w i t i a'trac'e of sulfuric acid as a caialyst. The 5-nitrofurfural diacetate is isolated and identified bv proton NMR, then i t is hydrolyzed in 50% sulfuric acid, setting free the aldehyde group. The 5-nitrofurfural produced in situ is then used for further reaction-in this experiment for the preparation of the semicarbazone. In the preparation of 5-nitrofurfural semicarbazone, an antibacterial drug, there is no need t o isolate the 5-nitrofurfural from the hydrolytic solution. The entire preparation includes four steps as follows:
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B O , p H 2.5-2.7 55 T
step h
2
Step c
3
o"4~H='NH"-NH2 5
The intermediate 2 and the product 5-nitrofurfural are not isolated. The structure of the intermediate 3,5-nitrofurfural diacetate, is determined by its proton NMR, using CDC13as the solvent and TMS as the standard. The chemical shifts (in ppm) are 2.18 (singlet, 6 H), 6.74 (double doublet, 2 H), 7.30 (doublet, 2 H), and 7.71 (singlet, 1H) (see figure). The assignments are based upon the number of peaks observed and the coupling constants. The singlet at 2.18 ppm, representing six protons, is no doubt the methyl protons of the diacetate. The singlet at 7.71 ppm must be proton b (see figure), which is away from the other protons. The protons c and d split each other into doublets with a coupling constant of 3.74 Hz. This coupling constant is typical of the value of coupling constant of 3.6 Hz (4) for these two protons on a furan ring. The doublet at 7.30 ppm is
assigned to proton d because proton c is its only neighbor. The doublet at 6.74 ppm of proton c is further split slightly, probably by the weak interaction of proton b. Although the preparation of 5-nitrofurfural diacetate was made almost 50 years ago (5),the procedure was not suitable for undergraduate laboratory. Also, no proton NMR spectrum of this compound was reported. In the literature (6), the semicarbazaone was prepared by reacting semicarhazide hydrochloride directly with the diacetate in the presence of strong mineral acid. In this experiment, the diacetate is hydrolyzed first, so that the students can have an understanding of the formation of the semicarhazone, not from the diacetate but from the aldehyde, 5-nitrofurfural. Other carbazones can be formed if other carhazides are used for the reaction. Certain cautions should be observed during the preparation. In step a, the temperature of the reaction must he lower than 5 'C. An icesalt mixture can achieve this condition very easily; however, the temperature should be monitored. The furfural should be added to the nitration mixture rlowly, so that excessive heat is not produced to raise the temperature above 5 OC. In step b, the temperature should not exceed 57 O C . In step c, the hydrolsis must be stopped as soon as the oily substance in the hydrolytic solution disappears. The next reaction should be started immediately when the hydrolysis is completed. The time required for the entire experiment is 6 h. For a laboratory course with 3-h laboratory periods, the logical stopping point for the first period is the completion of the preparation of 5-nitrofurfural diacetate (step b). -
Dswy. W.:Gwilt, J.R. J. Cham.Sm. 1950.20P208. Davey. W.; Gwilt, J. R. J. Chem. SN. 1950,331&3349. Dauey, W.:Guilf, J.R.J.Chem.Soc. 1955,13861385. Silveratein, R. M.; Baaaler. G. C. Speefromatrie 1dantii;colion of Orgonie Commmda, 2nd od.: Wiley: New Ymk, 1967; p 145. 5. Gilman, H.:Wright. G. F. J . Am. Chsm. SN. 19SO,52,416S4166. Cham. Abalr. 1951,45,8S69e 6. Raffavf,R.F. U.S.Patent2,5~,173,1951:tbrough
1. 2. 3. 4.
Volume 67
Number 11
November 1990
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