BENZOIC ACID 231 6 Provide methods for preparing the following compounds by the Grignard method: (a) CH,CH,CHCH,CH, 9 on (©) CHCH,CH,CH,CH,—C—on iw on -o— 1 % Experiment 32 NITRATION OF METHYL BENZOATE Aromatic Substitution Crystallization The nitration of methyl benzoate to prepare methyl m-nitrobenzoate is an example of an electrophilic aromatic substitution reaction, in which a proton of the aromatic ring is replaced by a nitro group: i i x Z or Sock, + HONO, ey + HO “c Sy NO, Methy! mntrobenzoate substitution reactions are known to occur when an aro- matic substrate is allowed to react with a suitable electrophilic reagent, and many other groups besides nitro may be introduced into the ring You may recall that alkenes (which are electron-rich due to an excess of electrons in the 7 system) can react with an electrophilic reagent. The interme- diate formed is electron-deficient. It reacts with the nucleophile to complete the reaction. The overall sequence is called electrophilic addition. Addition of HX to cyclohexene is an example. Nucleophite oe"! [ H] H rn oe 4 [ ai x cytoneene ATTACK OF ALKENE CARBoMIUM Ion NET AoDITION (ON ELECTROPHILE (1) INTERMEDIATE oF Hx292 THE EXPERIMENTS Aromatic compounds are not fundamentally different from eyclohexene. ‘They can also react with electrophiles. However, due to resonance in the ring, the electrons of the = system are generally less available for addition reactions since an addition would mean the loss of the stabilization that resonance pro- Hides. In practice this means that aromatic compounds react only with poner- fally electrophilic reagents, usually at somewhat elevated temperatures Benzene, for example, can be nitrated at $0 °C with a mixture of concen- trated nitric and sulfuric acids; the electrophile is NO,* (nitronium ion), whose formation is promoted by action of the concentrated sulfuric acid on nitric acid =O: + HO Nite sete teontum ton The nitronium ion thus formed is sufficiently electrophilic to add to the ben- zene ring temporarily interrupting ring resonance: Ons 4. b The intermediate first formed is somewhat stabilized by resonance and does not rapidly undergo reaction with a nucleophile; in this behavior, it is different from the unstabilized carbonium ion formed from cyclohexene plus an elec trophile. In fact, aromaticity can be restored to the ring if elimination occurs instead. (Recall that elimination is often a Teaction of carbonium ions.) Re- moval of a proton, probably by HSO,-, from the sp’-ring carbon restores the aromatic system and yields a ‘net substitution wherein a hydrogen has been replaced by a nitro group. Many similar reactions are known, and they are called electrophilic aromatic substitution reactions, ‘The substitution of a nitro group for a ring hydrogen occurs with methyl benzoate in the same way it does with benzene. In principle, one might expect that any hydrogen on the ring could be replaced by a nitro group. However, for reasons beyond our scope here (see your lecture textbook), the carbomethoxy group directs the aromatic substitution preferentially to those positions that are meta to it, Asa result, methyl m-nitrobenzoate is the principal product formed. Additionally, one might expect the nitration to occur more than once on the ring, However, both the carbomethoxy group and the nitro group that has just been attached to the ring deactivate the ring against further substitution. Conse. quently, the formation of a methyl dinitrobenzoate product is much less favora. ble than the formation of the mononitration product. While the products described above are the principal ones formed in the Teaction, it is possible to obtain as impurities in the reaction small amounts of the ortho and para isomers of methyl m-nitrobenzoate and also of the dinitra: tion products. These side products are removed when the desired product is Purified by crystallization. Water has a retarding effect on the nitration since it interferes with the nitric acid-sulfuric acid equilibria that form the nitronium ions. The smaller Ch Ch ChNITRATION OF METHYL BENZOATE 233 the amount of water present, the more active the nitrating mixture. Also, the seanra) Of the nitrating mixture can be controlled by varying the amount of suffi acid used. This acid must protonate nitric acid, which is a weak base, and the larger the amount of acid available, the more numerous the protonated species (and hence NO,*) in the solution. Water interferes since it it a stronger base than H,SO, or HNO,. Temperature is also a factor in determining the Extent of nitration. The higher the temperature, the greater will be the amounts Of dinitration products formed in the reaction, SPECIAL INSTRUCTIONS Before starting this experiment you should read Technique 3. Its impor- ‘ant that the temperature of the reaction mixture be maintained at or below 15 a, Nite acid and sulfuric acid, especially when mixed, are very corrosive PROCEDURE n'a 150-mL beaker cool 12 mL of concentrated sulfuric acid to about 0 *C and add 6.1 g of methyl benzoate. Using an ice-salt bath (ses Tech, VERY Siaeation 1.10, p. 472), coo! the mixture to 0 °C or below and add, VERY SLOWLY, using a Pasteur pipet, a cool mixture of 4 ml of cones, {rated sulfuric acid and 4 mL of concentrated nitric acid. During the addi. {ion of the acids, stir the mixture continuously and maintain the tempera. {ure ‘of the reaction below 15°C. If the mixture rises above this Rempperature, the formation of by-product increases rapidly, bringing about a decrease in the yield of the desired product, Afterall the acid has been added, warm the mixture to room tempera- {ure. After 15 minutes, pour the acid mixture over 50 g of crushed les In a 250-mL beaker. After the ice has melted, isolate the product by vacuum 1 ratquency x’) 10004400 s200 2800 24002000. MERYENCY CM 200 1000000 an rita ma Noon, ne Infrared spectrum of methyl mnitrobenzoate. Nujol mull& a» 21 — filtration through a Buchner funnel and wash it with two 25-mL portions of cold water and then with two 10-mL portions of ice-cold methanol. Weigh the product and recrystallize it from an equal weight of methanol (Tech- nique 3, Section 3.4, p. 484). The melting point of the recrystallized prod- uct should be 78 °C. Determine the infrared spectrum of the product as a Nujol mull (Technique 17, Section 17.4, p. 622). Submit the product to your instructor in a labeled vial, along with your infrared spectrum QUESTIONS 1, Why is methyl m-nitrobenzoate formed in this reaction instead of the ortho or para 2. Why does the amount of the dinitration increase at high temperatures? 3. Interpret the infrared spectrum of methyl m-nitrobenzoate. 4. Indicate the product formed on nitration of exch ofthe following compounds: benzene, toluene, chlorobenzene, and benzoic acid. pene Experiment 3 3 p-NITROANILINE Electrophilic Aromatic Substitution Hydrolysis of an Amide Protective Groups Crystallization Thin-Layer Chromatography In this experiment, we convert acetanilide to p-nitroaniline. The sequence of reactions, beginning with aniline, is as shown. The conversion of aniline to acetanilide, the first step, was performed in Experiment 2. ‘The mechanism for the nitration is essentially identical to that given for the nitration in Experiment 32. The nitronium ion is directed to the positions ortho and para to the acetamido (—NHCOCH,) group. This occurs because the resonance electron-releasing effect of that group increases the electron density at those positions, helping to stabilize the intermediates that are formed, Substi- ° me gg vor ten, Cy dota, Cy + exscoox