Gku Chemistry SI 4 (Chapter 7 , < 9) Supplemental Instruction Chpta k Explain eflective nuxlear chxge . and both e stimate (quick method of text) and calculate I...

SYNTHETIC STRATEGIES Part of the skill in planning a synthesis is deciding in what order to carry out the reactions. Let us suppose, for example, that we want to synthcsize $\theta$ bromonitrobenzenc. We can see very quickly that we should introduce the bromine into the ring first because it is an ortho-para director: (FIGURE CANNOT COPY) O-Bromonitro- benzene $p$ -Bromonitrobenzene The ortho and para products can be scparated by various methods because they have different physical propertics. However, had we introduced the nitro group first, we would have obtained $m$ -bromonitrobenzene as the major product. Other examples in which choosing the proper order for the reactions is important are the syntheses of the ortho-, meta-, and para-nitrobenzoic acids. Because the methyl group of toluene is an electron-donating group (shown in red below), we can synthesize the ortbo- and para-nitrobenzoic acids from toluene by nitrating it, separating the ortbo-and para-nitrotoluenes, and then oxidizing the methyl groups to carboxyl groups: (FIGURE CANNOT COPY) We can synthesize $m$ nitrobenzoic acid by reversing the order of the reactions. We oxidize the methyl group to a carboxylic acid, then use the carboxyl as an electron-withdrawing group (shown in blue) to direct nitration to the meta position. (FIGURE CANNOT COPY) B Use of Protecting and Blocking Groups Very powerful activating groups such as amino groups and hydroxyl groups cause the benzene ring to be so reactive that undesirable reactions may take place. Some reagents used for electrophilic substitution reactions, such as nitric acid, are also strong oxidizing agents. Both clectrophiles and oxidizing agents seek electrons. Thus, amino groups and hydroxyl groups not only activate the ring toward electrophilic substitution but also activate it toward oxidation. Nitration of aniline, for example, results in considerable destruction of the benzene ring because it is oxidized by the nitric acid. Direct nitration of aniline, consequently, is not a satisfactory method for the preparation of $o$ -and $p$ nitroaniline. Treating aniline with acetyl chloride, $\mathrm{CH}_{3} \mathrm{COCl},$ or acetic anhydride, $\left(\mathrm{CH}_{3} \mathrm{CO}\right)_{2} \mathrm{O},$ converts the amino group of aniline to an amide (specifically an acctamido group, $-\mathrm{NHCOCH}_{3}$ ), forming acctanilide. An amide group is only moderately activating, and it docs not make the ring highly susceptible to oxidation during nitration. Thus, with the amino group of aniline blocked in acetanilide, direct nitration becomes possible: (FIGURE CANNOT COPY) Aniline Acetanilide $p-$ Nitroacetanilide $(90 \%)$ o-Nitro- acetanilide (trace). (FIGURE CANNOT COPY) Nitration of acetanilide gives $p$ -nitroacctanilide in excellent yield with only a trace of the ortho isomer. Acidic hydrolysis of $p$ -nitroacetanilide (Section $17.8 \mathrm{F}$ ) removes the acetyl group and gives $p$ -nitroaniline, also in good yield. Suppose, however, that we need $o$ -nitroaniline. The synthesis that we just outlined would obviously not be a satisfactory method, for only a trace of $o$ -nitroacetanilide is obtained in the nitration reaction. (The acetamido group is purely a para director in many reactions. Bromination of acetanilide, for example, gives $p$ -bromoacetanilide almost exclusively.) We can synthesize $o$ -nitroaniline, however, through the reactions below. (FIGURE CANNOT COPY) Acetanilide o-Nitroaniline $(56 \%)$ Here we see how a sulfonic acid group can be used as a blocking group. We can remove the sulfonic acid group by desulfonation at a later stage. In this example, the reagent used for desulfonation (dilute $\mathrm{H}_{2} \mathrm{SO}_{4}$ ) also conveniently removes the acetyl group that we employed to "protect" the benzene ring from oxidation by nitric acid.

Predict results for the two foreign reaction. One finger prep. In with its shell, it's you will return it while a figure prepping and bread use a more stable Ben Zizek crocodile ritual. Capture CR minus on Give the world the alternative. Kavika Tile at this carbon would be less stable because of the leg off education with it benzene for hundreds inoculation. The reaction proceeds through Make uranium on the press. The charge will be distributed between America and roaster gerbils, and this carbon will have more positive charge because it will be better. Gillick allies back in education with the benzene. So this position, well being attacked with water with the bunt with maker comes off on America is a benched through the other carbon and then deport the nation and removal, or for America by reducing agent Junior it in Alcohol River Bridge Group in the bin Zigic position

Predict products or the fallen reactions. Dorian L. Sulfuric. That's Ah. So finish which goes toe the pair in the positions because 63 group is a hearted contributed a dollar dessert. Is it liberation? The car parks. A group is a resonance except her. Yeah, the try substitution goes to the net position Bremen nation off matter benzene. The letter group is an inductive, except er and business, except er so substitution goes to the net position insulation or for isopropyl Benzia I support group. That's ah Harper conjugated donor. So substitution goes toe the parrot in Ortho position. However you to the stereo hinderance imposed by the I support group. The author I, Samir is almost not existent. Just traces its most repaired. I, Samir.

Explain why the connection without good excites and we've been excited. It's two different products. Let's look at the mechanism with our without backsides but the Nation actress first step and it produces Benzie like Come Pick a Time which is further stabilized by untraditional. Were fifteens in it in, for instance. Oh, structure was shows conjugation and this camera car time is most stable with public art time at this common, which is making conjugation with the benzene in. That's why this the assured direction off the reaction and a combination with BR minus gives you the major product in the prisons or both sides they have taken. Spacious is different. That's the radical of woman and unethical of woman. Also wants toe form Benzia political fishhook, and it's, ah, most able than medical at this carbon. For the same reason that would be liking education off the benzene green. And then on the next step over chain propagation, the medical reacts with them. HBR Junior is another. They are dark and gives the product

Explain white maturation in the presence over a sulfuric and nitric acid is much faster than alliteration by just nitric cases. Consider in there. Vicki is I'm very qualitative level. Sulfuric patient is much stronger than nitric tasted because it is much lower. PK started. X isn't a said in Quetta. Needs not tasted, which forms later on you, which is essential for men. Trish on that more quantitative basis to provide a good concentration off matrimonial. We need tohave a high concentration of nitrate tasted em portals at the same time. So let's right there. Councils off association. That's for magic, is it? And this for sulfuric incident. Both of them are very strong s it's so concentrations or firm hydrogen and in three approximately equal and concentrations off portals and age is or four minus are approximately equal. It brings us toe those creations. Okay, this career consideration of each plus is this and this correct? It's interational off each Plus, is there so not express? Not is it through concentration off sulfuric issue. Now you can see it. That concentration of not a sin exceeds concentration of sulfuric acid by almost eight orders off magnitude and at this point, there is a lot of hydrogen. Almost all agents are dissociated at the same time. There is a significant concentration or not. Is it rich? Provides the aggression legion through the night. Urgent Angel Metro? No.