How would you synthesize the following substances starting from benzene? (a)(EQUATION CAN'T COPY

How would you synthesize the following substances starting...

Key Concepts

Oxidation and Reduction of Benzylic Positions

Oxidation at the benzylic position, which often involves converting a benzylic alkyl substituent into a carbonyl or carboxylic acid group, is a useful transformation when additional functionality is required on the aromatic ring. Similarly, reduction reactions can be employed to modify carbonyl groups or to remove protecting groups. These redox transformations are critical for fine-tuning the oxidation state of molecules in multi-step syntheses, ensuring that subsequent reactions occur selectively.

Friedel-Crafts Reactions

Friedel-Crafts reactions, including both alkylation and acylation, are key methods for attaching carbon side chains to the benzene ring. These reactions use Lewis acid catalysts to generate potent electrophiles that attack the aromatic ring, allowing for the introduction of alkyl or acyl groups. They are particularly important because they offer a strategic route to build carbon-carbon bonds and prepare aromatic intermediates that can be transformed into a range of functional groups.

Substituent Effects and Directing Groups

In aromatic chemistry, substituents already present on the benzene ring influence both the reactivity of the ring and the orientation of new substituents during electrophilic aromatic substitution. Activating groups typically direct incoming electrophiles ortho/para, while deactivating groups tend to direct them meta. Understanding these directing effects is essential for planning sequential reactions to achieve the correct regioselectivity in the synthesis of complex aromatic compounds.

Retrosynthetic Analysis

Retrosynthetic analysis is the process of deconstructing a target molecule into simpler precursor structures until readily available starting materials are reached. In the context of synthesizing substituted aromatic compounds starting from benzene, this method helps to identify key disconnections and determine the sequence of reactions needed—such as initial installation of substituents via electrophilic aromatic substitution followed by further functional group transformations—to build the desired structure.

Electrophilic Aromatic Substitution (EAS)

Electrophilic aromatic substitution is a fundamental reaction mechanism for the modification of benzene rings. The process involves the formation of a sigma complex where an electrophile temporarily disrupts the aromaticity of benzene, which is then restored through deprotonation. This concept underpins many transformations—including nitration, sulfonation, halogenation, Friedel?Crafts alkylation, and acylation—making it essential for introducing substituents onto the ring in a controlled manner.

Transcript

00:01 Okay, so we've got three molecules here that we have to make only from benzene.

00:07 So we're going to start with benzene.

00:12 And you'll notice that the relationship between the substituents is para.

00:15 So the way that i approach these is identify the relationship between the substituents, then look at the substituents and see if either of the groups that you can add will direct that second group to the position that is at.

00:29 So the chlorine group is a deactivator, but it's orthoparidirecting.

00:35 But you don't know of a way to add a vinyl group.

00:39 You can't do frito -crafts with a vinyl chloride because the carbocadion, the vinyl cation is too high in energy.

00:48 So you can add an ethyl group, though, right? you know how to add afl groups.

00:55 And then you'll have to find a way to remove two of those hydrogen atoms.

01:01 So i'm going to go ahead and add the ethel group first, only because the ring will be more activated for chlorination.

01:16 You'll probably end up getting a polysubstituted, a diethylbenzine just based off over the poly substitution.

01:26 Right? that's what the book says.

01:32 This ring is more active for a second frito crafts with another ethel group.

01:38 So now we can chlorinate and assuming that we can separate our ortho and para products.

01:47 Assume we could separate the monoethylbenzine from the diethylbenzine initially.

01:53 So now we're left with something that somewhat resembles our product.

01:56 We have to figure out how to lose the saturation in the ethel group now.

02:02 So you know of a reaction that would allow you to add a leaving group here.

02:08 And that's going to be free radical bromination at the benzal position.

02:16 Right.

02:16 So you can use a reagent called nbs.

02:20 In the presence of some organic peroxide, generally those ours are, usually you would use benzoyle peroxide is what the book uses.

02:36 You just need a radical initiator.

02:38 That's going to add a single bromine to the benzol position.

02:44 And that will give us our leaving group, right? and then you can go ahead and do an e2, which will form that, which will pluck off the proton here.

02:54 So i went ahead and i just used sodium methoxide to do that in methanol.

03:02 Fine.

03:04 And that will give us, that will give us the unsaturated product.

03:08 Cool.

03:09 So now we have this symmetrical alcohol here.

03:13 So we have a para ch2 -o -h group on the ring.

03:19 So how are we going to add those? well, you can't do, you wouldn't be able to do, or the textbook didn't show you any examples of doing fidel crafts when you have some other substituent close enough to, like you don't, you haven't seen an example like this, for example.

03:43 So we probably we can't do that.

03:47 We can do something similar to what we just did, though, right? so we could add the alcohol groups first.

03:54 You know the relationship is para.

03:56 So if you add an alcohol group, maybe like methyl chloride and aluminum chloride, you'll probably end up getting the paramehyl.

04:04 You probably end up making p.

04:05 Zyline anyway.

04:07 So you can use two equivalents just to make more of it, i guess.

04:12 But even if you add one equivalent, you know poly substitution is preferred.

04:16 Then something we can do is we can do two equivalents of nbs again with the organic peroxide.

04:24 That will give us bromines at both of those benzopositions.

04:31 Sorry, i just made an extra carbon.

04:35 I was reminding myself of the last problem.

04:39 And then i just did it again.

04:45 And then the last thing that you would probably have to do is an ethyl, an sn2 with a hydroxide...

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