How would you synthesize the following substances starting from benzene or phenol? Assume that o

step 1 All right. These are the questions. These are the questions that we should be practicing for exa

How would you synthesize the following substances starting...

Key Concepts

Electrophilic Aromatic Substitution (EAS)

This reaction class involves the replacement of a hydrogen atom on an aromatic ring with an electrophile. It is fundamental in aromatic synthesis and includes reactions such as nitration, bromination, sulfonation, and Friedel–Crafts reactions. Understanding the mechanism and conditions of EAS is crucial for planning aromatic substitutions and controlling product regiochemistry.

Substituent Directing Effects in Aromatic Substitution

The electronic properties of substituents already present on an aromatic ring dramatically influence subsequent electrophilic substitutions by activating or deactivating the ring and directing incoming groups to ortho, meta, or para positions. Recognizing these directing effects enables chemists to predict and control the regioselectivity of substitution reactions.

Regioselective Synthesis and Reaction Order Strategies

When synthesizing multi-substituted aromatic compounds, the sequence of reactions is critical, as different substituents can affect both the reactivity and the position at which further substituents are introduced. Strategic planning and sometimes the use of blocking groups or protective groups are necessary to obtain the desired regiochemical outcomes.

Protecting Group Strategies in Aromatic Synthesis

Certain functional groups, such as amino groups, are highly activating and can lead to undesired regioisomer formation in electrophilic aromatic substitution. The use of protecting groups to temporarily mask these functional groups alters their reactivity and directing properties, allowing for controlled introduction of other substituents, after which the protecting group can be removed.

Oxidation of Aromatic Side Chains

Alkyl groups attached to an aromatic ring can be transformed into carboxylic acids through oxidation processes. This conversion is particularly useful when a side-chain must be altered to introduce functionality such as a carboxyl group while taking into account the possible effects on the aromatic substitution pattern.

Nitration Reactions in Aromatics

Nitration involves the introduction of a nitro group using a mixture of nitric and sulfuric acids. This reaction is highly dependent on the nature and position of existing substituents on the ring, especially when targeting compounds with multiple nitro groups, as each successive nitration can be more challenging due to the deactivating effect of the nitro groups themselves.

Transcript

0:00 All right.

00:01 These are the questions.

00:03 These are the questions that we should be practicing for exams and stuff, how to make synthesis.

00:10 How do syntheses, right? so we're allowed to start from benzene and orphanol.

00:16 And you can assume that ortho and parent substitution products can be separated.

00:22 That's awesome.

00:23 That's so cool.

00:25 So we don't have to worry about favoring the paraposition over the ortho position.

00:30 And then our yields can be complete garbage.

00:32 That's great.

00:33 So i actually didn't know that i could have started from phenol.

00:38 And it's a good thing i didn't because i think only b is a decent place to start from phenol right now anyway, based on what you know.

00:49 So i use benzene for all four examples.

00:51 So i'm going to show you those.

00:52 I might show you an alternative synthesis with b.

00:58 But so we have to make orthobromo benzoic acid great so the way that i approach these right look at the relationship between the substituents and see if there's an order that you have to add these first but the carboxylic acid is a group that you don't know how to add directly you have to the only way you know how to make those is by oxidizing an alkalot chain right so you're going to want to, so realistically, you probably would have to add some r group by friedel crafts and then do bromination that would favor the benzo position, right? and then cut off the chain with oxidation.

01:47 But what's great is that regardless if you add the bromine or if you add the alkaline group first, you're going to have an orthoparadirector.

01:54 So you will be able to get the ortho product either way before you do that final oxidation.

02:00 Right.

02:01 So you know that you'll have to use potassium permanganate lasts, and you need to do an aqueous workup to get to that carboxylic acid.

02:14 And you can't do that before you add the bromine because then the carboxylic acid will favor the metaposition for the next substitution.

02:21 So you can't do that here.

02:22 So i decided to add the methyl group first because the ring will be more activated for bromination.

02:35 None of that matters here because you're not actually doing it in the laboratory.

02:38 We're going to make tonyene.

02:40 That's a very expensive tonyuine synthesis.

02:42 You might as well just buy it and start from that, but that's okay.

02:45 Right.

02:45 And then we're going to do bromination, br2, an iron tribromide.

02:52 That will give us, and we can separate away the para product, right? who cares? so that'll give us the orthobromo, and then we could cut off that chain with potassium permanganate to give us the carboxylic acid.

03:07 That is a fine way of making that.

03:09 So i started from benzbo, with this b example, but you could also start from, um, from phenol.

03:16 And i guess i'll do both, um, but this is really the only example that i, now that i'm thinking about it, you could, it could have, it would have been a little easier with phenol.

03:26 It'd be different.

03:26 I wouldn't say it's easier.

03:28 Um, right.

03:29 So the first thing i think we should do is brominate.

03:33 And the reason for that is the only way that you know to add any type of or group, whether that's going from benzene to phenol.

03:42 You don't know how to add a methoxy directly, or at least the textbook never explicitly did that, but you can make an extension of some of the benzine chemistry that you learned.

03:53 So with a good leaving group on the benzene ring, you could do benzene chemistry.

03:58 In the presence of water, you can make phenol, right? that was in the chapter.

04:02 So if you do that in the presence of methanol, you can make a methoxy group through the same mechanism that the water is generated, water is technically just an alcohol where the r group is h.

04:15 Right.

04:15 In this case, the r group is methyl.

04:17 But once you make the benzine with a strong base and a leaving group, and you will favor the methanol being the nucleophile and attacking the benzine.

04:28 So what i'm going to do is i'm going to add an iodide.

04:31 So i think i'm going to use either icl, which is an i plus source that was in one of the previous chapters, sorry, one of the previous questions, or if you also want to iodate in the way that was presented earlier in your textbook, you could also use i -2 in the presence of some copper -2 salt.

04:55 So instead of doing i -c -l, you could also do i -2 with some copper -2 chloride.

05:04 Sorry, yeah, copper -c -u -c -l -2 or just copper -2, that's probably fine for a scheme.

05:09 That will give you an iodine product.

05:13 And iodine's a fantastic leaving group.

05:15 So now if i decide to do benzyne chemistry, i want to use a base that i want to use a strong base that will pluck off this proton here, push electrons down, kick off that iodide, so i'll be able to get the benzine.

05:32 So if i wanted to react with methanol, i need to use the conjugate base of methanol, which is methoxide.

05:38 So i'm going to use sodium methoxide in methanol and honestly you'll probably have to heat the crap out of it.

05:46 So that will go through a benzyne intermediate that will give me the methoxy benzene.

06:01 And then methoxy is a ortho -power director.

06:05 So in that case you could just do frito crafts with methyl chloride and aluminum trichloride.

06:10 Did i add that? yeah, i did before.

06:12 So that'll give you this.

06:13 I know i did i didn't make the constituents in the same place, but just spin that ring around for me.

06:20 So with phenol, i can see an easier synthesis because you already added the oxygen here...

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