Meta director

Because substitution m (trifluoromethyl)benzene occurs primarily at positions meta to the substituent we say that a trifluoromethyl group is a meta director... 

This makes the nitro group a powerful electron withdrawing deactivating substituent and a meta director... 

Meta (Section 117) Term descnbing a 1 3 relationship be tween substituents on a benzene nng Meta director (Section 12 9) A group that when present on a benzene nng directs an incoming electrophile to a position meta to itself... 

What is an immediate precursor of j i-chloropropylbenzene " Because the two substituents have a meta relationship, the first substituent placed on the ring must be a meta director so that the second substitution will take place at the proper position. Furthermore, because primary alkyl groups such as propyl can t be introduced directly by Friedel-Crafts alkylation, the precursor of... 

Next, ask yourself what an immediate precursor of the target might be. Since an acetyl group is a meta director while a hydroxyl group is an ortho and para director, acetophenone might be a precursor of m-hydroxyacetophenone. Benzene, in turn, is a precursor of acetophenone. 

A The aldehyde group is a meta director. Thus, the product of the mononitration of benzaldehyde should be the compound whose structure is drawn below ... 

Some substituents are meta-directors, encouraging electrophilic attack upon the meta position. The presence of a meta-director means the major (or only) product of the reaction will be a meta-disubstituted benzene. 

Any substituent whose atom attached to the benzene contains a lone pair of electrons is ortho-para directing (but not necessarily a ring activator). Substituents without a lone pair on the atom attached to the ring are likely meta directors (with the exception of alkyl groups and aromatic rings, which turn out to be ortho-para directors). 

Many students get into trouble when writing synthetic procedures because they overlook steric effects. For example, if the task is to synthesize the ortho product starting with propylbenzene, you can t rely on the o-p-directing ability of the propyl group. One solution is to place an easily removable substituent in the para position, leaving only the ortho position available for further attack. (If the para substituent is a meta-director, then both the meta-director and the propyl group favor attack at the Scime position.)... 

Oxidation of an alkylated benzene (making an aryl carboxylic acid) is a method of converting an ortho-para activator into a meta director. The reduction of a nitro group to make an aryl amine is a way of changing a meta director into an ortho-para activator. 

The regiochemistry is important. For example, does the reaction follow Markovnikov s rule or is the reaction anti-Markovnikov Or is the substituent a meta-director or ortho-para-director You learned rules such as this for a reason make sure you continually apply them. 

Two electrophilic aromatic substitution reactions need to be performed chlorination and Friedel-Crafts acylation. The order in which the reactions are carried out is important chlorine is an ortho, para director, and the acetyl group is a meta director. Since the groups are meta in the desired compound, introduce the acetyl group first. 

The acetyl group is attached to the ring by Friedel-Crafts acylation. It is a meta director, and its nitration gives the proper orientation of substituents. The order of the first two steps cannot be reversed, because Friedel-Crafts acylation of nitrobenzene is not possible (Section 12.16). Once prepared, m-nitroacetophenone can be reduced to m-nitroaniline by any of a number of reagents. Indeed, all three reducing combinations described in the text have been employed for this transformation. 

Answer The substitution pattern on the ring is important. Tile —NOj group is a meta director while the Br is an ortho lxira director with regard to an incoming electrophile. The meta relationship of the substituents on V-f dictates that the — NOj group should be placed on the ring before the Br. 

Answer The -Ca H5 group and Br are both or//io para directors while the —NOj is a strong meta director with regard to aromatic electrophilic substitution. The ortho relationship of the — NO and —CaHs groups dictates that... 

Answer Since the -C02n group is a meta director, wc can nitrate benzoic acid via procedure V-6. 

Answer The important item of this synthesis is the met a orientation of (he substituents. The aldehyde group is a meta director, but if wc attempt to nitrate bcnzaldehydc A. the aldehyde function would be oxidized up to the corresponding nitro substituted acid B under the conditions of the reaction. q... 

Answer The -OCH, group is an ortho, para director while the ketone function ls a meta director. Thus, to get the desired para arrangement of the groups, the ketone function should be added to B which is a permitted starting material. Let us use procedure X-6 to incorporate the acyl group onto the aromatic ring. 

C-CHaCHj group (meta director) on the ring and convert it to a H-propyl group. ... 

Answer The meta substitution pattern of Xll-g looms as the major difficulty in this-synthesis. The ethoxy group is an ortho iara director while the cyano function is a meta director. It appears that an easy approach to take would be to nitrate benzonitrile, reduce the -NO, group to the amine, diazotizc, and treat the diazonium salt with ethanol. However, jl is not feasible to reduce the -NO, group of meta-nitrobenzonitrilc without also reducing the -CN group. 

So far, groups have been either activating and ortho/para directors or deactivating and meta directors. The halogens are exceptions to this generalization. They are slightly deactivating compared to benzene but still direct to the ortho and para positions. For example, chlorobenzene is nitrated 17 times slower than benzene and produces predominantly ortho- and /Mra-chloronitrobenzene. 

Route A works fine. Toluene is readily nitrated, and the methyl group is an ortho/para director. The only problem is that both the desired compound and its ortho-isomer are produced and must be separated. (This is a common problem, and we usually assume that the separation can be accomplished, although it is not always easy in the laboratory.) Route B is unsatisfactory because the Friedel-Crafts alkylation reaction does not work with deactivated compounds such as nitrobenzene. Furthermore, even if the alkylation could be made to go, the nitro group is a meta director, so the desired product would not be formed. 

The first examples illustrate that the order of addition of the substituents is important in controlling their orientation. For example, suppose we needed to prepare m-chloronitrobenzene from benzene. Because the chlorine is an ortho/para director and the nitro group is a meta director, it is apparent that the nitro group must be added first if the meta product is desired ... 

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