Ortho-relationship

The ortholithiation of benzenesulphinamides 119 is of use in the regioselective synthesis of mefa-substituted compounds 120 the sulphinamide group is used to set up two ortho relationships and then removed reductively (Scheme 52) . The same concept has been explored with other sulphur-containing orf/zo-directors °. 

Acidity data for 2-substituted pyridinium ions may be correlated using a Hammett equation and am values. Although it is not obvious that am parameters ought to be applied to a reaction series in which a substituent and the reactive site are in an ortho relationship, the correlation clearly shows that inductive effects have an important influence on acidities. 

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... 

The marked instability of aspirin is due to two structural features one, that it is an aromatic ester and, for reasons previously discussed, it is, therefore, more labile than an aliphatic ester and two, the ortho relationship of the acetoxy group to the carboxylate. Owing to this proximity, aspirin is subject to intramolecular catalysis of the ester hydrolysis. The pATa of aspirin is 3.6, and, therefore, it exists predominately... 

The derived instability seemingly comes from the ortho relationship of two OH/Cl pairs of substituents. The c 11 kJ mol instability of 2,3-dichlorobenzene-l,4-diol, relative to the 2,5-isomer, is due to the additional crowding of substituents on the aromatic ring and whatever difference there may be between the electronic effects of ortho vs. para chlorines. For comparison, the stability difference between solid o- and p-dichlorobenzene is ca 9 kJ mol . The stability of the 2,6-isomer is intermediate between its other two isomers. Relative to the 2,5-isomer, it is less stable by ca 4 kJ mol, the same as the difference between m- and p-dichlorobenzene. Evidently, but surprisingly, additional steric effects are unimportant here. 

One reaction much used to produce the ortho relationship is the Claisen rearrangement.9 An allyl ether 36 from a phenol and an allylic halide 35 undergoes [3,3] sigmatropic rearrangement to give an intermediate 37 that is the keto form of a new phenol 38 with the allyl group now in the ortho position. 

Note the ortho relationship between the lithium and fluorine atoms on the benzene ring. We have previously seen lithium next to the fluorine without benzyne formation and yet here the very same species forms benzyne The crucial difference between the two cases is temperature. The or/Z/o-fluoro-aryl lithium is stable at -78 °C and the benzyne does not form until the temperature reaches -40 °C to -50 °C. Aromatic rings with lithium adjacent to other halogens (such as bromine) are less stable and form benzynes at lower temperatures. 

An ortho relationship between a triflate and a silyl group is another way to generate benzynes.26 The benzyne 149 is formed when the silyl group is removed11,27 using the fluoride ion 148. 

An interesting compound apparently violating the ortho relationship was reported (Gringauz, 1976). This compound, which might be considered a biphenyl aspirin, ... 

Confirmation of the structure of hazuntinine (49) came from the CMR spectrum, which showed close similarity with the spectrum of vincadifformine (2) except for C-14 and C-15, and C-10 and C-ll (20). The former two carbons at 51.8 and 57.0 ppm were clearly attached to oxygen from their chemical shift and are therefore the site of the epoxide linkage. The chemical shift differences of C-10 (+23.0ppm) and C-ll (+22 ppm) in comparison with vincadifformine (2) demonstrate the ortho relationship of the two aromatic methoxyl groups. 

There are lots of ortho relationships in this compound And somehow we have to join the two aromatic rings together to make an ether. This can only really be done by nucleophilic aromatic substitution, so we need to look for an electron-withdrawing group to help us. The nitrile is in the right place, provided we have a leaving group (such as fluoride) ortho to it. So our last step can be as shown here ... 

A cunning way to get unusual regioselectivity is to make the reaction intramolecular. The synthesis from benzene of the cyclic ketone known as tetralone may look difficult as we must get an ortho relationship on the benzene ring. But if we make the final bond in the ring by a Frledel-Crafts acylation there is no problem. The alkyl group is ortho,para-diiecting and the acid cannot reach the para position. 

Three compounds also have two carboxyl groups the dicarboxylic acids. 1,2-Benzenedioc acid (phthalic acid, 35) has two carboxyl groups with an ortho relationship. In 1,3-benzenedioc acid (isophthalic acid), the carboxyl groups are meta, and in 1,4-benzenedioc acid (terephthalic acid) the carboxyl groups have a para relationship The dialdehyde compounds have related names 1,2-ben-zenedial (phthalaldehyde 36 also phthalic dicarboxaldehyde), 1,3-benzenedial (isophthalaldehyde also isophthalic dicarboxaldehyde), and 1,4-benzenedial (terephthalaldehyde also terephthalic dicarboxaldehyde). 

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