Meta ring positions

NE is synthesized by tyrosine hydroxylation (meta ring position) followed by decarboxylation and side chain p carbon hydroxylation. The synthesis of this catecholamine is regulated by tyrosine hydroxylase. Tyrosine hydroxylation is also a key step in the synthesis of two other important catecholamines, dopamine and epinephrine. NE is packaged via active transport into synaptic (or chromaffin) vesicles prior to release by neuronal depolarization. The effects of NE are mediated by adrenergic receptors (a or P) which are G protein coupled resulting in either increases or decreases in smooth muscle tone as well as increases in cardiac rate and contractility. These effects arise out of receptor mediated increases in intracellular Ca and activation or inhibition of various protein kinases. The effects of NE are terminated essentially as a result of its active transport into the presynaptic nerve ending via an energy and Na" dependent process which utilizes the norepinephrine transporter (NET). Ultimately, NE and other catecholamines are metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). 

All the ring positions of (trifluoromethyl)benzene are deactivated compared with benzene The meta position is simply deactivated less than the ortho and para positions The partial rate factors for nitration of (trifluoromethyl)benzene are... 

Figure 12 11 compares the energy profile for nitration of benzene with those for attack at the ortho meta and para positions of (trifluoromethyl)benzene The presence of the electron withdrawing trifluoromethyl group raises the activation energy for attack at all the ring positions but the increase is least for attack at the meta position... 

Occasionally, a phenol may have more than one substituent on the ring before alkylation with aldehyde. If the groups are meta to one another and activating, they will enhance the electron density of the same ring positions and reinforce one another. If they are ortho or para to one another, they may increase or reduce reactivity, depending on the nature of the groups. The most common... 

In a study with captive male American kestrels (Drouillard et al. 2001), birds were dosed with Aroclor-contaminated diet and the toxicokinetics of 42 PCB congeners contained therein was stndied. Those congeners that were most rapidly cleared contained vicinal meta-para hydrogen substituents on at least one phenyl ring. This provides further evidence for the importance of open (i.e., not substituted by chlorine) meta-para positions for metabolic attack, an issue that will be returned to in the next section (Section 6.2.3). 

Arylnitrenium ions are likewise capable of adding to n nucleophiles. With substituted aromatics (e.g., toluene) there exists the possibility of three reactive sites on the nitrenium ion (the nitrogen, ortho- and para-ring positions), along with up to three possible sites on the arene (ortho, para, and meta in the case of a monosub-stituted trap). Thus in a typical case there is the possibility of nine distinct regio-isomers. Obviously, any synthetic utility of such chemistry relies on the ability of the reagents to react in a selective manner. 

When there are two or more substituents on a benzene ring, position isomerism arises. Thus there are three possible isomeric disubstituted benzene derivatives according to whether the substituents have the 1,2, 1,3, or 1,4 relationship. The isomers commonly are designated as ortho, meta, and para (or o, m, and p) for the 1,2-, 1,3-, and 1,4-isomers, respectively. The actual symmetry of the benzene ring is such that only one 1,2-disubstitution product is found, despite the fact that two would be predicted if benzene had the 1,3,5-cyclohexatriene structure ... 

If we compare the acid strengths Ka) of a series of substituted benzoic acids with the strength of benzoic acid itself (Table 26-4), we see that there are considerable variations with the nature of the substituent and its ring position, ortho, meta, or para. Thus all three nitrobenzoic acids are appreciably stronger than benzoic acid in the order ortho para > meta. A methoxy substituent in the ortho or meta position has a smaller acid-strengthening effect, and in the para position decreases the acid strength relative to benzoic acid. Rate effects also are produced by different substituents, as is evident from the data in Table 26-5 for basic hydrolysis of some substituted ethyl benzoates. A nitro substituent increases the rate, whereas methyl and methoxy substituents decrease the rate relative to that of the unsubstituted ester. 

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