Substitutions on the Ring

The dinitro derivative of compound 2 reacts with anhydro bases of pyridine and quinoline to give zwitterions such as 215 (99RCB1391). Compound 216 has been made from the 3-bromo derivative of compound 3 by reaction with an amine, as an intermediate in the production of stomach secretion inhibitors (80EUP48555), 

Compounds 4 and 5 have reactions in the six-membered ring similar to those of pyridine. As examples, compound 199 is aminated (92MI3), and compound 218 reacts with a number of primary and secondary amines to give compounds such as 219 (97UKZ64). Triazolopyridinone 220 can be converted into the hydrazine 221 either via the chloro compound or via the thione and methylthiol (85LA1922). 

Side chain reaction in derivatives of compound 2 has largely been concerned with the production of compounds with pharmaceutical activity by reaction between chloroalkyl side chains in position 2 and suitable amines. A selection of such compounds are 224 (82JAP(K)206684), and 225 (81FRP2450259) both are antihypertensive. Use of a dichloromethyl side chain provides an unsaturated amine, as in compound 226 (81FRP2450259). 

An acid chloride of compound 3 reacts with a bicyclic amine to give compound 227 (88EUP254584) while the zwitterion 228 reacts with a range of alcohols to give esters such as 229 (83BCSJ2974) the 2-isomer reacts similarly 

As part of a strategy for adding rings to system 4 the cyanide 232 was converted into the iminoether and treated with amines to give tricycle 233 (96JHC319). 

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Nucleophilic reactivity of the sulfur atom has received most attention. When neutral or very acidic medium is used, the nucleophilic reactivity occurs through the exocyclic sulfur atom. Kinetic studies (110) measure this nucleophilicity- towards methyl iodide for various 3-methyl-A-4-thiazoline-2-thiones. Rate constants are 200 times greater for these compounds than for the isomeric 2-(methylthio)thiazole. Thus 3-(2-pyridyl)-A-4-thiazoline-2-thione reacts at sulfur with methyl iodide (111). Methyl substitution on the ring doubles the rate constant. This high reactivity at sulfur means that, even when an amino (112, 113) or imino group (114) occupies the 5-position of the ring, alkylation takes place on sulfiu. For the same reason, 2-acetonyi derivatives are sometimes observed as by-products in the heterocyclization reaction of dithiocarba-mates with a-haloketones (115, 116). 

The structure of guanine illustrates an important feature of substituted pyrimidines and purines Oxygen substitution on the ring favors the keto form rather than the enol Ammo substitution does not... 

When o-Nitroaniline is treated by sodium nitrite in acid medium and then by an inorganic sulphide, it forms an explosive diazonium sulphide. Note that even though the presence of a nitrated group does not help, it certainly is not a factor that is vital to cause the explosion, since this is a property that is common to all these diazonium salts whatever the nature of the substitution on the ring. The situation is exactly the same with p-nitroaniline. 

While iron(III) complexes of thiosemicarbazones with different functional groups involving have been prepared from 2-acetylpyridine, substitution on the ring has been more popular with thiosemicarbazones derived from 2-formylpyridine. The only thiosemicarbazones in which the 2-acetylpyridine ring has been substituted are 15a and 15b, prepared from 6-methyl-2-acetyl-pyridine [120]. Both of these iron(III) complexes have rhombic spectra and values of g, are similar to those found for the 2-acetylpyridine thiosemicarbazones. Solution studies have been carried out on the iron(III) complex of 2,6-diacetylpyridine mono-thiosemicarbazone, but the solid complex was not isolated [143]. 

The cycloadditions of nitrones to methylenecyclopropanes 285-287 (Table 23), 299 (Table 24, entry 3), and 311 (Table 25, entry 7) substituted on the ring occur with very high diastereofacial selectivity. Nitrone 256 gives with 1-methyl-ene-2-phenylcyclopropane (285) a mixture of four isomers in a 2 2 1 1 ratio... 

Reactions such as this are electrophilic substitutions, and other electrophiles such as N02 , Cl l3CO, or Cl IO can be substituted on the rings without destroying the complex. Such chemical behavior illustrates the extreme stability of complexes of this type. It is apparent that the nature of the bonding in the chelate rings is as important as is their size. Other reactions of coordinated ligands will be shown in later chapters. 

With these guidelines, the results from the metathesis of 4-methyl-2-pentene now appear to be reasonably accountable for. Most importantly, the lack of formation of c7s-2,5-dimethyl-3-hexene indicates that cis- 1,2-diisopropyl-substitution on the ring is highly unfavored, and trans-1,2-substitution leading to adjacent equatorial substituents is acceptable ... 

Figure 6.5 Substitution on the ring of an O-methyl-N-oxide of pyridine.

In the following paragraphs, we examine bioactive cyclic imides substituted on the ring and/or on the N-atoms, and begin with N-substituted suc-cinimides. CP-93,393 (4.177, R=R =H) is a selective 5-HT, serotonin autoreceptor agonist developed for the treatment of anxiety and depression. In the rat, hydrolysis of the succinimide bond was observed for the parent drug as well as for metabolites hydroxylated on the succinimide ring (4.177, R=OH,... 

Pyridines with an allenyl ether group and an iodine atom substituted on the ring undergo a cyclization reaction to afford furo[3,2-3]pyridine derivatives in moderate yields (Equation 49) <2001T7729>. 

Naphthalene undergoes electrophilic substitutions on the ring, resulting in its various derivatives. In addition to the usual electrophilic substitutions, naphthalene can also undergo oxidation and reduction reactions under specific conditions as outlined below. 

We note from Table VIII a strong interest in halogenated resists, particularly those substituted with chlorine. The addition of chlorine to the aromatic structure of polystyrene has a marked effect on cross-linking efficiency. Monodisperse polystyrene, for example, has a sensitivity on the order of 50 p C/cm2, yet with as little as 20% chloromethyl groups substituted on the ring, the sensitivity is improved to 2 C/cm2 for comparable molecular weight and distribution. 

Porphyrins are intensely coloured, with a strong absorption band at 400 nm (e 105), the Soret band. The large ring current effect in the H NMR (< NH x — 5, <5, 10p.p.m.), the stable parent mass peaks, electrophilic substitutions on the ring peripheries, the planarity and intermediate bond lengths in their X-ray structures and the large heat of combustion all reflect the aromaticity of porphyrins,2... 

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