Ring directions

The N-oxide function has proved useful for the activation of the pyridine ring, directed toward both nucleophilic and electrophilic attack (see Amine oxides). However, pyridine N-oxides have not been used widely ia iadustrial practice, because reactions involving them almost iavariably produce at least some isomeric by-products, a dding to the cost of purification of the desired isomer. Frequently, attack takes place first at the O-substituent, with subsequent rearrangement iato the ring. For example, 3-picoline N-oxide [1003-73-2] (40) reacts with acetic anhydride to give a mixture of pyridone products ia equal amounts, 5-methyl-2-pyridone [1003-68-5] and 3-methyl-2-pyridone [1003-56-1] (11). 

Exo Bond. A bond which is attached to a ring directly. 

Meta director (Section 12.9) A group that when present on a benzene ring directs an incoming electrophile to a position meta to itself. 

Several other Heck cyclizations that do not involve the indole ring directly have been developed. Kelly employed the Heck cyclization of 266 to synthesize (and revise the structure of) maxonine (267) [281], The product resulting from attack at C-8 was also obtained. 

Careful studies by C. Eabom have shown that electrophilic aromatic substitution of silicon is faster than substitution of hydrogen. Thus a silicon in an aromatic ring directs substitution with hardly any rearrangement. This technique is particularly useful for preparation of specifically deuterated arenes as protolysis (deuterolysis) or aryl silanes is rapid. 

X. C. Ding, B. F. Rasmussen, G. A. Petsko, D. Ringe, Direct Structural Observation of an Acyl-Enzyme Intermediate in the Hydrolysis of an Ester Substrate by Elastase , Biochemistry 1994, 33, 9285-9293. 

However, if there is another bond joining the two rings directly elsewhere (see 25a) then a "core bond" is still a candidate for strategic bond designation because the... 

Replacement by iodide ion Iodine is not easHy introduced Into the benzene ring directly, but, when the diazonlum salt solution is treated with potassium iodide, iodobenzene is formed. 

When the ruthenium complex 247 is reacted with an excess of isothiocyanates, the 2-imino-l,3-thiazine-4-thione ruthenium complexes 248 and 10 are formed by a [2+2+2] cycloaddition together with the [2+2] adduct 249, formed from cycloaddition of C C with the C=S (Scheme 32) <19980M2534, 2002JOM(660)127>. Treatment of 247 with an excess of isothiocyanate gives the six-membered ring directly and in improved yields. 

Orientation Similarly, groups already present on the benzene ring direct the orientation of the new substituent to ortho, para or meta positions. For example, nitration of chlorobenzene yields ort/io-nitrochlorobenzene (30%) and para-nitrochlorobenzene (70%). 

Ring expansions are generally not of synthetic value, primarily because it is usually easier to make a five-membered ring directly than to form a three- or four-membered ring and carry out the subsequent expansion. 

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