Methoxybenzene synthesis from

Synthesis from methoxybenzene(s) or fluoro or bromo derivatives by reaction with organometallic reagents. 

The Y appendage of 2-cyclohexenone 191 cannot be directly disconnected by an alkylation transform. (y-Extended enolates derived from 2-cyclohexenones undergo alkylation a- rather than y- to the carbonyl group). However, 191 can be converted to 192 by application of the retro-Michael transform. The synthesis of 192 from methoxybenzene by way of the Birch reduction product 193 is straightforward. Another synthesis of 191 (free acid) is outlined in... 

The structure of the products is determined by the site of protonation of the radical anion intermediate formed after the first electron transfer step. In general, ERG substituents favor protonation at the ortho position, whereas EWGs favor protonation at the para position.215 Addition of a second electron gives a pentadienyl anion, which is protonated at the center carbon. As a result, 2,5-dihydro products are formed with alkyl or alkoxy substituents and 1,4-products are formed from EWG substituents. The preference for protonation of the central carbon of the pentadienyl anion is believed to be the result of the greater 1,2 and 4,5 bond order and a higher concentration of negative charge at C(3).216 The reduction of methoxybenzenes is of importance in the synthesis of cyclohexenones via hydrolysis of the intermediate enol ethers. 

Q Suggest a synthesis of the letracycle 3.1 from 4-methoxyben-zaldehydc and 1-(2-bromoethyl)-3-methoxybenzene. 

Specifically substituted, functionalized benzenamines (anUines) are important synthetic intermediates in medicinal chemistry and the dye industry. Propose a selective synthesis of 5-chloro-2-methoxy-l,3-benzenediamine, B, from methoxybenzene, A. 

Methoxyphenyl)methanol (anisyl alcohol) (see below) contributes both to the flavor of licorice and to the fragrance of lavender. Propose a synthesis of this compound from methoxybenzene (anisole). (Hint Consider your range of options for alcohol synthesis. If necessary, refer to Problem 55 of Chapter 15.)... 

Another q>pToach to the aoidone skeleton, developed by Watanabe et al. 314), was based on an earlio- obsravation that small amounts of aoidones woe formed when benzynes were generated by diazotization of anthranilic acids 315-317). The acridones result in these cases from the reaction of benzynes with undiazotized anthranilic acids. Therefore, a new route was developed through tandem metallation synthesis. The lithium salt of methyl iV-methylanthranilate (250) could be easily coupled with the benzynes 251, 252, and 253, generated by treatment of chlorobenzene, 1 -bromo-2-methoxybenzene, and l-chloro-3,5-... 

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