Substitution by methoxy

By comparison, substitution by methoxy groups at the chromophore center does not significantly affect TPA as shown for the data obtained for 58a and 58c (Table 3.7). Quantum chemical calculations show that the transition dipole moments possess the largest value along the molecular axis. 

Substitution by methoxy in the aromatic nucleus is readily apparent. The typical shift for the carbon bearing the methoxy group is 30 ppm down field, for an ortho carbon 15 ppm and for a para carbon 7 ppm. The point of attachment is therefore simply determined. 

The para direct deactivation (toward excess piperidine, 45°) by a 4-methyl substituent on 2-nitrobromobenzene (164) is greater than para indirect deactivation by a 5-methyl group (rate of displacement equivalent to absence of a methyl group). A similar result was obtained with 2-nitrochlorobenzenes substituted by methyl or methoxy groups in the reaction with piperidine in benzene. 

When a hydrogen atom is peri to an azine-nitrogen, there is no steric inhibition of resonance activation as there is in 1-nitronaph-thalene (4-methoxy-dechlorination of its 4-chloro derivative seems to be thereby decelerated only 2-fold in rate). Steric hindrance of nucleophihc substitution by the co-planar peri hydrogen is sometimes... 

Quinoxalinyl, 4-cinnolinyl, and 1-phthalazinyl derivatives, which are all activated by a combination of induction and resonance, have very similar kinetic characteristics (Table XV, p. 352) in ethoxylation and piperidination, but 2-chloroquinoxaline is stated (no data) to be more slowly phenoxylated. In nucleophilic substitution of methoxy groups with ethoxy or isopropoxy groups, the quinoxaline compound is less reactive than the cinnoline and phthalazine derivatives and more reactive than the quinoline and isoquinoline analogs. 2-Chloroquinoxaline is more reactive than its monocyclic analog, 2-chloropyrazine, with thiourea or with piperidine (Scheme VI, p. 350). 

Practicable yields of 5-substituted 2-methoxy-3//-azepines 94 can be obtained by photolysis of aryl azides 56 bearing an electron-withdrawing group para to the azide function, although irradiation times tend to be longer and, in general, yields lower than with the corresponding 2-substituted azides.197... 

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

Carbocations are intermediates in several kinds of reactions. The more stable ones have been prepared in solution and in some cases even as solid salts, and X-ray crystallographic structures have been obtained in some cases. An isolable dioxa-stabilized pentadienylium ion was isolated and its structure was determined by h, C NMR, mass spectrometry (MS), and IR. A P-fluoro substituted 4-methoxy-phenethyl cation has been observed directly by laser flash photolysis. In solution, the carbocation may be free (this is more likely in polar solvents, in which it is solvated) or it may exist as an ion pair, which means that it is closely associated with a negative ion, called a counterion or gegenion. Ion pairs are more likely in nonpolar solvents. 

The p-thiolactams 50 are obtained by the action of Lawesson s or Davy s reagent on 3-substituted 1-methoxy- or 1-benzyloxy-azetidinones followed by reductive N-deprotection. The simple P-thiolactam can be modified to give the thiolactam analogues of monobactams <96LA141>. 

Combined activation by nitro and methoxy makes fluorine susceptible to substitution by water. 

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