M-Methoxyacetophenone

Mannich condensation of the primary amine corresponding to ephedrine (32) with formaldehyde and m-methoxyacetophenone yields oxyfedrine (33), this agent retains the vasodilating activity of ephedrine and is in fact denoted a coronary vasodilating agent. 

Methoxyacetonitrile, 21, 79 m-Methoxyacetophenone, 21, 79 5t(3-Methoxy-4 hydroxybenzal)-creatinine, 22, 90, 93 5-(3-Methoxy-4-hydroxybenzyl)-CREATININE, 22, 90... 

The ODPM reactivity of (B.y-unsaturated aldehydes is not restricted to y-phenyl-substituted compounds but can also be extended to systems in which the intermediate biradicals are stabilized by conjugation with a vinyl group. Thus, m-methoxyacetophenone-sensitized irradiation of 40 (Structures 40-49) for 20 min, affords the cyclopropane derivative 41 (47%) as a 1 8 mixture of cisitrans isomers. Similarly, irradiation of 42, for 15 min, under the same conditions, yields 43 (52%) as the trans isomer exclusively [51]. 

Fig. 1. Concentration dependence of the efficiency of energy transfer A, p-methoxy-acetophenone o, m-methoxyacetophenone A, 3,4-methylenedioxyacetophenone , thioxanthone. (From Chapman and Wampfler48 with permission of the American Chemical Society.)...

The ewrfo-configuration of the hydroxyketones 82 and 83 formed from camphorquinone has been unequivocally established 15> and shown to be related to configurations of the aldehyde adducts. This stereochemical result requires attack from the normally more hindered side of the molecule. As discussed earlier (cf. Table 4) m-methoxyacetophenone sensitized the reduction of camphorquinone in 2-propanol, and benzo-... 

Coincident with the decrease in the quantum yield of photoreduction with lowest ir- -it and CT triplet states, there is an increase in the triplet lifetime. This behavior is also observed in the photoreduction of substituted acetophenones, the data for which are presented in Table 3.8. ° In this case the quantum yield for photoreduction in isopropanol drops by a factor of 1000 from that of acetophenone itself to that m-methoxyacetophenone although there is only a minor difference in their triplet energies. These facts again indicate that a factor related to the electronic structure of the lowest triplet state must be responsible for the change in reactivity with substitution. We note in Table 3.8 that the lowest triplet of acetophenone is an n->n statd while that of m-methoxyacetophenone is A qualitative idea of the differences in electronic structure in these three types of triplet states can be obtained from the following exaggerated structures ... 

A mixture of 250 mg 3,3-dimethyl-1,5,5-triphenyl-2-aza-l,4-pentadiene (0.80 mmol), 550 mg m-methoxyacetophenone (3.7 mmol) and 450 mL dry -BuOH was put into a quartz immersion well apparatus with a Pyrex filter. The solution was purged with argon for 1 h and was irradiated with a 400-W medium-pressure mercury arc lamp for 6 h. After completion of the irradiation, the solvent and the sensitizer were removed under reduced pressure, the residue was chromatographed with hexane/Et20 (99 1) as an eluent to afford 65.0 mg benzaldehyde, and 13.0 mg of cyclopropylimine as a colorless oil, in a yield of 5%. Further elution with Et20 yielded 25 mg of a highly polar material. Final elution with EtOH afforded 148 mg l,l-dimethyl-3,3-diphenyl-2-propenylamine, in a yield of 81%. 

In another area, the asymmetric reductive acylation of ketoxime of m-methoxyacetophenone was developed by Kim and co-workers, in 2010. This process was catalysed by a combination of lipase CALB with a palladium nanocatalyst in the presence of ethyl methoig acetate as an acyl donor, molecular sieves in toluene at 70 °C under 0.1 bar of hydrogen pressure. It allowed the formation of the corresponding almost enantiopure amide in high yields of up to 91% and with enantioselectivity of 98% ee, as shown in Scheme 8.77. The utility of this novel methodology was applied to the total synthesis of the calcimimetic (-l-)-NPS R-568. 

To avoid synthetic problems, we prepared aldehyde 47, a substrate in which isomerization of the C-C double bond to the endocyclic position is less likely due to the extended conjugation of the alkene moiety. Compound 47 was obtained as a pure substance and also presents a substitution pattern that, according to the above postulates, should favor the ODPM rearrangement. However, irradiation of 47, using m-methoxyacetophenone as sensitizer, led to formation of the diene 48 (38%), as a result of photodecar-bonylation (Scheme 9). No ODPM product was formed in this process.Irradiation of the corresponding methyl ketone 49, under the same conditions as used for 47, afforded the product of 1,3-acyl migration 50 in 24% yield (Scheme 9). Again, no ODPM product was formed in this instance. The formation of 48 and 50 is reminiscent of Norrish Type 1 processes. However, in these cases, homolytic bond fission does not occur in the carbonyl nit excited state, as is the case in normal Norrish Type 1 reactions. ... 

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