5-methylresorcinol reaction

A conduction of a reaction under parallel flow in microreactor system was also demonstrated by Kitamori et al. where high conversions were achieved for phase-transfer catalyzed reactions [214]. With the use of a glass microchip, the reaction ofp-nitrobenzene diazonium tetrafluoroborate in water and in ethyl acetate took place in the aqueous layer after rapid phase transfer of 5-methylresorcinol used in excess. Not only higher yields than a conventional reaction in a flask were observed as a result of the large specific interfacial area in the microreactor but also no side products could be detected by fast removal of the main product from the aqueous to the organic phase. The separation of the two phases was easily achieved by splitting the reaction channel into two channels at the end (Figure 4.22). 

Figure 4.22 Reaction of 5-methylresorcinol with p-nitrobenzene diazonium tetrafluoroborate.

By the addition of hydrogen peroxide to a solution of 4-methylphenol in antimony pentafluoride/hydrogen fluoride (2 5) at -40°C and reaction with stirring during 30 mins., 4-methylresorcinol was formed in 78% yield (ref. 14). 

In 1997, Harrison and coworkers reported on the synthesis of an azobenzene compound in microfluidic channels [37] for the purpose of combinatorial synthesis. The azo coupling of N,N-dimethylaniline and 4-nitrobenzene diazonium tetrafluor-oborate (Scheme 4.17) was carried out in a Pyrex microreactor driven by electro-osmotic flow. A few years later, Hisamoto et al. described a phase transfer diazo coupling reaction carried out in a microfluidic chip [38]. By providing a huge liquid-liquid interface between a solution of 5-methylresorcinol dissolved in ethyl acetate and an aqueous solution of 4-nitrobenzenediazonium tetrafluoroborate (Scheme 4.18), 100% conversion within a 2.3 s residence time was achieved. In contrast to macroscale experiments, the reaction could be accelerated and the formation of unwanted precipitates and bisazo side products was successfully suppressed. 

Preparation by reaction of benzoic acid with 2-methylresorcinol in tetrachloro-ethane in the presence of boron trifluoride at 80° for 4 h (70%) [224]. 

Preparation by reaction of benzoyl chloride with 4-methylresorcinol in the presence of aluminium chloride [887]. 

Preparation by reaction of benzonitrile with 5-methoxy-4-methylresorcinol according to Hoesch method (50%) [805]. 

Preparation by condensation of m-acetoxy-benzonitrile with 2-methylresorcinol in the presence of zinc chloride in ethyl ether (Hoesch reaction) (42%) [413]. 

Preparation by reaction of acetic acid on 4-methylresorcinol with zinc chloride (Nencki reaction) (46-60%) [2330,2680-2682]. 

Also obtained by reaction of phenylacetic acid with 2-methylresorcinol in the presence of phosphorous oxychloride and zinc chloride, heating on a water bath for 3 h (45%) [5320]. 

Also obtained by reaction of phenylacetonitrile with 2-methylresorcinol (Hoesch reaction) [5321]. 

Obtained by reaction of isobutyric acid with 2,4-di-methylresorcinol in the presence of boron trifluoride etherate at 120° for 1-2 h under an argon atmosphere. Then, the resulting complex was refluxed for 30 min to 1 h in an aqueous THF (70-80%) [8155]. 

---