Kolbe-Schmitt synthesis

Section 24 10 The Kolbe-Schmitt synthesis of salicylic acid is a vital step m the preparation of aspirin Phenols as their sodium salts undergo highly regioselective ortho carboxylation on treatment with carbon dioxide at elevated temperature and pressure... 

In this way, the operational range of the Kolbe-Schmitt synthesis using resorcinol with water as solvent to give 2,4-dihydroxy benzoic acid was extended by about 120°C to 220°C, as compared to a standard batch protocol under reflux conditions (100°C) [18], The yields were at best close to 40% (160°C 40 bar 500 ml h 56 s) at full conversion, which approaches good practice in a laboratory-scale flask. Compared to the latter, the 120°C-higher microreactor operation results in a 130-fold decrease in reaction time and a 440-fold increase in space-time yield. The use of still higher temperatures, however, is limited by the increasing decarboxylation of the product, which was monitored at various residence times (t). 

Aqueous Kolbe-Schmitt synthesis from resorcinol to 2,4 dihydroxy cartaoxylic acad... 

Hessel V, Hofmann C, Lob P, Lohndorf J, Lowe H, Ziogas A (2005) Aqueous Kolbe-Schmitt synthesis using resorcinol in a microreactor laboratory rig under high-P,T conditions. Org Process Res Dev 9 479-489 Inoue T, Schmidt MA, Jensen KF (2007) Microfabricated multiphase reactors for the direct synthesis of hydrogen peroxide from hydrogen and oxygen. Ind Eng Chem Res 46 1153-1160... 

Case of Low Plant Costs Kolbe-Schmitt Synthesis.209... 

Fig. 2. Cost analysis for the aqueous Kolbe-Schmitt synthesis for the high-p,T...

Using the high-p,T microreactor processing, the Kolbe-Schmitt synthesis was completed within less than 1 min at comparable yields, i.e., a reaction time reduced by a factor of approximately 2,000 was achieved (see Fig. 6). This corresponds to an increase in space-time yield by a factor of 440. 

Fig. 6. Process intensification of the aqueous Kolbe-Schmitt synthesis of resorcinol using high-p,T processing. (Courtesy of ACS)...

Hessel V, Lowe H, Muller A, Kolb G (2005d) Chemical micro process engineering—processing and plants. Wiley-VCH, Weinheim Hessel V, Hofmann C, Lob P, Lowe H, Parals M (2007) Micro-reactor processing for the aqueous Kolbe-Schmitt synthesis of hydroquinone and phloro-glucinol. Chem Eng Technol 31, (in press)... 

Kolbe hydrocarbon synthesis orgchem The production of an alkane by the electrolysis of a water-soluble salt of a carboxylic acid. kol-bo. hT-dro kar-bon, sin-th3-s3s Kolbe-Schmitt synthesis org chem The reaction of carbon dioxide with sodium phenoxide at 125°C to give salicyclic acid. kol-bo shmit, sin-th3-s3s Konowaioff ruie phys chem An empirical rule which states that in the vapor over a liquid mixture there is a higher proportion of that component which, when added to the liquid, raises its vapor pressure, than of other components., k6-n9 va-lof, rul ... 

Formation of Aromatic Carboxylic Acids The Kolbe-Schmitt Synthesis... 

Figure 5.2 Proposed structures for the PhOK-C02 complex in the Kolbe-Schmitt synthesis.

Scheme 5.3 Structure of the first ortho- and para-intermediates formed in the Kolbe-Schmitt synthesis, as proposed by Markovic et al. [24c, d].

Tommasi et al. recently reported the carboxylation of l,3-dialkyHmidazoHum-2-carboxylates, which can be seen as a remarkable variant of the Kolbe-Schmitt synthesis [27]. In this case, it was shown that l,3-dialkyBmidazolium-2-carboxylates could be synthesized from 1,3-diaIkylimidazolium chlorides and C02 via a Kolbe-Schmitt-type reaction (actually, this was more of a Marasse variant, run in solution). The starting compounds were carboxylated in anhydrous dimeth-ylformamide (DMF) under approximately 5 MPa C02, at temperatures ranging from 353 to 408 K and with Na2C03/C02 as a catalyst, according to Scheme 5.4. 

Scheme 8 Kolbe-Schmitt synthesis of 2,4-dihydrobenzoic acid 29 from resorcinol 28.

There are many other approaches to industrial applications of flash chemistry, although available information is limited. Let us briefly touch on some examples. The Kolbe-Schmitt synthesis serves as a useful standard method to introduce a carboxyl group into phenols (Scheme 10.6). The Kolbe-Schmitt synthesis has been widely used in industry, and there are many variants of this transformation. Microflow systems can be used for conducting the Kolbe-Schmitt synthesis under aqueous high-pressure conditions.A decrease in reaction times by an order of magnitude (a few tens of seconds instead of minutes) and increase in space-time yields by orders of magnitude can be attained using a microflow system. For example, a microflow system composed of five parallel capillaries (inner volume 9 ml) has a productivity of 555 g/h, whereas the productivity of a macrobatch reactor (IL flask) is 28 g/h. 

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