Methyl formate synthesis

The synthesis of methyl formate is a typical esterification reaction with a conversion limitation due to chemical equilibrium. Such reactions are suitably carried out in an RD column [1, 13, 62], Methanol (MeOH) and formic acid (FA) are converted to methyl formate (MF) and water (W) according to the reversible reaction 

In contrast to other esterifications, a significant extent of reaction can be reached even without a catalyst though the reaction equilibrium constant is approximately one. A compilation of the major physical property data can be found elsewhere [25, 87]. Fig. 10.2 shows the residue curve map in transformed coordinates as introduced by Doherty and coworkers [108] at a pressure of 1.013 bar. Due to a single maximum azeotrope, there are two distillation regions. The concentration profile in a single feed, two product lab-scale column with 45 bubble cap trays is also displayed in Fig. 10.2. The column is fed with a stoichiometric feed of formic acid and methanol and operated at a reflux ratio of 5. Water and the desired methyl formate are recovered at purities of about 97 % molar concentration in the bottoms and at the top, respectively. 

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Formamide Process. The formamide process was developed by several companies, but in 2001 it was only used by BASF. The process involves the following steps 46 (1) methyl formate synthesis, (2) formamide synthesis, and (3) HCN formation/dehydration. 

Bianchini, C. Glendenning, L. Catalytic production of dimethylformamide from supercritical carbon dioxide. Methyl formate synthesis by hydrogenation of supercritical carbon dioxide in the presence of methanol. Selectivity for hydrogenation or hydroformylation of olefins by hydridopentacarbonylmanganese(I) in supercritical carbon dioxide. Chemtracts Org. Chem. 1996, 9 (6), 318-321. 

Due to the simplicity of the model, the phenomena causing multiplicity can easily be verified. The multiplicity is caused by the relations between the heat of vaporization and the boiling points of the educts, which are Tfl MeOH < f s.PA and AH MeOH > ffvFA- Such relations have also been identified by Jacobsen and Sko-gestad [48] to cause multiplicity in a separation of non-reacting binary mixtures in a one-stage column. Hence, multiplicity is not caused by the reaction but is just the result of the separation only in methyl formate synthesis. Similar results have also been foimd for the esterification of ethanol with acetic acid [25, 50]. 

The bottom row of diagrams in Fig. 10.10 show the results of a comparable study for methyl formate synthesis. There is always a unique steady state, regardless the assumptions on the flow pattern on a tray. Hence, the flow pattern on a tray seems to influence the qualitative behavior of a column tray only in those cases, when complex reaction networks with strongly nonlinear reaction models are considered. 

Fig. 10.10 Cell model to represent cross-flow pattern on distillation tray. Ethyiene glycoi synthesis top row), methyl formate synthesis (bottom row). Well-mixed liquid (left) and liquid plug flow with dispersion for four cells (right)... 

Nonlinear waves in RD have been studied by Balasubramhanya and Doyle III [4] who treat an idealized esterification system, and by Griiner et al. [33] who study a fairly complex, industrial multireaction process. An experimental study of methyl formate synthesis has been carried out by Reder [25, 87] using the lab-scale column introduced above (Fig. 10.2). In all cases the columns are close to chemical equilibrium and therefore behave similar to non-reactive separations. 

Y, and Kato, N. (2004) Alcohol dehydrogenases that catalyse methyl formate synthesis participate in formaldehyde detoxification in the methylotrophic yeast Candida boidinii. Yeast, 21,... 

Pt/AT-ethylpiperidine catalysts have also been described for methyl formate synthesis via methanol carbonylation. Methyl formate is itself a versatile... 

Even though form amide was synthesized as early as 1863 by W. A. Hoffmann from ethyl formate [109-94-4] and ammonia, it only became accessible on a large scale, and thus iadustrially important, after development of high pressure production technology. In the 1990s, form amide is mainly manufactured either by direct synthesis from carbon monoxide and ammonia, or more importandy ia a two-stage process by reaction of methyl formate (from carbon monoxide and methanol) with ammonia. 

However, BASF developed a two-step process (25). After methyl formate [107-31-3] became available in satisfactory yields at high pressure and low temperatures, its conversion to formamide by reaction with ammonia gave a product of improved quaUty and yield in comparison with the earlier direct synthesis. 

Two-Step Process. The significant advantage of the two-step process is that it only requkes commercial-grade methyl formate and ammonia. Thus the cmde product leaving the reactor comprises, in addition to excess starting materials, only low boiling substances, which are easily separated off by distillation. The formamide obtained is of sufficient purity to meet all quaUty requkements without recourse to the costiy overhead distillation that is necessary after the dkect synthesis from carbon monoxide and ammonia. 

Ethanol can also be obtained by the reaction of methanol with synthesis gas at 185°C and under pressure (6.9—20.7 MPa or 68—204 atm) in the presence of a cobalt octacarbonyl catalyst (177). However, although ethanol was the primary product, methyl formate, methyl, propyl and butyl acetates, propyl and butyl alcohols, and methane were all present in the product. 

This is the reverse reaction of the industrial synthesis of methyl formate. This decomposition usually occurs at the end of the synthesis, if a quick treatment of the compound does not free it from the base in the medium. 

The synthesis of (-)-hirsutine (2-795) was concluded by removal of the Boc-group, condensation with methyl formate, and methylation of the formed enol moiety. In a similar manner as was described for 2-795, (+)-dihydrocorynantheine (2-797) [399] with the (3S)- and (15 k)-configuration was synthesized from ent-2-800. 

The treatment of the bromoacetal (255) with catalytic amounts ( 10%) of a Co(I) species, generated by the electroreduction of cobaloxime (232) in an Me0H-LiCl04 system at —1.8 V, produces the cis-fused adduct (256) in 60 70% yield (Scheme 96) [392]. Cathodic reduction is used for the synthesis of a [Co(CO)3PBu3] complex in a methanol-methyl formate medium, which catalyzes the alkoxycarbonylation of dichloromethane to dimethyl mal-onate in up to 75% yield [393]. The Co(II) complexes are found to be effective for the homogeneous reduction of gem-dichlorocyclopropanes in the presence of anthracene [394]. The formation of the C—C double bond of (258) may be ascribed to the a-elimination of the Co-H species. Thus, benzalchloride (257) can be converted to a mixture consisting primarily of ds- and trans-stilbenes (258) by the action of electrogenerated Co(I)(salen) (Scheme 97) [395-398]. 

A highly modified methyl testosterone derivative also exhibits antiandrogenic activity. One synthesis of this compound involves initial alkylation of methyl testosterone (35) by means of strong base and methyl iodide to afford the 4,4-dimethyl derivative 6. Formylation with alkoxide and methyl formate leads to the 2-hydroxymethyl derivative 37. Reaction of this last with hydroxyl amine leads to formation of an isoxazole ring. There is then obtained azastene (38) . 

An interesting reaction of methyl formate is its isomerization to give acetic acid. Based on patent literature, a number of companies have recently reinvestigated this isomerization which has been known for over 30 years ( ). It is unlikely that it can compete with the Monsanto process however, since it doesn t need pure CO and may be operable at milder reaction conditions, some potential may be seen. Combining isomerization to acetic acid and decarbonylation to methanol and CO, could provide a direct synthesis for acetic anhydride starting directly from methyl formate (Equation 13). 

When trimethylorthoformate is utilized as the dehydration agent (Equation 8.), heavies due to Aldol condensation are eliminated. Methyl formate can be easily recovered from the reaction products, but synthetic routes to regenerate trimethylorthoformate are very involved and costly. An advancement to improve trimethylorthoformate synthesis would enhance the attractiveness of the homogeneous oxycarbonylation route to adipic acid. 

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