Formamide Process

Several companies developed the Formamide process, but in 2001 it was only practiced by BASF. The process involves the following steps46  

With excess methanol the conversion to methyl formate is 95% with nearly 100% selectivity. 

The dehydration of formamide is conducted in iron catalyst tubes at 380°C to 430°C under reduced pressure. The tubes are filled with Fe or A1 phosphate catalyst that also contains Mg, Ca, Zn or Mn as promoters. The selectivity to HCN is 92% to 95%46. 

The overall performance of the reaction system is listed below  

BASF has obtained European patent 1,110,913, which describes HCN production by the thermolytic reaction of gaseous formamide in the presence of a fine-particle, solid catalyst in a fluidized bed. They claim that the process is more economical and results in less equipment damage. They also received patent DE 10,144,891 for production of HCN from formamide in a flow-type reactor with electric resistance heating. 

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Early in the twentieth century, the first attempts to manufacture formamide directiy from ammonia and carbon monoxide under high temperature and pressure encountered difficult technical problems and low yields (23). Only the introduction of alkaU alkoxides in alcohoHc solution, ie, the presence of alcoholate as a catalyst, led to the development of satisfactory large-scale formamide processes (24). 

The Formamide process is useful for sites with inexpensive carbon monoxide,... 

Elements of the existing formamide process are included in a methyl methacrylate process that Mitsubishi Gas Chemical started up in 1997. The formamide is obtained by reacting hydroxyisobutyramide with methyl formate. Therefore the external requirements for HCN are reduced to the replacement of yield losses131. The process is described in US patent 6,075,162 and the catalyst is described in European patent 1,086,744. 

Six processes are presently of economic significance the Andrussow process is currently the principal HCN manufacturing process in the world, the BMA process is practiced by two companies and provides high yield and selectivity by using a complex reaction system, the Fluohmic process is of interest in locations where electricity is inexpensive, the formamide process is useful for sites with inexpensive carbon monoxide, the BP (British Petroleum) acrylonitrile process produces HCN as a byproduct, and the methanol process. 

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. 

Formamide Process. Developed independently by Du Pont and BSAF, this process was used commercially in Japan and Western Europe but since the 1950s it largely has been replaced by the Andrussow process except for BASF in Germany. The reaction involves the following steps ... 

Formic acid is currently produced iadustriaHy by three main processes (/) acidolysis of formate salts, which are ia turn by-products of other processes (2) as a coproduct with acetic acid ia the Hquid-phase oxidation of hydrocarbons or (3) carbonylation of methanol to methyl formate, followed either by direct hydrolysis of the ester or by the iatermediacy of formamide. 

The carbonylation of methanol [67-56-1] to methyl formate ia the presence of basic catalysts has been practiced iadustriaHy for many years. Ia older processes for formic acid utili2ing this reactioa, the methyl formate [107-31-3] reacts with ammonia to give formamide [75-12-7] which is hydroly2ed to formic acid ia the preseace of sulfuric acid ... 

Coproductioa of ammonium sulfate is a disadvantage of the formamide route, and it has largely been supplanted by processes based on the direct hydrolysis of methyl formate. If the methanol is recycled to the carbonylation step the stoichiometry corresponds to the production of formic acid by hydration of carbon monoxide, a reaction which is too thermodynamicaHy unfavorable to be carried out directly on an iadustrial scale. 

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. 

In addition to the processes mentioned above, there are also ongoing efforts to synthesize formamide direcdy from carbon dioxide [124-38-9J, hydrogen [1333-74-0] and ammonia [7664-41-7] (29—32). Catalysts that have been proposed are Group VIII transition-metal coordination compounds. Under moderate reaction conditions, ie, 100—180°C, 1—10 MPa (10—100 bar), turnovers of up to 1000 mole formamide per mole catalyst have been achieved. However, since expensive noble metal catalysts are needed, further work is required prior to the technical realization of an industrial process for formamide synthesis based on carbon dioxide. 

The reaction is mn for several hours at temperatures typically below 100°C under a pressure of carbon monoxide to minimise formamide decomposition (73). Conversions of a-hydroxyisobutyramide are near 65% with selectivities to methyl a-hydroxyisobutyrate and formamide in excess of 99%. It is this step that is responsible for the elimination of the acid sludge stream characteristic of the conventional H2SO4—ACH processes. Because methyl formate, and not methanol, is used as the methylating agent, formamide is the co-product instead of ammonium sulfate. Formamide can be dehydrated to recover HCN for recycle to ACH generation. 

The best way to make pyrimidine in quantity is from 1,1,3,3-tetraethoxypropane (or other such acetal of malondialdehyde) and formamide, by either a continuous (58CB2832) or a batch process (57CB942). Other practical ways to make small amounts in the laboratory are thermal decarboxylation of pyrimidine-4,6-dicarboxylic acid (744), prepared by oxidation of 4,6-dimethylpyrimidine (59JCS525), or hydrogenolysis of 2,4-dichloropyrimidine over palladium-charcoal in the presence of magnesium oxide (53JCS1646). 

Oxazoles are also obtained by the reaction of a-halogenoketones (78) with primary amides (the Bliimlein-Lewy synthesis), and this method is particularly appropriate for oxazoles containing one or more aryl groups as in (79). Formamide may also be used in this process, resulting in a free 2-position in the oxazole, and when a urea derivative (80) is used, 2-aminooxazoles (81) are formed (80ZOR2185, 78IJC(B)1030, 78JIC264). Numerous applications of these procedures are described in Chapter 4.18. 

Thermoplastic xylan derivatives have been prepared by in-hne modification with propylene oxide of the xylan present in the alkaline extract of barley husks [424,425]. Following peracetylation of the hydroxypropylated xylan in formamide solution yielded the water-insoluble acetoxypropyl xylan. The thermal properties of the derivative quahfy this material as a potential biodegradable and thermoplastic additive to melt-processed plastics. Xylan from oat spelts was oxidized to 2,3-dicarboxyhc derivatives in a two-step procedure using HI04/NaC102 as oxidants [426]. 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

Imino esters with any or all of the three groups being alkyl also rearrange, but they require catalysis by H2SO4 or a trace of methyl iodide or methyl sulfate. The mechanism is different, involving an intermolecular process.This is also true for derivatives for formamide (Ar = H). 

Several reactions have been demonstrated using microreactors. One of the potentially more important is the direct synthesis of MIC from oxygen and methyl formamide over a silver catalyst. Dupont have demonstrated this process using a microreactor cell similar to that described above in which the two reactants are mixed, then heated to 300 °C in a separate layer and subsequently passed through another tube coated with the silver catalyst. The estimated capacity of a single cell with tube diameters of a few millimetres is 18 tpa. 

Allyl chloride and a-phenylethyl chloride are reduced by Cr(II) sulphate in aqueous dimethyl formamide (DMF) in a simple second-order process. At 29.7... 

Transition metal complexes have been used in a number of reactions leading to the direct synthesis of pyridine derivatives from acyclic compounds and from other heterocycles. It is pertinent also to describe two methods that have been employed to prepare difficultly accessible 3-alkyl-, 3-formyl-, and 3-acylpyridines. By elaborating on reported194,195 procedures used in aromatic reactions, it is possible to convert 3-bromopyridines to products containing a 3-oxoalkyl function196 (Scheme 129). A minor problem in this simple catalytic process is caused by the formation in some cases of 2-substituted pyridines but this is minimized by using dimethyl-formamide as the solvent.196... 

In 2001, Sarko and coworkers disclosed the synthesis of an 800-membered solution-phase library of substituted prolines based on multicomponent chemistry (Scheme 6.187) [349]. The process involved microwave irradiation of an a-amino ester with 1.1 equivalents of an aldehyde in 1,2-dichloroethane or N,N-dimethyl-formamide at 180 °C for 2 min. After cooling, 0.8 equivalents of a maleimide dipo-larophile was added to the solution of the imine, and the mixture was subjected to microwave irradiation at 180 °C for a further 5 min. This produced the desired products in good yields and purities, as determined by HPLC, after scavenging excess aldehyde with polymer-supported sulfonylhydrazide resin. Analysis of each compound by LC-MS verified its purity and identity, thus indicating that a high quality library had been produced. 

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