Amines carbon dioxide elimination

When a carbonyl group is bonded to a substituent group that can potentially depart as a Lewis base, addition of a nucleophile to the carbonyl carbon leads to elimination and the regeneration of a carbon-oxygen double bond. Esters undergo hydrolysis with alkali hydroxides to form alkali metal salts of carboxylic acids and alcohols. Amides undergo hydrolysis with mineral acids to form carboxylic acids and amine salts. Carbamates undergo alkaline hydrolysis to form amines, carbon dioxide, and alcohols. 

Union Carbide has developed Amine Guard, which essentially eliminates corrosion in amine systems (32—35). It permits the use of substantially higher amine concentrations and greater carbon dioxide pick-up rates without corrosive attack. This results in an energy requirement comparable to that of the carbonate process and allows the use of smaller equipment for a specific C02-removal appHcation thereby reducing the capital cost. 

Ethoxy-6-methylpyrimidine 1-oxide (499) reacts with phenyl isocyanate to eliminate carbon dioxide and give a mixture of 4-ethoxy-6-methyl-N-phenylpyrimidin-2-amine (SOO) and (the derived) 7V-(4-ethoxy-6-methylpyrimidin-2-yl)-7V,7V -diphenylurea (SOI) phenyl isothiocyanate reacts quite differently (79CPB2642). 

The [8 + 2] cycloaddition reactions between substituted cyclohcpta h]furan-2-ones and enamines have been described by Kuroda and coworkers312. The cycloaddition reactions proceeded with concomitant elimination of carbon dioxide and amine. Thus, the reaction between 527 and enamine 528 afforded [8 + 2] cycloadduct 529 with good yield (equation 153)312c. 

Although these protecting groups may seem bizarre, their value lies in the fact that they can be removed easily by acid-catalyzed hydrolysis under very mild conditions. The sequence of steps is shown in Equation 23-10 and involves proton transfer to the carbonyl oxygen and cleavage of the carbon-oxygen bond by an SN1 process (R = tert-butyl) or SN2 process (R = phenyl-methyl). The product of this step is a carbamic acid. Acids of this type are unstable and readily eliminate carbon dioxide, leaving only the free amine (also see Section 23-12E) ... 

A pharmaceutical intermediate was initially produced at a scale of 500 kg (product) per batch in a 2.5 m3 reactor. The reaction was the condensation of an amino-aromatic compound with an aromatic chloride to form a di-phenyl amine by elimination of hydrochloric acid. This acid was neutralized in situ by sodium carbonate, forming water, sodium chloride, and carbon dioxide. The manufacturing procedure was very simple The reactants were mixed at 80 °C, a temperature above the melting point of the reaction mass. Then the reactor was heated with steam in the jacket to a temperature of 150 °C. At this temperature, the steam valve had to be closed and the reaction left to proceed for a further 16 hours. During this time, the temperature increased to a maximum of 165 °C. Several years later, the batch size was increased to 1000 kg per batch in a 4 m3 reactor. Two years after this a further increase to 1100 kg was decided. 

In aprotic media a l-(acyloxycarbonyl)imidazole such as 16 is formed primarily which reacts to the acylimidazole and carbon dioxide. Imidazole now serves as a good leaving group and so the previously synthesized amine 6 could be added and the desired amide was formed via the usual addition elimination mechanism. One of the advantages of using this more expensive way of activation is the possibility to run the nitro reduction, acid activation and acylation in the same solvent (ethyl acetate) thus all three reactions could be telescoped into a single step during production. 

The polymerisation of a-aminoacid A-carboxyanhydride, which is accompanied with the elimination of carbon dioxide, constitutes a convenient method for preparing high molecular weight polypeptide. This polymerisation, with the use of a-aminopropionic acid (alanine) A-carboxylic acid anhydride as a monomer, was also carried out in the presence of coordination catalysts such as group 2 and 3 metal alkyls [168-174] or their combinations with water, secondary amine or alcohol [168,173] and yielded polyalanine (Table 9.2). 

The product contains the carbamate functional group, which has characteristics of both an amide and an ester. Thus, the amine is protected as an amide, but the ester part of the carbamate can be readily removed. In fact, the /-butyl group of the carbamate can be removed by treatment with dilute acid. (This is the same SN1 process that is described in Section 23.3) The resulting carbamic acid is unstable and spontaneously eliminates carbon dioxide, regenerating the amine. An example is provided by the following equation ... 

Polyurethane foams are prepared by including some water when the monomers are mixed. The reaction of an isocyanate with water produces a carbamic acid. As discussed in Section 23.4, a carbamic acid is unstable and spontaneously eliminates carbon dioxide to form an amine. This reaction is illustrated for toluene diisocyanate in the following equation ... 

The ester bond of the carbamate group is hydrolyzed more rapidly than either amide bond. The resulting carbamic acid then eliminates carbon dioxide to produce the amine. Conditions drastic enough to hydrolyze an amide bond are never employed in this process. 

Mixed carbonic anhydrides are a form of activated esters that can react with amines to form amides. The addition-elimination mechanism, illustrated below using arrow pushing, involves addition of an amine followed by an elimination step driven by the release of carbon dioxide. 

Nitrogen is eliminated chiefly as ammonia from nitrides or carbo-nitrides. Frequently, a white crystalline solid, which can be decomposed thermally to ammonia and carbon dioxide, is found in product receivers, especially in the initial stages of the synthesis with nitrides. Presumably this solid results from a reaction of gaseous ammonia and carbon dioxide in the product receivers which are at room temperature. Qualitative evidence has been obtained for the presence of small amounts of methyl amine in the aqueous product. 

Another interesting application is the selective reduction of aldehyde functions under water-gas shift reaction conditions [21]. Starting from Rh6(CO)i6 in the presence of an amine in aqueous media, the anionic cluster anion [Rh6(CO)i5H] forms via nucleophilic attack of hydroxide, followed by elimination of carbon dioxide. The anionic hydride cluster is thought to be the active species in the reduction of a number of aldehydes according to eq. (10). 

If the attempt is made to eliminate hydrobromic add in the presence of water by the use of caustic potash solution, the above reaction takes place, but the isocyanate is unstable in the presence of alkalies, and decomposes immediately by taking up the water forming carbon dioxide and a primary amine ... 

The Hofmann reaction is capable of general application. By use of it, the primary amine of the next lower series may be obtained from any acid-amide, since the elimination of carbon dioxide takes place-With the higher members of the series, the reaction in part proceeds still further, since the bromine acts upon the primary amine to form a nitrile ... 

In a number of catalytic reactions, carbon monoxide can serve to eliminate oxygen from organic substrates. In particular, nitrogen-containing functions can be reduced in this way to give imine, amine, or even nitro functions. Accordingly, carbon dioxide is formed in these reactions. 

Japanese workers have developed a new synthesis of ureas and thioureas through the reaction of carbon dioxide or carbon disulphide with diphenyl phosphite and primary amines. The reaction is thought to take place via an intermediate (85), followed by elimination to give isocyanate or direct displacement by amine. The principles of this new synthesis have also been applied to the preparation of peptides and amino-acid esters. 

Wada14 claimed that it was advantageous first to convert the a-amino acid by, e.g.9 urea into the hydantoin and to boil this with aqueous acid or alkali, thus obtaining the next lower amine by simultaneous hydrolysis and elimination of carbon dioxide. However, the process has been tested by several authors who failed to reproduce it under the conditions given by Wada. 

The penicillins are hydrolysed by hot dilute inorganic acids one carbon atom is eliminated as carbon dioxide (CO2) and two products are obtained in equimolecular proportions, one being an amine, Pencillamine and the other an aldehyde, Penniloaldehyde. 

---