Carboxylation of amines

A surprising A-carboxylation of amines and anilines using (33) as EGB in MeGN-Et4NGl04 has been reported [114]. Despite the fact that amines and anilines have pK... 

Other base catalyzed methods for N-carboxylation of amines and hydrazines using CO2 and CS2 to generate the corresponding carbamate or thiocarbamate, respectively, are provided (1). Urea derivatives of Step 1 have also been prepared and are described (2). 

This electrochemical synthesis of carbamates is related to the direct cathodic reduction of CO, carboxylation of amine via carbonate anion yielding the carbamate anion and the alkylation of the carbamate anion. For the last step of the whole synthetic process, two possible routes are possible the N-aUcylation of the carbamate anion (yielding nitrogen-derived products and CO elimination) and the... 

Isocyanates. (V-Carboxylation of amines with carbon dioxide followed by treatment with Ph P-DIAD delivers RN=C=0. 

The photochemical carboxylation of amines in aqueous solutions has also been carried out (8,9,10). In addition we have communicated some data on the carboxylation and simultaneous incorporation of sulfur and phosphorus, respectively, in amines under the influence of ultraviolet light (8, 9) or gamma-rays (9, 28). 

The synthesis described met some difficulties. D-Valyl-L-prolyl resin was found to undergo intramolecular aminoiysis during the coupling step with DCC. 70< o of the dipeptide was cleaved from the polymer, and the diketopiperazine of D-valyl-L-proline was excreted into solution. The reaction was catalyzed by small amounts of acetic acid and inhibited by a higher concentration (protonation of amine). This side-reaction can be suppressed by adding the DCC prior to the carboxyl component. In this way, the carboxyl component is "consumed immediately to form the DCC adduct and cannot catalyze the cyclization. 

It IS possible to use only one molar equivalent of amine m these reactions if some other base such as sodium hydroxide is present m the reaction mixture to react with the hydro gen chloride or carboxylic acid that is formed This is a useful procedure m those cases m which the amine is a valuable one or is available only m small quantities... 

Reaction (5.N) describes the nylon salt nylon equilibrium. Reactions (5.0) and (5.P) show proton transfer with water between carboxyl and amine groups. Since proton transfer equilibria are involved, the self-ionization of water, reaction (5.Q), must also be included. Especially in the presence of acidic catalysts, reactions (5.R) and (5.S) are the equilibria of the acid-catalyzed intermediate described in general in reaction (5.G). The main point in including all of these equilibria is to indicate that the precise concentration of A and B... 

Some of the physical properties of fatty acid nitriles are Hsted in Table 14 (see also Carboxylic acids). Eatty acid nitriles are produced as intermediates for a large variety of amines and amides. Estimated U.S. production capacity (1980) was >140, 000 t/yr. Eatty acid nitriles are produced from the corresponding acids by a catalytic reaction with ammonia in the Hquid phase. They have Httie use other than as intermediates but could have some utility as surfactants (qv), mst inhibitors, and plastici2ers (qv). 

Soluble Salt Flotation. KCl separation from NaCl and media containing other soluble salts such as MgCl (eg, The Dead Sea works in Israel and Jordan) or insoluble materials such as clays is accompHshed by the flotation of crystals using amines as coUectors. The mechanism of adsorption of amines on soluble salts such as KCl has been shown to be due to the matching of coUector ion size and lattice vacancies (in KCl flotation) as well as surface charges carried by the soflds floated (22). Although cation-type coUectors (eg, amines) are commonly used, the utUity of sulfonates and carboxylates has also been demonstrated in laboratory experiments. 

Reaction of amines with acyl chlorides (Section 20.4) Amines are converted to amides on reaction with acyl chlorides. Other acylating agents, such as carboxylic acid anhydrides and esters, may also be used but are less reactive. 

AcCl, MeOH, 95-100% yield. This is a convenient method for generating anhydrous HCl in methanol. These conditions are also used to prepare methyl esters from carboxylic acids and for the formation of amine hydrochlorides. ... 

The synthesis of flavones has also seen modifications over the years. One of the primary modifications has been substituting the carboxylate salt for other bases. Kohn and Low showed that catalytic amounts of triethylamine allowed for the reaction to be run at 160 Looker and coworkers expanded on the Kohn and Low modification by using amines as the solvent, and thus reduced the reaction temperatures. They typically found that the reaction could be run at the refluxing temperatures of the amine. They showcased this modification by converting oi-methoxyphloroacetophenone (35) to the methyl ether of galangin (36) using a variety of amines in 60-75% yield with benzoic anhydride. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Amines are derived from ammonia by the replacement of hydrogen atoms with organic groups. Amides result from the condensation of amines with carboxylic acids. Amines and many amides take part in hydrogen bonding. 

Condensation polymerization of amines with carboxylic acids leads to the polyamides, substances more commonly known as nylons. A common polyamide is nylon-66, which is a polymer of 1,6-diaminohexane, H2N(GH2)6NH2, and adipic acid, HOOC(CH2)4COOH. The 66 in the name indicates the numbers of carbon atoms in the two monomers. 

Linking the ketone and carboxylic acid components together in an Ugi reaction facilitates the synthesis of pyrrolidinones amenable to library design. The three-component condensation of levulinic acid 30, an amine and isocyanide proceeds under microwave irradiation to give lactams 31 [65]. The optimum conditions were established by a design of experiments approach, varying the equivalents of amine, concentration, imine pre-formation time, microwave reaction time and reaction temperature, yielding lactams 31 at 100 °C in poor to excellent yield, after only 30 min compared to 48 h under ambient conditions (Scheme 11). 

Although the aminolysis of esters to amides is auseful synthetic operation, usually it presents some disadvantages in terms of drastic reaction conditions, long reaction times or strong alkali metal as catalyst, which are usually not compatible with other functional groups in the molecule [6]. For this reason, enzymatic aminolysis of carboxylic acid derivatives offers a clean and ecological way for the preparation of different kind of amines and amides in a regio-, chemo-, and enantioselective manner. 

Scheme 7.4 Enzymatic acylation of amines with carboxylic acids...

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