Amides temperature conditions

Microwave-promoted palladium-catalysed processes have found wide general application (see Chapter 2). A Larock-type heteroannulation of an iodoaniline and an internal alkyne has been employed in the synthesis of substituted indoles9 (Scheme 3.7). The microwave conditions were carefully optimised using a focused microwave reactor. Application of microwave heating provided clear advantages in reaction rate and yield over conventional thermal conditions. It is interesting to note that fixed microwave power input provided improved yields over constant temperature conditions (variable microwave power input). This chemistry was successfully extended to a solid-phase format (Rink amide resin)10. 

Reactions between a representative range of alkyl- and aryl-amines and of aliphatic and aromatic acids showed that the direct formation of amides from primary amines and carboxylic acids without catalyst occurs under relatively low-temperature conditions (Scheme 1). The best result obtained was a 60% yield of N-bcnzyl-4-phenylbutan-amide from benzylamine and 4-phenylbutanoic acid. For all these reactions, an anhydride intermediate was proposed. Boric and boronic acid-based catalysts improved the reaction, especially for the less reactive aromatic acids, and initial results indicated that bifunctional catalysts showed even greater potential. Again, anhydride intermediates were proposed, in these cases mixed anhydrides of carboxylic acids and arylboronic acids, e.g. (I).1... 

There has been some recent criticism of the Maillard reaction as a possible humification pathway (Burdon, 2001 Sutton and Sposito, 2005 von Liitzow et al., 2006). First, the critics argue that the Maillard reaction results in the formation of heterocyclic N, whereas soil N consists primarily of amide N based on 15N CPMAS NMR (Knicker and Liidemann, 1995 Knicker, 2004) studies. However, Jokic et al. (2004a) clearly showed, using N K-edge XANES, that the Maillard reaction catalyzed by bimessite under ambient temperature conditions and environmentally relevant pH not only produces heterocyclic N but also a significant amount of amide N (Figure 2.8). 

The most predictable results are obtained with conformation-ally rigid systems, such as those represented in eqs 5 and 6, which possess axially oriented a-protons. This minimizes complications resulting from the presence of diastereotopic a-protons, although unexpected modes of deprotonation have been described with related chiral amides, which may involve boat conformations. To prevent enolate equilibration (with the resulting loss of stereoselectivity), Corey s internal quench method for enolate trapping with silyl chlorides is frequently used. The stereospecificity of this deprotonation is highly dependent on solvent and temperature conditions. Best results are obtained at —100 °C or lower temperatures, with THF as the solvent. 

Alitame is stable in dry, room temperature conditions but undergoes degradation at elevated temperatures or when in solution at low pH. Alitame can degrade in a one-stage process to aspartic acid and alanine amide (under harsh conditions) or in a slow two-stage process by first degrading to its P-aspartic isomer and then to aspartic acid and alanine amide. At pH 5-8, alitame solutions at 23°C have a half-life of approximately 4 years. At pH 2 and 23°C the half-life is 1 year. 

A similar basket-handle porphyrin in which the bridges are linked to the macrocycle by means of amide groups has also been reported by Momenteau et al. (Scheme 8) [75]. The possibility of isolating the atropisomer of mesotetra(o-aminophenyl)porphyrin in pure form and acylating it with a diacid chloride at room temperature (conditions that do not cause significant isomerization of the atropisomers) allows us to obtain the desired cross-Zraui-linked porphyrin (22) in 32% yield after chromatography. 

Ammonolysis anhydrous ammonia reacts with PET producing terephthalic acid amide. Reaction conditions include a temperature range of 120-180 C, 2 MPa and 1-7 h duration [33]. 

Cyclic and secondary amides, such as 2-pyrrolidinone, can be amidocarbony-lated only with formaldehyde (12). Lin and Knifton reported on the catalytic performance of various cobalt/ligand systems in the synthesis of iV-acetylglycine. Basic phosphines, such as PBus, allowed low pressure conditions (55 bar). The addition of Ph2SO or succinonitrile resulted in improved selectivity and facilitated the catalyst recovery (13-15). The addition of acid cocatalysts (plfa < 3 e.g., trifluoroacetic acid) allowed for low temperature conditions and the absence of hydrogen (16) (Scheme 3). 

Some years ago we developed novel families of polydentate hgands of Schiff base and oxime type (L1-L4). Combining at least one imine with oxygen or nitrogen coordination sites (Scheme 1), they facilitate coupling of numerous azole and cyclic amide derivatives (Table 1, entry 1) with aryl bromides under nuld temperature conditions [36-39], [41-43]. With aryl iodides, some reactions were even performed at 25°C and a turnover of about 1,500 was achieved with pyrazole at higher temperature (80°C). This catalytic system is one of the rare examples amongst modem copper chemistry that has already been industrially applied. 

The product of this reaction can be removed as an azeotrope (84.1% amide, 15.9% acetic acid) which boils at 170.8—170.9°C. Acid present in the azeotrope can be removed by the addition of soHd caustic soda [1310-73-2] followed by distillation (2). The reaction can also take place in a solution having a DMAC-acetic acid ratio higher than the azeotropic composition, so that an azeotrope does not form. For this purpose, dimethylamine is added in excess of the stoichiometric proportion (3). If a substantial excess of dimethylamine reacts with acetic acid under conditions of elevated temperature and pressure, a reduced amount of azeotrope is formed. Optimum temperatures are between 250—325°C, and pressures in excess of 6200 kPa (900 psi) are requited (4). DMAC can also be made by the reaction of acetic anhydride [108-24-7] and dimethylamine ... 

Hydrolysis of primary amides cataly2ed by acids or bases is very slow. Even more difficult is the hydrolysis of substituted amides. The dehydration of amides which produces nitriles is of great commercial value (8). Amides can also be reduced to primary and secondary amines using copper chromite catalyst (9) or metallic hydrides (10). The generally unreactive nature of amides makes them attractive for many appHcations where harsh conditions exist, such as high temperature, pressure, and physical shear. 

The cubic 2inc blende form of boron nitride is usually prepared from the hexagonal or rhombohedral form at high (4—6 GPa (40—60 kbar)) pressures and temperatures (1400—1700°C). The reaction is accelerated by lithium or alkaline-earth nitrides or amides, which are the best catalysts, and form intermediate Hquid compounds with BN, which are molten under synthesis conditions (11,16). Many other substances can aid the transformation. At higher pressures (6—13 GPa) the cubic or wurt2itic forms are obtained without catalysts (17). 

Reduction of Carboxylic Acids to Alcohols. In addition to the nonsupported catalysts mentioned for the hydrogenation of amides to amines, mthenium and rhenium on alumina can be used to reduce carboxyHc acids to alcohols. The conditions for this reduction are somewhat more severe than for most other hydrogenation reactions and require higher temperatures, >150° C, and pressures, >5 MPa (725 psi) (55). Various solvents can be used including water. 

Under conditions similar to those already outlined, stable aziridin imine derivatives, e.g. (422) and (423), can be prepared in excellent yields (70-80%) by treating the appropriate a-bromoamidines (easily accessible from the amide precursor) with potassium t-butoxide in ether <70AG(E)38l). At low temperatures the elimination proceeds with high regio- and stereo-selectivity at -40 °C (421) yields predominantly (422). 

The isomerization of oxaziridines (1) to acid amides with migration of a substituent from C to N is a general reaction and is always observed when no other reactions predominate under the relatively harsh conditions (heating to above 150 °C or photolysis). Even then one can make acid amide formation the main reaction by working at 300 °C (57JA5739) and by dilution techniques. For example, caprolactam (63) is formed in 88% yield by flash pyrolysis of oxaziridine (52) at about 300 °C, whereas decomposition of (52) at lower temperatures gives almost no (63) (77JPR274). 

Tetrahydroharman, m.p. 179-80°, has been prepared by a number of workers by a modification of this reaction, viz., by the interaction of tryptamine (3-)5-aminoethylindole) with acetaldehyde or paraldehyde and Hahn et al. have obtained a series of derivatives of tetrahydronorharman by the use of other aldehydes and a-ketonic acids under biological conditions of pH and temperature, while Asahina and Osada, by the action of aromatic acid chlorides on the same amine, have prepared a series of amides from which the corresponding substituted dihydronorharmans have been made by effecting ring closure with phosphorus pentoxide in xylene solution. 

The most common conditions employed in the Madelung process are sodium/potassium alkoxide or sodium amide at elevated temperature (200-400 C). The Madelung reaction could be effected at lower temperature when -BuLi or LDA are employed as bases/ The useful scope of the synthesis is, therefore, limited to molecules which can survive strongly basic conditions. The process has been successfully applied to indoles bearing alkyl substituents. ... 

Bond-Huper [69JCS(C)2453] synthesis, no traces of the described high-melting dark red substance were found. Only tolane-2-carboxylic acid amide (yield 65%) was obtained—the white crystals with a melting temperature of 156-157°C— which coincided with the results of Castro et al. (66JOC4071). Thus, in conditions of acetylide synthesis, o-iodobenzamide forms no bicyclic product. 

The product is relatively stable towards water and aqueous alkalies in which it proves to be insoluble even after dwelling therein several hours at room temperature. It reacts, better if at elevated temperature, with lower alcohols with which it forms the corresponding esters, and with ammonia under suitable conditions for forming the amide (melting point 219°C to 221°C). 

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