Study On The Synthesis Of Amide And Nitrile

Amide and nitrile are useful organic synthetic intermediates, and play an important role in organic chemistry field. Amides have widely been utilized as industrially important raw materials for lubricants, detergent additives, functional polymers, and pharmaceutical intermediates. The applications of nitriles are also very broad, some nitriles even might be used as pesticides, perfumes, metal inhibitors or liquid crystal materials directly. Amide can be synthesized through many reaction routes, nitrile hydration is an important method to synthesise amide. Classically the reaction was carried out in the presence of a strong acid or base catalyst, methods which usually cause over-hydrolysis of the amide into the corresponding carboxylic acid-a faster reaction especially under basic conditions. To overcome these limitations, chemists have always been looking for an effective method which is able to convert nitrile to the corresponding amide with very high selectivity. Beckmann rearrangement reaction is also an important method to prepare amide because its atom efficiency is theoretically100%. In the Beckmann rearrangement, migration of alkyl or aryl group is facile rather than hydrogen. Hence it is not a general process for the transformation of aldoxime into the corresponding amide. To achieve the conversion of aldoxime into the corresponding amide, metal catalyzed approach for the rearrangement of aldoxime into primary amide has been widely reported. The methods of the synthesis of nitriles are numerous, conversion of aldoxime into nitrile is the famous one of them. The dehydration of aldoxime with a dehydrating agent is a conventional method for the preparation of nitrile, however, the approach suffers from a number of disadvantages such as the use of stoichiometric amounts of reagents, and limitations arising from the sensitivity of some functional groups to the reaction conditions. To overcome these limitations, the development of metal-catalyzed dehydration of aldoxime has received much attention.In this dissertation, three methods for synthesis of amide and a method for synthesis of nitrile were studied. The specific research contents include the following aspects.An improved method for the hydration of nitrile to amide by employing hydroxylamine derivatives is afforded. Under the improved protocol, amides were obtained using hydroxylamine derivative in water at refluxing temperature. This method has an advantage of simple operation and no carboxylic acid was detected in the reaction mixture at high temperature. Nitrile having electron-withdrawing groups could be converted into the corresponding amide in good yield at room temperature. A method for the selective hydration of nitrile to amide using inexpensive metal catalysts and commercially available acetaldoxime in environmentally friendly water is disclosed. Simple transition-metal catalysts such as nickel salts, copper salts, zinc salts, cobalt salts, manganese salts, sodium molybdate(VI), sodium metavanadate(V), sodium tungstate(VI) and sodium phosphotungstate display catalytic property in the hydrolysis of nitrile to the corresponding amide. Nickel salt and copper salt are relatively efficient than the other catalysts to perform the hydrolysis reaction. Various nitriles including aromatic nitriles having electron-donating or electron-withdrawing substituents, heterocyclic nitriles, and aliphatic nitriles were converted into the corresponding amides in good to excellent yields. Nitriles having electron-withdrawing groups could be converted into the corresponding amides in good yields at room temperature.2-Cyanopyridine,2-furonitrile,2-thiophenecarbonitrile and their derivatives show high reactivity, these nitriles could be hydrated using metal catalyst and water in the absence of acetaldoxime.In the copper(II) acetate-catalyzed conversion of aldoxime to the corresponding amide, the addition of a catalytic amount of nitrile accelerated the reaction rate. In addition, the addition of nitrile improved the conversion rate of aldoxime and the selectivity for amide formation. Furan-2-carbaldehyde oxime, thiophene-2-carbaldehyde oxime and their derivatives show high reactivity and high selectivity for amide formation, the corresponding amides were obtained in high yield without the addition of nitrile.In the metal-catalyzed conversion of aldoxime to nitrile, all the simple transition-metal catalysts such as copper salts, nickel salts, zinc salts, cobalt salts, iron salts and manganese salts display catalytic property, and cupric acetate shows the highest catalytic activity. The reaction time is short in the copper(II) acetate-catalyzed conversion of aldoximes to nitrile, the corresponding amide was obtained as a by-product in almost all cases. A possible reaction pathway was proposed to explain the formation of amide.