For dehydration of amides

Dehydration of amides to nitriles. Lawton and McRitchie (1, 287-288) introduced the use of thionyl chloride and DMF for dehydration of amides. Merck chemists1 obtained improved yields by use of phosphoryl chloride in DMF. For... 

Butylation of phenylacetonitrile with aqueous NaOH, as shown in Scheme 25, proceeds faster by use of high DF (>0.5) anion exchange resins.The strongly alkaline conditions degrade the quaternary ammonium ions of the catalyst. Catalyst (64) (1% DVB) is active for alkylation of phenylacetonitrile and benzyl phenyl ketone, and for Williamson ether synthesis, and it is much more stable in base than AERs. AERs in OH form are catalysts for dichlorocyclopropane syntheses from alkenes, chloroform and solid sodium hydroxide, and for dehydration of amides to nitriles. AERs in the appropriate hydroxide, acetate, or cyanide form are catalysts for aldol condensations, Michael reactions, Knoevenagel condensations, cyanoethylations and cyanohydrin syntheses. " ... 

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. 

In addition to the procedures listed in Table 3.38, further reactions have been used to generate halides upon cleavage. In Section 3.5.2, iodolactonization is presented as a method for the preparation of iodomethyl lactones from resin-bound pentenoic or hexenoic acid derivatives. Closely related to the iodolactonization is the iodine-mediated formation of 2-(iodomethyl)tetrahydrofurans from resin-bound isoxazoli-dines (Entry 9, Table 3.38 for the mechanism, see Figure 15.5). Nitriles can also be prepared by cleavage and simultaneous dehydration of amides RCONH2 from the Rink or Sieber linkers with TFA anhydride (Entry 10, Table 3.38). 

Chiral nitriles.2 This reagent is recommended for the dehydration in 60% yield of primary amides with an asymmetric center at the a-position to chiral nitriles with negligible racemization. The most satisfactory reagents for dehydration of optically active oximes to chiral nitriles is l,l -carbonyldiimidazole or N,N -tlicyclohexylcarbodiimide. 

Amides being formally hydrated ynamines would constitute cheap starting materials for the latter and many stratagems have been devised to achieve this goal. It must be kept in mind, however, that direct dehydration of amides is not feasible. One indirect approach has already been exemplified, namely the prior conversion of amides into thioamides. Another classical method involves halogen chloride elimination from amide chlorides. These versatile salts have received only scant attention prior to 1960. 

Unsaturated nitriles prepared by the dehydration of amides include 1-cyano-1-alkynes, e.g. 1-cyano-l-heptyne (85%), and 1-cyano-l-alkenes, e.g. /3-isopropylacrylonitrile (80%). Some dehydrating agents such as phosphorus pentachloride may lead to the formation of halogen-containing products phosphorus pentoxide is preferred in these cases. In a comparison of methods for preparing olefinic nitriles, it has been shown that... 

Some of these transformations were accompanied by additional reactions, e.g. formylation of the aromatic or heteroaromatic - nucleus or CH-acidic methyl groups further dehydration of amides to nitriles was observed. Adducts from amides and PCI3, sulfonyl halides or SO2CI2/SCXZI2 from which amidines can be obtained by reaction with amine derivatives (compare Section 2.7.2.5 and refs. 5 and 14) have not found wide application for this purpose. An interesting reaction is the preparation of the amidine (294 equation 158) from 7V-pentafluorophenylformamide. By thermal decomposition of the adducts from secondary amides and 7V,iV-dialkylcarbamoyl chlorides amidinium salts were synthesized from which the amidines (295 equation 159) were set free by treatment with bases. " ... 

Dehydration of amides. For eifleient dehydration of the diamide (1), Linstead and co-workers " bubbled phosgene (dried by passage through HjSOJ into a suspension of (1) in pyridine, with cooling to control the temperature to 60-65°. The procedure also proved satisfactory for the conversion of (3) into (4). ... 

Dehydration of amides. Nitriles are conveniently prepared by dehydration of amides with PPE.7 The amide (1 part) and PPE (5 parts) are refluxed in chloroform for about two hours. Yields are in the range 35-90%. 

Another two-step procedure for synthesis of 1 -Rp-isoquinohnes was reported by Pastor and Cambon. The cyclization step involves dehydration of amides 59 by... 

Titanium (IV) chloride in pyridine was found to be a convenient dehydrating agent for aliphatic aldoximes at room temperature [55] yields of 80—90% were obtained. A higher temperature (80°) was necessary for dehydrating syn-ben-zenoid aldoximes thiophen-2-aldoxime gave a 96% yield of nitrile. This reagent is useful also for the dehydration of amides (p. 251). 

General procedure. Nitriles from amides [1128] The procedure used for the dehydration of amides is the same as that described above, except that the reaction mixture is refluxed for 1 h after stirring for 8 h at room temperature. It is then cooled and worked-up as described above. 

Due to their synthetic utility and pharmaceutical applications, a number of synthetic routes to a,P-unsatuiated nitriles have been developed. Classical methods include dehydration of amides [15] or aldoximes [16], Wittig- [17] and Peterson-type [18, 19] olefination processes, ammoxidation of alkenes [20], and carbocyanation of alkynes [21], These approaches suffer variously from high waste generation, low yields and poor stereoselectivity. As such the transition metal-catalysed cyanation of vinyl halides is an attractive route for the synthesis of alkaiyl nitriles. Whilst several instances of such transformations have been reported in the literature, the area remains underdeveloped, particularly in comparison to analagous cyanations of aryl halides. 

The dehydration of amides is one of the most important methods for the preparation of nitriles, and many reagents are known to effect this transformation. Two new reagents have now been reported " which significantly add to the available methodology. In one, amides (and thioamides) undergo conversion into the corresponding nitriles when treated with cyanuric chloride in DMF solution at room temperature (Scheme 22). In the other, " the preformed Vilsmeier reagent (16) and pyridine in DMF also effect the dehydration within minutes at 0°C this method is especially useful for the synthesis of a ,/3-unsaturated nitriles (Scheme 23). 

Nitriles are important organic intermediates for a variety of ene products. Rao tt al. reported the dehydration of amides to nitriles by passing the vapor of amides through ZSM-5 zeolites at 673 Benzamide, phenacetamide, nicotinamide and isovaleramide gave the corresponding nitriles in 90%, 85%, 89% and 85% yields, respectively. 

The dehydration of amides is probably the best known of the elimination reactions for the preparation of nitriles. One method, the dehydration with phosphorus pentoxide, has been used for many years although it is undoubtedly one of the most messy synthetic procedures available. The procedure normally involves a dry distillation... 

Dehydration of Amides to Nitriles. Dehydration of amides with P2O5 is one of many methods for the synthesis of nitriles. Distillation of an unsubstituted amide from an excess of P2O5... 

T1CI4 with a tertiary base provides mild conditions for dehydration of both aldoximes and primary acid amides to form nitriles. Vinyl sulfides are formed from 0x0 compounds using TiCU and a... 

Introduction. The Ph3PBr2 adduct was first used in synthesis in 1959 for the preparation of alkyl and acyl bromides from alcohols and carboxylic acids, and for the dehydration of amides and oximes to nitriles. Since then it has been widely employed as a versatile reagent for a number of synthetic reactions. 

Itagaki S, KamataK, Yamaguchi K, Mizuno N (2013) Amonovacantlacunary silicotungstate as an efficient heterogeneous catalyst for dehydration of primary amides to nitriles. ChemCatChem 5 1725-1728... 

By the dehydration of primary amides with phosphorus pentoxide or with thionyl chloride, for example ... 

Nitrile Process. Fatty nitriles are readily prepared via batch, Hquid-phase, or continuous gas-phase processes from fatty acids and ammonia. Nitrile formation is carried out at an elevated temperature (usually >250° C) with catalyst. An ammonia soap which initially forms, readily dehydrates at temperatures above 150°C to form an amide. In the presence of catalyst, zinc (ZnO) for batch and bauxite for continuous processes, and temperatures >250° C, dehydration of the amide occurs to produce nitrile. Removal of water drives the reaction to completion. 

The formation of amides can be accompHshed by dehydration of the ammonium salts of sahcyhc acid. The more common method for amines is the reaction of the ester, acyl hahde, or anhydride with an amine or ammonia. Each step is fast and essentially irreversible. 

The great reactivity of the sulfurane prepared by this procedure toward active hydrogen compounds, coupled with an indefinite shelf life in the absence of moisture, makes this compound a useful reagent for dehydrations,amide cleavage reactions, epoxide formation, sulfilimine syntheses, and certain oxidations and coupling reactions. 

The simplest method of nitrile preparation is the Sj 2 reaction of CN with a primary or secondary alkyl halide, as discussed in Section 20.5. Another method for preparing nitriles is by dehydration of a primary amide, RCONH2. Thionyl chloride is often used for the reaction, although other dehydrating agents such as POCI3 also work. 

Hajek et al. [173] have reported a detailed kinetic study of the solid phase decomposition of the ammonium salts of terephthalic and iso-phthalic acids in an inert-gas fluidized bed (373—473 K). Simultaneous release of both NH3 molecules occurred in the diammonium salts, without dehydration or amide formation. Reactant crystallites maintained their external shape and size during decomposition, the rate obeying the contracting volume equation [eqn. (7), n = 3]. For reaction at 423 K of material having particle sizes 0.25—0.40 mm, the rate coefficients for decompositions of diammonium terephthalate, monoammonium tere-phthalate and diammonium isophthalate were in the ratio 7.4 1.0 134 and values of E (in the same sequence) were 87,108 and 99 kJ mole-1. 

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