Amide displacement reactions

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Diuretic activity can be retained in the face of replacement of one of the sulfonamide groups by a carboxylic acid or amide. Reaction of the dichlorobenzoic acid, 174, with chlorsulfonic acid gives the sulfonyl chloride, 175 this is then converted to the amide (176). Reaction of that compound with furfuryl ine leads to nucleophilic aromatic displacement of the highly activated chlorine at the 2 position. There is thus obtained the very potent diuretic furosemide (177). ... 

Extractive alkylation is used to derivatize acids, phenols, alcohols or amides in aqueous solution [435,441,448,502]. The pH of the aqueous phase is adjusted to ensure complete ionization of the acidic substance which is then extracted as an ion pair with a tetraalkylammonium hydroxide into a suitable immiscible organic solvent. In the poorly solvating organic medium, the substrate anion possesses high reactivity and the nucleophilic displacement reaction with an alkyl halide occurs under favorable conditions. 

Displacement reactions in the benzo ring can also occur via aryne intermediates. Treatment of 6-choroquinoline with a fourfold excess of potassium amide in ether at -33 °C... 

As a consequence of the polarity of the amide group, the lower-molecular-weight amides are relatively high-melting and water-soluble, as compared to esters, amines, alcohols, and the like. The few that are liquids, such as 7V,7V-dimethylmethanamide and l-methyl-l-aza-2-cyclopentanone, have excellent solvent properties for both polar and nonpolar substances. Therefore they are good solvents for displacement reactions of the SN type (Table 8-5). 

Amines are at the same low oxidation level as alcohols and consequently are easily prepared by reduction. Amides and nitriles are reduced efficiently by LAH to amines. Nitriles give only primary amines while amides give 1°, 2°, or 3° amines depending on the number of carbon substituents on the amide nitrogen. The advantage of this method is that amides are easy to prepare from acid chlorides and amines while nitriles are available by displacement reactions. 

The most common method to decrease the reactivity of an unshared pair of electrons on an atom is to attach a carbonyl group to that atom. Therefore, the amine is first reacted with acetyl chloride to form an amide. (This reaction and its mechanism are described in detail in Section 19.6. To help you remember the reaction for now, note that the nitrogen nucleophile attacks the carbonyl carbon electrophile, displacing the chloride leaving group.)... 

The reactions of the homocyclic ring of benzofuroxans, which are described in detail in Section 4.22.3.3, provide access to numerous derivatives. Nucleophilic displacement of halides is facile when activating nitro groups are present, allowing alkoxy, aryloxy, thio and amino groups to be introduced. Electrophilic substitutions, e.g. nitration, are also valuable. Further transformations may also be performed on benzo-ring substituents. Such modifications include acetoxy to hydroxy acetamido to amino and acyl halides to esters and amides. Some reactions of the substituents of monocyclic furoxans allow hetero-substituted analogues of benzofuroxans to be prepared. For example, pyridazinofuroxans are formed by condensation of diacylfuroxans with hydrazine. 

R R P(S)SC1, have been synthesized as a unique probe for the study of nucleophilic displacement reactions at a dicoordinate sulphur atom. The key intermediate in their preparation was the amide (188 R = L-menthyl) the diastereoisomers of which were readily separated in their ensuing reaction with Me SiCl each afforded the corresponding sulphenyl chloride each of the latter... 

Syntheses that exploit the solubility of the alkaline-earth metals in liquid ammonia have proven practical for alkoxide work, as they generate high yields, reaction rates, and purity (Table 8, Equation (3)). In a refinement of this approach, Caulton and co-workers have used dissolved ammonia in an ethereal solvent, usually THF, to effect the production of a number of alkoxides of barium, and this method has also been examined with calcium and strontium (Table 8, Equations (4a) to (4c)). Displacement reactions using alkali metal alkoxides and alkaline-earth dihalides (Table 8, Equation (5)), and between alkaline-earth hydrides or amides and alcohols (Table 8, Equations (6) and (7)), have been examined, but alkali-metal halide impurities, incomplete reactions, and unexpected equilibria and byproducts can affect the usefulness of these approaches. 

The reactivity of pyridine toward nucleophilic substitution is so great that even the powerfully basic hydride ion, H", can be displaced. Two important examples of this reaction are amination by sodium amide (Chichibabin reaction), and alkylation or arylation by organolithium compounds. 

An extensive study of the decomposition of the N,N-dimethylbenzyl-anilinium ion 22 was recently carried out by Lepley and coworkers 93.99) As expected, displacement reactions occur exclusively with hydroxide and alkoxide, an orf/io-rearrangement occurs with amide, and a variety of products are formed with various organolithium reagents. The products found when butyllithium was employed are listed below. 

A new complex hydride system based on lithium amide has been developed. For this system, the following reversible displacement reaction takes place at 285°C and 1 atm ... 

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