Amide—► alkyl exchange

Rolgamidine (14) is a dihydropyrrole derivative which has antidiarrheal activity It can be synthesized by alkylation of trans 2,5-dimethyl-3 pyrroline (12) with methyl bromoacefate to give 13 An amide-ester exchange reaction with guanidine hydrochloride completes the synthesis of rolgamidine (14) [3]... 

The reaction of N-arylsulfonylsuinmides with a range of trivalent phosphorus compounds gave near quantitative yields of the phosphinimides and the sulfide. I Addition of protic solvents led to reduction products, which contain, besides the original sulfides, an alkyl-exchanged sulfide in which the alkyl group derived from the alcohol. 126.127 other derivatives, (acid anhydride, amide, ester or thioester) were formed in the presence of carboxylic acid derivatives. 128,129 xhese reactions were favoured by the dipolar nature of the intermediately formed sulfurane. 127... 

A-Tosylsulphimides (90) are reduced to sulphides (92) in DMF in high yields by the action of phosphines or cyanide ion " (Scheme 5). This reaction proceeds by initial attack of the nucleophile on tervalent sulphur (5n2-S mechanism). The intermediate 1,3-dipoles (91) were shown to be powerful dehydrating reagents which converted carbonic acids into anhydrides, or, in the presence of alcohols and amines, into esters and amides, respectively." The use of alcohols alone led to alkyl-exchanged sulphides (93). Thiophenolate ion and (90) gave quantitatively the sulphide arising by a SN2-type reaction on the carbon atom... 

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

Alkyl-CON H2/-CON H R 9-7 Often broad but frequently couple. Primary amides often appear as two broad signals due to partial double bond character of amide bond. Often slow to exchange and may require warming/mild base... 

As with the above pyrrolidine, proline-type chiral auxiliaries also show different behaviors toward zirconium or lithium enolate mediated aldol reactions. Evans found that lithium enolates derived from prolinol amides exhibit excellent diastereofacial selectivities in alkylation reactions (see Section 2.2.32), while the lithium enolates of proline amides are unsuccessful in aldol condensations. Effective chiral reagents were zirconium enolates, which can be obtained from the corresponding lithium enolates via metal exchange with Cp2ZrCl2. For example, excellent levels of asymmetric induction in the aldol process with synj anti selectivity of 96-98% and diastereofacial selectivity of 50-200 116a can be achieved in the Zr-enolate-mediated aldol reaction (see Scheme 3-10). 

O-Protonated cations of eimides in concentrated and anhydrous acids are now well characterized by nmr spectroscopy. O-Protonated cations of N,N-dimethyl amides are most easily observed, even in 72% perchloric acid which has a water activity of about 10 , because for tertiary amides the N-protonated forms is relatively less stabilized by hydration (Liler, 1972a). O-Protonated cations of N-alkyl amides show considerable exchange of NH-protons with the solvent in 72% perchloric acid owing to the intervention of the N-protonated form. For primary amides (acetamide), however, O-protonated cations are not observable in that solvent (Liler, 1972b),... 

Formation of a-Sulfinyl carbanions has been widely investigated17. Several bases were found to be suitable for the generation of these species, e.g., methyllithium and lithium diisopropyl-amide. Butyllithium and rm-butyllithium, however, must be used with caution since they can cause cleavage of the carbon sulfur bond, resulting in an exchange of the ligand at sulfur by a nucleophilic displacement28-29. This method has been used for the preparation of optically active alkyl methyl sulfoxides 28. 

Bridged hydrido- or chloro-Ln amides include [ Lu(45b)(p-H)(thf) 2] and [ Y(45b)-(thf) 2(p-H)(p-Cl)] they were made by hydrogenolysis, or ligand exchange using PhSiHa, from the appropriate alkyl (e.g., CH2,SiMe3) precursor. ... 

The preparation of N-alkyl imides by exchange reaction of an imide with an alkyl amine was documented [104] well before the application of this chemistry to the preparation of polyimides [105], see Scheme 30. Although no experimental details are provided, the initial reaction of pyromellitimide with p,p-methylene dianiline in NMP takes place at reflux temperatures to apparently yield a poly(amic amide). Subsequent heating of this intermediate at elevated temperatures ( 300 °C) provides the desired polyimide with evolution of ammonia. The final polyimide is quoted to be thermally and chemically stable, however, no mechanical properties are given. 

The isoselenazole ring in unsubstituted 3-hydroxy-l-benzo-l,2-selenazole (26) and in its 7-azaanalog (27) exists in nonaromatic amide form such as in 28 or 29 (Scheme 4). The amide proton is easily exchanged, via potassium salt, by alkyl, acyl, or sulfonyl groups. The additional evidence for amide structure is based on spectral data. For example, the amide band nc=0 = 1646 cm 1 in the IR spectrum and the broad singlet at 9.34 ppm in the 11 NMR spectrum were observed for 29 [49-51],... 

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