Amidations 4-dimethylaminopyridine

Reaction of N,N-dimethylaniline with 1-cyanobenziodoxol 1783 to afford N-methyl-N-cyanomethylaniline 1784 in 97% yield has been discussed in Section 12.1 [31]. Analogously, oxidation of dimethylaniline with iodosobenzene and trimethylsilyl azide 19 at 0°C in CDCI3 gives the azido compound 2040 in 95% yield, iodobenzene, and HMDSO 7 [194, 195] (Scheme 12.56). Likewise, the nucleophilic catalyst 4-dimethylaminopyridine (DMAP) is oxidized, in 95% yield, to the azide 2041, which is too sensitive toward hydrolysis to 4-N-methylaminopyri-dine to enable isolation [194, 195]. Amides such as 2042, in combination with tri-... 

Tetrazolides can also be formed from phosphoramidites (phosphorous amides) by reaction of tetrazoles in the presence of p-dimethylaminopyridine [ 105]... 

Since formamide is a weak nucleophile, the use of imidazole or 4-dimethylaminopyridine (DMAP) is necessary for acyl transfer to formamide via an activated amide (imidazolide) or acylpyridinium ion. As Scheme 22 illustrates, the reaction starts with the oxidative addition of aryl bromide 152 to Pd(0) species, followed by CO insertion to form acyl-Pd complex 154. Imidazole receives the aroyl group to form imidazolide 155 and liberates HPdBr species. Then, imidazolide 155 reacts with formamide to form imide 156. Finally, decarbonylation of imide 156 gives amide 157. In fact, the formations of imidazolide intermediate 155 and imide 156 as well as the subsequent slow transformation of imide 156 to amide 157 by releasing CO were observed. This mechanism can accommodate the CO pressure variations observed during the first few hours of aminocarbonylation. When the reaction temperature (120 °C) was reached, a fast drop of pressure occurred. This corresponds to the formation of the intermediary imide 156. Then, the increase of pressure after 3 h of reaction was observed. This phenomenon corresponds to the release of CO from imide 156 to form amide 157. ... 

The reaction of methyl 10, l l -dihydropyrrolo[ l, Z-b [ l, 2,5]bcnzothiadiazcpinc-l l -acetate 5,5-dioxide 73 or the corresponding ethyl ester 74 with potassium hydroxide in EtOH at 25 °C gave the acid 75 (Scheme 14), which upon treatment with trifluoroacetic anhydride in tetrahydrofuran (THF) underwent intramolecular cyclization to afford 76. The 1,2,5-thiadiazepines 73 and 74 were then heated with an excess of concentrated ammonium hydroxide to give the carboxamide 77. The acid 75 upon reaction with 4-chlorophenol, 4-chlorobenzyl alcohol, or 4-chloroaniline in the presence of iV-(3-dimethylaminopropyl)-iV -ethylcarbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) afforded the respective esters and amide 78-80 <1996FES425>. 

SCHEME 14.8 Synthesis of the Re-type lipid A from Escherichia coli. DCC, A,A -dicyclo-hexylcarbodiimide DMAP, 4-dimethylaminopyridine LHMDS, lithium bis(trimethylsilyl) amide TES, triethylsilyl. 

Such ionic species could also be detected in solution by 29Si NMR spectroscopy. Nucleophiles like TV-methylimidazole, pA M-dimethylaminopyridine and HMPA showed the strongest coordinating effects110. Mixtures of electrophilic trimethylsilyl compounds and nucleophiles(L), such as amines and amides, are common silylation agents111 and salts Me3SiL+X have been discussed as the active silylation species112. 

Polymer-bound reagents have also been used. The synthetically important Weinreb amides [RCON(Me)OMe, see 16-82] can be prepared from the carboxylic acid and MeO(Me)NH HCl in the presence of tributylphosphine and 2-pyridine-A -oxide disulfide. Di(2-pyridyl)carbonate has been used in a related reaction that generates amides directly. The reaction of a carboxylic acid and imidazole under microwave irradiation gives the amide. Microwave irradiation of a secondary amine, formic acid, 2-chloro-4,6-dimethoxy[l,3,5]tria-zine, and a catalytic amount of DMAP (4-dimethylaminopyridine) leads to the formamide. ° Ammonium bicarbonate and formamide converts acids to amides with microwave irradiation. Lactams are readily produced from y- or 8-amino acids, for example. 

The dimethylamino group was displaced when 4-dimethylaminopyridine was treated with sodium amide under pressure to give a 69% yield of 4-aminopyridine (83USP4386209). At atmospheric pressure, a low yield, 30%, of the normal Chichibabin product, 2-amino-4-dimethylaminopyridine, was obtained (73CHE1119). 

The effect of a halogen atom on the ring of 4-dimethylaminopyridine has been described. Amination of 3-bromo-4-dimethylaminopyridine with potassium amide under homogeneous conditions in liquid ammonia and without an oxidant afforded a 10% yield of 2-amino-5-bromo-4-dimethylaminopyridine and 3-amino-4-dimethylaminopyridine (32%) (87H2905). 

Carboxylic, and arylsulfonic acid halides react rapidly with pyridines generating 1-acyl- and 1-arylsulfonylpyridinium salts in solution, and in suitable cases some of these can even be isolated as crystalline solids. The solutions, generally in excess pyridine, are commonly used for the preparation of esters and sulfonates from alcohols and of amides and sulfonamides from amines. 4-Dimethylaminopyridine (DMAP) is widely used (in catalytic quantities) to activate anhydrides in a similar manner. The salt derived from DMAP and t-butyl chloroformate is stable even in aqueous solution at room temperature. " ... 

N-[3-(Dimethylamino) propyl] wheat germ oil amides, N-oxide. See Wheat germamidopropylamine oxide 4-Dimethylaminopyridine CAS 1122-58-3 El NECS/ELINCS 214-353-5 Synonyms 4-Dimethylaminepyridine y-(Dimethylamino) pyridine p-Dimethylaminopyridine Dimethylpyridin-4-ylamine DMAP 4-DMAP... 

The aprotic solvents, which do not possess hydrogen bond, are highly polar. Therefore, the aprotic solvents possess high alkalinity and nucleophilicity required to obtain a high conversion of o-phenylene diamine in the synthesis of mercaptobenzimidazole (MBI). A larger conversion is obtained when using a protic solvent or aprotic solvent of high polarity. However, the structure of DMF, which is an amide, is similar to that the tertiary amine. It possesses similar catalytic property to dimethylaminopyridine (DMAP). The effect of DMF on the conversion of o-phenylene diamine is more pronounced than that of DMSO. The Arrhenius rate equations in various solvents for the reaction of o-phenylene diamine and carbon disulfide catalyzed by tributylamine are as follows ... 

Trimethylsilyl) ethoxy acetylene jmercuric oxide 14-dimethylaminopyridine Carboxylic acid amides from carboxylic acids COOH... 

In the 3-substituted pyridines, the 2-amino regio-isomer can form selectively. In 3-dimethylaminopyridine (14) case, amination gives 15 exclusively in a 62% yield the product is favored due to the strong ion-dipole interaction of the sodium amide with the dimethyl amino-substituent. ... 

For the addition of the first amino acid to supports derivatized with peptide amide-forming linkers, such as trialkoxybenzhydrylamine 9, trialkoxybenzyl-amine 10, and aminoxanthenyl 11 resins, any of the standard peptide coupling methods described in Section 7 can be used. Since basic reagents such as 4-dimethylaminopyridine are not required to effect this transformation, there is no risk of enantiomerization or dipeptide formation. Many resins of this type are supplied Fmoc-protected and these should be treated with piperidine prior to the addition of the first amino acid. With automated peptide synthesizers, Fmoc removal and loading with the C-terminal residue can be programmed to occur as part of the normal coupling cycle. 

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