Pyridines, acylation amination

There is evidence from a detailed study of the photolyses of 2-alkyl-substituted aryl azides 40 in diethylamine that A3,7V-diethyl-1 //-azepin-2-amines are formed as oxygen-sensitive, meta-stablc intermediates that can give rise to a variety of byproducts, including 5-acyl- A%V-diethyl-pyridin-2-amines and 6-alkyl-7-(diethylamino)-2//-azepin-2-ones 11 however, formation of these oxidation products can be avoided by refluxing the photolysate mixture with methanol prior to exposure to oxygen, in which case practicable yields of the /V,/V-diethyl-3W-azepin-2-amines 41 result. 

In a related procedure, even benzene and substituted benzenes (e.g., PhMe, PhCl, xylenes) can be converted to phenols in good yields with sodium perborate F3CS020H. " Aromatic amines, N-acyl amines, and phenols were hydroxylated with H2O2 in SbFs—HF. Pyridine and quinoline were converted to their 2-acetoxy derivatives in high yields with acetyl hypofluorite AcOF at -75°C. ... 

Hydrogenolytic ring opening of the 5-substituted 1,2,4-oxadiazole ring of 3-(l,2,4-oxadia-zol-3-yl)pyridin-2-amines 5 in the 3-position creates a C-N -C side chain in the form of an acylated amidine 6. In refluxing xylene this cyclizes with the amino group in the 2-position to yield pyrido[2,3-c/]pyrimidin-4-amines 7.9... 

It is recommended that these reactions be conducted in the presence of bases without active hydrogen atoms (pyridine, triethyl amine, etc.). These basic media are necessary for the conversion of acidic by-products into non-volatile salts to protect the acid-sensitive analytes from decomposition and to avoid the appearance of extra peaks of by-products on the chromatograms. Exceptions are indicated by reagent/(H ). Phenols can be converted into Na salts before acylation. A large variety of anhydrides of perfluormated carboxylic acids are recommended for derivatization because of the favorable chromatographic properties of perfluoroacyl derivatives. 

Isomerization of 3-cephems (27) to 2-cephems (28) takes place in the presence of organic bases (e.g. pyridine) and is most facile when the carboxyl is esterified. Normally an equilibrium mixture of 3 7 (3-cephem/2-cephem) is reached. Since the 2-cephem isomers are not active as antibacterial agents, the rearrangement proved to be an undesirable side reaction that complicated acylation of the C-7 amine under certain conditions. A method for converting such mixtures to the desired 3-cephem isomer involves oxidation with concomitant rearrangement to the 3-cephem sulfoxide followed by reduction. Additions... 

Purine, 9- -D-ribofuranosyl-6-selenoxo- 1,6-dihydro-synthesis, 5, 597 Purine, 6-thiocyanato-acylation, 5, 559 Purine, 2-thioxo-synthesis, 5, 589 Purine, 8-thioxo-iodination, 5, 559 synthesis, 5, 577, 597 Purine, 2-thioxo-2,3-dihydro-synthesis, 5, 572 Purine, 6-thioxo-1,6-dihydro-acylation, 5, 559 dethiation, 5, 558 halogenation, 5, 559 hydrolysis, 5, 560 methylation, 5, 535 oxidation, 5, 560 synthesis, 5, 572, 596 Purine, 8-thioxo-7,8-dihydro-acylation, 5, 559 Purine, 2,6,8-trichloro-alkylation, 5, 530 amination, 5, 562 reactions, 5, 561, 562 with hydriodic acid, 5, 563 with pyridine, 5, 562 synthesis, 5, 598 Purine, 2,6,8-trichloro-7-methyl-synthesis, 5, 557 Purine, 8-trifluoromethyl-synthesis, 5, 574... 

Pyridine, 3-(dimethylamino)-amination, 2, 236 methylation, 2, 342 nitration, 2, 192 iV-oxide synthesis, 2, 342 Pyridine, 4-(dimethylamino)-in acylation, 2, 180 alkyl derivatives pK, 2, 171 amination, 2, 234 Arrhenius parameters, 2, 172 as base catalysts, 1, 475 hydrogen-deuterium exchange, 2, 286 ionization constants, 2, 172 methylation, 2, 342 nitration, 2, 192 iV-oxide synthesis, 2, 342... 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

Novel amine chemistry based on 4-(dimethylamino)pyridine-catalyzed acylation 98ACR494. 

The ring contraction of 3//-azepines is also promoted by acylating agents,54 35 and by arenesulfonyl halides.34 For example, in refluxing acetic anhydride A,-phenyl-3//-azepin-2-amine yields 2-acetamidodiphenylamine (22% mp 121-122°C),34 whereas A,A,-diethyl-3/7-azepin-2-amine (30) with 4-nitrobenzoyl chloride in pyridine yields the benzanilide 31.35... 

Thermolysis of the 3-acyl-3/f-azepine 32 in Decalin at 250°C also gives the phenacylpyridine but in much reduced yield (6%). In a similar manner, 4-chloro-yV,/V-diethyl-3-phenacylpyridin-2-amine (53 % bp 160 C/0.18 Torr) is produced by the photolysis or thermolysis of 3-benzoyl-5-chloro-Ar,Ar-diethyl-3/f-azepin-2-amine.246 However, if the 3ff-azepine bears a secondary amine residue at the 2-position, e.g. 36, then photolysis or thermolysis yields a pyrrolo[2,3-/>]pyridine by intramolecular cyclization of the 3-phenacylpyridin-2-amine intermediate. 

In the course of this study, the authors determined /Lvalues for dibenzyl, methyl phenyl, methyl p-nitrophenyl, di-p-tolyl, di-isopropyl and tetramethylene sulphoxides and for diethyl, dipropyl and dibutyl sulphites. The /Lscales are applied to the various reactions or the spectral measurements. The /Lscales have been divided into either family-dependent (FD) types, which means two or more compounds can share the same /Lscale, family-independent (FI) types. Consequently, a variety of /Lscales are now available for various families of the bases, including 29 aldehydes and ketones, 17 carboxylic amides and ureas, 14 carboxylic acids esters, 4 acyl halides, 5 nitriles, 10 ethers, 16 phosphine oxides, 12 sulphinyl compounds, 15 pyridines and pyrimidines, 16 sp3 hybridized amines and 10 alcohols. The enthalpies of formation of the hydrogen bond of 4-fluorophenol with both sulphoxides and phosphine oxides and related derivatives fit the empirical equation 18, where the standard deviation is y = 0.983. Several averaged scales are shown in Table 1588. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Derivatives are prepared from the appropriate acid anhydride, or occasionally the acid chloride, usually in the presence of a base such as pyridine, triethylamine, or N,N-dimethyl-4-amlnopyridine at elevated temperatures [474-482]. Acylation of amines and phenols (not alcohols) in aqueous solution in the presence of potassium carbonate has been demonstrated (448,483,484), but does not constitute m l practice as reactions are generally performed under i Arous conditions. 

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

It must further be mentioned that the acylation of alcohols, phenols, and amines with acid chlorides (and also anhydrides) is now frequently carried out in pyridine solution instead of according to the older Schotten-Baumann method (action of acid chloride in aqueous-alkaline suspension). The hydrogen chloride is fixed by the pyridine. 

The reaction of AK6-amino-4-quinazolinyl)aminomethylenemalonate (1460, R = NH2) and acyl chloride in methylene chloride in the presence of pyridine at 0°C afforded the 6-acylamido derivatives (1505) (81EUP30156). When the amine (1460, R = NH2) was repeatedly reacted with acetic anhydride in pyridine, the /V,/V-diacetylamino derivative (1506) was obtained. Treatment of the amine (1460, R = NH2) with pivaloyl chloride in methylene chloride in the presence of pyridine gave the pivaloylamido derivative (1505, R = Me3C—), while in DMF in the presence of pyridine a mixture of the pivaloylamido and 6-formamido derivatives (1505, R = Me3C— and H) was obtained. 

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