Pyridine bases, acylation

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

The solvent system N2O4/DMF has been employed for the preparation of inorganic esters, e.g., phosphates and sulfates [221] as well as organic esters. The latter products were obtained by reacting the polymer with acyl chlorides, or acid anhydrides in the presence of a pyridine base. The nitrite ester formed has been successfully trans-esterified by the reaction with RCOCl... 

Uncommon IPRs were tested recently. Polymerized acyl monoglydnate surfactant was found to be as effective as sodium dodecylsulfate for the resolution of organic amines [126]. For the analysis of pyridine-based vitamins in infant formnlas, dioc-tylsulfosuccinate produced a unique retention pattern [133], Among bizarre IPRs, tris(hydroxymethyl)aminomethane was used for the determination of cyclamate in foods. It was selected over different ion-pair reagents such as triethylamine and dibu-tylamine, based on sensitivity and time economies [134]. Hexamethonium bromide, a divalent IPR, was used successfully to separate sulfonates and carboxylates [135]. 

Reissert compounds are readily available from both quinolines and isoquinolines upon treatment with an acyl halide and a cyanide source such as AlCl /TMSCN or tri-n -butyltin cyanide. Pyridine-based analogues of Reissert compounds have proved much more elusive, although the use of ethyl chloroformate with either potassium cyanide or aluminium chloride/cyanotrimethylsilane would seem to have overcome this problem. 

Oxazoles were used in the Kondrat eva reaction for the synthesis of pyridine-based compounds (13OL2530, 13OL3550). A continuous flow procedure was reported for a scalable synthesis of benzoxazoles 137 starting form 3-halo-N-acyl anilines 136 (130L5546). The reaction proceeded via a base-mediated elimination of the 3-halo substituents to give an aryne intermediate that underwent intramolecular cyclization to provide lithiated benzoxazoles that were quenched in-line by addition of electrophiles (E ). 

The reaction of benzoyl chloride with ethanol and pyridine to form ethyl benzoate and pyridinium chloride can proceed either by nucleophilic attack of the ethanol or pyridine in the first step. With nucleophilic attack by pyridine, an acyl-pyri-dinium species forms, so this kind of reaction amounts to nucleophilic catalysis by this added base. If ethanol attacks first, the pyridine only acts to scavenge the HCl formed in the reaction. Write these two possible mechani.sms, and derive rate laws that distinguish these possibilities. 

Samal M, Misek J, Stara IG, Stary I (2009) Organocatalysis with azahelicenes the first use of helically chiral pyridine-based catalysts in the asymmetric acyl transfer reaction. Collect Czech Chem Commun 74 1151... 

Acyl chlorides react with carboxylic acids to yield acid anhydrides When this reaction is used for preparative purposes a weak organic base such as pyridine is normally added Pyridine is a catalyst for the reaction and also acts as a base to neutralize the hydrogen chloride that is formed... 

Vinylpyridine (23) came into prominence around 1950 as a component of latex. Butadiene and styrene monomers were used with (23) to make a terpolymer that bonded fabric cords to the mbber matrix of automobile tires (25). More recendy, the abiUty of (23) to act as a Michael acceptor has been exploited in a synthesis of 4-dimethylaminopyridine (DMAP) (24) (26). The sequence consists of a Michael addition of (23) to 4-cyanopyridine (15), replacement of the 4-cyano substituent by dimethylamine (taking advantage of the activation of the cyano group by quatemization of the pyridine ring), and base-cataly2ed dequatemization (retro Michael addition). 4-r)imethyl aminopyri dine is one of the most effective acylation catalysts known (27). 

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... 

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... 

Acylation of alcohols is often performed in the presence of an organic base such as pyridine. The base serves two purposes. It neutralizes the protons generated in the reaction and prevents the development of high acid concentrations. Pyridine also becomes directly involved in the reaction as a nucleophilic catalyst (see Section 8.5). 

Acetonides are quite stable to base, and to oxidation, dehydration and acylation reactions carried out in pyridine. They are cleaved by acid hydrolysis. The 17,21-acetonides of 17a,21-dihydroxy-20-keto steroids and related acetals are split by very mild acid conditions. ... 

Acyl transfer from an acid anhydride to an alcohol is a standard method for the preparation of esters. The reaction is subject to catalysis by either acids (H2SO4) or bases (pyridine). 

From acyl chlorides (Sections 15.8 and 20.4) Alcohols react with acyl chlorides by nucleophilic acyl substitution to yield esters. These reactions are typically performed in the presence of a weak base such as pyridine. 

Enamine acylations have been extended to include the Vilsmeier reaction (409) and thus provide a method for the generation of formyl ketones without the use of strong base. By this method an unsaturated potential trialdehyde could be formed as an intermediate in a pyridine-3-carboxaldehyde synthesis (410). 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

Elimination of the hydroxyaminomethyl moiety from nitro oxime 15 by treatment with a diazonium salt gave hydrazone 43 (75LA1029) (Scheme 15). The same product was obtained by coupling the diazonium salt with the compound 16. On heating in aniline, oxime 15 was transformed into Schiff base 42. Acylation of the oxime 15 with benzoyl chloride in pyridine led to a mixture of furazan 44 and dinitrile 45. 

Due to the nonaromatic character of the oxepin system the oxepinones do not usually form stable enol structures. By O-acylation or O-alkylation, however, the enol forms can be stabilized as enol esters and ethers, respectively. A large number of substituted 1-benzoxepins have been synthesized by this route. Acetylation of l-benzoxepin-3(2//)-ones 1 and l-benzoxepin-5(2/T)-ones 3 was readily achieved with acetic anhydride in the presence of an appropriate base such as pyridine, triethylamine or sodium acetate.t5,t6 t72 176... 

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