Pyridines base-catalyzed

It has generally been assumed that phosphorous oxychloride-pyridine dehydrations, the elimination of sulfonates, and other base catalyzed eliminations (see below) proceed by an E2 mechanism (see e.g. ref. 214, 215, 216). Concerted base catalyzed eliminations in acyclic systems follow the Saytzelf orientation rule i.e., proceed toward the most substituted carbon), as do eliminations (see ref 214). However, the best geometrical arrangement of the four centers involved in 2 eliminations is anti-coplanar and in the cyclohexane system only the tran -diaxial situation provides this. 

Ester eliminations are normally one of two types, base catalyzed or pyrolytic. The usual choice for base catalyzed j5-elimination is a sulfonate ester, generally the tosylate or mesylate. The traditional conditions for elimination are treatment with refluxing collidine or other pyridine base, and rearrangement may occur. Alternative conditions include treatment with variously prepared aluminas, amide-metal halide-carbonate combinations, and recently, the use of DMSO either alone or in the presence of potassium -butoxide. 

The reaction is usually carried out in ether or benzene, but since pyridine markedly catalyzes the rate of the reaction,the use of this base as the sole solvent is recommended. ... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

The alternative product from pyridine-3,4-diamine and ethyl acetoacetate, compound 12, is obtained by the base-catalyzed cyclization of the ester 11, which is formed from the diamine and ethyl acetoacetate in the presence of zinc(II) chloride.298... 

The base-catalyzed Michael addition of 2-chlorocyanoacetate to a,p-unsaturated ketones or aldehydes affords 5-oxopentenenitrile derivatives. In the presence of anhydrous HCl, these compounds cyclize to yield 2-chloro-3-pyridinecarboxylates. The process is highly regiospecific and usefiil in the synthesis of 2,Xdisubstituted pyridines <95T(51)13177>. 

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

Acid (PSTA)-catalyzed acetal hydrolysis followed by base-catalyzed [4-(dialkylamino) pyridine] Baylis-Hillman addition of MVK Catalysts are part of the monomers used to make the resulting star polymer-encapsulated catalysts... 

As mentioned already in CHEC-II(1996) <1996CHEC-II(8)411>, some tetrazolo[l,5- ]pyridines can react with their C(5)-C(6) and C(7)-C(8) double bonds as dienophiles in Diels-Alder reactions. A novel study again supported this recognition Goumont et al. described that 6,8-dinitrotetrazolo[l,5- ]pyridine 11 easily react with some 2,3-disub-stituted butadienes to give bis-cycloadducts 48 <2002T3249>. These products when treated with potassium /-butoxide undergo base catalyzed elimination of nitric acid followed by oxidation reaction to yield the fully aromatic tetracyclic compounds 49 (Scheme 14). 

The third procedure illustrated by this preparation involves the reaotion of ketones with trifluoromethanesulfonic anhydride in a solvent such as pentane, methylene chloride, or carbon tetrachloride and in the presence of a base such as pyridine, lutidine, or anhydrous sodium carbonate.7-11,15 This procedure, which presumably involves either acid-catalyzed or base-catalyzed enolization of the ketone followed by acylation of the enol with the acid anhydride, has also been used to prepare other vinyl sulfonate esters such as tosylates12 or methanesulfonates.13... 

Base-catalyzed addition of glycosyl oxides for anomeric O-activation has been extended meanwhile to trifluoroacetonitrile (see Scheme 9), to dichlor-oacetonitrile, to l-aryl-l,l-dichloroacetonitriles, and to ketene imines (46,51,52). Also 2-(glycosyloxy)-pyridine and -pyrimidine derivatives were readily prepared from the corresponding 2-halo precursors (78). However,... 

The alternative method for making activated esters is base-catalyzed transesterification. Fmoc-amino acids are esterified in excellent yields by reaction with pentafluorophenyl trifluoroacetate at 40°C in the presence of pyridine (Figure 7.13). A mixed anhydride is formed initially, and the anhydride is then attacked by the pentafluorophenoxy anion that is generated by the pyridine. Succinimido, chlorophe-nyl, and nitrophenyl esters were made by this method when it was introduced decades ago. A unique variant of this approach is the use of mixed carbonates that contain an isopropenyl group [Cf C CfyO-COjR]. These react with hydroxy compounds in the presence of triethylamine or 4-dimethylaminopyridine (see Section 4.19) to give the esters and acetone.30 35... 

Another important site of structural variation in cephalosporins is C(3) (Table 5.4.J). Electron-withdrawing substituents at C(3) such as a Cl-atom or a MeO group increase base-catalyzed hydrolysis of cephalosporins by both resonance and inductive effects [92], For cephalosporins carrying 3-methylene-linked substituents with leaving group ability (e.g., acetate, thiol, or pyridine), it has been postulated that a concerted expulsion of the substituent facilitates the nucleophilic attack on the /3-lactam carbonyl group [104][105]. However, there are also arguments for a stepwise process in which the ex-... 

The base-catalyzed deuteration of 4-amino- and 4-A,A-dimethyl-aminopyridine (54) takes place at both the a- and j3-positions, although that at the a-positions strongly predominates in the weakly alkaline solutions made by adding the amine to D2O. The mechanism of the exchange at both positions is similar to that in other pyridines. ... 

Base-catalyzed deprotonation of pjn idine 1-oxides should occur much more readily than in the pjrridines themselves and this prediction has been borne out by several workers. These compounds exhibit the same relative positional reactivity as do the pyridinium ions. For example, for 3-bromopyridine 1-oxide in 0.1 N NaOD-DjO the order is 2>6>4>>5, as would be expected on the basis of the net (it -t- a) electron densities at the various nuclear positions. For pyridine 1-oxide the relative rates of exchange in methanolic methoxide solutions at 50° are... 

Base-catalyzed hydrogen exchange in pyridazine (74) occurs in NaOD-DgO and MeONa-MeOD, ° the positional reactivity being 4(5) > 3(6) in both cases. Once more the decreased reactivity of a center ortho to a nitrogen atom relative to a more removed center is evident like pyridine, pyridazine does not have the regular geometry of benzene. 

Related to the pyridine studies are the results of base-catalyzed hydrogen exchange in cyclobutabenzene derivatives, which suggest that cyclobutyl annelation increases both the kinetic and thermodynamic acidity at the a-position. The most significant study is the thermodynamic deprotonation/carboxylation reaction of cyclobutabenzene with amyl sodium/COj, in which only the a-carboxy isomer is formed (Figure 6). This is consistent with the value for the a-proton being several p units lower than that for the P-proton in cyclobutabenzene (38). 

While arylnitrile oxides dimerize in protic solvents and in pure pyridine (cf. 4.04.8.1.3.), they form bis(adducts) (191) and (192) via zwitterions (189) with pyridine in apolar solvents (Scheme 83) <89JHC757,90Gi>. Significantly, the cycloaddition of the nitrile oxide to pyridine to give (190) is not a concerted process. Heterocycles (191) undergo base catalyzed ring cleavage (Scheme 84). 

Mechanism for Base-Catalyzed Autoxidation of 9,10-Dihydroanthracene. The autoxidation of 9,10-dihydroanthracene in pyridine as the solvent and in the presence of benzyltrimethylammonium hydroxide, a strong base, is believed to involve the reaction of a carbanion and molecular oxygen. Indirect evidence of the existence of the carbanion of dihydroanthracene in pyridine solution comes from the color that forms in the presence of the base. When dihydroanthracene is added to a pyridine solution of the base, a deep blood-red color develops immediately. This color is not completely attributable to carbanions since a trace of anthra-quinone alone will produce it. However, under an inert atmosphere (nitrogen) in which no anthraquinone can be formed, a deep red color is also formed. 

It has been pointed out (75TL213) that path A behavior might be more complex in some instances, and involve initial ylide formation followed by intramolecular proton abstraction (Scheme 202). The aryloxy quaternary salt (274), formed by reaction of pyridine 1-oxide with an arenediazonium salt, undergoes an interesting base-catalyzed rearrangement that is believed to take the course (path E) indicated (Scheme 203) (71JA3074). 

The intermediacy of an anhydro base (57) was referred to in Scheme 46. Analogous anhydro bases (pyridone methides) can be formed by deprotonation of quaternary salts of 2- and 4-benzylpyridines and the like. The pyridone methides are usually highly reactive and not readily isolable some stable examples are shown in Scheme 49. Pyridine methides are intermediates in the base-catalyzed alkylation and acylation reactions of pyridinium salts at the exocyclic carbon. Compounds of type (60) have been estimated to have 25-30% dipolar character. Protonation of (60) occurs at the 2 - and 3 -positions in the ratio 4 1 respectively (70JCS(C)800). 

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