Pyridines mechanism

Dichlorobutane. Place 22-5g. of redistilled 1 4-butanediol and 3 ml. of dry pyridine in a 500 ml. three necked flask fitted with a reflux condenser, mechanical stirrer and thermometer. Immerse the flask in an ice bath. Add 116 g. (71 ml.) of redistilled thionyl chloride dropwise fix>m a dropping funnel (inserted into the top of the condenser) to the vigorously stirred mixture at such a rate that the temperature remains at 5-10°. When the addition is complete, remove the ice bath, keep the mixture overnight, and then reflux for 3 hours. Cool, add ice water cautiously and extract with ether. Wash the ethereal extract successively with 10 per cent sodium bicarbonate solution and water, dry with anhydrous magnesium sulphate and distil. Collect the 1 4-dichloro-butane at 55-5-56-5°/14 mm. the yield is 35 g. The b.p. under atmospheric pressure is 154 155°. 

Mount a I litre bolt-head flask, fitted with a mechanical stirrer, on a water bath. Place 168 g. of powdered copper sulphate pentahydrate, 210 g. (214 ml.) of pyridine and 90 ml. of water in the flask, start the... 

Tetrahydrofurfuryl chloride. Place 204 g. (194 ml.) of freshly distilled tetrahydrofurfuryl alcohol (b.p. 177°) and 174 g. (178 ml.) of dry pyridine in a 1-litre three-necked flask, fitted with a dropping funnel, mechanical stirrer and thermometer. Cool in an ice bath, stir vigorously and add 250 g. (153 ml.) of freshly distilled thionyl chloride at the rate of 3-5 drops per second. A pasty crystalline mass begins to separate and the temperar ture commences to rise rapidly when one-third to one-half of the thionyl chloride has been added subsequently the mass largely redissolves and a dark brown liquid forms. Remove the ice bath when the addition is complete and stir the mixture for 3-4 hours. Pour the reaction product into a large separatory funnel and extract with seven 250 ml. portions of ether break up any lumps that may form with a glass rod. Remove the ether from the combined extracts by distillation, wash the residue with three 50 ml. portions of water, dry with anhydrous magnesium sulphate and distil under reduced pressure. The yield of tetrahydrofurfuryl chloride, b.p. 47-48°/15 mm., is 180 g. 

Aminopyridine. In a 1 litre three-neoked flask, equipped with a sealed mechanical stirrer, reflux condenser, thermometer and inlet tube for nitrogen, place 300 ml. of dry toluene (1) aud 75 g. of fine granular sodamide (2) bubble a steady stream of nitrogen thi ough the toluene. Stir the mixtiue vigorously and heat the flask in an oil bath until the internal temperatime is 110° (the bath temperatime required is approximately 130°). Add 100 g. of pure dry pyridine (compare Section 11,47,22)... 

Later, fireflv oxyluciferin was successfully synthesi2ed (403. 408) and has been isolated and identified in firefly lanterns (luciola cruaciata) after the lanterns were treated with pyridine and acetic anhydride to prevent decomposition (409). In 1972, Suzuki and Goto firmly established that oxyluciferin is involved in the bioluminescence of firefly lanterns and in the chemiluminescence of firefly luciferin (403. 410).. A. mechanism involving a four-membered ring cyclic peroxide has been proposed for the reaction (406. 411). However, it was not confirmed by 0 -labelinE experiments (412). 

In the case of a pyridinium salt, an indirect proof of the correctness of this mechanism can be found in the presence of a heptamethine thiazolo-cyanine, together with monomethine. which results unambiguously from 19 by the known opening of the pyridine ring (Scheme 25) (52). 

Likewise, quantum mechanical calculation succeeds in giving a theoretical explanation of some facts that the resonance theory could not explain, for example, why bis(pyridine-2)monomethine cyanine and bis(pyridine-4)monomethine cyanine possess the same lowest energy transition contrary to the 2,2 - and 2,4 -quinoline monomethine dyes, together with a molecular coefficient extinction lower than that of the 4,4 -quinoline dye (11). Calculation shows also that there is no theoretical reason for observing a relationship between and pK in a large series of dyes with different nuclei as it has been postulated, even if limited observations and calculations in short homogeneous series could lead to this conclusion (105). 

Tschitschibabin amination of pyridine, the mechanism of which has been established as involving an intermediate charge distribution of the thiazole molecule as well as of the thiazolium ion. 

Chain-Growth Associative Thickeners. Preparation of hydrophobically modified, water-soluble polymer in aqueous media by a chain-growth mechanism presents a unique challenge in that the hydrophobically modified monomers are surface active and form micelles (50). Although the initiation and propagation occurs primarily in the aqueous phase, when the propagating radical enters the micelle the hydrophobically modified monomers then polymerize in blocks. In addition, the hydrophobically modified monomer possesses a different reactivity ratio (42) than the unmodified monomer, and the composition of the polymer chain therefore varies considerably with conversion (57). The most extensively studied monomer of this class has been acrylamide, but there have been others such as the modification of PVAlc. Pyridine (58) was one of the first chain-growth polymers to be hydrophobically modified. This modification is a post-polymerization alkylation reaction and produces a random distribution of hydrophobic units. 

Homopolymer. Formaldehyde polymerises by both anionic and cationic mechanisms. Strong acids are needed to initiate cationic polymerisation. Anionic polymerisation, which can be initiated by relatively weak bases (eg, pyridine), can be represented by the following equations Initiation... 

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid iacorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted iadole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteiae (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used ia the United States only as a poly antimicrobial vetetinary ointment (Panalog, Squibb), but thiazole antibiotics have, ia the past, been used as feed additives ia various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

The reaction of 1-aminopyridinium iodide (429) with dimethyl chlorofumarate in ethanol/K2C03 to form, ultimately, a pyrazolo[l,5-n]pyridine also occurs via a 1,5-dipolar mechanism. The initially formed 1 1 adduct (430), stabilized by delocalization of the negative charge, underwent disrotatory ring closure as shown to give (431) in which the 3... 

Copper(II), di-/Lt-bromobis[bromo(pyridine)-structure, 2, 108 Copper 8-hydroxyquinolinate biocidal activity mechanism, 1, 401 fungicide, 1, 399 Copper nitrotetrazole as propellants, 5, 837 Copper phthalocyanine, 1, 333-334 colour and constitution, 1, 345 Coproporphyrin, 4, 382 Coproporphyrin, dehydro-, 4, 382... 

Benzyl carbamates are readily cleaved under strongly acidic conditions HBr, AcOH 50% CF3COOH (25°, 14 days, partially cleaved) - 70% HF, pyridine CF3S03H FSOaH, or CHjSO.H.- In cleaving benzyl carbamates from peptides, 0.5 M 4-(methylmercapto)phenol in CF3CO2H has been recommended to suppress Bn additions to aromatic amino acids. To achieve deprotection via an Sn2 mechanism that also reduces the problem of Bn addition, HF-Me2S-p-cresol (25 65 10, v/v) has been recommended for peptide deprotection. 

B. cis-1,2-Gyclohexanedimethanol Dimethanesulfonate. In a 5-1., three-necked, round-bottomed flask, immersed in an ice-salt bath and fitted with a mechanical stirrer and an addition funnel, is plaeed a solution of 111 g. (0.97 mole) of methanesulfonyl chloride in 1.21. of pyridine. While cooling and stirring, a solution of 46.4 g. (0.322 mole) of m-l,2-cyclohexanedimethanol in 250 ml. of pyridine is added dropwise at a rate such that the temperature does not exceed 0° (Note 5). Upon completion of the addition, the mixture is stirred at — 5° to 0° for an additional 2 hours. Two liters of cold 10% hydrochloric acid is introduced at a rate which maintains the reaction mixture below 20° (Note 5). The solid which separates is isolated by suction filtration, washed sequentially with 11. of dilute hydrochloric acid and 21. of water, and air-dried. There is isolated 93-95 g. (96-98%) of the dimethanesulfonate having m.p. 66-67.5°. Reorystallization from methanol gives needles melting at 75-76° (Note 6). 

The product distribution can be shifted to favor the 1 -product by use of such milder brominating agents as the pyridine-bromine complex or the tribromide ion, Br3. It is believed that molecular bromine reacts through a cationic intermediate, whereas the less reactive brominating agents involve a process more like the AdgS and-addition mechanism. 

Pyridine is more nucleophilic than an alcohol toward the carbonyl center of an acyl chloride. The product that results, an acylpyridinium ion, is, in turn, more reactive toward an alcohol than the original acyl chloride. The conditions required for nucleophilic catalysis therefore exist, and acylation of the alcohol by acyl chloride is faster in the presence of pyridine than in its absence. Among the evidence that supports this mechanism is spectroscopic observation of the acetylpyridinium ion. An even more effective catalyst is 4-dimeftiyIaminopyridine (DMAP), which functions in the same wsy but is more reactive because of the electron-donating dimethylamino substituent. ... 

The main results of this miero-mechanical model in the quasi-static regime have been compared with experimental results obtained by placing polystyrene (PS)-polyvinyl pyridine (PVP) diblock copolymers with a short PVP block between PS and PVP homopolymers. The fracture toughness was found to increase linearly with E from that of the bare PS/PVP interface, while the slope of the line increased with the degree of polymerization of the block being pulled out. If the data for the different copolymers were plotted as AG vs. (where... 

Two surprising observations were made in the course of this work first that the enol acetate (5) is stable under the conditions for formation of (6) from (4) second, that the course of the buffered bromination of (5) depends on the conditions used. Thus, in the presence of epichlorohydrin, (7) is the sole isomer produced, whereas in pyridine-acetic acid approximately equal amounts of (7) and (8) are formed. It was suggested that this difference is inherent in the mechanism and not a result of isomerization of (7) to (8) during the course of the reaction. 

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. 

A large number of Brpnsted and Lewis acid catalysts have been employed in the Fischer indole synthesis. Only a few have been found to be sufficiently useful for general use. It is worth noting that some Fischer indolizations are unsuccessful simply due to the sensitivity of the reaction intermediates or products under acidic conditions. In many such cases the thermal indolization process may be of use if the reaction intermediates or products are thermally stable (vide infra). If the products (intermediates) are labile to either thermal or acidic conditions, the use of pyridine chloride in pyridine or biphasic conditions are employed. The general mechanism for the acid catalyzed reaction is believed to be facilitated by the equilibrium between the aryl-hydrazone 13 (R = FF or Lewis acid) and the ene-hydrazine tautomer 14, presumably stabilizing the latter intermediate 14 by either protonation or complex formation (i.e. Lewis acid) at the more basic nitrogen atom (i.e. the 2-nitrogen atom in the arylhydrazone) is important. 

Bohlmann and Rahtz, in 1957, reported the preparation of 2,3,6-trisubstituted pyridines. Their method employed the Michael addition of acetylenic ketones 35 with enamines 36. The 5-aminoketones 37 are typically isolated and subsequently heated at temperatures greater than 120°C to facilitate the cyclodehydration to afford 38. Again one can see the parallels in this mechanism with that for the Hantzsch protocol. However, in this case the pyridine is formed directly removing the need for the oxidation step in the Hantzsch procedure. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

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