Pyridine—continued reaction

In the production of 4,4 -bipyridyl from pyridine, the reaction between pyridine and metallic. sodium in liquid ammonia is involved, followed by oxidation. By adopting a continuous reactor, the process has been made safer and yields have probably improved. For a hazardous chemical like diazomethane, even at a capacity of 60 tpa a continous plant has been adopted. 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Darr and Poliakoff conducted one of the first studies where SC-CO2 was used in a two-stage continuous reaction and purification process to form pure organo-metallic products. The ds-W(CO)4(pyridine)2 or novel c/ -W(CO)4(3,5 lutidine)2 were formed in a continuous flow reactor at 488 K and were then removed from solution via precipitation, with a second flow of CO2 used to remove the excess solvent and reactant for reclamation and recycle. The benefits of this system, aside from the production of novel materials, include reduction of organic solvent consumption, decrease in number of stages and time, and production of 100% purity product. 

In the production of 2-isothiocyanatopyridine (208) from 2-aminopyridine and thiophosgene,177 continued reaction yields 2f/-l,2,4-thiadiazolo[2,3-a]-pyridine-2-thione (209, 48%) by a mechanism so far not elucidated.178... 

Cycloadditions continue to be a powerful way to build pyridines. Indeed, a recent review describes the Diels—Alder reaction of azadienes to form pyridines either by the traditional thermocyclic manner or when catalyzed by transition metals (140rganic Chemistry FrontierslOlO). In addition to cycloaddition approaches, the other main route to pyridines continues to be cyclocondensations. 

Mutorotation continues to receive attention. Studies of the mutarotation of 2,3,4,6-tetra-O-methyl-a-D-glucopyranose in aqueous dioxan and aqueous DMSO by optical rotation over a wide range of water concentration, with and without catalysts, have shown that the uncatalysed reaction transition-state contains one mole of sugar and two moles of water in an acyclic bonded structure (6). In the pyridine-catalysed reaction one mole of water may be replaced by one mole of pyridine (Scheme 3). The evidence suggests that the reaction takes place by an intimate step-wise mechanism rather than synchronously. 

Dissolve 10 g. of salicylic acid (o-hydroxybenzoic acid) in 7 ml. of dry pyridine contained in a too ml. conical flask. Then without delay (since this solution if allowed to stand tends to become a semi-solid mass) run in 7 5 ml. (8 3 g.) of acetyl chloride, adding about i ml. of the chloride at a time, and shaking the mixture continuously during the addition. The heat of the reaction causes the temperature of the mixture to rise rapidly ... 

A iridine traces in aqueous solution can be determined by reaction with 4-(p-nitroben25l)pyridine [1083-48-3] and potassium carbonate [584-08-7]. Quantitative determination is carried out by photometric measurement of the absorption of the blue dye formed (367,368). Alkylating reagents interfere in the determination. A iridine traces in the air can be detected discontinuously by absorption in Folin s reagent (l,2-naphthoquinone-4-sulfonate) [2066-93-5] (369,370) with subsequent chloroform extraction and hplc analysis of the red dye formed (371,372). The detection limit is ca 0.1 ppm. Nitrogen-specific thermal ionisation detectors can be used for continuous monitoring of the ambient air. 

A solution of 7.2 g of sodium borohydride (analyzing at 87 % purity) in 300 ml of pyridine is added dropwise, with vigorous stirring, over 7 hr to a solution of 50 g of pregnane-3,11,20-trione in 100 ml of pyridine and 18 ml of water. The temperature is kept at 18-20°. The stirring at this temperature is continued for another 2 hr, after which the reaction mixture is poured slowly into dilute hydrochloric acid (575 ml of cone hydrochloric acid in 5.2 liters of water) and the stirring continued for 1 hr. The precipitate is filtered, washed with... 

Kondrat eva pyridine synthesis. This methodology to pyridine rings continues to be applied in total synthesis. An approach to the antitumor compound ellipticine 34 ° makes use of a Diels-Alder reaction of acrylonitrile and oxazole 32 to form pyridiyl derivative 33. Addition of methyllithium and hydrolysis transforms 33 into 34. 

Other factors which are known to lower the yield of 2,2 -bipyridine include dilution of the pyridine with a solvent (such as xylene) and the presence of pyrroles. The formation of pyrroles in the reaction, and the accumulation of 2,2 -bipyridine, are no doubt responsible for the fact that the production of 2,2 -bipyridine ceases after about 50 hr. The catalyst can be used for longer periods only if the reaction is carried out under conditions of continuous flow, or if the products of the reaction are removed as they are formed. 

The most important by-product formed in the reaction of pyridine with degassed Raney nickel is an organonickel complex which has been shown to be a complex of one molecule of 2,2 -bipyridine, two molecules of 2,2 -pyrrolylpyridine (17), and one nickel II ion. It is significant that, although the formation of 2,2 -bipyridine ceases after 50 hr refluxing, the formation of this complex continues for at least another 140 hr. 

Preparation of 11-Keto-6 -Methy progesterone 3,20-Bis-(Ethylene Ketal) A mixture of 5 g of 11-keto-6(3-methylprogesterone (Spero et al, 7. Am. them. Soc., 78, 6213 (1956)], 503 ml of benzene, 26 ml of ethylene glycol, and 0.152 g of p-toluenesulfonic acid monohydrate was stirred and heated under reflux for 22 hours while water was removed by means of a water trap. The reaction mixture was then cooled to 30°C, 0.4 ml of pyridine was added, and stirring was continued for 10 minutes. 

To the aqueous suspension of the palladized charcoal catalyst thus obtained are added 20.8 kg of 3-cyano-pyridine (96% purity) and then are added 70 liters of a hydrochloric acid solution prepared by diluting 30 liters of 36% HCI with 40 liters of water. This represents approximately 1.75 mols of HCI for each mol of 3-cyano-pyridine. The suspension is maintained at 10° to 15°C and stirred continuously while introducing a current of hydrogen at a pressure of 3 to 5 psi. When absorption of hydrogen ceases and the 3-cyano-pyridine is completely reduced, the reaction mixture is filtered to remove the catalyst. 

A mixture of 16.8 g of 2-aminobenzophenone, 11.9 g of glycine ethyl ester hydrochloride and 200 cc of pyridine was heated to reflux. After one hour, 20 cc of pyridine was distilled off. The solution was refluxed for 15 hours, then 11.9 g of glycine ethyl ester hydrochloride was added and the refluxing was continued for an additional 4 hours. The reaction mixture was continued for an additional 4 hours. The reaction mixture was concentrated in vacuo, then diluted with ether and water. The reaction product, 5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one, crystallized out, was filtered off, and then recrystallized from acetone in the form of colorless rhombic prisms, MP 182°Cto 183°C. 

The stream of dry air is continued for about six hours or until most of the hydrogen chloride has been expelled and then another 55 grams of thionyl chloride is added. The reaction mixture is allowed to stand twenty-four hours, a few drops of pyridine are added and the mixture heated 4 hours on the steam bath. The cooled reaction mixture is poured into water, the crude product is washed with dilute sodium bicarbonate solution and finally taken up in benzene. The benzene is distilled at ordinary pressure and the residue distilled in vacuo to yield 60-70% of Tphenoxy-2-chloropropane, BP 93°-94°C/5 mm. 

A solution of a 2-aminobenzophenone (0.1 mol) and an z-amino acid ethyl ester hydrochloride (0.15 mol) in pyridine (200 mL) was refluxed. During the first 4h, 20-50 mL of liquid was allowed to distill and was replaced by fresh pyridine. Heating was continued for a further 11 h, the mixture was evaporated under reduced pressure and H20 and Et20 were added. In most cases some of the reaction product remained undissolved and was filtered off. The aqueous layer was separated, made alkaline and extracted with Et20. The comhined F.t20 phases were washed with H20. dried and evaporated and the reaction product was separated from unchanged amino ketone by crystallization. 

In a flask was placed pyridine-2,3-dicarbonitrile (2.58 g, 20 mmol), Cu powder (0.32 g, 5 mmol) and quinoline (5mL). The suspension was stirred and heated to 212 C for 4h. Upon completion of the reaction, the mixture was suspended in MeOH and filtered. This solid was collected, was suspended in MeOH and stirred. The heavier unreacted Cu settled quickly and the solid was decanted off. This was continued repeatedly until the solid was removed from any unreacted Cu. The solid was filtered and dried at 195 C for 2 h yield 2.67 g (92 %). 

The Balz-Schiemann reaction continues to attract attention, with much of it generated by the interest in fluoroquinolones, e.g., (7), which is a potential antibacterial. Two approaches to its synthesis are possible—introduction of fluorine prior to or post ring construction. Decomposition of the tetrafluoroborate salt was unsuccessful, whereas the PF6 salt (8) gave only a poor yield (84JMC292). A more successful approach was the introduction of F into the pyridine nucleus prior to formation of the 1,8-naphthyridine ring (84JHC673). A comparison of decomposition media showed that cyclohexane was the best with regard to yield and time. 

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