Benzoyl reaction 4- piperidine

Trimethylene dibromide (Section 111,35) is easily prepared from commercial trimethj lene glycol, whilst hexamethylene dibromide (1 O dibromohexane) is obtained by the red P - Br reaction upon the glycol 1 6-hexanediol is prepared by the reduction of diethyl adipate (sodium and alcohol lithium aluminium hydride or copper-chromium oxide and hydrogen under pressure). Penta-methylene dibromide (1 5-dibromopentane) is readily produced by the red P-Brj method from the commercially available 1 5 pentanediol or tetra-hydropyran (Section 111,37). Pentamethylene dibromide is also formed by the action of phosphorus pentabromide upon benzoyl piperidine (I) (from benzoyl chloride and piperidine) ... 

Dicyano-2,4,8-triphenyl-7-phenylsulfonyl-6/f-pyrido[], 2-a]pyrimi-dine-6-thione was obtained in the reaction of 6-amino-1-benzoyl-5-cyano-4-phenyl-3-phenylsulfonylpyridin-2(]//)-one and benzylidenemalononitrile in the presence of piperidine in boiling dioxane for 4h in 59% yields (98M1049). 

Pinacolone, o-(diphenylphosphino)benzoyl-coordination chemistry, 2, 401 Ping-pong reactions copper(II) complexes, 5, 717 Piperidine, /V-hydroxy-metal complexes, 2, 797 P a values azole ligands, 2, 77 Plant roots amino acids, 2, 962 carboxylic adds, 2,962 Plants... 

The same reaction sequence performed in methanol affords a mixture of diastereo-mers of the phosphorylated phosphinic ester 48b, of which one pure isomer can be isolated32 . In the presence of piperidine, reductive elimination of nitrogen 28,29) from 45 to give bis(diphenylphosphoryI)methane competes with the prevailing formation of the phosphinic piperidide 48c32). Expected trapping of 47 by [2 + 2]-cycloaddition with benzaldehyde fails to occur in place of 1,2k5-oxaphosphetanes, products are obtained which arise mainly by way of the benzoyl radical32,33). 

Benzoguanamine has been prepared by the reaction of dicyandiamide with benzonitrile in a sealed tube at 220-230°,2 with an excess of benzonitrile in the presence of piperidine and potassium carbonate,3 with benzonitrile in a solvent in the presence of a basic catalyst,4 and with benzamidine hydrochloride at elevated temperatures.5 It has also been prepared from the reaction of biguanide acetate with benzamidine hydrochloride,5 or of bigua-nide sulfate with benzoyl chloride in an alkaline medium,7 and by the distillation of guanidine benzoate.5... 

The bicyclic tropane ring of cocaine of course presented serious synthetic difficulties. In one attempt to find an appropriate substitute for this structural unit, a piperidine was prepared that contained methyl groups at the point of attachment of the deleted ring. Condensation of acetone with ammonia affords the piperidone, 17. Isophorone (15) may well be an intermediate in this process conjugate addition of ammonia would then give the aminoketone, 16. Further aldol reaction followed by ammonolysis would afford the observed product. Hydrogenation of the piperidone (18) followed then by reaction with benzoyl chloride gives the ester, 19. Ethanolysis of the nitrile (20) affords alpha-eucaine (21), an effective, albeit somewhat toxic, local anesthetic. 

A group from Spain patented a similar synthesis of risperidone (1) using similar synthetic transformations but in a different sequence (Scheme 2). Reaction of 2-aminopyridine with 2-acetylbutyrolactone in polyphosphoric acid at 160 °C afforded alcohol 15, which was hydrogenated to 16 and then converted to chloride 10 with thionyl chloride. Benzoyl piperidine 19 was prepared in a similar manner as in Scheme 1. In contrast to Scheme 1, 19 was alkylated with 10 prior to conversion to the 1,2-... 

The cyclization of 5-oxonitriles offers an attractive route to 2-amino-4//-pyrans (Scheme 18) (78JHC57). The starting materials, a-benzoylcinnamonitriles, are available from benzoyl-acetonitrile and an aromatic aldehyde. Michael addition of ethyl cyanoacetate or malononitrile to the benzoylcinnamonitrile affords the oxonitrile and is followed by cyclization to the imine. The reaction proceeds at room temperature in the presence of either piperidine or sodium ethoxide. 

Treatment of quinolizinium bromide with two equivalents of piperidine gives a high yield of a product A, C14H18N2. Reaction of A with phenacyl bromide followed by quenching of the reaction mixture with water gives a product B which was originally claimed to be 3-benzoyl-2-vinylindolizine. Subsequent reinvestigation of the structure of B, however, showed that it was in fact 3-(2-phenyl-l-indolizinyl)prop-2-ene-l-al 1. 

N-Methyl-N-phenyl-2,3-dihydro-lH-pyrrolizine-l-carboxamide (480 mmol) and toluene (100 mL) were added to a mixture of benzoylpiperidine (1.05 eq.) and phosphorus oxychloride (0.96 eq.), which had been stirred at 25°C for 1 hour. An additional 100 mL toluene was added. The suspension was heated to at 40-45°C for 4 hours. The resulting syrup was transferred into a rapidly stirring solution of sodium hydroxide (4.5 mol), piperidine (1.0 mL), and water (650 mL) at 25-35°C and the mixture was stirred for 1 hour. A mixture of toluene (100 mL), water (50 mL), and sodium hydroxide (12 g, 300 mmol) was added to the reaction flask, and the reaction mixture was stirred at 25°C for 1 hour. The suspension was then heated to 75°C and the layers were separated. The organic layer was cooled to 60°C and hexane (100 mL) was slowly added, and the solution slowly stirred and cooled to -15°C. The precipitate was filtered, washed with toluene/hexane (2 1) and then with hexane, and dried under vacuum at 25°C to yield 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-lH-pyrrolizine-l-carboxamide (83.5% yield). 

The reaction between acetyl- and benzoyl- thioacetamides and oijl-unsaturatcd aldehydes in refluxing pyridine yields a dienic thioamide through a Claisen-like condensation. Spontaneous electrocyclization affords the ZH-thiopyran (Scheme 111). Substituted piperidine-2-thione derivatives result when the reaction is carried out in ethanol using triethylamine as the base <2003T4183>. 

This synthesis involves Michael cycloaddition reaction of the readily available 4-hydroxycoumarine 1 with a cyanocrotonitrile 2 in ethanolic piperidine to afforded 2-amino-3-cyano-4-methyl-4H, 5H-pyrano-benzopyran-5-one (3). Treatment of 3 with acetic anhydride for 0.5 h and/or 3 h under reflux afforded N-acetyl and [l]benzopyrano[3/,4/ 5,6]pyrano(2,3-d) pyrimidine-6,8-dione derivatives (4) and (5a), respectively. Also, interaction of 3 with benzoyl chloride or formic acid gave the corresponding pyrimidine derivatives (5b,c) while its treatment with formamide afforded the aminopyrimi-dine derivative (6). 

Two other nucleophilic substitution reactions of pyridine iV-oxides deserve mention and further study to determine the effects of substituents. Pyridine N-oxide, benzoyl chloride, and the piperidine enamine of cyclohexanone give a good yield of 2-(2 -pyridyl)cyclo-hexanone (155) (63%).360 When W-methoxy-4-picolinium methyl... 

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