Nitrogen heterocycles, saturated, reactions

Nitrogen heterocycles more electrophilic than benzene are susceptible to attack by hydride ion from a complex metal hydride anion. In protic solvents the intermediate cyclic enamines can undergo further reduction. The proper choice of reducing agent and reaction conditions thus allows the preparation of many partially reduced nitrogen heterocycles unavailable by other routes. These reduction procedures provide a valuable adjunct to catalytic hydrogenation155 for the syntheses of saturated nitrogen heterocycles. 

A related intramolecular N-alkylation leading to saturated nitrogen heterocycles 99 can proceed via dehydration of intermediates 98 (Eq. 39) [96]. Unsaturated nitrogen heterocycles such as pyrroles [97], indoles [98], benzo-azoles [99], 2,3-dihydroimidazol-2-ones [100], and imidazo[l,2-a]pyridines [101] were obtained through similar cyclocondensation reactions. Interesting ruthenium-catalyzed syntheses of quinolines have been achieved by means of cyclocondensations of aniline derivatives with propanediols, aminoalcohols, or... 

Nitrogen heterocycles are attacked by cyanogen halides at the nitrogen. In the reaction of cyanogen bromide with the saturated, fused oxazole (182), a fused medium-ring heterocycle (183) is formed when the reaction is carried out under solvolytic conditions... 

In many reactions the simple saturated nitrogen heterocycles—piperidine, pyrrolidine, piperazine, and morpholine—behave simply as secondary amines that happen to be cyclic. They do the sorts of things that other amines do, acting as nucleophiles in addition and substitution reactions. Morpholine, for example, is acylated by 3,4,5-trimethoxybenzoyl chloride to form the tranquillizer and muscle relaxant trimetozine, and N-methyl piperazine can be alkylated in an S l reaction with diphenylmethyl chloride to give the travel-sickness drug cyclizine. 

Nitrogen heterocycles see also N-Heterocyclic compounds) advances in amination of, 49, 117 aromatic six-membered. regioselective substitution in, 44, 199 conformational equilibria in saturated six-membered rings, 36, I covalent hydration in, 20, 117 photochemistry of, 30, 239 reactions of acetylenecarboxylic esters with, 23, 263... 

The hydroamination reactions which are assisted or catalyzed by transition metal species can be utilized in the cyclization of unsaturated amines. Palladium(II) is not recommended for such transformations, since low yields were obtained even using stoichiometric amounts of palladium chloride47. Since an enamide is formed by /J-hydride elimination, a reduction step must be performed to obtain the saturated nitrogen heterocycle. A catalytic cyclization reaction, analogous to the Wacker process, was performed from /V-alkenyl tosylamides, such as 1, using... 

The kinetics of the carbamoylation reaction of alkyl isothiocyanates with diphenylphosphinic hydrazide, Ph2P(0)NHNH2, in benzene, and of the same reaction in the presence of saturated nitrogen heterocycles (as catalysts), have been studied in detail. 

Six-membered heterocycles Saturated as well as unsaturated nitrogen heterocycles have been prepared. The malononitrile derivative 139 underwent a ring-closure reaction with... 

As part of a larger review on synthesis of saturated nitrogen heterocycles, Steele reviewed piperidines, piperidinones, tetrahydroisoquinolines, indolizidines, quinolizidines, and hetero Diels-Alder reactions <94COS95>. 

The methodology based on nitroso DieIs-alder reaction that proved useful in the synthesis of tropane alkaloids also seemed to open an attractive route to some other alkaloids. Compared to the intramolecular imino Diels-Alder reaction (ref. Ic) the intramolecular variant of the nitroso Diels-Alder reaction has received far less attention (refs. 6b 12), despite the enormous potential it holds for alkaloid synthesis. With this in mind we proceeded to examine the application of the intramolecular nitroso Diels-Alder cycloaddition in the synthesis of alkaloids possessing saturated nitrogen heterocyclic ring systems. 

Hydrolysis of imidazolylidenes has been studied by DFT calculations and NMR experiments. The outcome of the reaction has been shown to be highly dependent on the amount of water involved in the reaction, and an equilibrium between the carbene and hydroxide ion has been identified. Related to this study, the pAT s of a range of NHCs have been determined via deuterium exchange experiments monitored by H NMR and found to increase markedly with electron donation from nitrogen substituents. Saturation was found to have only minor influence on the acidity of the flve-membered heterocycles. In contrast, the ring size has a major influence (moving from five- to six-membered heterocycles raised the pAT by up to 5 units). 

Over the past several decades, research in the field of palladium catalysis has resulted in the development of a myriad of transformations that provide access to saturated nitrogen heterocycles. Many of these transformations effect the formation of several bonds, and/or proceed with good to excellent levels of stereocontrol. Despite the many advances made in this field, discoveries of new reactivity are still being reported with great frequency, and this promises to remain a fruitful area of research for many years to come. In particular, the development of new palladium catalysts will likely lead to improvements in the scope of existing transformations, and will also open up new reaction pathways that can be applied to unsolved problems in heterocydic chemistry. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

The electrolysis of asymmetric ketones 43 led to the formation of isomers and stereoisomers. Kinetic measurements for the formation of ketimine 43 in saturated ammoniacal methanol indicated that at least 12 h of the reaction time were required to reach the equilibrium in which approximately 40% of 42 was converted into the ketimine 43. However, the electrolysis was completed within 2.5 h and the products 44 were isolated in 50-76% yields. It seems that the sluggish equilibrium gives a significant concentration of ketimine 43 which is oxidized by the 1 generated at the anode, and the equilibrium is shifted towards formation of the product 44. 2,5-Dihydro-IH-imidazols of type 44, which were unsubstituted on nitrogen, are rare compounds. They can be hydrolyzed with hydrochloric acid to afford the corresponding a-amino ketones as versatile synthetic intermediates for a wide variety of heterocyclic compounds, that are otherwise difficult to prepare. 

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