Hydrogenation of Nitrogen Heterocycles

While metal complexes capable of desulfurizing or hydrodesulfurizing thiophenes are relatively numerous, homogeneous catalysts are very rare, being limited to rhodium and iridium TRIPHOS precursors that are unique in tolerating the harsh experimental conditions required for the second C-S bond cleavage of thiophenes [2 b]. 

The most efficient single-site HDS catalyst remains the polystyrene-supported complex [Rh(COD)(POLYTRIPHOS)]PF6 (5), which has been shown to catalyze the HDS of BT yielding ethylbenzene with a TOF of 2 [31 a]. 

In conclusion, unlike heterogeneous processes with commercial HDS catalysts, single-site catalysts have been found to desulfurize thiophenes (T, BT, DBT) exclusively after these have been converted to saturated thiols or thiolates. No example of catalytic desulfurization of THT or DHBT by a single-site catalyst has ever been reported, although stoichiometric reactions assisted by both mononuclear and polynuclear complexes are known for THT and other cyclic thioethers [2 b, 32]. 

As previously mentioned, the stoichiometric desulfurization of thiophenes has been achieved with a relatively large number and variety of metal complexes. In general, polynuclear complexes containing both component (Mo or W) and promoter (Ni, Co, Ir, Ru) metals turn out to be more active than mononuclear complexes containing promoter metals [1, 2]. A paradigmatic case has been reported in which the hydrogenolysis of BT to either 2-vinylthiophenol or 2-ethylthiophe-nol is a facile process for the promoter (Rh), but the desulfurization step to ethylbenzene requires the compulsory assistance of a component metal (W) to take place [33]. 

C-N bond scission. Understanding the hydrogenation mechanism is thus of utmost importance for designing improved HDN catalysts. 

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Norrish Type II photocyclizations have been employed in many instances in the synthesis of nitrogen heterocycles. Type II cyclizations are the result of an intramolecular hydrogen abstraction by an excited carbonyl group followed by cyclization of the resulting biradical. Hydrogen abstraction from the y-carbon atom is normally preferred. The introduction of a nitrogen atom... 

Aromaticity varies with change of state because of the influence of the molecular environment on the interactions that determine aromaticity quantitatively, particularly in nonsymmetrical heterocycles. Comparative calculations of aromaticity indices for molecules in the gas phase and in condensed media with dielectric constants > 1, with or without hydrogen-bonding, showed coherent results for a set of nitrogen heterocycles, including imidazole, pyrrole, pyrazole, 1//-1,2,4-triazole, and benzimidazole. The... 

Aubagnac, J.L. Campion, p. Mass Spectrometry of Nitrogen Heterocycles. X. Contribution to the Behavior of the Aniline Ion and TVminopyridine Ions Prior to Fragmentation by Loss of Hydrogen Cyanide. Org. Mass Spectrom. 1979, 14, 425-429. 

Tetrahydrofolate (THF, 6) is a coenzyme that can transfer Cj residues in different oxidation states. THF arises from the vitamin folic acid (see p. 366) by double hydrogenation of the heterocyclic pterin ring. The Ci units being transferred are bound to N-5, N-10, or both nitrogen atoms. The most important derivatives are ... 

Amination of Nitrogen Heterocycles Amination or Amino-de-hydrogenation... 

Alkylation, Acylation, and Carbalkoxylation of Nitrogen Heterocycles Alkylation or Alkyl-de-hydrogenation, and so on... 

The mechanism of this last reaction may be postulated as shown in Scheme 52. Here, the initial nucleophilic attack by the sulfonamide anion (129) is followed by protonation of the intermediate and attack by the chloride anion to yield two moles of the sulfamoyl chloride (125). A wide range of sulfamoyl derivatives can be prepared by nucleophilic displacement of the chlorine atom in sulfamoyl chlorides (125). Examples include condensations with ureas, alcohols, compounds containing acidic hydrogens and nitrogen heterocycles to give the corresponding sulfamoyl derivatives (130)-(133) (Scheme 53). 

Rearrangement in nitrogen-containing carbonyl compounds merits brief discussion in this section as well as in Part III, Chapter 1. Type II photocyclizations are of particular value and have in the past been extensively used in the construction of nitrogen heterocycles. Competitive y- and 6-hydrogen abstractions have been observed in the a-alkyl-B-oxoamides (82), the former leading to benzoylacetamides (83) via Type II photoelimination and... 

If other active groups are present y or S to the reducible nitro group, hydrogenation can result in formation of nitrogen heterocyclic products. Several such cyclizations provide an entry to indoles, such as reductive cyclizations of dinitrostyrene 1 [equation (a)], of o-nitrobenzyl ketone 2 [equation (b)], and of nitro nitrile 3 [equation (c)] , all of them carried out on palladium-on-carbon. 

Iminyl radicals are particularly useful for the construction of nitrogen heterocycles, since the cyclization products are functionally disposed for further elaboration into a variety of useful systems. Zard and coworkers have pioneered the development of methodology for the generation and cyclization of iminyl radicals (Table 8) [5, 71]. Iminyl radicals cyclize one order of magnitude more rapidly than the related neutral aminyl radicals but react less rapidly than the aminyl radicals with hydrogen atom transfer trapping agents, and one would predict that iminyl radicals formed in chain reaction sequences could prove to be as versatile as carbon radicals [78]. 

Meot-Ner M (1979) Ion thermochemistry of low-volatility compounds in the gas phase. 2. Intrinsic basicities and hydrogen-bonded dimers of nitrogen heterocyclics and nucleic bases. J Am Chem Soc 101 2396-2403. doi 10.1021/ja00503a027... 

The Antonchick group demonstrated the oxidative coupling of nitrogen heterocycles with alkanes. °° Combination of phenyliodine(lll) bis(trifluoroacetate) with TMSNj is a known method of generating azide radicals. The azide radical abstracts a hydrogen atom from an alkane to form a carbon-centered radical. The carbon-centered... 

Two synthetic bridged nitrogen heterocycles are also prepared on a commercial scale. The pentazocine synthesis consists of a reductive alkylation of a pyridinium ring, a remarkable and puzzling addition to the most hindered position, hydrogenation of an enamine, and acid-catalyzed substitution of a phenol derivative. The synthesis is an application of the reactivity rules discussed in the alkaloid section. The same applies for clidinium bromide. 

These contracted names of heterocyclic nitrogen compounds are retained as alternatives for systematic names, sometimes with indicated hydrogen. In addition, names of 0x0 derivatives of fully saturated nitrogen heterocycles that systematically end in -idinone are often contracted to end in -idone when no ambiguity might result. For example. 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

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