Formation of N- Heterocycles

H OTMS (1,20 mol%) PhCOjH (10mol%), EtOAc or EtOAc/EtjO 0 °C, 4 d 

C2 halogenated tryptamine precursor 261, followed by intramolecular aza-Michael addition. In this example, by Stewart and Pfeifer, the order of these reaction was controlled by the type of protecting group on the nitrogen, while a range of acrylate systems were reported in good to excellent yields. Others have also reported similar Heck/Michael processes [129-131]. 

The group of Rueping has developed an enantioselective synthesis of chromenones through a Michael reaction and cychzation process between diketones and unsaturated aldehydes [136]. Furthermore, this reaction can be also followed with the addition of tryptamine to afford indoloquinolizidines [137]. An aza-MBH reaction was used in the enantioselective synthesis of isoindoHnes. In this 

An aza-Michael/aldol reaction analogous to the oxa-Michael process discussed earlier was used in the synthesis of 1,2-dihydroquinohdines 279 [139]. In this example for dihydroquinolines, phenyl or alkyl a,p-unsaturated aldehydes 278 

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Transition metal-catalyzed heterocyclizations with formation of N-heterocycles 98AG(E)2046. 

Formation of N-heterocycles from phosphorus-containing diazo compounds 92UK564. 

Zeolites have also been shown to catalyze a variety of acid-promoted cyclizations. Many of these involve the formation of N-heterocycles via intramolecular amination reactions [75-77]. Some examples are shown in Fig. 2.24. 

Mousiness is a wine fault most often attributed to Brettanomyces but can also originate from L. brevis, L. fermentum, and L. hilgardii (Du Toit and Pretorius 2000). The metabolism of ornithine and lysine is associated with the formation of N-heterocycles, 2-acetyl-1-pyrrolene, 2-acetyltetrahydropyridine and... 

Reactions of epoxides with amines, azides, hydrazines, etc., formation of N-heterocycles by epoxide ring opening 04ZOR11. 

N-N Bond scission and synthesis of N-heterocycles 86UK1785. Carbodiimides, formation of N-heterocycles from 82UK848 81AG855. Catalytic synthesis of N-heterocycles 83KGS1587, 83YGK604. Condensed N-heterocycles, syntheses using modified Japp-Klingemann... 

Cycloaddition of isocyanates with formation of N-heterocycles 86ZC117. Cycloaddition of nitrones in synthesis of N-heterocycles 85OPP23. Dioxopyrrolidines, synthesis of N-heterocycles from 84YGK340. 

Iminyl radicals, formation of N-heterocycles from 78YGK368. Intramolecular cycloaddition of o-quinodimethanes in synthesis of bi- and... 

Nitrenium ions and direct electrophilic aromatic amination (cyclic nitrenium ions, formation of N-heterocycles by intramolecular amination, N-aminopyridinium salts) 05ZOR487. 

Oxidation of anionic o -adducts of 1,3,5-trinitrobenzene (93) [72] by action of CuBr/CCL) provides an access to 3-substituted 4,6-dinitrobenzo[c]isoxazoles 94 (Scheme 42). This approach gives one more example of the formation of N-heterocycles based on the ONS process in nitroarenes. 

This section deals with the reactions in which the formation of N-heterocycles proceeds through the Mannich-type cyclocondensations of anionic o-adducts of nitroarenes. The reactions of o-adducts with formaldehyde and primary amines result in 1,3-annelation of the piperidine ring to the core structure of nitroarenes. Depending on nitroarene structure, there are two main routes for these reactions to take (a) the o-adduct is formed via the addition of C-nucleophile to a nitroarene bearing the hydroxy group and (b) cyclocondensation of hydride adducts of nitroarenes, where the hydride ion acts as a nucleophile. At least two wcta-positioned nitro groups in aromatic ring are necessary for these reactions to proceed. Scheme 52 demonstrates both of these options. 

A chiral selenophosphoramide catalyst was employed for the intramolecular cyclization of an alkenyl sulfonamide to achieve the enantioselective formation of N-heterocycles including an azepane derivative via a mechanism proposed to include formation of a three-membered sulfur-containing ring (14JA8915). A [4 + 3]-cycloaddition reaction of methyl coumalate 12 with an azomethine ylide, formed from imine esters 13 yielded functionalized azepine derivatives 14 (14OL4508). 

Chemistry of bridged lactams and related heterocycles 13CRV5701. Copper-catalyzed synthesis of N-heterocyclic compounds 12S2805. The cyanamide moiety, synthesis, and reactivity, in particular, formation of N-heterocycles 12S1279. 

Zeolites have also known as efficient catalysts for a wide variety of acid-promoted cyclization reactions. Most of them involves the formation of N-heterocycles through the intramolecular amination reaction pathway [48-50]. See examples are shown in Figure 11.13. Pyridines are also being produced by the reaction of ammonia over solid support acid catalyst with various aldehydes [50]. 

The growing demand for ILs that present better inertness xmder reaction conditions is increasing exponentially. The activation of the C(2)-H of the imidazolium for the formation of N-heterocyclic carbene in the presence of base is largely reported as a chemically stable IL [45]. Methimazole-based ILs (1) have been developed in which the C(2) proton is replaced by a thiol linkage (Figure 5) [46]. 

Formation of N- and N,0-heterocycles from fluoro-substituted nitrogen ylides 99MI23. 

Heterocyclization by catalytic formation of N—Car bond to give indoles, amino-pyridines, and N-aryl-substituted saturated heterocycles 98ACR805. 

Synthesis of N-heterocycles with C—N bond formation catalyzed by transition metal catalysts 97SL749. 

Rearangement of furoxans leads to the formation of new heterocyclic systems derivatives of triazoles, diazoles, isoxazoles, and pyrimidinones. For example, on the basis of the experimental results using labeled compound 52-15N , the formation of 8-phenyltheophylline 53, the 1,3-dimethylalloxazines (54 n = 0, 1), and l,3,7,9-tetramethyl-l//,9//-pyrimido[5,4-g]-pteridine-2,4,6,8-tetraone 55 in the thermal reaction of the iV-oxide 52 with benzylamine, aniline, or piperidine and the generation of NO or NO-related species in the reaction with iV-acetylcysteamine were reasonably explained by... 

The cyclizahon of amino alcohols should be an attractive method for the synthesis of N-heterocyclic compounds, mainly because they can be obtained in a single step and without the generation of wasteful byproducts. Carbon-nitrogen bond formation catalyzed by Cp lr complexes has been extended to the synthesis of N-hetero-cyclic compounds by the cyclization of amino alcohols. 

Amyes, T. L. et al.. Formation and stability of N-heterocyclic carbenes in water The carbon acid pK(a) of imidazolium cations in aqueous solution. J. Am. Chem. 

The gaseous oxidation of n-alkanes can, in suitable circumstances, yield substantial amounts of O-heterocycles of the same carbon number as the initial hydrocarbon. A comparative study has been carried out of the formation of O-heterocyclic products during the combustion of n-butane, n-pentane, and n-hexane. The way in which the yields of such compounds vary with reaction conditions has been investigated. As a result of the optimization of the amounts of O-heterocycles it has been possible to obtain maximum yields of these compounds of up to 30% from n-pentane but only about 10% from n-butane and n-hexane. An attempt is made to account for the observed differences in the amounts and nature of the O-heterocyclic products formed from the three n-alkanes. 

In the present work, therefore, a comparative study of the production of O-heterocycles during the cool-flame combustion of three consecutive n-alkanes—viz., n-butane, n-pentane, and n-hexane—was carried out under a wide range of reaction conditions in a static system. The importance of carbon chain length, mixture composition, pressure, temperature, and time of reaction was assessed. In addition, the optimum conditions for the formation of O-heterocycles and the maximum yields of these products were determined. The results are discussed in the light of currently accepted oxidation mechanisms. 

Anodic oxidation of JV,N-dimethyl-co-hydroxyamides (57) in CH3OH-Bu4NBF4 at a platinum anode leads to formation of N-methoxy-JV-methyl-co-hydroxyamides (58) in high yield.116 The latter could in some cases (formation of five-, six-, and seven-membered rings) easily be transformed to l,3-oxaza-4-oxo heterocyclic systems (59) by acid catalysis [Eq. (49)]. No direct formation of the 1,3-oxazaheterocycles was observed, e.g., 57++59. An intramolecular addition of the hydroxy group to the intermediate acylam-monium ion is believed to be hindered by adsorption phenomena at the anode surface. 

Sec. III.A] ELECTROLYSIS OF N-HETEROCYCLIC COMPOUNDS 4. Formation of Nitrogen-Nitrogen Bonds... 

The unusual formation of N,N-dimethylaminophenyl substituted pyrimido[4,5-c]-pyridazines (74) by the reaction of the oxo compound (73) with phosphorus oxychloride and iV,AT-dimethylaniline has been reported (71CPB1849). The chlorination of other oxo substituted pyrimido[4,5-c]pyridazines with phosphorus oxychloride has been reported to be unsuccessful. Chloro derivatives of this heterocyclic ring undergo nucleophilic displacement with amines and hydrazine to give the corresponding amino and hydrazino substituted products. The catalytic dechlorination of these chloro substituted heterocycles has also been reported (68JHC523). 

Torok and co-workers312 have reported the one-pot synthesis of /V-arylsulfonyl heterocycles through the reaction of primary aromatic sulfonamides with 2,5-dimethoxytetrahydrofuran. When triflic acid is used in catalytic amount, IV-arylsulfonylpyrroles are formed (Scheme 5.34). Equimolar amount of triflic acid results in the formation of N- ary I s u I fo n y I i n do I e s, whereas /V-arylsu Ifonylcar-bazoles are isolated in excess acid (Scheme 5.34). In the reaction sequence 1,4-butanedial formed in situ from 2,5-dimethoxytetrahydrofurane reacts with the sulfonamide to give the pyrrole derivative (Paal-Knorr synthesis). Subsequently, one of the formyl groups of 1,4-butanal alkylates the pyrrole ring followed by a second, intramolecular alkylation (cyclialkylation) step. 

Ytterbium and lutetium ionic complexes, derived from enantiopure substituted (R)-binaphthylamine ligands of the general formula [Li(THF) ][Ln[(f )C2oHi2(NR)2]2], have been investigated as catalysts for hydroamination/cyclization of several unsatu- rated amines CH2=CH(CH2) C(R2)CH2NH2 (n = 1 or 2). Complexes with isopropyl or cyclohexyl substituents on nitrogen atoms were found to be efficient catalysts for the formation of N-containing heterocycles under mild conditions with enantiomeric excesses up to 78%.124... 

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