Catalysts heterocyclic amine

Pyrrole, the simplest five-membered unsaturated heterocyclic amine, is obtained commercially by treatment of furan with ammonia over an alumina catalyst at 400 °C. Furan, the oxygen-containing analog of pyrrole, is obtained by acid-catalyzed dehydration of the five-carbon sugars found in oat hulls and... 

Reactions of heterocyclic amines 208 with 2-chloro-3-iodopyridine 209 in the presence of a palladium catalyst provide dipyridoimidazole and its benzo- and aza-analogues 210. The synthesis represents the first tandem double palladium-catalyzed amination reaction (Equation 23) <2004CC2466>. 

Heterocyclic amines have also been used as phase transfer catalysts. However, because these amines quaternize easily, the question is whether the operative catalyst is the tertiary amine or the quaternary ammonium salt formed in situ Furukawa et al.286 have shown that a methyl 2-pyridyl sulfoxide may be used as a phase transfer catalyst and promote substitution reactions between lithium chloride or sodium cyanide and benzyl bromide. According to the authors, the catalyst behaves as a cation complexer and not as a quaternary ammonium salt formed in situ by a Menschutkin reaction. 

Reeves and Hilbrich288 have reported the catalysis by pyridines of benzyl ketone alkylation they are less efficient than aliphatic trialkylamines. Reeves and White289 have also described the reaction of alkyl bromides with sodium cyanide, where pyrazine is a better catalyst (99% yield) compared to pyridine (12% yield). Isakawa et al.289 have also carried out addition of dichloro-carbene to cyclohexene under biphasic conditions, using heterocyclic amines as catalysts (e.g., iV-butylpiperidine gives 76% yield). 

Tertiary amines catalyze the homopolymerization of epoxy resins in the presence of hydroxyl groups, a condition which generally exists since most commercial resins contain varying amounts of hydroxyl functionality (B-68MI11501). The efficiency of the catalyst depends on its basicity and steric requirements (B-67MI11501) in the way already discussed for amine-catalyzed isocyanate reactions. A number of heterocyclic amines have been used as catalytic curatives pyridine, pyrazine, iV,A-dimethylpiperazine, (V-methylmorpholine and DABCO. Mild heat is usually required to achieve optimum performance which, however, is limited due to the low molecular weight polymers obtained by this type of cure. 

Tertiary amines are used to accelerate both amine and anhydride cures of epoxy resins (B-67MI11501). Certain heterocyclic amines have been used for this purpose, including pyridine and piperidine. In the case of anhydride cures, the use of an amine catalyst not only accelerates the cure, but also improves the thermal stability of the cured resin. 

There are many examples of the preparation of tertiary aliphatic amines by the reductive alkylation of dialkylamines or secondary non-aromatic heterocyclic amines with ketones using platinum5-13, palladium12"17, mixtures of platinum and palladium18,and nickel12. 13. 9-22 catalysts. 

An enantioselective organocatalytic reductive amination has been achieved using Hantzsch ester for hydrogen transfer and compound (21) as catalyst. This mild and operationally simple fragment coupling has been accomplished with a wide range of ketones in combination with aryl and heterocyclic amines.359... 

The same rule was revealed in [101] while studying the interaction of acetophenones 92 with heterocyclic amines 91 with an acid catalyst. Since the amino groups of the starting diamine are nonequivalent, there exist two possible directions of the reaction but only one of them, i.e., direction A, is observed, with the formation of diazepines 93 but not their regioisomers 94 (Scheme 4.29). 

There are limitations with A/-heterocycles. Amines are not compatible with the catalyst. Thus, the cyclization of bisallylaminc 29 to dihydropyrrole 30 is not possible. 

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

Certain amines are readily prepared by the reduction of aromatic, aryl aliphatic, and heterocyclic amines. For example, aniline is reduced to cyclohexylamine by high-pressure hydrogenation in the presence of Raney nickel catalyst or a cobalt oxide-calcium oxide catalyst. The reaction occurs at a temperature above 200°, where condensation of the primary amine also takes place, viz., 2CjHiiNHj — (CjHn),NH + NH,. If this side reaction is repressed by the presence of dicyclohexylamine at the start of the reaction, a 94% yield of cyclohexylamine is obtained. Hydrogenation of aryl aliphatic amines proceeds more readily, occurring at moderate temperatures and pressures over platinum catalyst in glacial acetic acid. Other reductions using this catalyst are best performed on the amines in the form of their hydrochlorides. ... 

Extensive mechanistic studies have been conducted on the oxidative addition of aryl halides to Pd(0) complexes ligated by PPh3 in different media and with different additives175, 176. However, palladium complexes containing these ligands are not active catalysts for amination. Instead, one must consider the addition of aryl halides to palladium complexes bound by ligands relevant to amination. Studies of the mechanism of oxidative addition to palladium(O) complexes of P(tol-o)3, DPPF, BINAP, Q-phos, P(Bu-f)3 and an /V-heterocyclic carbene ligand have been reported. 

Decomposition of aryl diazonium salts. Cuprous oxide (1, 169-170) has been the catalyst of choice for homolytic decomposition of aryl diazonium salts.2 It has the disadvantage of being effective only in an acidic medium. Lewin and Michl3 have examined the effectiveness of various copper(I) perchlorates complexed with heterocyclic amines. Of the various copper(I) salts, tetrakis(pyridine)copper(l) perchlorate is... 

Complex 9 remains one of the most broadly applicable catalysts for this reaction, catalyzing hydroaminoalkylation with A -arylalkylamines, including controlled monoalkylation of dienes. This reactive catalyst 9 even displays tolerance of oxygen-containing substrates. Most importantly, this remains the only catalytic system capable of the direct C—H alkylation a to N of unprotected heterocyclic amine substrates. Such products are potentially important structural motifs for exploration in medicinal chemistry. In all cases this precatalyst shows regioselective hydroaminoalkylation to generate the branched product, and excellent diastereoselectivity when applicable (Scheme 20). [79]... 

N-Arylation. (5)-2-(Imidazolylmethyl)pyrrolidine 11 is yet another derivative of the series, and it functions as a catalyst for A -arylation of heterocyclic amines. 

Compound 141 produced broad spectra at room temperature, due to slow rotation of about the N-CO bond of the two A-methyl tertiary amides. Spectroscopic studies were therefore carried out at 50°C, at which temperature sharp, well-resolved spectra were obtained. Cleavage of the crotyl ester and preparative TLC removed most eontaminants from 142, which, however, strongly retained Ph3P=0 (from the Pd catalyst). It was difficult to completely eliminate this contaminant, but at this juncture we were not overly concerned about its presence. In fact, a Russian group had found that certain heterocyclic amine A-oxides act as nucleophilic... 

Heterocyclic Amines. Heterocyclic amines can be alkylated with alkyl halides or with alcohols in the presence of hydrogen plus a nickel catalyst. The Wallach reaction for the alkylation of amines by the action of aldehydes or ketones and formic acid has been studied for piperidine. Reactions between toluene and cyclohexanone with piperidine and formic acid yielded 1-benzyl- and 1-cyclohexylpiperidine, respectively. An optimum amount of formic acid is desired since large amounts are harmful and wasteful. 

The effects of catalyst structure (secondary and tertiary aliphatic and heterocyclic amines), solvent, temperature, and substrate structure on rates and products of prototropic isomerizations of /3,y-unsaturated nitriles and esters were studied by Miaihe and Vessiere" . 

Many reports of aerobic alcohol oxidation involve homogeneous Pd- [7] and Ru-based [8] catalysts that are effective with benzylic, allylic, and ahphatic primary and secondary alcohols. These catalysts are often inhibited by coordinating functional groups such as heterocycles, amines, and oxygen- or sulfur-containing moieties and are capable of oxidizing alkenes. Efforts to develop scalable applications of Pd-based catalysts raised concerns about large-scale prospects for these... 

Lindlar s catalyst is often used for the reduction of alkynes to alkenes. The catalyst consists of palladium which is deposited in a finely divided state of barium sulfate, which is subsequently treated with a heterocyclic amine called quinoline. Which of the following is the most likely function of quinoline ... 

In the formation of the first synthetic intermediate in Sequence D, the very effective Verley-Doebner modification of the fundamental Knoevenagel condensation is used. This modification uses malonic acid in place of the conventional ester to promote enoUzation. In addition, the heterocyclic amine, pyridine, functions as both the base catalyst and the solvent. A cocatalyst, P-alanine (an amino acid), is also introduced. Mechanistically, the reaction closely resembles the aldol condensation in that in both cases a carbanion is generated by abstraction, by base, of a proton alpha to a carbonyl group. The resulting carbanion is stabilized as an enolate anion (see below). 

Dianionic cyclopentadienylbis(oxazolinyl)borates 163 were prepared as diprotonated species in two steps from the appropriate oxazolines. The corresponding Ti, Zr, and FIf diamide complexes behaved as highly efficient, enantioselective catalysts for cyclization of aminoalkenes to afford five-, six-, and seven-membered AT-heterocyclic amines (13JA7235). 

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