Piperidine-based catalysts

Tetrahydrofurfuryl alcohol reacts with ammonia to give a variety of nitrogen containing compounds depending on the conditions employed. Over a barium hydroxide-promoted skeletal nickel—aluminum catalyst, 2-tetrahydrofurfur5iarnine [4795-29-3] is produced (113—115). With paHadium on alumina catalyst in the vapor phase (250—300°C), pyridine [110-86-1] is the principal product (116—117) pyridine also is formed using Zn and Cr based catalysts (118,119). At low pressure and 200°C over a reduced nickel catalyst, piperidine is obtained in good yield (120,121). 

The results in Table 2 show that the pyridine is less active than any of the X zeolites and Ge faujasite except the lithium form which shows slightly lower activity, whereas all Y zeolites show lower activity than pyridine. Piperidine, however, is more active than any of the zeolite samples studied here. From this comparison, it appears that, most of the basic sites of the zeolites must have pK<10.3. However, the fact that zeolites are also active for catalyzing the condensation of benzaldehyde with ethyl malonate, indicate that these samples have some basic sites with pK< 13.3. On a quantitative bases, and comparing the activity of zeolites for condensation with ethyl cyanoacetate, ethyl acetoacetate and ethyl malonate (Fig. 2), we can conclude that most of the basic sites of the zeolite have pK<9.0 with a sensible amount with 9.0basic strength of different solid base catalysts. 

Recently, Soleiman et al. [136] have published the synthesis of novel class of spiro-(3-lactams 237 using chloroacetylchloride and Schiff bases 236 in the presence of triethylamine and dioxane (Scheme 53). The new Schiff bases 236 were prepared by reaction of 234 with different aromatic amines using ethanol and piperidine as catalysts. 

Two examples of such situations are sketched in Scheme 1.11. Quatemization of tropane occurs mainly from the less hindered pyrrolidine side (equatorial attack at the piperidine ring), even though the main conformer of tropane has an equatorial methyl group. Similarly, l-methyl-2-phenylpyrrolidine yields mainly an anti alkylated product via alkylation of the minor cis conformer when treated with phenacyl bromide [33], In both instances the less stable conformer is more reactive to such an extent that the major product of the reaction results from this minor conformer. A further notable example of a reaction in which the main product results from a minor but more reactive intermediate is the enantioselective hydrogenation of a-acetamidocinnamates with a chiral rhodium-based catalyst [34],... 

As described above, zeolites can also act as solid base catalysts when the Si Al ratio is low and the extra framework cation is a large one such as The most basic common exchanged zeolite is CsX. With this material the aldol condensation of cyclooctanone with benzaldehyde gave only the monobenzylidene compound (Eqn. 10.23) 5 while reactions using piperidine, m nesium oxide or amorphous cesium aluminosilicate gave both the mono- and di-benzylidene products(Eqn. 10.12). The smaller ketones, cyclohexanone and... 

Freifelder el al. found rhodium on carbon to be better suited than rhodium on alumina for reduction of the pyridine ring. The poisoning effect of the piperidine base formed can be overcome by use of sufficient catalyst. 

Piperidine-based aminoketones similar to 456 also featured in syntheses of (+ )-427 by Munchhof and Meyers (Scheme 57) 412), and by Solladie and Chu (Scheme 58) 413). In the former, the enantiomerically pure bicyclic oxazolidine-thione 457 underwent Eschenmoser sulfide contraction under forcing conditions to produce the vinylogous urethane 458, which was simultaneously hydrogenated and hydrogenolyzed over Pearlman s catalyst to give the 2,6-c/s-disubstituted piperidine... 

Group 4 bis(amidate)bis(amido) complexes have also been identified as precatalysts for the more challenging hydroamination of alkenes. The majority of investigations in this field focus on the intramolecular cychzation of aminoalkenes with zirconium-based catalysts. [64e] Neutral group 4 bis(amidate) zirconium amido or imido complexes are efficient precatalysts for the intramolecular cychzation of primary amines to form pyrrolidine and piperidine products (Scheme 12). The monomeric imido complex can be generated by reaction of the bis(amido) complex with 2,6-dimethylaniline and trapped with triphenylphosphine oxide. [64e] The bis(amido) and imido complexes... 

The role of catalyst can be illustrated by the amination of tetrahydrofurfuryl alcohol. Cu/Zn0-Al203 furnishes mainly the primary amine, whereas piperidine was the major product over Co- and Ni-based catalysts (Scheme 3) [11]. 

Several groups developed other catalysts for enantioselective PTC alkylation of 1—for example, quanidine-based catalysts (XXXVIII, Scheme 8.8) (Kita et al. [65]), Cs-symmetrical ammonium PTC (XXXXI) [66], biphenyl ammonium PTC (XXXX, Scheme 8.9) (Lygo et al. [67]), spiro bis-ammonium PTC (XXXIX) (Sasai, [68]), L-menthol-derived PTC (XXXXII, XXXXIII) (Ramachandran and coworkers [69]), pyrrolidine and piperidine-derived PTC (XXXXIV) (MacFarland and co-workers [70]), bimorpholine (XXXXV) (Kanger and co-workers [71]), but their use in asymmetric procedures involving alkylation is only hmited. 

The Hajos and Wiechert research groups looked at a number of other potential proline based catalysts for their intramolecular Robinson annulation. (. -(-)-Hygrinic acid, Af-methylproline 13, was examined, but only the racemic intermediate ketol product 2 was obtained. In a similar manner, the proline methyl ester 14 also produced the racemic ketol intermediate. No reaction was observed with the piperidine analog 15. The homo-proline analog 16 gave the enantiomeric product. An explanation for this change in selectivity has not been provided yet. Please note that the use of (i )-proline provides the enantiomeric product. 

The observation of general base catalysis in some substitutions by amines is additional evidence for the presence of an intermediate. It is particularly significant that plots of the second-order rate constant versns the concentration of added base may be curved. Examples reported early on are in the reactions of 4-nitrophenylphosphate with secondary amines in water [22] and of 2,4-dinitrophe-nyl ether with piperidine [23]. At low concentrations of the base catalyst, the base-assisted second step is rate determining so that increases in catalyst concentration result in rate increases. However, a point is reached at high base concentrations, when the second step is sufficiently rapid, that the first step becomes rate limiting. 

The first selective monoarylation of (W-pyridin-2-yl)piperidme was made possible by introduction of a trifluoromethyl substituent at the 3-position of the pyridin-2-yl directing group (Scheme 24) [16]. The steric hindrance brought by this substituent favoured the sole formation of monoarylated piperidines. A beneficial effect of metal salt additives to the Ru3(CO)i2-based catalyst was observed on... 

Knoevenagel reaction. The condensation of an aldehyde with an active methylene compound (usually malonic acid or its derivatives) in the presence of a base is generally called the Knoevenagel reaction. Knoevenagel found that condensations between aldehydes and malonic acid are effectively catalysed by ammonia and by primary and secondary amines in alcoholic solution of the organic amines piperidine was regarded as the best catalyst. 

Palladium-catalyzed reactions have been used for the formation of thienoindolizines the following reaction, which is carried out in presence of a mild base, gives different ratios of the endo- (thienopyridone) and exo- (thienoindolizine) products according to the specific catalyst and base used (Equation 36). The latter is almost exclusively formed when the base used is sodium formate or piperidine <1997TL1057>. For the conditions favoring the 5 6 6-fused product, see Section 11.17.4.1.1.3. 

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