Piperidines, addition

Piperazine, N-alkylation with benzyl chloride, 42, 19 Piperazine, 1-benzyl-, 42,19 Piperidine, addition to ethylene, 43, 45 as catalyst for Claisen-Schmidt condensation, 41, 40 Piperidine, 1-ethyl-, 43, 45 Piperidine, 1-(2-naphthyl)-, 40,74 Pivalic acid, oxidative coupling to a,a,-a, a -tetramethyladipic add, 40, 92... 

This finding is in agreement with a result obtained in 1958-59 by B. Huisgen and K. Herbig i.e., in a reaction of 3,4-pyridyne with piperidine addition products were formed in a 52 48 ratio. See B. Huisgen, in Organometallic Chemistry (H. Zeiss, ed.), p. 78, Beinhold, New York, 1960. 

RhCl(C2H4)pip2] is formed as the actual catalyst. The complex, whose structure is established by X-ray crystal structure analysis [18], can be easily prepared by piperidine addition to the well-known [Rh(C2H4)2Cl]2, which shows identical catalytic properties. The catalytic efficiency is limited by the thermal instability of the bis(piperidine) ethylene complex at higher temperatures. The thermal decomposition proceeds with formation of metallic rhodium, presumably according to eq. (5). 

Another interesting comparison is that between the reactions of 1 and 3. The equilibrium constant for piperidine addition to 1, = 31.8, is almost the same as that for... 

Ethylamine, piperidine, aniline, and trimethylamine are less reactive in the addition to 1,3-butadiene. Ethylamine and piperidine addition reactions proceed at 373 K and 453 K, respectively. Addition of aniline or trimethylamine does not take place at 473 K. 

In addition to their antiknock properties, organic lead compounds possess bactericidal properties and motor fuels with lead are known to inhibit bacterial growth during storage in contact with water. With the disappearance of lead-based compounds, it is necessary to incorporate biocides from the cyclic imine family, (piperidine, pyrrolidine, hexamethyleneimine), alkylpropylene diamines or imidazolines (Figure 9.2). 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

Like butadiene, allene undergoes dimerization and addition of nucleophiles to give 1-substituted 3-methyl-2-methylene-3-butenyl compounds. Dimerization-hydration of allene is catalyzed by Pd(0) in the presence of CO2 to give 3-methyl-2-methylene-3-buten-l-ol (1). An addition reaction with. MleOH proceeds without CO2 to give 2-methyl-4-methoxy-3-inethylene-1-butene (2)[1]. Similarly, piperidine reacts with allene to give the dimeric amine 3, and the reaction of malonate affords 4 in good yields. Pd(0) coordinated by maleic anhydride (MA) IS used as a catalyst[2]. 

Protonated /V-chloroalkyl amines under the influence of heat or uv light rearrange to piperidines or pyrroHdines (Hofmann-Lriffler reaction) (88). The free-radical addition of alkyl and dialkyl-/V-chloramines to olefins and acetylenes yields P-chloroalkji-, P-chloroalkenyl-, and 8-chloroalkenylamines (89). Various N-hiomo- and N-chloropolyfluoroaLkylarnines have been synthesized whose addition products to olefinic double bonds can be photolyzed to fluoroazaalkenes (90). 

The Perkin reaction is of importance for the iadustrial production of coumarin and a number of modifications have been studied to improve it, such as addition of a trace of iodine (46) addition of oxides or salts of metals such as iron, nickel, manganese, or cobalt (47) addition of catalytic amounts of pyridine (48) or piperidine (49) replacement of sodium acetate by potassium carbonate (50,51) or by cesium acetate (52) and use of alkaU metal biacetate... 

With secondary amines such as piperidine or dimethylamine the formal products (169) of cine substitution are obtained with primary amines e.g. /-butylamine), in addition to the displacement product (173), a rearranged product (174) is obtained in which the nitrogen-bearing methyl becomes exocyclic 80CC123). Earlier studies on the reaction of... 

Intramolecular Michael addition of acrylamides (149) in the presence of piperidine gives /3-lactams (65T449). The method requires that R must be a strongly electron withdrawing... 

A dry 1-1. three-necked round-bottomed flask is fitted in the center neck with a sweep-blade stirrer whose shaft passes through an airtight bearing (Note 1). One side neck is fitted with a condenser topped by a soda-lime drying tube, and the other is fitted with a solid stopper. In the flask are placed 75 ml. of piperidine (Note 2) and 15.6 g. (0.4 mole) of sodium amide (Note 3), and the mixture is heated at reflux (Note 4) for 15 minutes with good stirring. The mixture is cooled just below reflux temperature, and 46 g. (0.2 mole) of sodium -naphtha-lenesulfonate (Note 5) is added, followed by an additional 75 ml. of piperidine. The mixture is then heated at reflux for 12 hours with stirring. 

To the cooled reaction mixture, 200 ml. of water is added carefully with stirring. Potassium carbonate is added with continued stirring until the water layer is saturated the mixture is now transferred to a separatory funnel and extracted three times with 60-ml. portions of ether. The combined ether extracts are dried over solid sodium hydroxide and are then transferred to a simple distillation apparatus. Distillation is commenced with a steam bath as source of heat when most of the ether has been removed, the steam bath is replaced by a flame. Distillation is continued until most of the piperidine (b.p. 106°) has been removed. The cooled residue in the distillation flask is recrystallized from petroleum ether (boiling range 30-60°) with the use of charcoal. There is obtained 30.0 g. (71%) of N-/3-naphthyl-piperidine as tan crystals, m.p. 52-56°. An additional recrystallization from the same solvent gives crystals, m.p. 56-58°, with about 10% loss in weight (Note 6). 

The striking effect of the catalyst is exemplified by the reaction of pregna-4, 16-diene-3,20-dione (10) with benzyl mercaptan. In the presence of piperidine only conjugate addition occurs to give (11) whereas with pyridine hydrochloride only the 3-benzyl thioenol ether (12) is formed. In the presence of p-toluenesulphonic acid both reactions take place to yield (13). 

Powdered potassium permanganate (94 mg) is added to an ice-cold, stirred solution of 0.1 g of the unsaturated nitrile in 3.5 ml of acetone containing 0.11 ml of piperidine. The reaction mixture is stirred at 0° for 1.5 hr, allowed to warm to room temperature (30 min) and then treated with 0.02 ml of acetic acid in 0.2 ml of acetone. After stirring at room temperature for an additional 1.5 hr the mixture is treated with chloroform, aqueous sodium bisulfite and sufficient 1 N sulfuric acid to reduce all of the manganese dioxide. 

Additional evidence that a dynamic equilibrium exists between an enamine, N-hemiacetal, and aminal has been presented by Marchese (41). It should be noted that no acid catalysts were used in the reactions of aldehydes and amines discussed thus far. The piperidino enamine of 2-ethylhexanal (0.125 mole), morpholine (0.375 mole), and p-toluene-sulfonic acid (1.25 x 10 mole) diluted with benzene to 500 ml were refluxed for 5 hr. At the end of this time the enamine mixture was analyzed by vapor-phase chromatography, which revealed that exchange of the amino residue had occurred in a ratio of eight morpholine to one piperidine. Marchese proposed a scheme [Eqs. (4), (5) and (6)] to account for these... 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

Likewise, a cis-2,6-disubstituted piperidine natural product, (-)-lobeline (98, Scheme 8.4.30) was synthesized from the chiral Af-alkyl pyridinium salt ent-80 via a sequence that included addition of a Reformatsky reagent to an intermediate oxazolidine. °... 

By treating 3-bromo- (27, X = Br) or 3-chloropyridine (27, X = Cl) with lithium piperidide (2.2 equivalents) and piperidine (2.8 equivalents) in boiling ether, mixtures of 3- (29, Y = NC5H10) and 4-piper-idinopyridine (34, Y = NC5H10) were obtained in 85-90% total yield. In both reactions the ratio of the 3- to 4-piperidino compounds was 48 52. Support for the hetaryne mechanism as the sole pathway for these reactions comes from the fact that increasing the amounts of lithium piperidide and piperidine to 5 and 10 equivalents, respectively, scarcely changed the composition of the reaction products. If addition-elimination had occurred concomitantly with reaction via the hetaryne, more of the 3-piperidino compound would have been formed, since the reconversion of the hthium intermediate 30 into 27 by piperidine would be accelerated by the enhancement of the concentration of this substance. 

Those reactions of halogenopyridines with potassium amide and lithium piperidide which proceed via 3,4-pyridyne form the 3- and 4-substituted pyridine derivatives in ratios of 1 2 and 1 1, respectively (see Section II, A, 1). It appears that the ring nitrogen atom has an orienting effect on these additions, but the quantitative divergence of the addition of ammonia and piperidine is not understood at present. 

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