Pure amines

In the pyrolysis of pure amine oxides, temperature has a significant effect on the ratio of products obtained (22). The principal reaction during thermal decomposition of /V,/V-dimetby11 amyl amine oxide [1643-20-5] at 80—100°C is deoxygenation to /V,/V-dimetby11 amyl amine [112-18-5] (lauryl = dodecyl). 

Isomer separation beyond physical fractional crystallization has been accompHshed by derivatization using methyl formate to make /V-formyl derivatives and acetic anhydride to prepare the corresponding acetamides (1). Alkaline hydrolysis regenerates the analytically pure amine configurational isomers. 

If very pure amine is desired the product described above is dissolved with 1.04 parts of crystalline oxalic acid in eight parts of hot water. After clarification with Norite, the filtered solution on cooling deposits crystals of the acid oxalate. About 5 g. of the salt remains in each 100 cc. of the mother liquor most of this can be obtained by evaporation and further crystallization. The amine is liberated from the pure oxalate with potassium hydroxide, distilled with steam, and purified as described above. When a known amount of amine is desired in water solution (as for optical resolution) a weighed amount of the (anhydrous) oxalate is decomposed and the amine is distilled quantitatively with steam. 

The pure malate (mol. wt. 255) is decomposed by warming with very slightly more (Note 5) than two equivalents of approximately 2 N sodium hydroxide. The amine is extracted, after cooling with three or four 25-cc. portions of pure benzene, the solution is dried thoroughly with powdered sodium hydroxide, and the pure amine, b.p., 184-185°, [app + 39.2° to +39.7° (without solvent), is obtained by distillation (Note 6). A small amount of the amine distils with the benzene. The yield is 35-40 g. (92-94 per cent of the theoretical amount based on the pure malate). 

The physical solvent sulfolane provides the system with bulk removal capacity. Sulfolane is an excellent solvent of sulfur compounds such as H2S, COS, and CS2. Aromatic and heavy hydrocarbons and CO2 are soluble in sulfolane to a lesser degree. The relative amounts of DIPA and sulfolane are adjusted for each gas stream to custom fit each application. Sulfinol is usually used for streams with an H2S to CO2 ratio greater than 1 1 or where it is not necessary to remove the CO2 to the same levels as is required for H2S removal. The physical solvent allows much greater solution loadings of acid gas than for pure amine-based systems. Typically, a Sulfinol solution of 40% sulfolane, 40% DIPA and 20% water can remove 1.5 moles of acid gas per mole of Sulfinol solution. 

It s often possible to lake advantage of their basicity to purify amines. For example, if a mixture of a basic amine and a neutral compound such as a ketone or alcohol is dissolved in an organic solvent and aqueous acid is added, the basic amine dissolves in the water layer as its protonated salt, while the neutral compound remains in the organic solvent layer. Separation of the water layer and neutralization of the ammonium ion by addition of NaOH then provides the pure amine (Figure 24.2). 

Commercial triethylamine (obtained from Eastman Organic Chemicals), was distilled from phosphorus pentoxide, and the pure amine (b.p. 86-90°) was stored under a nitrogen atmosphere. Since the presence of even a small excess of triethylamine is deleterious in these reactions, the quantities of this amine used should be measured by weight rather than volume. 

Reaction of benzylideneaniline with optically active methyl p-tolyl sulphoxide 449 in the presence of lithium diethylamide produces the corresponding jS-anilinosulphoxide 450 with 100% asymmetric induction. Its reductive desulphurization with Raney nickel leads to the enantiomerically pure amine 451524 (equation 270). When the same optically active... 

To a slurry of 33.5-33.9 g. of the pure (-)-amine (-)-DAG salt in 130 ml. of water is added 56 ml. of aqueous 2AT sodium hydroxide, and the resulting oily suspension is extracted with four 80-ml. portions of ether. The combined ether extracts are washed with 50 ml. of water and dried over anhydrous magnesium sulfate. After filtration and removal of the ether on a rotary evaporator, the crude base is distilled under reduced pressure through a 20-cm. Vigreux column (Note 8). This operation affords 10.9-11.7 g. (85-90% yield, based on the amount of the salt used) of the pure ()-amine as a colorless liquid, b.p. 156-157° (11mm.), n2i d 1.6211-1.6212, df 1.056, [a]2D5 -80.1° (neat), [oc]2d3 -60.4° (c 10.0%, methanol), [a] -59.3° (c 0.65%, methanol) (Notes 9 and 10). 

Symmetrical N, N -disubstituted imidazolium salts are usually obtained by addition of paraformaldehyde on a bis-imine of glyoxal under acidic conditions. A one-pot procedure has been developed. Several enantiomerically pure amines were used to prepare the corresponding symmetrical salts 6 (Scheme 4) [12,13]. 

No stereoselectivity was observed in the formation of a 1 1 diastereomeric mixture of 2-hydroxy-2-phenylethyl p-tolyl sulfoxide 145 from treatment of (R)-methyl p-tolyl sulfoxide 144 with lithium diethylamide . However, a considerable stereoselectivity was observed in the reaction of this carbanion with unsymmetrical, especially aromatic, ketones The carbanion derived from (R)-144 was found to add to N-benzylideneaniline stereoselectivity, affording only one diastereomer, i.e. (Rs,SJ-( + )-iV-phenyl-2-amino-2-phenyl p-tolyl sulfoxide, which upon treatment with Raney Ni afforded the corresponding optically pure amine . The reaction of the lithio-derivative of (-t-)-(S)-p-tolyl p-tolylthiomethyl sulfoxide 146 with benzaldehyde gave a mixture of 3 out of 4 possible isomers, i.e. (IS, 2S, 3R)-, (IS, 2R, 3R)- and (IS, 2S, 3S)-147 in a ratio of 55 30 15. Methylation of the diastereomeric mixture, reduction of the sulfinyl group and further hydrolysis gave (—)-(R)-2-methoxy-2-phenylacetaldehyde 148 in 70% e.e. This addition is considered to proceed through a six-membered cyclic transition state, formed by chelation with lithium, as shown below . ... 

One of the potentially most useful aspects of the imine anions is that they can be prepared from enantiomerically pure amines. When imines derived from chiral amines are alkylated, the new carbon-carbon bond is formed with a bias for one of the two possible stereochemical configurations. Hydrolysis of the imine then leads to enantiomerically enriched ketone. Table 1.4 lists some examples that have been reported.118... 

Secondary amines, such as pyrrolidine, must be alkylated with care too polar a solvent leads to participation of a second nearby polymer-bound alkylant in the formation of a quaternary ammonium salt, along with the desired immobilized trialkyl amine. The exception, as seen above, is diisopropylamine, which refuses to displace tosylate even in the refluxing pure amine, or in hot dimethyl-formamide or other polar solvent, while metal diisopropylamide is notorious as a powerful non-nucleophilic base. However, carboxamide is not difficult to form from (carboxymethyl)polystyrene, again using toluenesulfonyl chloride as condensing agent this can then be reduced to (diisopropyl-ethylaminoethyl)polystyrene, which is of interest as a polymer-bound non-nucleophilic base. ... 

MP borohydride catches one equivalent of the titanium catalyst, while the polystyrene-bound diethanolamine resin (PS-DEAM) can scavenge the remaining titanium catalyst. The borohydride reagent also assists in the reductive animation reaction. Final purification of the crude amine product is achieved with a polystyrene-bound toluene sulfonic acid resin scavenger that holds the amine through an ion exchange reaction, while impurities are washed off. The pure amine can be recovered with methanol containing 2M ammonium hydroxide. 

Enantiomerically pure amines are extremely important building blocks for biologically active molecules, and whilst numerous methods are available for their preparation, the catalytic enantioselective hydrogenation of a C=N bond potentially offers a cheap and industrially viable process. The multi-ton synthesis of (S)-metolachlor fully demonstrates this [108]. Although phospholane-based ligands have not proven to be the ligands of choice for this substrate class, several examples of their effective use have been reported. 

The combined crops of crude (—)-amine (-f)-hydrogen tartarate are pulverized in a mortar and redissolved in 450-500 ml. of boiling methanol. The resulting hot solution is concentrated to 350 ml. (Note 3) and then allowed to cool and stand for 24 hours. After the initial crop (14.3-16.2 g.) of pure (—)-amine (-(-)-hydrogen tartarate has been collected as white prisms (Note 2) (m.p. 179-182° dec.), the mother liquors and washings are concentrated to 75 ml. and again allowed to stand for 24 hours. In this way a second crop (2.9-3.6 g.) of the pure (—) -amine salt is obtained. The total yield of the pure (—)-amine salt is 17.9-19.1 g. (64-68%). 

A mixture of the pure (—)-amine salt (17.9-19.1 g.) and 90 ml. of water is treated with 15 ml. of aqueous 50% sodium hydroxide and the resulting mixture is extracted with four 75-ml. portions of ether. After the combined ether extracts have been washed with 50 ml. of saturated aqueous sodium chloride and dried over magnesium sulfate, the bulk of the ether is distilled from the mixture through a 30-cm. Vigreux column and the residual liciuid is distilled under reduced pressure. The (—)-amine is collected as 6.9-7.2 g. (55-58 () of colorless liquid, b.p. 94 95° (28 mm.), 1.5241-1.5244, —39.4° (neat) (Notes 4, 5). 

A second example of the use of ionic chiral auxiliaries for asymmetric synthesis is found in the work of Chong et al. on the cis.trans photoisomerization of certain cyclopropane derivatives [33]. Based on the report by Zimmerman and Flechtner [34] that achiral tmns,trans-2,3-diphenyl-l-benzoylcyclopropane (35a, Scheme 7) undergoes very efficient (0=0.94) photoisomerization in solution to afford the racemic cis,trans isomer 36a, the correspondingp-carboxylic acid 35b was synthesized and treated with a variety of optically pure amines to give salts of general structure 35c (CA=chiral auxiliary). Irradiation of crystals of these salts followed by diazomethane workup yielded methyl ester 36d, which was analyzed by chiral HPLC for enantiomeric excess. The results are summarized in Table 3. 

The photochemical reaction that has been most thoroughly investigated from the ionic chiral auxiliary point of view is the well-known Norrish/Yang type II reaction. One example, taken from the work of Patrick, Scheffer, and Scott [36], deals with derivatives of 7-methyl-7-benzoylnorbornane-p-car-boxylic acid (37a, Scheme 8). This compound was treated with a variety of optically pure amines to afford the corresponding 1 1 salts (37b), and in an... 

A closely related example involving a seven-membered transition state (6) hydrogen atom abstraction in the crystalline state is shown in Scheme 9. Based on earlier work by Wagner and coworkers [38], Cheung, Rademacher, Scheffer, and Trotter prepared carboxylic acid 41a and treated it with a variety of optically pure amines to form chiral salts 41b [39]. Irradiation of crystalline samples of the salts followed by workup with ethereal diazomethane afforded the chiral in-... 

Analogous to the reactions of chiral alcohols, enantiomerically pure amines can be prepared by (D)KR of the racemate via enzymatic acylation. In the case of alcohols the subsequent hydrolysis of the ester product to the enantiomerically pure alcohol is trivial and is generally not even mentioned. In contrast, the product of enzymatic acylation of an amine is an amide and hydrolysis of an amide is by no means trivial, often requiring forcing conditions. 

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