Amines without additives

Reactions of aryl halides with amines without additives. 502... 

To transfonn a haloalkane selectively into the corresponding amine without additional carbons requires a modified nitrogen nucleophile that is unreactive after the first alkylation. Such a nucleophile is the azide ion, N3, which reacts with haloalkanes to furnish alkyl azides. These azides in turn are reduced by catalytic hydrogenation (Pd-C) or by Uthium aluminum hydride to the primary amines. 

A new family of peroxide-cured dipolymers was introduced in 1991. The peroxide cure provides copolymers that cure faster and exhibit good compression set properties without a postcure. The removal of the cure-site has also made the polymer less susceptible to attack from amine-based additives. By varying the methyl acrylate level in the dipolymer, two offerings in this family have been synthesized, VAMAC D and its more oil-resistant... 

Resoles are usually those phenolics made under alkaline conditions with an excess of aldehyde. The name denotes a phenol alcohol, which is the dominant species in most resoles. The most common catalyst is sodium hydroxide, though lithium, potassium, magnesium, calcium, strontium, and barium hydroxides or oxides are also frequently used. Amine catalysis is also common. Occasionally, a Lewis acid salt, such as zinc acetate or tin chloride will be used to achieve some special property. Due to inclusion of excess aldehyde, resoles are capable of curing without addition of methylene donors. Although cure accelerators are available, it is common to cure resoles by application of heat alone. 

The addition of primary amines to fluoroolefins under anhydrous conditions yields imines The hexafluoropropene dimer, perfluoro-2-methyl-2-pcntcne, and ten butylamine react to yield a mixture of two compounds m a 9 4 ratio [4] (equation 3) rather than just the major keteiiimme-imine, as previously reported [5] It IS claimed that this result is possible by means of isomerization to the terminally unsaturated difluoromethylene isomer prior to nucleophilic attack Secondary amines add to fluoroolefins under anhydrous conditions to give fluonnated ternary amines m good yields If the fluoroolefin is added to the amine without cooling the reaction mixture, or if an excess of the secondary armne is used, there is a tendency toward dehvdrofluonnation of the ternary amine The products... 

In 1974, Hegedus and coworkers reported the pa]ladium(II)-promoted addition of secondary amines to a-olefins by analogy to the Wacker oxidation of terminal olefins and the platinum(II) promoted variant described earlier. This transformation provided an early example of (formally) alkene hydroamination and a remarkably direct route to tertiary amines without the usual problems associated with the use of alkyl halide electrophiles. 

On the other hand, there is at least one case of an aromatic amine without a hydroxy group in the 2-position, namely 1-aminophenazine (2.29) which, after the initial diazotization, is oxidized within minutes by air or additional nitrous acid to the quinone diazide 2.31 (Olson, 1977). 

Use an onium salt-based reagent such as PyBOP, T/HBTU (see Sections 2.18-2.21), PyAOP (see Section 7.19), or other with me corresponding additive and diisopropylethylamine or trimethylpyridine as tertiary amine without an excess. The additive may, however, promote epimerization. 

Imines and enamines under hydroformylation conditions can also be reduced to give saturated amines. With or without additional reduction, these conversions can be used in synthesis of various types of heterocycles. 

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

Without additives, radical formation is the main reaction in the manganese-catalyzed oxidation of alkenes and epoxide yields are poor. The heterolytic peroxide-bond-cleavage and therefore epoxide formation can be favored by using nitrogen heterocycles as cocatalysts (imidazoles, pyridines , tertiary amine Af-oxides ) acting as bases or as axial ligands on the metal catalyst. With the Mn-salen complex Mn-[AI,AI -ethylenebis(5,5 -dinitrosalicylideneaminato)], and in the presence of imidazole as cocatalyst and TBHP as oxidant, various alkenes could be epoxidized with yields between 6% and 90% (in some cases ionol was employed as additive), whereby the yields based on the amount of TBHP consumed were low (10-15%). Sterically hindered additives like 2,6-di-f-butylpyridine did not promote the epoxidation. 

As indicated in Table 3, reducing the excess methanol to only a 3 fold molar excess (rendering a nearly solvent free process) far exceeded expectations and allowed significant reductions in the catalyst levels. Under these conditions, catalyst turnover numbers exceeding 10,000 mol MPA/mol Pd were achieved with a turnover frequency of >3400 mol MPA/mol Pd/h. The reaction mixtures obtained from this process formed two liquid phases and the product spontaneously separated from the amine and amine hydrochloride. As a consequence of eliminating large methanol excesses, the methyl pivaloylacetate concentration in the product was raised to 26 wt. % without additional reaction time being required. This represents an additional ca. 2.5 fold improvement in reactor productivity. No attempt was made to reduce the methanol further. 

The physical constants of several other imines prepared by a similar procedure are shown in Table X. The aldimines listed in the Table can be obtained only if certain precautions are strictly observed [4b]. The method of Emerson, Hess, and Uhle [4c] could not be extended satisfactorily and the method described in Preparation 2-2 is a modification of the one described by Chancel [4d] for propylidenepropylamine. The reaction is best carried out by adding the aldehyde to the amine, without a solvent, at 0°C. When the order of addition is reversed, the yields are much lower. Potassium hydroxide is added at the end in order to remove the water formed during the reaction. The use of other drying agents such as potassium carbonate or magnesium sulfate failed to yield aldimines on distillation. The aldimines should always be distilled from fresh potassium hydroxide to yield water-white products. The aldimines are unstable and should be used within a few hours after their distillation otherwise polymeric products are obtained. 

It has been reported that tertiary amines (as additives or as the solvent) lead to increased yields when etherifying tyrosine derivatives with polystyrene-bound benzyl alcohols [175]. Nevertheless, other phenols react smoothly without the addition of a base [47,176], When only a slight excess of phenol is used for the etherification of support-bound alcohols, AyV -bi s (eth oxycarbonyl)hydrazi n e (the by-product of the Mit-sunobu reaction) can compete with the phenol to a significant extent and become attached to the support. This reaction can be suppressed by the use of a greater excess of phenol [168]. 

In the 1,3,2-dioxaphosphole method a bis(2-butene-2,3-diyl) pyrophosphate is used as the condensing agent. It allows two successive esterifications of one phosphate group to be performed without additional activation. First a 5 -O-protected nucleoside is added in methylene chloride in the second reaction an unprotected nucleoside can be used, since only the 3 OH group is able to attack the cyclic enediol 3 -nucleosidyl phosphotriester. Protected dinucleoside triesters are obtained in 80% yield. Removals of protective groups, methoxytrityl by means of trifluoroacetic acid in methylene chloride and 1-methylacetonyl by aqueous triethyl-amine, also give about 80% yield (F. Ramirez, 1975, 1977). 

G. S. Wayne, G. J. Snyder and D. W. Rogers, J. Am. Chem. Soc., 115, 9860 (1993). In this paper, the enthalpies of formation of the requisite azides were determined by hydrogenation to the amine and estimation of the latter enthalpies of formation. While far less is known about the enthalpies of formation of azides than amines, this approach seems without additional complication or significant error. 

Reeve and Christian compared Raney Ni and Raney Co (W-7 type) for the hydrogenation of six aliphatic and aromatic aldoximes and ketoximes in the presence or absence of ammonia.26 From the results summarized in Table 8.1, it is notable that Raney Co gives high yields of primary amine in ethanol or dioxane without addition of ammonia as seen in the results with butyraldoxime, 2-butanone oxime, and acetophenone oxime. On the other hand, Raney Ni usually requires an ammoniacal solvent for best results, with the exception of acetophenone oxime, which gave high yields of primary amine in the absence of ammonia. 

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