Hindered amines synthesis

The group of Caddick has described the synthesis of functionalized sulfonamides by microwave-assisted displacement of pentafluorophenyl (PFP) sulfonate esters with amines (Scheme 6.159) [306]. Their ease of handling due to their higher crystallinity, along with their long shelf-life and their ability to react under aqueous reaction conditions, makes these an attractive alternative to sulfonyl chlorides. The microwave-assisted reaction of alkyl PFP esters with amines is a facile process which proceeds cleanly and in good yields with a number of different amines, including primary, secondary, and sterically hindered amines, and anilines. Optimum condi-... 

FIGURE 2.23 Some tertiary amines used as bases in peptide synthesis. The less hindered amines are able to abstract protons more readily, but the more basic amines bind the protons more tightly. 

More recently, Polish chemists have reported a synthesis of both aryl and aliphatic secondary nitramines by treating amine substrates with ethyl magnesium bromide followed by reaction with n-butyl nitrate (Equation 5.8). This method, which uses nonpolar solvents like hexane or benzene, has been used to synthesize aliphatic secondary nitramines, and At-nitro-A-methylanilines which otherwise undergo facile Bamberger rearrangement in the presence of acid. The direct nitration of At-unsubstituted arylamines usually requires the presence of an electron-withdrawing group. Reactions are retarded and yields are low for sterically hindered amines. 

M. Dagonneau, E.S. Kagan, VI. Mikhailov, E.G. Rozantsev u. V.D. Sholle, Synthesis 1984, 895-916 . .Chemistry of Hindered Amines from the Piperidine Series". 

Ph NH2 17 Kig. 13. Synthesis of primary ketoamine by using a hindered amine reagent. ... 

Exxon Chemical Process. The Exxon Chemical process [1092], [1093] was specifically designed for the company s own site in Canada and so far not built for third parties. It uses a proprietary bottom-fired primary reformer furnace and a proprietary hot potash carbon dioxide removal system with a sterically hindered amine activator. Synthesis loop and converter are licensed by Haldor Topsoe A/S. Synthesis is carried out at 140 bar in a Topsoe S-200 converter and total energy consumption is reported to be 29 GJ/t NH3. 

In the course of studies on cyclopropanone—)5-lactam conversions, Wasserman and coworkers developed a route to the nocardicins by taking advantage of the reactivity of primary amines with cyclopropanone. The unusual susceptibility of the carbonyl group of cyclopropanone to attack by nucleophiles is well exemplified in this synthesis which involves the addition of the highly hindered malonate derivative (156) to generate the cyclopropanol adduct (157). The hindered amine (156) was previously found to be completely unreactive as a nucleophile in a displacement reaction with dibromoester (158) in an attempt to form the azetidine carboxylate (159). The further conversion of the amino malonate adduct (157) to the -lactam through a nitrenium ion rearrangement is illustrated in Scheme 59. 

The first synthesis of 2,2,6,6-tetramethyl-4-oxypiperidine-N-oxyl was described in a paper by M. B. Neiman, E. G. Rozantsev, and Y. G. Mamedova (2). The synthesis was achieved by the oxidation of triacetoneamine with hydrogen peroxide in the presence of sodium tungstate. The key properties of the tetramethyloxypiperidine-N-oxyl, which subsequently led to the whole family of hindered amine stabilizers, were outstanding thermal and chemical stability. 

And so, the work on mechanisms of autooxidation at the British Rubber Producers Association, the early work on the synthesis and reaction of stable free radicals, the recognition of the rale of stable free radicals in polymer stabilization, the discovery of stable triacetonamine-N-oxyl, and the search for practical candidates for commercialization, have led to the development of hindered amine stabilizers, a new class of polymer stabilizers. They are effective in many polymers against photodegradation and also are effective against thermooxidation in some polymers. The structures of the current commercially available products for polymer stabilization may be seen in Figure 7. These compounds are effective in meeting the stabilizer requirements in many commercial polymers however, others are under development to satisfy requirements not being met by them. 

Methods of hindered amine stabilizer synthesis are being developed with the purpose of reducing cost and using available raw materials. 

Since their initial production by our laboratories about ten years ago, hindered amine light stabilizers (HALS) have become established as excellent light stabilizers of polymers. This review deals with their synthesis, evaluation and development. 

The first radicals we looked at, the alkylaminotropone nitroxy radicals (1), were unstable (2 ). However, since Neiman et al. ( 3) had reported that 2,2,6,6-tetramethyl-4-oxopiperidine-l-oxyl (2) was extremely stable, we turned to nitroxyl radicals derived from fully hindered amines. In this section we will describe the synthesis of new stable nitroxyl radicals and their evaluation in polypropylene. 

Elimination of the yellowing introduced by the stable nitroxyl radicals was essential for commercial development of these excellent stabilizers. Since phenolic antioxidants are necessary for the thermal stabilization of polymers during processing, we turned our attention to ways in which unfavorable interactions between the hindered phenols and the stabilizing nitroxyl radicals could be avoided. In this section we describe the discovery of the light-stabilizing activity of hindered amine compounds, an improved synthetic method for these compounds, the synthesis of a number of derivatives, and the evaluation of their stabilizing activity. 

Synthesis and Stabilizing Activity of Hindered Amines. As mentioned previously, the hindered piperidine compounds showed excellent light-stabilizing activity in polypropylene. In order to find more efficient compounds, various derivatives of 2,2,6,6-tetramethyl-4-oxopi-peridine (42) were synthesized and tested. In this section we describe some typical examples from the great number of derivatives prepared in our laboratory. 

Uvasil 299. [Enichem Synthesis SpA] Hindered amine light stabilizer. 

Scheme 26. Synthesis of a hindered amine through a transient nitroxide intermediate...

The tendency toward small ring formation precludes the synthesis of linear polymers by elimination of Hj or HCl from such compounds as RNHjBHj or RNHjBClj. Even such compounds with highly hindered amines tend toward ring formation (four- or eight-membered rings) rather than polymer formation when pyrolyzed ( 15.2.5.1.1). 

Water-immiscible amines are highly selective in the differentiation between acids (selectivity of about 10 for HCI/H3PO4 separation [44] compared to <2 in extraction by alkanols) and between them and their salts. They are widely used in extraction of metals (their anionic complexes) and of carboxylic acids, but most of them are too strongly basic for mineral acids. The convex distribution curve shows that extraction is very efficient, but back-extraction in free acid form would require huge amounts of water, resulting in extremely dilute, useless back-extracts. Only the very weak amines—highly branched trialkyl amines [52,53] or amines with at least one aryl group—combine efficient extraction with reversibility. Only few such water-immiscible aniline derivates and sterically hindered amines are currently produced on an industrial scale. Adjustment of their properties to treat a variety of feeds would require laborious synthesis. 

N(3)-Hydroxytriazolo[4,5-b]pyridine plOl, HOAt], as its uronium or phosphonium salts, demonstrated superior performance in solid state peptide synthesis as compared to N-hydroxybenzotriazole [102, HOBt]. This feature enhances the automated synthesis of peptides containing hindered amino acids or hindered amines [94CC201]. 

N-Subst. pyrrolidines. A 10 M soln. of BH3-dimethyl sulfide in THF added dropwise via syringe to a soln. of startg. succinamic ester in the same solvent under N2, the mixture refluxed 7-9 h, and quenched with methanol and 2 N NaOH N-phenylpyr-rolidine. Y 82%. The method failed for highly hindered amines. F.e. incl. N-subst. piperidines s. M.C. Venuti, O. Ort, Synthesis 1988, 985-8 review of pyrrole, pyrrolidine, piperidine, pyridine and azepine alkaloids (1986-7 literature) s. A.R. Pinder, Nat. Prod. Reports 6, 67-78 (1989). 

Recently, Rapolu et al. (2013) synthesized primary amides by the Ritter reaction of secondary and tertiary alcohols with nitriles catalyzed by SSA catalyst in toluene at 90°C (Scheme 5.55). As the catalyst is cost-effective, stable to air, and recyclable, the present method constitutes a noteworthy modification to the Ritter reaction for the synthesis of amides. Under these conditions, a variety of amines including sterically hindered amines were successfully reacted to form the corresponding amides in excellent yields. The reaction was observed to be chemoselective in nature. Mirjalilia and Sadeghi (2009) studied the Ritter reaction under solvent-free conditions (Scheme 5.56). 

Solid-phase Synthesis. The Ns strategy can be applied to solid-phase s3mthesis since the alkylation and deprotection steps proceed smoothly on the resin (eq 5). After attachment of the diamine to the trityl t5qje resin, protection of the less-hindered amine of 11 was carried out by treatment with NsCl and collidine. Elongation of the polyamlne chain was performed by stepwise alkylation with dibromobutane and Ns amide to give the protected spermine derivative 12. 

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