4-Hydroxy-2,2,6,6-tetramethylpiperidine, derivatives

Another chemically more interesting spin labeled B12 derivative involves coordinate attachment of the nitroxyl function to the cobalt atom of a cobinamide. Fig. 22 shows a reaction in which an alkyl cobin-amide is mixed with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl. The nitroxide displaces water from the 6th coordination position very slowly and therefore this reaction is usually allowed to proceed for a few days with a large excess of nitroxide. From the properties of the coordinated nitroxide derivative discussed below, it is certain that the cobalt is coordinated by the N—O functional group. An analogous compound to that shown in Fig. 22 can be made with a similar nitroxide in which the 4-hydroxyl-group is missing. In this case the N—O-function is the only basic site on the molecule and therefore must be the position of attachment to the cobalt 119). 

The u.v.-visible spectrum of the 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl-methyl-cobinamide is very similar to methyl-cobin-amide itself and as a result this technique cannot be used to rigorously identify the spin labeled derivative. The spin labeled compound does show a spectral change with pH between pH 7.0 and pH 2.0 which methyl-cobinamide does not exhibit. Despite the similarities between methyl-cobinamide and nitroxylmethylcobinamide, the circular dichroism spectrum of the two derivatives are quite different. Fig. 23 shows the marked difference in C. D. spectra of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, methylcobinamide, and a methylcobinamide solution containing an equimolar amount of uncoordinated nitroxide. 

Fig. 25. Electron spin resonance spectra of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl aquocobinamide before and after treatment with CN (a) spectrum of aquo derivative, (b) Expanded view of center line before addition of CN-. (c) Spectrum of liberated nitroxide. (d) Expanded view of centerline after CN- treatment showing additional proton hyperfine...

We now turn to the remaining two hydroxylamines that are N-hydroxylated derivatives of 2,2,6,6-tetramethyl-4-piperidone and -4-piperidinol. The enthalpies of formation of some simple 4-piperidones and their corresponding 4-piperidinols have recently been determined. The values of gaseous N-methyl-4-piperidone and Af-methyl-4-piperidinol are —160.7 1.7 and —226.8 1.8 kJmol (also see Reference 18). The difference between these contemporary values is — 66.1 2.5 kJmol while for the hydroxylated and methylated counterpart species the difference is —47.0 4.8 kJmoH. For comparison, the formal enthalpy of reduction of 3-hexanone to 3-hexanol is ca —54 kJmoH. As has been discussed earlier, reduction enthalpies are not necessarily constant . Relatedly, reaction 8 that exchanges N-methyl and N-hydroxy and parent and tetramethylpiperidines is endothermic by 19.1 5.4 kJmol . The deviation from thermoneutrality is more... 

Derivatives of l-hydroxy-2,2,6,6-tetramethylpiperidine have been widely investigated electrochemically, mainly due to the interest in the nitroxyl radicals derived from them [427]. The application of TEMPO and that of A-hydroxyphthalimide [428] as agents for indirect oxidations are discussed in Chapter 29. 

Great attention has been paid to HAS and their safety application in plastics and coatings. The 4-unsubstituted 2,2,6,6-tetramethylpiperidine is considered as relatively toxic, the acute oral toxicity being about 1 g/kg. The substitution in position 4 (i.e. the general mode in the synthesis of HAS for polymer purposes) dramatically improves the situation. Therefore, commercial HAS like 28 (R = H), 34,35a or 35b were approved for stabilization of packaging materials in contact with food [307]. Some data are available on properties of TEMPO (2,2,6,6-tetramethylpiperidinyl-l-oxyl) and its 4-amino or 4-hydroxy derivatives. They were found to act as weak intrinsic direct mutagens in Salmonella typhimurium. TEMPO increases intracellular hydroperoxide concentration. This may indicate its pro-oxidative effect which does not result, however, in cellular toxicity [314]. 

Eucatropine (Euphthalmin) was the first successful mydriatic not containing the tropane nucleus it is the mandelic ester (VI) of the /3-form of 4-hydroxy-l, 2,2,6-tetramethylpiperidine. It is a relatively weak mydriatic and does not paralyze accommodation. The benzilic esters of both the a- and /3-forms of the same 4-hydroxypiperidine derivative, and their methochlorides, were prepared by Ford-Moore and Ing (36). The metho-salts were about 50 % more active than atropine in the mouse, but the more active /3-metho-salt proved to be a very weak mydriatic in man like eucatropine it was not cycloplegic. 

Other hindered amines used with good results in the stabilization promotion of polyolefin, pol3mrethanes, polystyrene, ABS, acrylonitrile st)Tene copolymers, are derivatives of piperidine such as 2,2,6,6-tetramethylpiperidine, 2,2,6,6-tetramethyl-4-hydroxy-phosphonopiperineor by stable free radicals such as 4-[cyan (phenylmethylene)-2,2,6,6-tetramethyl piperidinoxil], 4-(ureidoimino)-2,2,6,6,-tetramethyl-piperidinoxil, 2, 2, 6, 6 tetramethylspiro(benzimidazoline)-2,4-piperi dinoxil. 

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