2,2,6,6-Tetramethylpiperidines

Most of the commercial hindered-amiae light stabilizers (HALS) are derivatives of 2,2,6,6-tetramethylpiperidine [768-66-1] (15). 

Acetamido-2,2,6,6-tetramethylpiperidine-l-oxyl (acetamidoTEMPO) [14691-89-5] M 213.3, m 144-146, 146-147. Dissolve in CH2CI2. wash with saturated K2CO3, then saturated aqueous NaCl, dry (Na2S04>, filter and evaporate. The red solid is recrystd fi om aqueous MeOH, m 147.5°. [J Org Chem 56 6110 1991 , Bull Acad Sci USSR. Div Chem Set 15 1422 7966.]... 

Primary and secondary aliphatic amines, morpholine and 2-methylaziridine and aniline and even the sterically hindered 2.2,6,6-tetramethylpiperidine readily react with 6-bromo-trithiadiazepine 7, in certain cases in the presence of /V./V-diisopropylethylamine, at room temperature by substitution of the bromine atom ammonia, for example, yields trithiadiazepin-6-amine 22 (R1 = R2 = H). There is compelling evidence that these reactions proceed by an elimination-addition mechanism via the heteroaryne, trithiadiazepyne 21.391... 

Due to their tendency to form (Z)-enolates, ketones usually provide syn-aldols, and anti-se ec-tive chiral ketone enolates are rare. When, however, (S)-5,5-dimethyl-4-trimethylsiloxy-3-hex-anone is deprotonated with (V-(bromomagnesio)-2,2,6,6-tetramethylpiperidine, the (E)-enolate la is assumed to be formed. Subsequent addition to aldehydes delivers anh-aldols 2a and 3a in ratios of between 92 8 and 95 5 and yields of 75-85%53b. 

On the other hand, the predominant formation of the diastereomeric aldols 3 b results from the titanium enolate 1 b of (S )-5,5-dimethyl-4-tert-butyldimethylsilyloxy-3-hexanone. For this purpose, the ketone is first deprotonated with A-(bromomagnesio)-2,2,6,6-tetramethylpiperidine and the magnesium enolate, presumably (E) configurated, formed is thereby treated with hexamethylphosphoric triamide and triisopropyloxytitanium chloride. After sonification, the aldehyde is added to give predominantly aldol adducts 3b the diastereomeric ratio of 3b/2b surpasses 95 5 and the chemical yields range from 85 to 88%53b. 

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

Tetramethylpiperidine (99+%) was purchased from Aldrich Chemical Company, Inc.and used... 

Cp pentamethylcyclopentadienyl Tmp 2,2,6,6-tetramethylpiperidine Dipp 2,6-di(iso-propyl)phenyl Trip 2,4,6-tri(iso-propyl)phenyl Mes 2,4,6-trimethylphenyl Mes 2,4,6-tri(tert-butyl)phenyl Ada adamantyl dmap 4-(dimethylamino)pyridine Tms trimethylsilyl (SiMe3)... 

Tetramethylpiperidine tetra-n-Propylammonium perruthenate Tolyl Trityl... 

Fig. 19. Alkylation of Bias with 4 bromoacetamido 2,2,6,6-tetramethylpiperidine-N-oxyl to give nitroxalkylcobalamin, and (after hydrolysis) the corresponding cobinamide...

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...

The most extensive and informative enzyme work with B12 spin labels has been carried out on the enzyme ethanolamine ammonia-lyase 123). This work has employed six-coordinate 4-hydroxy-2,2,6,6-tetra-methylpiperidine-N-oxyl-5 -deoxyadenosylcobinamide. Ethanolamine ammonia lyase uses 5 -deoxyadenosylcobalamin as cofactor. Spin labeled 5 -deoxyadenosylcobinamide was used in order to determine the nature of the first step in the mechanism of action of ethanolamine ammonia lyase by determining the manner in which the Co—C bond is broken. Spin labeled 5 -deoxyadenosylcobinamide was synthesized by taking reduced diaquocobinamide and reacting it with an excess of 5 -tosyl-adenosine to give 5 -deoxyadenosylcobinamide. This was stirred for three days with a 20 fold excess of 4-hydroxy-2,2,6,6-tetramethylpiperidine... 

The hindered secondary amines can be highly effective photostabilizers for various polymers (]+.,5.,.6) Various hindered amines have been shown to retard oxidation, but most share the common feature of being secondary or tertiary amines with the a-carbons fully substituted. The most widely exploited representatives of this class are based on 2,2,6,6-tetramethylpiperidine either in the form of relatively simple low molecular weight compounds, or more recently as backbone or pendant groups on quite high molecular weight additives ( i.,5.,6). The more successful commercial hindered amines contain two or more piperidine groups per molecule. Photo-protection by tetra-methylpiperidines (near UV transparent) must result from the interruption of one or more of the reactions 1 to 3. Relatively recent results from our own laboratories, and in the open literature will be outlined in this context. 

M. x 108M 1s 1 at 25°C, but may be appreciably lower in the solid state. In comparison k2 for oxygen competition for the alkyl radical is 2 x 109M-1s 1. Thus for air-saturated PPH ([02] 8 x 10-1,M)reaction7 will be protection against xenon irradiation was improved as compared to the parent piperidine by about 25, but the nitroxide itself was reduced to the 1 x 10 M level within the first lOOh and persisted at this level until brittle failure (7,) In contrast the parent amine is completely destroyed in the first lOOh of xenon exposure. 

Chakraborty and Scott have reported the detection of N-OH groups in the photo-oxidation of methylcyclohexane containing a bis-piperidine or a nitroxide, based on their observation of an IR absorption at 2765 cm-1(13). However we have found the )>N-0H absorption to occur at 3 60 cm 1 (ll) in 1-hydroxyl-2,2,6,6-tetramethylpiperidines which throws some doubt on their IR detection of >N0H. 

The polymer degradation scheme discussed above and shown in Figure 1 is valid in polymers without any additives. However, most commercially available materials are doped with UV absorbers and with light and thermal stabilizers in order to extend their lifetime. The HAS rank among the most important additives used for light and heat stabilization of polymers [9,15,16]. Most commercially available HAS stabilizers are 4-substituted 2,2,6,6-tetramethylpiperidines, as shown below [17],... 

The second synthesis of crystalline 43 was reported by Mori as summarized in Scheme 62 [93]. The building block (4.R,5S)-A was prepared by an enzymatic process, while another building block C was synthesized via Sharpless asymmetric epoxidation. Coupling of A with C gave D, which was cyclized under Op-polzer s conditions to give crystalline E. When E was oxidized with Dess-Martin periodinane or tetra(n-propyl)ammonium perruthenate or Jones chromic acid, crystalline 43 was obtained. Swern oxidation or oxidation with 2,2,6,6-tetramethylpiperidin-1 -oxyl of E afforded only oily materials. Accordingly, oxidation of E to 43 must be executed extremely carefully. A synthesis of oily 43 was reported by Gil [94]. 

FIGURE 10.3 The structure of TEMPO. The compound 2,2,6,6-tetramethylpiperidine-l-oxyl is a stable radical. 

Tetramethylpiperidine, dibromomethane (99%) and 1,1,1,3,3,3-hexamethyldisilazane (98%) were purchased from Aldrich Chemical Company, Inc., and used without further purification. Use of less hindered secondary amines (such as diisopropylamine) in place of tetramethylpiperidine results in lower yields because of the formation of carboxamide by-products. 

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