Alcohols tritiated

Cyclohepta-amylose has been converted into the phosphates (21)—(23), which were examined as catalysts for the hydrolysis of 4-nitrophenyl tetrahydropyranyl ether at low pH and for the exchange of 4-t-butylphenacyl alcohol (tritiated in the a-methylene group) at high pH. All three isomers, as the phosphate dianions, were effective catalysts for the latter reaction in which the functional group assists enolization of the bound ketone. Only the 3-phosphate (22) showed net catalysis of the hydrolysis of the ether, which was bound and hydrolysed with the assistance of a monoanionic phosphoric acid group. 

In studying two-component polymerization catalysts, beginning with Feldman and Perry (161), a radioactive label was introduced into the growing polymer chain by quenching the polymerization with tritiated alcohols. The use of these quenching agents is based on the concept of the anionic coordination mechanism of olefin polymerization occurring... 

However, in olefin polymerization by two-component catalysts during polymerization not only active transition metal-polymer bonds are formed, but also inactive aluminum-polymer ones, as a result of the transfer process with the participation of a co-catalyst (11, 162-164). The aluminum-polymer bonds are quenched by tritiated alcohol according to the scheme (25), so an additional tagging of the polymer occurs. The use of iodine (165, 166) as a quenching agent also results in decomposing inactive metal-polymer bonds. 

Olefin polymerization by catalysts based on transition metal halogenides is usually designated as coordinated anionic, after Natta (194). It is believed that the active metal-carbon bond in Ziegler-Natta catalysts is polarized following the type M+ - C. The polarization of the active metal-carbon bond should influence the route of its decomposition by some compounds ( polar-type inhibitors), e.g. by alcohols. When studying polymerization by Ziegler-Natta catalysts tritiated alcohols were used in many works to determine the number of metal-polymer bonds. However, as it was noted above (see Section IV), in two-component systems the polarization of the active bond cannot be judged by the results of the treatment of the system by alcohol, as the radioactivity of the polymer thus obtained results mainly from the decomposition of the aluminum-polymer bonds. 

Under the experimental conditions dehalogenation proved to be extremely rapid and was complete within 1 min. This contrasts with the 90-270 min at 100 °C required for thermal debromination of 2-bromonapthalene. No dehalogenation takes place in the absence of the formate donor and when the deuterium is located in the cosolvent rather than the donor (i. e. HCOOK + D20) hardly any deuterium incorporation takes place. Another interesting observation was that the amount (%) deuterium incorporation was always lower when protic solvents such as alcohols were used than aprotic solvents such as dimethyl sulfoxide (DMSO). These are both interesting and useful findings which are valuable for proposed tritiation studies. 

The rate of dehydration of the cis diol was about fifty times slower than that of the trans diol and the product of the reaction consisted mainly of cyclohexenol. The 1,4-epoxycyclohexane formed in the reaction was formed after a prior epimerization of the cis to the trans diol this was demonstrated by means of tritium tracer technique. When irons-1,4-cyclohexanediol was dissolved in ieri-butyl alcohol-T having the hydroxyl hydrogen marked with tritium (C4H,OT) the 1,4-epoxycyclohexane produced in this reaction had a very low tritium content. A similar reaction carried out with cis-1,4-cyclohexanediol produced a highly tritiated 1,4-epoxycyclohexane. The insertion of tritium in the 1,4-epoxycyclohexane produced from the cis diol can be explained as follows ... 

By Reduction of Unsaturated Precursors The method of choice for labeling with tritium is the reduction of a suitable unsaturated precursor (containing a double bond, carbonyl group, etc.) with carrier-free tritium gas or tritiated metal hydrides. The major limitation of this method is the availability of a suitable unsaturated precursor of the desired compound. It is essential to carry out the synthesis in a non-hydroxylic solvent (dioxane, ethyl acetate, etc.). Reductions carried out in alcohol or water will lead to almost complete exchange of the tritium gas with the solvent. 

Reduction with tritiated NaBH4 (NaB3H4), followed by analysis of the radioactive sugar alcohols by paper chromatography and liquid scintillation counting. 

It is very important to perform this reaction uncapped in a fume hood to prevent the room from filling with tritium gas. The mixture of tritiated sugar alcohols is then separated by paper chromatography on thin strips. These strips are divided into half-inch segments and analyzed by liquid scintillation counting. The total counts per minute of 3H in each sugar alcohol peak can then be used to calculate the amount of each carbohydrate present in the sample. 

The naturally occurring copabomeol (474) was oxidized to ketone 475 and then labelled with tritium at the bridgehead by heating with strong base and tritiated alcohol at high temperatures (Scheme 61) (231a). Reduction with sodium in ethanol yielded labelled copabomeol (474 ), which was administered to C.japonica (231b). 

D and E being atoms or groups of atoms easily detected in the polymer). BD and E (also called quenchers) are typically a hydroxy-tritiated alcohol and 35S02, respectively. The common feature of these methods is that the quenchers react not only with the growing chain, but also with non-propagative metal-polymer... 

P,P-Bis(alkylthio)-a,P-unsaturated ketones are selectively reduced in a 1,2-manner to the corresponding allylic alcohols by tritiated NaBH4 in ethanol. ° Enaminones are similarly reduced by tritiated... 

When using, however, two-component catalysts alcohols also react with inactive metal-polymer (aluminium-polymer) bonds which are formed in the chain transfer reactions with a cocatalyst. It is expedient to use the alcohol method only for catalytic systems and polymerization conditions for which the number of inactive metal-polymer bonds is low. Such a case is the polymerization of 4-methyl-1-pentene on vanadium trichloride activated with various organoaluminium compounds. For this system the influence of catalyst composition and polymerization conditions on Cp and kp was determined by quenching the polymerization with tritiated alcohol. 

With tritiated alcohols there is an isotope effect resulting from differential reactivity of normal and labelled alcohols with active chain ends. 

Inactivation of alcohol dehydrogenase from yeast with 14C-labeled [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate followed by oxidation showed the presence of 1-carboxymethyl histidine66. After inactivation of the enzyme with labeled [3-(4-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate followed by oxidation, S-carboxymethyl cysteine was identified in the protein. In the case of glyceraldehyde-3-phosphate dehydrogenase, treatment with either coenzyme analogue leads to the modification of the cysteine residue. Treatment with [14C]nicotinamide-5-bromo-4-methylimidazole dinucleotide did not reveal any modified amino-acid-residues. The labeled nicotinamide residue split off during the recovery of the inactivated enzyme. Attempts to synthesize an inactivator labeled with a 14C-acetyl residue did not give satisfactory yields. If the enzyme-coenzyme derivative was treated with tritiated sodium boron hydride, tritium could be introduced (Fig. 22). Studies with... 

The fact that the Simmons-Smith reaction is regio- and stereoselective enabled the preparation of tritium containing cyclopropane derivatives useful for biological studies. The tritiated diiodomethane was prepared by reduction of iodoform with sodium arsenite in the presence of tritiated water. The carbene generated from tritiodiiodomethane and triisobutylaluminum in chloroform underwent regioselective addition to the unhindered double bond in perillyl alcohol (34). ... 

A combination of SFE and SPE as a sample preparation technique for the ultratrace analysis of mebeverine alcohol in plasma has been proposed (123). Plasma containing the analyte was applied to conditioned octadecylsi-lane cartridges. After washing and drying, the packing was placed in an SFE system. Carbon dioxide with 5% methanol was used as the SCF at 40°C and 355 bar. The extract analysis was carried out by GC-MS. A similar method was used for the extraction of flavone, also from blood plasma, but the determination was performed by HPLC in this case (124). In other applications, plasma spiked with tritiated budesonide to 93 nM was deposited onto a filter paper placed in the extraction vessel, where the extraction was performed with pure CO2 for 30 min then, the budesonide in the extract was determined with a liquid scintillation counter. The recoveries were over 80% (125). " C-Fla-vone and C-ketorolac were extracted from plasma at various extraction pressures and times to test recovery (126). The SCF was CO2 at 60°C and 300 bar. The recoveries were determined by liquid scintillation counting and ranged from 85% to 98% for C-flavone (RSD = 3.8-5.8%, three replicates). 

Two other purely chemical routes to chiral acetic acid have been pursued in our laboratory. In one of these, outlined in Scheme 4, stereospecifically o-deuterated or -tritiated 3,5-dimethoxybenzyl alcohol is prepared by reduction of the aldehyde with Midland s reagent (B-3-pinanyl-9-borabicyclo [3.3.1 ] -nonane, cr-pinanyl-9-BBN) (35), followed by conversion to the tosylate and reductive displacement with lithium aluminum hydride or superhydride (lithium... 

Caspi and co-workers (56) have reported the synthesis of n-octane containing a chiral methyl group by the displacement of the mesylate of (R)- and (S)-l-[l-3H]octanol with superdeuteride. A unique feature of their approach (56,57) was the chemical conversion of the more readily available tritiated IS alcohol, obtained from the reduction of [l-3H]octanal by horse liver alcohol dehydrogenase, to the more difficult-to-obtain 1/ alcohol by the Mitsunobu reaction. Using the conditions shown in Scheme 10, the (IS)-alcohol was converted to the (l/ )-benzoate which gave the (17 )-alcohol by reductive cleavage with LiAlH4. 

C,3R,5- H2]mevalonic acid is [3Hi while lophenol is [ Hn, " 5]. It must be concluded that, contrary to earlier reports, the 4a-methyl group is lost first. This result is further substantiated by the incorporation of 4a-hydroxy-methyl-4j3-methylcholestan-3j8-ol but not the 4jff-hydroxymethyl isomer. Furthermore, 4j9-methylcholestan-3)S-ol is largely inert. The sequence of events would seem to be that the 4a-methyl is oxidised to a carboxyl group and the 3)3-hydroxyl to a 3-ketone. Decarboxylation of the jS-keto acid is followed by rapid reduction of the 3-ketone back to a 3/9-alcohol. In the presence of tritiated water C-3 and C-4 become radioactive. ... 

Several routes applicable to the large scale conversion of testosterone into 4,5a-dihydrotestosterone have been investigated. The method of choice appears to be via catalytic reduction of a 17-acyloxy-3,3-ethylenedioxyandrost-5-ene. Platinum-catalysed hydrogenation of 19-acetoxy, hydroxy-, or methoxy-cholestan-3-ones affords higher proportions of 3a-alcohols than does the 19-unsubstituted steroid. Tritiation of 17)S-hydroxyandrosta-l,4-dien-3-one affords testosterone having a tritium ratio of 1 3.4 (a P) at C-1 and 1 1.4 at C-2 implying that reduction must proceed, in part, by 1,4-addition. ... 

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