Preparation deuterated compounds using

It should be noted that there is a kinetic isotope effect on the normal reaction (9.11) when the a-deuterated compound is used as the substrate. A similar effect is found when the deuterated suicide inhibitor is used. Thus, both reactions involve a proton transfer in the rate-determining step of the reaction. It has also been shown that a sample of the allenic intermediate that is prepared chemically does in fact irreversibly inhibit the enzyme.18... 

Hydrogen isotope exchange reactions have long been used to prepare deuterated organic compounds (Miklukhin, 1961). The extension of the range of substances which can take part in hydrogen exchange reactions, which has been the result of the use of liquid deuterio-ammonia as the reactive medium, has opened new possibilities as far as such preparations are concerned (Shatenshtein and Izrailevich, 1957 Bardasova et al., 1960). 

What may prove to be the ultimate choice for an internal standard when using an MS (37) is the addition of a PGS standard as a deuterated compound to the initial sample preparation. The deuterated compound is quantified directly on the MS rather than having to subsequently subject the sample to conventional radioisotope detection methods. This procedure has been applied to ABA (29) and IAA (38, 39) analyses. A high deuterium content (labeled at five or more positions) should be sought to avoid confusion with naturally "heavy" isotopic compounds (39). 

As shown in Scheme 7, treatment of hydrocinnamaldehyde with a catalytic amount of Pd/C in 0.1 m NaOH at 250 °C for 4—5 h gave the coupling product 1,5-diphenylpentane in 90% yield [18]. The reaction pathway is supposed to be as follows. Aldol, which was formed by the aldol reaction under basic condition, was converted into enal. The enal was transformed into the product via reduction [19] and decarbonylation [18]. As shown in Scheme8, this reaction can be used for preparation of the fully deuterated compound. 

Deuterated compounds have recently aroused interest not only for the laboratory use but also for practical application. Deuterium-labeled polymers are regarded as feasible materials for wave guides in optical communication, because of their transparency in the 500-800 nm infrared region [20], For this purpose greater distribution of deuterium atoms on the polymer is preferable. The preparation of... 

However, the temperature-control method is used for the preparation of the deuterated compounds. Although the other method is safer, there are two reasons which justify using the temperature-control method in this case. First, special care must be taken to maintain isotopic purity in the preparation of the deuterated compounds. Hence the reactants must be free of water, and this is better accomplished if the solvent is dried and handled in the vacuum line, where it cannot come into contact wdth atmospheric water. Second, because the reaction is run on a small scale, the consequences would be minimal if it were to get out of control. 

Later, (5)-2-mcthylsuccinate and (25,35)-[2,3-2H]-2-methylsuccinate were prepared by biohydrogenation of 2-methylfumarate59. For that reaction resting cells of Proteus mirabilis were used under an atmosphere of hydrogen gas. Optically pure (S )-2-methylsuccmate was formed with a yield of > 95 %. Experiments with deuterated compounds have shown that the hydrogen is added in a Irons fashion. 

The deuterated compounds 79 and 80 have been prepared60 in the course of synthesis of 2,2,2(2H3)diazoethane 81 (equation 32). The latter is a very useful reagent for the synthesis of deuterated ethyl esters and is generated in excellent yield from 80, which is more stable61 and less toxic than other precursors62,63. 80 has been prepared in three steps from trideuterioacetonitrile in 71.3% overall yield. It is possible to suppress the formation of... 

A number of piperidine derivatives 180 have been rapidly methylated under MWI using formic acid-formaldehyde mixtures in DMSO to give the A-methyl derivatives 183. Methylation was extremely rapid and was complete within 1-3 min, while it required 24 h at 80 °C under conventional thermal conditions. The method was used for the preparation of the corresponding deuterated compounds (Scheme 38) (02TL9487). 

Organomagnesium and organolithium compounds are very strong bases. Therefore, they will react immediately with any acid present in the reaction mixture, even with very weak acids such as water and alcohols. When this happens, the organometallic compound is converted into an alkane. Although this is not how one would normally synthesize an alkane, it is a useful way to prepare deuterated hydrocarbons. Just use D2O instead of H2O. 

The microbial oxidation of benzene and its derivatives using Pseudomonas putida have been used in several cyclitol syntheses. These include the preparation of conduritol D and the deuterated compound 99", D-cA/ro-inositol and D-cAiro-3-inosose for which the key step involves a one pot oxidation-protection to an epoxy-acetonide derivative," " and racemic quebrachitol." Also reported are the syntheses of (+)-D-chrro-inositol, a//o-inositol, muco-inositol and neo-inositol from a halogenated conduritol epoxide." ... 

Scott and co-workers (1967, 1973) have used deuterated precursors to delineate patulin biosynthesis. The method involves preparing deuterated putative intermediates, feeding them to the fungi, and isolating the enriched products. The compounds are then purified by the usual organic methods and analyzed by mass spectrometry. The advantages of this technique are (a) it is much easier to synthesize precursors with rather than (b) mass... 

It is interesting to remark that classical hydrogenation is a method used to prepare deuterium-labeled compounds by aromatic dehalogenation, but the usual reaction conditions suffer from several limitations. A microwave-enhanced catalytic dehalogenation procedure for rapid and specific deuterium labeling of N-4-picolyl-4-halogenobenzamide 68, by use of deuterated formate, [41] was recently reported (Scheme 8.25). 

Wells and coworkers53 have prepared a series of deuterated tetramethyltin compounds, which they used to study the long-range deuterium isotope effects on the proton chemical shifts of tetramethyltin. The various deuterated tetramethyltin compounds, with one to four trideuteromethyl groups on the tin atom, were prepared by a series of methyl group exchanges beginning with tri-trideuteromethyltin chloride and undeuterated tetramethyltin (Scheme 12). 

---