DD154813A1 - METHOD FOR PRODUCING DEUTERICHALOFORMS - Google Patents

Abstract

The invention relates to a process for the preparation of deuterated haloforms, which is characterized in that haloforms are reacted with deuterium oxide in the presence of a basic catalyst and a salt with lipophilic cation or a complexing agent. The compounds prepared according to the invention serve as solvents for NMR spectoscopy and as intermediates for further deuterated preparations.

Description

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Process for the preparation of deuteriohaloforms

The invention relates to the replacement of hydrogen atoms baoeiikatalysierten durcli deuterium atoms .i ⁿ Halof ornien "The compounds according to the invention serve as a solvent for the] \ ~ TMR spectroscopy as well as intermediates for further deuterated preparations"

Characteristic of the known technical solutions

It is bekanntj "that Dian z. B _c chloroform-D by reacting chloral with dgo in the presence of ITaOD (P ₄ W * BREUER, J. Amer, Chem _c Soc _{c 57?} 22:36 [19351) _f by heating the calcium salt of trichloroacetic acid in D ₂ O above 100 ⁰ C (MH EARIrIG and J * B. CLOKE, J <i Amer. Chem Soc _{0. 73?} '769-70 [1951]) i by reaction of trichloroacetophenone with MAOD (Y /. M. BCEfER et al., J. A _m he "Chem Soc * ₄ 73 _5770-73 [1951) and by heating Trichloracetylchloridy CaCO-. and DPO (in the presence of sodium carbonate RX ₆ LORD et al · J ₀ A _m he. Chenu Soc. 77? I36p ~ 68 Γ1955]).

Furthermore .S comes as Syntheeemetliode for chloroform and bromoform D-D of the base-catalyzed hydrogen isotope exchange with deuterium oxide into consideration (J, MINE, Luc, and PECK B.Dc OMES, J..A _m he. Chen. ₀ C _76? 827 D954}).

The above methods have the disadvantage that they are expensive due to the chemicals used and the relatively expensive process technology. It is further known that in the base catalyzed process of the IKD exchange in

7 μ tu »-ioon * & * .- / ·} 1 '' Z o

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Haloforraen often inhibits the reaction by which the base enters during the reaction. The trihalomethyl salt formed as an intermediate was saponified in the aqueous phase. This led to consumption of the base used and to losses in the end product. A further significant disadvantage was that the end point of the reaction was not detectable without great analytical effort and the deuteration degree calculated from the ratio of reactants used was not reached. "A higher number of exchange stages and a greater use of DpO were required than theoretically calculated , Furthermore, the exchange reactions had to be carried out under reflux for longer reaction times (8 hours) until the equilibrium equilibrium reached.

The mentioned Machteile the previous methods have not allowed to represent deuterated Haloforme in an economically advantageous manner, optimal yield and in the required purity.

The object was to develop a process for the deuteration of haloforms without the disadvantages mentioned above. It has surprisingly been found that haloform in the presence of a basic catalyst and a salt with lipophilic cation or a complexing agent such. As crown ethers, at temperatures of 0 - 150 ⁰ C can advantageously deuterate. The products obtained in good yield have a high degree of purity and deuteration.

the invention

The disadvantages of the known processes for base-catalyzed H-D exchange in haloforms result from the fact that the trihalomethyl-ion formed as an intermediate

B ~ ^ = 11 = ^ QX ~ χ · halogen + BH '.

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forms a salt with the corresponding cation of the base used, which because of its distribution quotient is completely in the aqueous phase and is subject to saponification here.

Surprisingly, it has now been found that the equilibration in H-D exchange

CHX ₃ + D ₂ O ^ iL · ^ CDX ₃ + HOD X: halogen

can be significantly accelerated if one of the reaction mixture of Halofornij DGO and base (deuterated alkali or alkaline _earth? alkali carbonates ~ ₉ organic -Basen) either

a) adding a salt the cation of which _s capable of forming an ion pair with the formed intermediate Trihalogenmethylion whose partition coefficient _s is so low that this calibration are ion pairs in the _haloform? so the saponification can be withdrawn and the reaction can be led without delay to the exchange equilibrium or

b) a chelating agent (such as, _e B, crown ethers ·, _cryptands? octopus molecules ·, polyethylene glycols and veer ether) zusetzte for the introduced with the base cation

The inventively mentioned additives lead in amounts of 10 -10 mol% at temperatures of 0-150 ⁰ C and in the presence of 10 - 1 mol% base in less than 1/2 hour reaction time to equilibrate the HD Austausctu A base consumption and thus a Saponification is not detectable * The results of the exchange reactions are well reproducible and the consumption of the expensive DpO is reduced to the theoretically required amount _β The process is suitable for extensive enrichment of the DgO »The enrichment can be discontinuous or continuous in a cascade.

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A mixture of 92.1 ml of deuterium oxide (99-8 At % D), 80-6 ml of chloroform, 1 ml of 30% solution of NaOD in heavy water and 2jg of triethylbenzylammonium chloride (TEBA chloride) is heated at 50 for half an hour ⁰ C stirred ^ cooled to room temperature and DAS chloroform separated the separated chloroform containing 91 atom% deuterium and is brought without further purification again with the above amounts of DPO, TEBA chloride and NaOD solution under the same conditions for the reaction ^ the separated Chloroform of this second exchange stage contains 99 at % of deuterium and is either reacted again as above or distilled after drying with phosphorus pentoxide. 75-8Og of chloroform-D are obtained. After a third exchange step, under the same conditions as in the preceding stages, 71-78 g of deuteriochloroform having a content of 99.7-99.8 At % D are obtained after drying and distillation.

Beis £ iel_2

127 g bromoform ^ 50 ml heavy water (99-8 At % D), Ig tetrabutylammonium bromide. and 1 ml of 30% solution of NaOD in DpO are stirred for 1/2 hour at 60 ⁰ C, cooled to room temperature and then the bromoform separated. Nach.zweimaliger repetition of the exchange reaction, the bromoform is separated, dried over phosphorus pentoxide and distilled in vacuo. There were obtained 100-110 g of colorless bromoform-D with a deuterium content of 99 ^ 7 - 99j8 At % .

Claims (1)

r " 1e process for the preparation of deuterated Halof ormeiij characterized in that .man haloforms in the presence of a basic catalyst (such as alkali metal or Brdalkalih3rdr2d.de j alkali metal carbonates or organic bases) and a salt with lipophilic cation (such as' B. ₆ quaternary ammonium salts) or a complexing agent (such as, for example, K ₉ Kronenether, Kityptandeiij Krakenmolelcülej polyethylene glycols and their ethers) with deuterium oxide, 2 «Method according to item Ί, characterized in that the HD exchange takes place discontinuously or continuously in a cascade" 3 «process according to item 1, characterized in that _s 10 to 1 mol% js preferably 10% by mole of a basic catalyst employed" 4 ". The method according to item 1, characterized in that _'9 that -4 -2 10 to 10 mol%, preferably 10 mol%, of a salt with a lipophilic cation or of a complexing agent, 5o process according to item 1, characterized in that one carries out the reaction at a temperature of 0.-150 ⁰ C, preferably at 20 ° - 60 ⁰ G ·