IODOMETHANE-D3(Link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/organic-intermediate.html), also known as methyl deuterium iodide, is an important organic compound. The chemical formula is CD3I, where D represents a deuterium isotope (the relative atomic mass of deuterium is 2). According to the weighted average of isotope mass, the relative molecular mass of IODOMETHANE-D3 is about 131.92 g/mol. Some ionization reactions can occur in solvents. It can dissociate into methyl anion (CH3-) and iodide ion (I-), although this dissociation is relatively minor. It can be used as a reagent in organic synthesis. It can react with alkali metals, boron alcohols, haloalkanes, etc. to generate compounds with Deuterium (deuterium) labels. These labeled compounds can be used to study reaction mechanisms, track reaction paths, and analyze and characterize the properties of compounds. Deuterium-labeled compounds are widely used in the research field to track material transformation, solubility studies, nucleosynthesis reactions, etc.
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As a common reaction reagent and organic intermediate, IODOMETHANE-D3 has a wide range of uses in chemical experiments, so its synthetic route is also a key research direction for researchers. The common synthesis methods currently on the market are as follows.
method one:
A method for efficiently preparing iodomethane and its application. The method uses fluoromethanol and iodine simple substance as reaction raw materials, and adds a transition metal catalyst and a ligand in a hydrogen atmosphere to generate iodomethane in situ at 0C-120C. Its application is as a methylation reagent to prepare S-(methyl-D3) homocysteine, mainly by combining compound a (tert-butyl)-L-homocysteine methyl ester with fluoroiodine Methane was methylated in an organic solvent under the action of a base catalyst to obtain the product b, and the product b was deprotected to obtain the target product, namely S-(methyl-D3)homocysteine. The method utilizes a transition metal catalyst to catalyze the preparation of anhydrous hydrogen iodide, and adopts a one-pot method to directly react anhydrous hydrogen iodide and meta-methanol to obtain high-yield (88%) iodomethane, and use it as meta-methyl Reagents to prepare S-(methyl-D3)homocysteine with high element incorporation rate and yield (75%). The method of the invention is simple and easy to operate, and the reaction conditions are mild.
Method Two:
1. A method for efficiently preparing iodomethane, characterized in that, using fluoromethanol and iodine simple substance as reaction raw materials, adding transition metal catalysts and ligands in a hydrogen atmosphere, generating iodomethane in situ at 0C-120C , the general reaction formula is as follows:
2. The method for efficiently preparing iodomethane according to claim 1, wherein the transition metal catalyst is Pd(0Ac)Ni(0Tf)Co(0Ac)RhCl3H0, [Ir(COD)Cl]CHFNPRu or Rh (COD), BF3. according to the method for efficiently preparing iodomethane according to claim 1, it is characterized in that, described ligand is PPh.
Dppe, Dppf or ()-Binap racemic ligand. 4. The method for efficiently preparing iodomethane according to claim 1, wherein the organic solvent is toluene, tetrahydrofuran, tetrahydropyran, 1,4-dioxane, dichloromethane, 1,2-dichloroethane or N,N-dimethylformamide. 5. the method for efficiently preparing iodomethane according to claim 1, is characterized in that, the consumption of described hydrogen is phase 2-80bar
6. The method for efficiently preparing iodomethane according to claim 1, characterized in that the amounts of the iodine element, the catalyst, and the ligand are respectively 50%-500% and 0.01%-100% of the molar percentage of the carbinol compound. %, 0.01%-200%, the amount of the organic solvent is 0.1mol/L-10mol/L of the molar concentration of the methanol substitute compound.
7. A method for preparing S-(methyl-D3) homocysteine by using any one of claim 1-6 iodomethane as a methylation reagent is characterized in that compound a (tert-butoxy )-L-homocysteine methylation reaction with iodomethane in an organic solvent under the action of a base catalyst to obtain product b, and the product b is deprotected to obtain the target product c, namely S-(methyl-D3) Homocysteine, its general reaction formula is as follows:
8. S-(methyl-D according to claim 7) The preparation method of homocysteine organic compound is characterized in that the molar ratio of compound a, iodomethane, alkali is 2.2-2.5: 2:; The amount of the organic solvent is compound a molar concentration 0.1mol/L-10mol/L.
9. according to the preparation method of the S-(methyl-D3) homocysteine organic compound described in claim 7 or 8, it is characterized in that, described alkali is NaH, and described organic solvent is THF.
10. The preparation method of S-(methyl-D3) homocysteine organic compound according to claim 7, is characterized in that, described methylation reaction condition is to stir 1- at -50C-200C temperature. 5h.
Deuteroiodomethane is mostly prepared by the iodination reaction of deuterated methanol, and there are different synthesis methods according to the types of iodination reagents.
method one:
Red phosphorus reagent (50.0 g, 1.6 mol), H2O (100 mL) and elemental iodine (250.0 g, 1.0 mol) were slowly injected into a dry 250 mL flask equipped with a reflux condenser over 0.5 h at -15 °C . Deuterated methanol (30.0 g, 0.8 mol) was then gradually added to the reaction mixture. The reaction mixture was heated to 65°C and the stirring reaction was continued for approximately 2 hours. After the reaction, the reaction mixture was cooled to room temperature. Finally, the reaction mixture was distilled at 45° C., and the corresponding fractions were collected to obtain the target product molecule D3-iodomethane.
Method Two:
In a 20 mL round bottom flask, add deuterated methanol (CD3OD) (0.5 g, 1.13 mL, 0.0138 mol) to dry dichloromethane (10 mL). Then TMSI (2.77 g, 1.98 ml, 0.0138 mol) was added to the resulting reaction solution, and the resulting reaction mixture was slowly stirred at 0°C for several hours, then transferred to room temperature, and stirred at room temperature The reaction mixture was 8 hours. After the reaction, there is no need for further purification, and the deuterated methyl iodide obtained in the reaction can be directly used in the next reaction.
A common method for preparing IODOMETHANE-D3 in the laboratory is to use sodium deuterate (NaOD) to react with iodomethane (CH3I) to generate IODOMETHANE-D3.
1. Prepare sodium deuterate solution: react sodium deuterate solid with absolute ethanol solvent to obtain sodium deuterate solution.
NaOD + CH3CH2OH → CH3CH2OD + NaOH
2. Reaction: react sodium deuterate solution with methyl iodide to generate IODOMETHANE-D3.
NaOD + CH3I → CD3I + NaOH
3. Refining: Refining and purifying the product to obtain high-purity IODOMETHANE-D3.
Note that this is just a simplified method for preparing IODOMETHANE-D3. The actual synthesis process may need to consider factors such as reaction conditions, purity and ratio of reactants, solvent selection, etc., and operate in the laboratory according to appropriate operating procedures. Also, ensure that proper safety procedures are followed when performing laboratory synthesis and that relevant chemical management and waste disposal regulations are followed.