93390-81-9

Basic information

• Product Name: Caffeine Citrate
• Synonyms: XWLUWCNOOVRFPX-UHFFFAOYSA-N
• CAS NO: 93390-81-9
• Molecular Formula: C₁₆H₁₅N₂O₆P
• Molecular Weight: 386.3176
• Mol File: 93390-81-9.mol
• Article Data: 6

Chemical Properties

• Melting Point: 173-176.5°
• Appearance: /
• Density: 1.495g/cm³
• Refractive Index: 1.63
• PKA: 1.74±0.10(Predicted)
• CAS DataBase Reference: Caffeine Citrate(CAS DataBase Reference)
• NIST Chemistry Reference: Caffeine Citrate(93390-81-9)
• EPA Substance Registry System: Caffeine Citrate(93390-81-9)

Safety Data

• Hazardous Substances Data: 93390-81-9(Hazardous Substances Data)

Usage

Description

Caffeine Citrate is a water-soluble salt of caffeine and citric acid, commonly used as a stimulant and a treatment for certain medical conditions.
Used in Pharmaceutical Industry:
Caffeine Citrate is used as a central nervous system stimulant for the treatment of conditions such as status epilepticus and neurosurgery-derived seizures. It helps to increase alertness and reduce the severity of seizures.
Used in Drug Formulation:
Caffeine Citrate is used as a pharmaceutical excipient to improve the water solubility of poorly soluble drugs, such as phenytoin. This enhances the bioavailability and therapeutic efficacy of the drug.

InChI:InChI=1/C16H15N2O6P/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23/h1-10H,11H2,(H,17,20)(H2,21,22,23)

Synthetic route

phosphoric acid dibenzyl ester 2,5-dioxo-4,4-diphenylimidazolidin-1-ylmethyl ester (93360-08-8) → fosphenytoin (93390-81-9)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate under 3102.9 Torr; for 0.416667h;	54.5%
With hydrogen; palladium on activated charcoal In ethyl acetate
With hydrogen; palladium on activated charcoal In methanol at 25℃; under 2206.73 - 2574.52 Torr; for 2h;
With hydrogen; palladium 10% on activated carbon In ethyl acetate at 30℃; under 2206.72 - 2942.29 Torr; for 3h;
With 5%-palladium/activated carbon; hydrogen In methanol Large scale;	20 kg

phenythoin (57-41-0) → fosphenytoin (93390-81-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 92 percent / potassium carbonate / H2O / 24 h / Ambient temperature 2: 61 percent / phosphorous trichloride / CH2Cl2 / 24 h / Ambient temperature 3: 67 percent / benzene / 2 h / Heating 4: 54.5 percent / H2 / palladium on activated carbon / ethyl acetate / 0.42 h / 3102.9 Torr View Scheme
Multi-step reaction with 4 steps 1: ethanol / 50 °C / Large scale 2: N,N-dimethyl-formamide; thionyl chloride / ethyl acetate / 50 °C / Large scale 3: potassium carbonate; potassium iodide / ethyl acetate / 70 °C / Large scale 4: hydrogen; 5%-palladium/activated carbon / methanol / Large scale View Scheme

3-(chloromethyl)-5,5-diphenylhydantoin (93360-07-7) → fosphenytoin (93390-81-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 67 percent / benzene / 2 h / Heating 2: 54.5 percent / H2 / palladium on activated carbon / ethyl acetate / 0.42 h / 3102.9 Torr View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate; potassium iodide / ethyl acetate / 70 °C / Large scale 2: hydrogen; 5%-palladium/activated carbon / methanol / Large scale View Scheme

3-hydroxymethyl-5,5-diphenyl-imidazolidine-2,4-dione (21616-46-6) → fosphenytoin (93390-81-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 61 percent / phosphorous trichloride / CH2Cl2 / 24 h / Ambient temperature 2: 67 percent / benzene / 2 h / Heating 3: 54.5 percent / H2 / palladium on activated carbon / ethyl acetate / 0.42 h / 3102.9 Torr View Scheme
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide; thionyl chloride / ethyl acetate / 50 °C / Large scale 2: potassium carbonate; potassium iodide / ethyl acetate / 70 °C / Large scale 3: hydrogen; 5%-palladium/activated carbon / methanol / Large scale View Scheme

fosphenytoin (93390-81-9) → Fosphenytoin

Conditions	Yield
With sodium hydroxide In methanol; water
With sodium hydroxide In methanol at 5℃; for 0.666667h; Product distribution / selectivity;
With sodium hydroxide In ethanol; water pH=8.2 - Ca. 9.3; Large scale;

Upstream product

• 93360-08-8 phosphoric acid dibenzyl ester 2,5-dioxo-4,4-diphenylimidazolidin-1-ylmethyl ester 
• 57-41-0 phenythoin 
• 93360-07-7 3-(chloromethyl)-5,5-diphenylhydantoin 
• 21616-46-6 3-hydroxymethyl-5,5-diphenyl-imidazolidine-2,4-dione 

Relevant articles and documents

MANUFACTURING METHOD OF SODIUM FOSPHENYTOIN HYDRATE AND SYNTHETIC INTERMEDIATE THEREOF

PROBLEM TO BE SOLVED: To provide a manufacturing method of sodium fosphenytoin hydrate capable of shortening time for all manufacturing processes and reducing manufacturing cost and a synthetic intermediate thereof. SOLUTION: There is provided a method for manufacturing 3-hydroxymethyl-5,5-diphenyl-2,4-imidazolidinedione, including a process for heating 5,5-diphenyl-2,4-imidazolidinedione (phenytoin), formaldehyde and alcohol and using no alkaline material. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PROCESS FOR PREPARING FOSPHENYTOIN

Processes for preparing fosphenytoin.

Phenytoin prodrugs III: Water-soluble prodrugs for oral and/or parenteral use

Various bioreversible derivatives of phenytoin, a poorly water soluble and erratically absorbed drug after both oral and parenteral dosing, were synthesized. Initial evaluation of these expected prodrugs, i.e., their aqueous solubility, cleavage in the presence of various animal tissues, and anticonvulsant activity in mice, confirmed that a number of the derivatives did indeed behave as prodrugs. The more promising prodrugs were the disodium phosphate ester and various amino groups containing acyl esters of 3-(hydroxymethyl)-5,5-diphenylhydantoin.