58-08-2 Usage
Description
Caffeine is an alkaloid purine belonging to the group of organic compounds called methylxanthines. It is a white, crystalline, bitter-tasting compound that occurs naturally in coffee, tea, cocoa, and cola nuts. Caffeine functions as a natural pesticide in plants to deter insects and acts as a central nervous system stimulant in humans, temporarily warding off drowsiness and restoring alertness.
Uses
Used in Pharmaceutical Industry:
Caffeine is used as a mild vasoconstrictor for relieving headaches, particularly migraines. It is also used in medications to treat apnea in premature infants, stimulating the underdeveloped area of the brain controlling respiration.
Used in Dietary and Athletic Supplements:
The combination of caffeine and ephedrine is used as an appetite suppressant and energy booster in dietary and athletic supplements.
Used in Cosmetics:
Caffeine has a lipolytic effect on fatty cells, breaking down lipids and releasing fatty acids. It is used for skin firming and tightening, often incorporated into body product formulations targeting cellulite and slimming, as well as in eye creams that claim to reduce puffiness.
Used in Food and Beverage Industry:
Caffeine is consumed in coffee, tea, cocoa, chocolate, and soft drinks. It is used as a food additive in soft drinks for its mildly stimulating effect and distinctive taste note. It is also used in cola-type beverages and is optional in other soft drinks up to 0.02%.
Used in Medicine:
Caffeine is used as a cardiac and respiratory stimulant, as well as a diuretic. It is found in many drugs and acts as a reversible acetylcholinesterase inhibitor.
Used in Sun Protection:
Caffeine has been demonstrated to induce apoptosis in DNA damaged epidermal cells and tumors while sparing normal tissue. It also has a sunscreen-like effect and inhibits the formation of UVB-induced thymine dimers and sunburn skin lesions.
Originator
Caffedrine,Thompson Med.
History
Runge isolated caff eine from coffee in 1819. Caffeine derives its name from the Kaffa region of Ethiopia. Caffeine comes from the German kaffeine, which in turn is derived from the German word for coffee, kaffee. In 1827, a compound isolated from tea was named theine, but this was eventually shown to be caffeine.
Indications
This product is included in the Pharmacopoeia of the People’s Republic of China
(2015), the British Pharmacopoeia (2017), the United States Pharmacopeia (40), the
Japanese Pharmacopoeia (17th ed.), the European Pharmacopoeia (9.0th ed.), the
Indian Pharmacopoeia (2010), and the International Pharmacopoeia (5th ed.).
Commonly used dosage forms of caffeine include tablet, powder, and injection.
Mainly used dosage forms in the market include caffeine citrate tablets, amidopyrine caffeine tablets, amidopyrine caffeine, children acetaminophen aspirin caffeine
tablets, ergotamine caffeine tablets, caffeine sodium benzoate injection, cafe bromine agent, etc.
Manufacturing Process
Caffeine was synthesized by the reaction N-chloromethylation of theophylline
by action dimethylsulphate in dimethylsulfoxide.
Therapeutic Function
Neurotropic, Central stimulant
Air & Water Reactions
Efflorescent in air. Water soluble.
Reactivity Profile
Caffeine may be hygroscopic. Aqueous solutions (1.12 mg/mL) are stable for three weeks at 41° F if protected from light. In normal room lighting and at room temperature, solutions are stable for 3 days. Solutions of Caffeine in water, DMSO, 95% ethanol or acetone should be stable for 24 hours under normal lab conditions. REACTIVITY: Caffeine may react with strong oxidizing agents. Caffeine is also incompatible with iodine, silver salts and tannins. Caffeine is a very weak base. Caffeine is decomposed by strong solutions of caustic alkalis.
Hazard
One grain or more is toxic, 200 μg/m L has
been found to inhibit activity of the enzyme DNA
polymerase. Use in soft drinks not to exceed 0.02%.
Questionable carcinogen.
Health Hazard
Caffeine is a stimulant of the central nervoussystem. It eliminates fatigue and drowsiness. However, high doses cause gastrointestinal motility, restlessness, sleeplessness,nervousness, and tremor. Acute poisoningeffects include nausea, vomiting, headache,excitability, tremor, and sometimes, convulsive coma. Other symptoms may be respiratory depression, muscle contraction, distortedperception, and hallucination. Ingestion of15–20 g may be fatal to humans.LD50 value, oral (mice): 127 mg/kgLD50 value, oral (rabbits): 224 mg/kgAnimal studies indicate that caffeine athigh doses produces adverse reproductiveeffects, causing developmental abnormalities. It tested negative in the histidine reversion–Ames and TRP reversion tests.
Fire Hazard
Flash point data for Caffeine are not available; however, Caffeine is probably combustible.
Biological Activity
Central nervous system stimulant. Antagonist at A 1 and A 2A adenosine receptors and inhibitor of cyclic nucleotide phosphodiesterases. Mobilises calcium from intracellular stores and inhibits benzodiazepine binding to GABA receptors.
Clinical Use
The commonly used clinical preparations include caffeine sodium benzoate and
ergotamine caffeine. The preparation of caffeine sodium benzoate (injection) is constituted of 0.12?g/ml of caffeine, 0.13?g/ml of sodium benzoate, and cafe bromine
mixture (oral liquid). Clinically, it can be used for migraine headaches, cerebral artery dilated headache, or headache caused by histamine. However,
it is invalid in the prevention of headaches. The adverse reactions include nausea,
vomiting, abdominal pain, and fatigue. Other common symptoms include numbness
and tingling of the hands, toes, and face and swelling of the foot and lower limb.
Overdose causes severe poisoning, mental disorder, ataxia, convulsions, gray chills
of the hand and foot, sensory disturbance, and even death due to coma and respiratory paralysis. Caffeine citrate preparation, including injection and oral solution,
is the only internationally approved drug for the treatment of premature infant
apnea.
Safety Profile
A human poison by
ingestion. An experimental poison by
ingestion, subcutaneous, intraperitoneal,
intramuscular, rectal, and intravenous
routes. Human systemic effects: ataxia,
blood pressure elevation, change in heart
rate, changes in tubules, convulsions or
effect on seizure threshold, dtarrhea,
distorted perceptions, hallucinations,
hypermotility, muscle contraction,
musculoskeletal tumors, nausea or vomiting,
toxic psychosis, tremors. A human teratogen
causing developmental abnormalities of the
craniofacial and musculoskeletal systems,
pregnancy termination (abortion), and
stillbirth. Human maternal effects include an
unspecified effect on labor or chddbirth.
Human mutation data reported. An
experimental teratogen. Other experimental
reproductive effects. Questionable
carcinogen with experimental carcinogenic
data. Large doses (above 1.0 g> cause
palpitation, excitement, insomnia, dtzziness,
headache, and vomiting. Continued
excessive use of caffeine in tea or coffee
may lead to digestive disturbances,
constipation, palpitations, shortness of
breath, and depressed mental states. It is
also implicated in cardiac disorders under
those condttions. When heated to
decomposition it emits toxic fumes of NOx
Synthesis
Usually obtained from tea dust in which it is present up to 5% or as a by-product from the manufacture of caffeine-free
coffee; synthetically prepared starting with dimethylurea and malonic acid.
Environmental Fate
Caffeine can have profound effects on the cardiovascular
system. At least four mechanisms have been proposed for the
pro-arrhythmic potential of caffeine in overdose. First,
caffeine increases circulating catecholamines. Second, caffeine
inhibits phosphodiesterase. Increased circulating catecholamines
after caffeine overdose increase b1-receptor stimulation.
Stimulation of b1-receptors increases intracellular cAMP
by G protein stimulation of adenylate cyclase. The activity of
cAMP is prolonged due to its decreased metabolism as
phosphodiesterase is inhibited by caffeine. Subsequently,
b1-receptor effects are exaggerated and tachydysrhythmias are
induced. Third, caffeine increases myocardial intracellular calcium. Caffeine both induces release of calcium from the
sarcoplasmic reticulumand blocks calcium’s reuptake into the
sarcoplasmic reticulum. This resulting increase in cytosolic
calcium may provoke dysrhythmias. Fourth, caffeine blocks
cardiac adenosine receptors, which have been shown to be
antiarrhythmic.The hypotension that has been noted with overdoses of
caffeine is due primarily to two mechanisms. First, caffeineinduced
tachydysrhythmias lead to inadequate filling of the
heart and subsequent decrease in cardiac output. Second,
caffeine augments β2-effects and causes subsequent vasodilation
with resulting hypotension.
Purification Methods
Caffeine crystallises from water or absolute EtOH. [Beilstein 26 III/IV 2338.]
Toxicity evaluation
Caffeine’s production and widespread use as an additive to
food and as a stimulant may result in release to the environment
through waste systems. It has an estimated vapor pressure
of 7.3×10-9 mmHg (25°C), which indicates that it will exist as particulate in the atmosphere. Caffeine is not susceptible to
photolysis and if released into soil it has a high mobility based
on the Koc of 22.
Check Digit Verification of cas no
The CAS Registry Mumber 58-08-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 8 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 58-08:
(4*5)+(3*8)+(2*0)+(1*8)=52
52 % 10 = 2
So 58-08-2 is a valid CAS Registry Number.
InChI:InChI=1/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
58-08-2Relevant articles and documents
SERS multiplexing of methylxanthine drug isomersviahost-guest size matching and machine learning
Chio, Weng-I Katherine,Dinish, U. S.,Jones, Tabitha,Lee, Tung-Chun,Liu, Jia,Olivo, Malini,Parkin, Ivan P.,Perumal, Jayakumar
supporting information, p. 12624 - 12632 (2021/10/06)
Multiplexed detection and quantification of structurally similar drug molecules, methylxanthine MeX, incl. theobromine TBR, theophylline TPH and caffeine CAF, have been demonstratedviasolution-based surface-enhanced Raman spectroscopy (SERS), achieving highly reproducible SERS signals with detection limits down to ~50 nM for TBR and TPH, and ~1 μM for CAF. Our SERS substrates are formed by aqueous self-assembly of gold nanoparticles (Au NPs) and supramolecular host molecules, cucurbit[n]urils (CBn,n= 7, 8). We demonstrate that the binding constants can be significantly increased using a host-guest size matching approach, which enables effective enrichment of analyte molecules in close proximity to the plasmonic hotspots. The dynamic range and the robustness of the sensing scheme can be extended using machine learning algorithms, which shows promise for potential applications in therapeutic drug monitoring, food processing, forensics and veterinary science.
Green synthesis of caffeine based on methylating reagent dimethyl carbonate and environmental friendly separating method
Yang, Shu-Zhen,Dong, Zhi-Qiang,Yin, Cheng-Cheng,Yue, Hui-Juan,Gao, Wei-Wei,Yang, Feng-Ke
, p. 1715 - 1720 (2020/03/27)
In this paper, a green process for the synthesis and separation of caffeine was reported. Theophylline sodium is used as the raw material, diazabicyclo[5.4.0]undec-7-ene as the catalyst, and Turkey red oil as the solvent, particularly, dimethyl carbonate was adopted in place of high toxic dimethyl sulfate to form a mixture of caffeine and by-product sodium bicarbonate. After converting sodium bicarbonate to sodium carbonate, the solubility difference between caffeine and sodium carbonate at 40°C was for the first time utilized to achieve the purpose of separating caffeine with an excellent yield of 98.4% and a purity of greater than 99.0%. Furthermore, both the reaction mother liquor and separation mother liquor can be recycled and reused during the reaction and separation processes, respectively, with little caffeine loss. No industrial waste was discharged in the process of the improved synthesis and separation, which is therefore environmental friendly.
Dehydroxymethylation of Alcohols Enabled by Cerium Photocatalysis
Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
supporting information, p. 10556 - 10564 (2019/08/28)
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.