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58-08-2

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58-08-2 Usage

Description

Different sources of media describe the Description of 58-08-2 differently. You can refer to the following data:
1. Caffeine is an alkaloid purine belonging to the group of organic compounds called methylxanthines. Pure caffeine is a white, crystalline, bitter-tasting compound. Caffeine is found in a number of plants, principally coffee and tea plants, as well as cola and cacao nuts. In plants, caffeine functions as a natural pesticide to deter insects.
2. Caffeine is a purine alkaloid commonly found in coffee and tea. Several in vivo studies have demonstrated that topical and oral administration of caffeine exerts a photoprotective effect through various mechanisms. Specifically, caffeine has been demonstrated to induce apoptosis in DNA damaged epidermal cells and tumors while sparing normal tissue. Mouse models demonstrate that this apoptotic effect is secondary to increased expression of wild-type p53, a tumor suppressor gene that is commonly mutated in UV-related skin cancers. Moreover, caffeine also has a sunscreen-like effect and inhibits formation of UVB-induced thymine dimers and sunburn skin lesions.

Chemical Properties

Different sources of media describe the Chemical Properties of 58-08-2 differently. You can refer to the following data:
1. Caffeine is the alkaloid 1,3,7-trimethylxanthine. It is one of the xanthine derivatives present up to 1.5% in seeds of coffee (Coffea arabica L.) and up to 5% in the leaves of tea (Camelia sinensis). It is a component of the beverages made from these plants. Caffeine is also a component of chocolate (Theobroma cacao) and the cola nut (Cola acuminata Schott and Endel. and related species), the extract of which is used in cola drinks. It is virtually odorless. Caffeine is added to cola-type beverages for its enhancement of flavor. Subtle and subliminal flavors are widely appreciated by consumers and caffeine has a modifying effect on other components of the beverage. The threshold for detecting the presence of caffeine in liquid foods varies depending on the nature of other substances present, but lies close to the level characteristic of currently produced cola-type beverages. The threshold for detection of caffeine in water has been shown to be 0.0095%; in liquid foods, 0.0184%. In one study, panelists could distinguish a solution containing 0.0058% caffeine from the control. The threshold for detecting taste difference between an aqueous solution of caffeine and a water control was also shown to be 0.005% caffeine and to distinguish bitterness, 0.011% caffeine. In aqueous solutions containing threshold and subthreshold concentrations of caffeine, sucrose, citric acid and salt, all compounds depressed the taste intensity of each other.*
2. white to light yellow crystal powder

Physical properties

Appearance: odorless silky needle-like crystal or crystal powder with the color of white or a little yellowish green. Solubility: weathering, easily dissolved in water or chloroform and slightly soluble in water, ethanol, or acetone, very slightly dissolved in ether. Melting point: 235–238?°C.

Originator

Caffedrine,Thompson Med.

Occurrence

Reported found in coffee and guarana.

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.

Uses

Different sources of media describe the Uses of 58-08-2 differently. You can refer to the following data:
1. Caffeine has widespread therapeutic use. It is widely used in headache (migraine) remedies such as aspirin and other analgesics. Caffeine is a mild vasoconstrictor and its ability to constrict blood vessels serving the brain explains its use to relieve headache. Caffeine is a common substance in medications to treat apnea in premature infants. Apparently, the area of the brain controlling respiration in premature infants is not fully developed and caffeine helps to stimulate this portion of the brain. The combination of caffeine and ephedrine is used in dietary and athletic supplements, and their role as appetite suppressant and energy boosters has been extensively studied.
2. Caffeine is consumed in coffee, tea, cocoa,chocolate, and soft drinks. It occurs naturallyin the leaves of coffee, tea, and mate and in ′cola nuts. It is used in medicine and found inmany drugs. It is used as a cardiac stimulant.
3. caffeine has a lipolytic effect on fatty cells, able to break down lipids and release fatty acids. given this ability and its draining properties, caffeine is used for skin firming and tightening. It is often incorporated into body product formulations targeting cellulite and slimming, as well as in eye creams that claim to reduce puffiness. Among its constituents are tannin and the alkaloid methylxanthine. Caffeine is a bitter-tasting, odorless white powder that occurs naturally in coffee, cola, guana paste, kola nuts, and tea. It is obtained as a by-product of decaffeinated coffee.
4. Caffeine is a white powder or needles that are odorless and have a bitter taste. it occurs naturally in tea leaves, coffee, cocoa, and cola nuts. it is a food additive used in soft drinks for its mildly stimulat- ing effect and distinctive taste note. it is used in cola-type beverages and is optional in other soft drinks up to 0.02%.
5. Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug and a reversible acetylcholinesterase inhibitor. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants. In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness. Caffeine is a cardiac and respiratory stimulant; diuretic. Caffeine is toxic at sufficiently high doses.
6. CNS stimulant respiratory stimulant;adenosine receptors antagonist

Definition

ChEBI: A trimethylxanthine in which the three methyl groups are located at positions 1, 3, and 7. A purine alkaloid that occurs naturally in tea and coffee.

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.

Brand name

NoDoz Caplets and Chewable Tablets (Bristol-Myers Products).

Therapeutic Function

Neurotropic, Central stimulant

Aroma threshold values

Detection at 29 to 300 ppm. Also see description.

Taste threshold values

See Description.

General Description

Odorless white powder or white glistening needles, usually melted together. Bitter taste. Solutions in water are neutral to litmus. Odorless.

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

58-08-2SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 18, 2017

Revision Date: Aug 18, 2017

1.Identification

1.1 GHS Product identifier

Product name caffeine

1.2 Other means of identification

Product number -
Other names 1H-Purine-2,6-dione, 3,7-dihydro-1,3,7-trimethyl-

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only. Food additives -> Flavoring Agents
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:58-08-2 SDS

58-08-2Synthetic route

methyl bromide
74-83-9

methyl bromide

xanthin
69-89-6

xanthin

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With solution aqueuse d'hydroxide de sodium; tetrabutylammomium bromide In dichloromethane 1)room temp. 12h 2)reflux 3h;100%
2,6-dimethoxy-7,9-dimethylpurinium iodide

2,6-dimethoxy-7,9-dimethylpurinium iodide

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In xylene at 140℃; for 0.75h; Rearrangement;100%
theophylline sodium salt
3485-82-3

theophylline sodium salt

carbonic acid dimethyl ester
616-38-6

carbonic acid dimethyl ester

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In water; ethylene glycol at 135℃; for 4h; Autoclave; Green chemistry;98.4%
With PEG 400 In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 12h; Solvent; Concentration; Temperature; Reagent/catalyst;94.9%
With NaY (Y-type sodium zeolite catalyst); turkey red oil In water for 5h; Reflux;
methyl bromide
74-83-9

methyl bromide

theophylline
58-55-9

theophylline

A

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

B

3-benzyladenine
7280-81-1

3-benzyladenine

Conditions
ConditionsYield
With solution aqueuse d'hydroxide de sodium; tetrabutylammomium bromide In dichloromethane 1)20 deg C, 12h 2)40 deg C, 3h;A 98%
B n/a
Methyl formate
107-31-3

Methyl formate

1,3-Dimethylxanthine potassium salt
57533-87-6

1,3-Dimethylxanthine potassium salt

A

theophylline
58-55-9

theophylline

B

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In methanolA 97.5%
B n/a
methanol
67-56-1

methanol

1,3-Dimethylxanthine potassium salt
57533-87-6

1,3-Dimethylxanthine potassium salt

A

Methyl formate
107-31-3

Methyl formate

B

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With carbon monoxide at 140℃; under 37503 Torr; for 20h;A n/a
B 97%
theophylline
58-55-9

theophylline

methyl iodide
74-88-4

methyl iodide

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydride In dimethyl sulfoxide for 0.75h;95%
With sodium hydride In dimethyl sulfoxide at 20℃; for 24h; Reagent/catalyst;90%
methyl bromide
74-83-9

methyl bromide

theobromine /
83-67-0

theobromine /

A

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

B

3-benzyladenine
7280-81-1

3-benzyladenine

Conditions
ConditionsYield
With solution aqueuse d'hydroxide de sodium; tetrabutylammomium bromide In dichloromethane 1)20 deg C, 12h 2)40 deg C, 3h;A 94%
B n/a
3-methylxanthine
1076-22-8

3-methylxanthine

dimethyl sulfate
77-78-1

dimethyl sulfate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With tetramethyl ammoniumhydroxide; potassium carbonate In methanol; water at 65 - 70℃;92.5%
theobromine /
83-67-0

theobromine /

dimethyl sulfate
77-78-1

dimethyl sulfate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
potassium fluoride on basic alumina In acetonitrile for 24h; Ambient temperature;92%
With sodium hydroxide
theophylline
58-55-9

theophylline

carbonic acid dimethyl ester
616-38-6

carbonic acid dimethyl ester

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With cetyltrimethylammonium bromide; N-ethyl-N,N-diisopropylamine In toluene at 140℃; for 9h; Solvent; Concentration; Reagent/catalyst; Temperature;90.7%
With 18-crown-6 ether In N,N-dimethyl-formamide at 90℃; for 12h;67%
With DABCO-NaY (1:1 DABCO Y-type sodium zeolite catalyst); turkey red oil In water for 5h; Reagent/catalyst; Reflux;
theophylline
58-55-9

theophylline

methyl iodide
74-88-4

methyl iodide

A

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

B

3-benzyladenine
7280-81-1

3-benzyladenine

Conditions
ConditionsYield
With solution aqueuse d'hydroxide de sodium; tetrabutylammomium bromide In dichloromethane 1)20 deg C, 12h 2)40 deg C, 3h;A 90%
B n/a
theophylline
58-55-9

theophylline

dimethyl sulfate
77-78-1

dimethyl sulfate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
potassium fluoride on basic alumina In acetonitrile for 24h; Ambient temperature;88%
With sodium hydroxide
With sodium hydroxide
With potassium hydroxide; Aliquat 336 1.) 20 deg C, 2 h, 2.) 1 h; Yield given. Multistep reaction;
theophylline
58-55-9

theophylline

diphenylmethylsulfonium tetrafluoroborate
10504-60-6

diphenylmethylsulfonium tetrafluoroborate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With potassium hydroxide In water; N,N-dimethyl-formamide at 20℃; for 3h;88%
Trimethylsulfonium Fluoride
353-39-9

Trimethylsulfonium Fluoride

Theophylline
58-55-9

Theophylline

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In N,N-dimethyl-formamide at 100℃; for 1h;86%
xanthin
69-89-6

xanthin

N,N'-dicyclohexyl-O-methyl isourea
6257-10-9

N,N'-dicyclohexyl-O-methyl isourea

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In N,N-dimethyl-formamide at 100℃; for 48h;85%
theophylline
58-55-9

theophylline

acetic acid
64-19-7

acetic acid

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With copper(I) thiophene-2-carboxylate; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(5-methyl-2-(4-fluorophenyl)pyridine(-1H))-iridium(III) hexafluorophosphate; N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; bathophenanthroline; iodomesitylene diacetate In 1,4-dioxane at 20℃; for 1h; Inert atmosphere; Irradiation; regioselective reaction;82%
4--1-methyl-5-methylaminocarbonylimidazole
107605-83-4

4--1-methyl-5-methylaminocarbonylimidazole

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydride In ethanol for 1.5h; Heating;81%
theobromine /
83-67-0

theobromine /

carbonic acid dimethyl ester
616-38-6

carbonic acid dimethyl ester

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With 18-crown-6 ether In N,N-dimethyl-formamide at 90℃; for 12h;78%
1-methyl-9-aminoxanthine potassium salt
113613-79-9

1-methyl-9-aminoxanthine potassium salt

methyl iodide
74-88-4

methyl iodide

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In N,N-dimethyl-formamide at 100℃; for 3h;76%
carbonic acid dimethyl ester
616-38-6

carbonic acid dimethyl ester

xanthin
69-89-6

xanthin

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With 18-crown-6 ether In N,N-dimethyl-formamide at 90℃; for 12h;74%
8-bromocaffeine
10381-82-5

8-bromocaffeine

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With copper In N,N-dimethyl-formamide for 2h; Heating;72%
1-methyl-9-aminoxanthine
113613-76-6

1-methyl-9-aminoxanthine

methyl iodide
74-88-4

methyl iodide

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In N,N-dimethyl-formamide at 100℃; for 1h;71%
4-(N-trichloroacetyl-N-methylamino)-1-methyl-5-methylaminocarbonylimidazole
107605-87-8

4-(N-trichloroacetyl-N-methylamino)-1-methyl-5-methylaminocarbonylimidazole

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydride In ethanol for 2h; Heating;66%
7-(2-hydroxyethyl)theophylline
519-37-9

7-(2-hydroxyethyl)theophylline

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With cerium(III) chloride; 9,10-diphenylanthracene; 1,2-bis(2,4,6-triisopropylphenyl)disulfane; tetrabutyl-ammonium chloride In acetonitrile for 168h; Irradiation; Inert atmosphere;63%
dimethyl sulfate
77-78-1

dimethyl sulfate

xanthin
69-89-6

xanthin

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
potassium fluoride on basic alumina In acetonitrile for 24h; Ambient temperature;61%
With alkaline solution
With sodium hydroxide
theobromine /
83-67-0

theobromine /

methyl iodide
74-88-4

methyl iodide

A

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

B

3-benzyladenine
7280-81-1

3-benzyladenine

Conditions
ConditionsYield
With solution aqueuse d'hydroxide de sodium; tetrabutylammomium bromide In dichloromethane 1)20 deg C, 12h 2)40 deg C, 3h;A 56%
B n/a
1,3,7,9-tetramethylxanthinium methyl sulfate
18623-34-2

1,3,7,9-tetramethylxanthinium methyl sulfate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
at 260℃; for 15h;25%
theophylline
58-55-9

theophylline

methyl p-toluene sulfonate
80-48-8

methyl p-toluene sulfonate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydroxide
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

8-chlorocaffeine
4921-49-7

8-chlorocaffeine

Conditions
ConditionsYield
With chlorine In chloroform100%
With chlorine In chloroform at 50℃; for 2h;100%
With trichloroisocyanuric acid; brilliant green carbocation In acetonitrile at 20℃; for 2h; Irradiation; regioselective reaction;78%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

8-bromocaffeine
10381-82-5

8-bromocaffeine

Conditions
ConditionsYield
With N-Bromosuccinimide In dichloromethane; water for 120h;100%
With N-Bromosuccinimide In dichloromethane; water for 120h;99%
With N-Bromosuccinimide In dichloromethane; water for 120h;99%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

8-deuterio-1,3,7-trimethylxanthine

8-deuterio-1,3,7-trimethylxanthine

Conditions
ConditionsYield
With [(N,N’-bis(1R,2R,3R,5S)-(−)-isopinocampheyl-1,2-ethanediimine-radical)NiI(μ2-H)]2; deuterium In tetrahydrofuran at -196 - 45℃; under 760.051 Torr; for 24h; Sealed tube;100%
With deuteromethanol; silver carbonate; johnphos In dichloromethane at 50 - 80℃;98%
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; deuterium In tetrahydrofuran at 55℃; under 750.075 Torr; for 22h; Inert atmosphere;92%
With palladium 10% on activated carbon; hydrogen; water-d2 at 90℃; for 1.5h;86.9%
With water-d2 at 150℃; for 0.25h; Microwave irradiation;
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

para-chlorotoluene
106-43-4

para-chlorotoluene

1,3,7-trimethyl-8-(4-methylphenyl)-1H-purine-3,7-dihydro-2,6-dione

1,3,7-trimethyl-8-(4-methylphenyl)-1H-purine-3,7-dihydro-2,6-dione

Conditions
ConditionsYield
With palladium diacetate; caesium carbonate; tricyclohexylphosphine tetrafluoroborate In toluene at 20 - 130℃; for 24h; Inert atmosphere;99%
With potassium phosphate; palladium diacetate In 1-methyl-pyrrolidin-2-one at 125℃; for 24h;86%
1-bromo-4-methoxy-benzene
104-92-7

1-bromo-4-methoxy-benzene

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

1,3,7-trimethyl-8-(p-methoxyphenyl)-xanthine
439927-43-2

1,3,7-trimethyl-8-(p-methoxyphenyl)-xanthine

Conditions
ConditionsYield
With potassium phosphate; palladium diacetate; Trimethylacetic acid In N,N-dimethyl-formamide at 20 - 120℃; for 7.16667h; Inert atmosphere;99%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 5,5-dimethyl-1,3-cyclohexadiene; N,N-dimethyl-formamide at 20 - 140℃; for 36.1667h; Inert atmosphere; regioselective reaction;98%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

diphenyl acetylene
501-65-5

diphenyl acetylene

(E)-8-(1,2-Diphenylethenyl)-3,7-dihydro-1,3,7-trimethyl-1H-purin-2,6-dion
99765-12-5

(E)-8-(1,2-Diphenylethenyl)-3,7-dihydro-1,3,7-trimethyl-1H-purin-2,6-dion

Conditions
ConditionsYield
With chloro(1,5-cyclooctadiene)rhodium(I) dimer; cesium acetate; 1,2-bis-(diphenylphosphino)ethane In toluene at 120℃; for 24h; Sealed vial; optical yield given as %de; stereoselective reaction;99%
With bis(dibenzylideneacetone)-palladium(0); tricyclohexylphosphine; Trimethylacetic acid In N,N-dimethyl acetamide at 130℃; for 14h; Inert atmosphere; Glovebox; stereoselective reaction;69%
tert-butyl N-(thiophen-2-ylmethyl)carbamate
401485-19-6

tert-butyl N-(thiophen-2-ylmethyl)carbamate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

tert-butyl N-((5-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl) thiophen-2-yl)methyl)carbamate
1403938-43-1

tert-butyl N-((5-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl) thiophen-2-yl)methyl)carbamate

Conditions
ConditionsYield
With pyridine; palladium diacetate; copper(II) acetate monohydrate; copper(l) chloride In 1,4-dioxane at 120℃; for 20h; Schlenk technique; Inert atmosphere;99%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

2-iodonaphthalene
612-55-5

2-iodonaphthalene

1,3,7-trimethyl-8-(naphthalen-2-yl)-xanthine
1257390-78-5

1,3,7-trimethyl-8-(naphthalen-2-yl)-xanthine

Conditions
ConditionsYield
With (1-(2-(tert-butylamino)ethyl)-3-mesityl-2,3-dihydro-1H-imidazol-2-yl)copper(I) iodide; lithium tert-butoxide In N,N-dimethyl-formamide at 140℃; for 8h; Glovebox;99%
NH-pyrazole
288-13-1

NH-pyrazole

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

1,3,7-trimethyl-4,5,8-tri(1H-pyrazol-1-yl)-3,4,5,7-tetrahydro-1H-purine-2,6-dione

1,3,7-trimethyl-4,5,8-tri(1H-pyrazol-1-yl)-3,4,5,7-tetrahydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With tetrabutylammonium tetrafluoroborate In acetonitrile at 45℃; for 10h; Temperature; Inert atmosphere; Electrochemical reaction; Green chemistry; diastereoselective reaction;99%
4-bromo-1H-pyrazole
2075-45-8

4-bromo-1H-pyrazole

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

4,5,8-tris(4-bromo-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

4,5,8-tris(4-bromo-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With tetrabutylammonium tetrafluoroborate In acetonitrile at 45℃; for 10h; Inert atmosphere; Electrochemical reaction; Green chemistry; diastereoselective reaction;99%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

4-bromo-3-methyl-1H-pyrazole
13808-64-5

4-bromo-3-methyl-1H-pyrazole

4,5,8-tris(4-bromo-3-methyl-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

4,5,8-tris(4-bromo-3-methyl-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With tetrabutylammonium tetrafluoroborate In acetonitrile at 45℃; for 10h; Inert atmosphere; Electrochemical reaction; Green chemistry; diastereoselective reaction;99%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

oxalic acid
144-62-7

oxalic acid

oxalic acid caffeine, oxalic acid

oxalic acid caffeine, oxalic acid

Conditions
ConditionsYield
In methanol; cyclohexane at 17 - 22℃; under 724.572 - 782.178 Torr; for 0.5h;98.3%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

2,6-dithiocaffeine
32061-73-7

2,6-dithiocaffeine

Conditions
ConditionsYield
With Lawessons reagent; aluminum oxide for 0.1h; microwave irradiation;98%
With Lawessons reagent In toluene for 25h; Reflux;75%
With bis(1,5-cyclooctadiylboryl)sulfide In 1,3,5-trimethyl-benzene for 336h; Heating;62%
With kerosine
d6-dimethyl sulfate
15199-43-6

d6-dimethyl sulfate

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

C9H10(2)H3N4O2(1+)*C(2)H3O4S(1-)

C9H10(2)H3N4O2(1+)*C(2)H3O4S(1-)

Conditions
ConditionsYield
In nitrobenzene at 90 - 100℃; for 25h;98%
ethanol
64-17-5

ethanol

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

8-(1-hydroxyethyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
32086-89-8

8-(1-hydroxyethyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With tert.-butylhydroperoxide In decane at 120℃; for 0.333333h; Reagent/catalyst; Solvent; Temperature; Time; Microwave irradiation; Green chemistry;98%
With di-tert-butyl peroxide In water at 20℃; Inert atmosphere; UV-irradiation;96%
With benzophenone Ambient temperature; Irradiation;
bromobenzene
108-86-1

bromobenzene

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

1,3,7-trimethyl-8-phenylxanthine
6439-88-9

1,3,7-trimethyl-8-phenylxanthine

Conditions
ConditionsYield
With potassium phosphate; palladium diacetate; Trimethylacetic acid In N,N-dimethyl-formamide at 20 - 120℃; for 7.16667h; Inert atmosphere;98%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 5,5-dimethyl-1,3-cyclohexadiene; N,N-dimethyl-formamide at 20 - 140℃; for 36.1667h; Inert atmosphere; regioselective reaction;93%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

9-bromophenanthrene
573-17-1

9-bromophenanthrene

3,7-Dihydro-1,3,7-trimethyl-8-(9-phenanthryl)-1H-purin-2,6-dion
99765-06-7

3,7-Dihydro-1,3,7-trimethyl-8-(9-phenanthryl)-1H-purin-2,6-dion

Conditions
ConditionsYield
With potassium phosphate; palladium diacetate; Trimethylacetic acid In N,N-dimethyl-formamide at 20 - 120℃; for 7.16667h; Inert atmosphere;98%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 5,5-dimethyl-1,3-cyclohexadiene; N,N-dimethyl-formamide at 20 - 140℃; for 36.1667h; Inert atmosphere; regioselective reaction;95%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

8-deuterio-1,3,7-tris(trideuteriomethyl)xanthine
1220356-33-1

8-deuterio-1,3,7-tris(trideuteriomethyl)xanthine

Conditions
ConditionsYield
With palladium 10% on activated carbon; hydrogen; water-d2 at 160℃; for 24h;98%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

trimethoxonium tetrafluoroborate
420-37-1

trimethoxonium tetrafluoroborate

1,3,7,9-tetramethylxanthinium tetrafluoroborate

1,3,7,9-tetramethylxanthinium tetrafluoroborate

Conditions
ConditionsYield
Stage #1: 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione; trimethoxonium tetrafluoroborate In acetonitrile at 20℃; for 0.0833333h; Inert atmosphere; Schlenk technique;
Stage #2: With sodium carbonate In acetonitrile at 20℃; for 0.916667h;
97%
In 1,2-dichloro-ethane at 100℃; for 1h;66%
In 1,2-dichloro-ethane Inert atmosphere; Schlenk technique; Reflux;
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

para-iodoanisole
696-62-8

para-iodoanisole

1,3,7-trimethyl-8-(p-methoxyphenyl)-xanthine
439927-43-2

1,3,7-trimethyl-8-(p-methoxyphenyl)-xanthine

Conditions
ConditionsYield
With (1-(2-(tert-butylamino)ethyl)-3-mesityl-2,3-dihydro-1H-imidazol-2-yl)copper(I) iodide; lithium tert-butoxide In N,N-dimethyl-formamide at 140℃; for 8h; Glovebox;97%
With potassium phosphate; palladium diacetate; Trimethylacetic acid In N,N-dimethyl-formamide at 20 - 120℃; for 7.16667h; Inert atmosphere;92%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

4-iodo-3-methyl-1H-pyrazole
15802-75-2

4-iodo-3-methyl-1H-pyrazole

4,5,8-tris(4-iodo-3-methyl-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

4,5,8-tris(4-iodo-3-methyl-1H-pyrazol-1-yl)-1,3,7-trimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With tetrabutylammonium tetrafluoroborate In acetonitrile at 45℃; for 10h; Inert atmosphere; Electrochemical reaction; Green chemistry; diastereoselective reaction;97%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

para-bromotoluene
106-38-7

para-bromotoluene

1,3,7-trimethyl-8-(4-methylphenyl)-1H-purine-3,7-dihydro-2,6-dione

1,3,7-trimethyl-8-(4-methylphenyl)-1H-purine-3,7-dihydro-2,6-dione

Conditions
ConditionsYield
With potassium phosphate; palladium diacetate; Trimethylacetic acid In N,N-dimethyl-formamide at 20 - 120℃; for 7.16667h; Inert atmosphere;96%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 5,5-dimethyl-1,3-cyclohexadiene; N,N-dimethyl-formamide at 20 - 140℃; for 36.1667h; Inert atmosphere; regioselective reaction;96%
With 2-ethyl-[1,2,4] triazolo[4,3-a]pyridin-2-ium tetrafluoroborate; palladium diacetate; potassium carbonate In N,N-dimethyl-formamide at 115℃; for 22h; Inert atmosphere;94%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

2-methylphenyl bromide
95-46-5

2-methylphenyl bromide

1,3,7-trimethyl-8-(o-tolyl)-xanthine
1137486-72-6

1,3,7-trimethyl-8-(o-tolyl)-xanthine

Conditions
ConditionsYield
With potassium phosphate; palladium diacetate; Trimethylacetic acid In N,N-dimethyl-formamide at 20 - 120℃; for 7.16667h; Inert atmosphere;96%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 5,5-dimethyl-1,3-cyclohexadiene; N,N-dimethyl-formamide at 20 - 140℃; for 36.1667h; Inert atmosphere; regioselective reaction;88%
2-Methylthiophene
554-14-3

2-Methylthiophene

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

1,3,7-trimethyl-8-(5-methylthiophen-2-yl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione
1207995-92-3

1,3,7-trimethyl-8-(5-methylthiophen-2-yl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Conditions
ConditionsYield
Stage #1: 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione With pyridine; palladium diacetate; copper(II) acetate monohydrate In 1,4-dioxane at 20℃; for 0.166667h; Inert atmosphere;
Stage #2: 2-Methylthiophene In 1,4-dioxane at 120℃; for 20h; Inert atmosphere;
96%
With pyridine; palladium diacetate; copper(II) acetate monohydrate In 1,4-dioxane at 120℃; for 24h; Schlenk technique; Inert atmosphere;92%
With pyridine; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; oxygen; copper(II) acetate monohydrate In 1,4-dioxane at 140℃; under 760.051 Torr; for 30h; Schlenk technique; Green chemistry;89%

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.

Method for synthesizing caffeine

-

, (2021/01/04)

The invention discloses a method for synthesizing caffeine, and relates to the technical field of preparation of heterocyclic compounds containing purine ring systems. The preparation method comprisesthe following steps: mixing cyanoacetic acid and acetic anhydride at 30-80 DEG C for reaction, adding a solvent and dimethylurea, cooling to room temperature after reflux reaction is finished, filtering, concentrating filtrate, combining solids to obtain dimethylacetamide, adding liquid caustic soda to adjust the pH to 8-11, and reacting at 80-100 DEG C to generate dimethyl 4AU; the method comprises the following steps: completely dissolving dimethyl 4AU in formic acid, adding sodium nitrite, reacting at room temperature, adding a catalyst, keeping the temperature at 30-70 DEG C, recovering the catalyst after the reaction is finished, and concentrating mother liquor to recover formic acid, thereby obtaining dimethyl FAU; adding water and liquid caustic soda into dimethyl FAU, and carryingout a ring-closure reaction to obtain theophylline sodium salt; the theophylline sodium salt is subjected to methylation reaction and refining to obtain caffeine. The method has the advantages of accessible raw materials, mild and controllable reaction conditions, fewer steps, high yield and greatly higher product quality, is simple to operate, and can easily implement industrial production.

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.