113-45-1 Usage
Originator
Ritalin,Ciba,US,1958
History
Methylphenidate is a piperidine derivative that is a central nervous system stimulant. Methylphenidate, in its hydrochloride form, is the active ingredient in the common medication Ritalin. Methylphenidate was first synthesized from benzyl cyanide and 2-chloropyridine in Basel, Switzerland in 1944 by Ciba chemist Leandro Panizzon (1907 ?).Panizzon named the substance Ritaline after his wife, whose nickname was Rita. Panizzon and Max Hartmann proposed an improved synthesis for methylphenidate and obtained a U.S. patent for its preparation in 1950 (U.S. Patent Number 2507631). In 1954, methylphenidate was patented for use as an agent for treating psychological disorders under the name Ritalin by the Ciba pharmaceutical company.(Ciba subsequently merged with the Geigy company to become Ciba-Geigy, and then Ciba-Geigy merged with Sandoz to form Novartis.) Methylphenidate was first used to reverse drug-induced coma. Ritalin was approved by the Food and Drug Administration (FDA) in 1955 and introduced in the United States in 1956 for several conditions including depression, senile behavior, lethargy, and narcolepsy. Hyperactive children were first treated with stimulants in 1937. Since methylphenidate first appeared on the market, its use for treating ADHD has steadily increased. It is the most commonly used medication for treating children diagnosed with ADHD.
Uses
Different sources of media describe the Uses of 113-45-1 differently. You can refer to the following data:
1. Methylphenidate's mode of action is not completely known, but it is believed that ADHD symptoms are related to the dopaminergic areas of the brain. Animal studies indicate that methylphenidate affects several neurotransmitters to counteract ADHD behavior. Methylphenidate binds to dopamine transporters in the presynaptic neuron, blocking the reuptake of dopamine and increasing extracellular dopamine. Methylphenidate also infl uences norepinephrine reuptake and infl uences serotonin to a minor degree. In addition to ADHD, methylphenidate is used for several other medical conditions.It continues to be used for narcolepsy. It has also been used in treating depression, especially in elderly populations. Methylphenidate has been suggested for use in the treatment of brain injury from stroke or brain trauma; it has also been suggested to improve appetite and the mood of cancer and HIV patients. Another use is for pain control and/or sedation for patients using opiates.Health concerns are associated with the use of methylphenidate.Some of the commonly reported adverse effects associated with its use are insomnia, nervousness, hypertension, headache, anorexia, and tachycardia;less common effects include weight loss, nausea, and angina. Studies have indicated that methylphenidate lead to liver tumors in mice, but limited studies on its carcinogenicity in animals have not led the FDA to change recommendations on its use. Because methylphenidate is a stimulant and readily available, it has a potential for drug abuse.
2. Stimulant.
Manufacturing Process
As described in US Patent 2,507,631, 80 g of pulverized sodium amide are gradually added, while stirring and cooling, to a solution of 117 g of phenylacetonitrile and 113 g of 2-chloropyridine in 400 cc of absolute toluene. The mixture is then slowly heated to 110° to 120°C and maintained at this temperature for 1 hour. Water is added thereto after cooling, the toluene solution is shaken with dilute hydrochloric acid and the hydrochloric acid extracts are made alkaline with concentrated caustic soda solution. A solid mass is separated thereby which is taken up in acetic ester and distilled, αphenyl-α-pyridyl-(2)-acetonitrile passing over at 150° to 155°C under 0.5 mm pressure. When recrystallized from ethyl acetate it melts at 88° to 89°C, the
yield amounting to 135 g.
100 g of α-phenyl-α-pyridyl-(2)-acetonitrile are introduced into 400 cc of
concentrated sulfuric acid, allowed to stand overnight at room temperature,
poured into ice and rendered alkaline with sodium carbonate. α-Phenyl-αpyridyl-(2)-acetamide is precipitated thereby which melts at 134°C after
recrystallization from ethyl acetate.
100g of the resulting α-phenyl-α-pyridyl-(2)-acetamide, when dissolved in one
liter of methyl alcohol and treated for 6 hours at water-bath temperature with
hydrogen chloride, and after concentrating, diluting with water and rendering
alkaline with sodium carbonate, yield 90 g of the α-phenyl-α-pyridyl-(2)-acetic
acid methylester of MP 74° to 75°C (from alcohol of 50% strength).
The α-phenyl-α-piperidyl-(2)-acetic acid methylester of BP 135° to 137°C
under 0.6 mm pressure is obtained in theoretical yield by hydrogenation of 50
g of α-phenyl-α-pyridyl(2)-acetic acid methylester in glacial acetic acid in the
presence of 1 g of platinum catalyst at room temperature, while taking up 6
hydrogen atoms. Reaction with HCl gives the hydrochloride. Resolution of
stereoisomers is described in US Patent 2,957,880.
Brand name
Daytrana(Shire);4311 ciba;Centedrin;Cetedrin;Methidate;Ritalin sr;Ritaline.
Therapeutic Function
Psychostimulant
World Health Organization (WHO)
Methylphenidate, a piperidine derivative with mild central
stimulant activity, was introduced in 1956. Its pharmacological properties resemble
those of amfetamines and it shares their abuse potential. Methylphenidate retains a
place as an adjunct in the treatment of hyperkinetic syndromes in both children
and adults. It is controlled under Schedule II of the 1971 Convention on
Psychotropic Substances.
(Reference: (UNCPS2) United Nations Convention on Psychotropic Substances (II),
, , 1971)
Safety Profile
Poison experimentally
by ingestion, intraperitoneal, intravenous,
and subcutaneous routes. Moderately toxic
to humans by intravenous route. Human
systemic effects by intravenous route:
dyspnea. An experimental teratogen. When
heated to decomposition it emits toxic
fumes of NOx.
Check Digit Verification of cas no
The CAS Registry Mumber 113-45-1 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,1 and 3 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 113-45:
(5*1)+(4*1)+(3*3)+(2*4)+(1*5)=31
31 % 10 = 1
So 113-45-1 is a valid CAS Registry Number.
InChI:InChI=1/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3
113-45-1Relevant articles and documents
Resolution of (±)-threo-methylphenidate with (R)-(-)-binaphthyl-2,2′-diyl hydrogen phosphate: 0.5 M equiv of resolving agent is better than 1 M equiv
Prashad, Mahavir,Hu, Bin,Repi?, Oljan,Blacklock, Thomas J.,Giannousis, Peter
, p. 55 - 59 (2000)
Resolution of (±)-threo-methylphenidate (1) with 0.5 M equiv of (R)-(-)-binaphthyl-2,2′-diyl hydrogen phosphate (4) is described. Use of 0.5 M equiv of 4 was found to be better than 1 M equiv for the resolution of (±)-threo-methylphenidate (1) under diffe
α-C-H Bond Functionalization of Unprotected Alicyclic Amines: Lewis-Acid-Promoted Addition of Enolates to Transient Imines
Kim, Jae Hyun,Paul, Anirudra,Ghiviriga, Ion,Seidel, Daniel
, p. 797 - 801 (2021/02/06)
Enolizable cyclic imines, obtained in situ from their corresponding lithium amides by oxidation with simple ketone oxidants, are readily alkylated with a range of enolates to provide mono- and polycyclic β-aminoketones in a single operation, including the natural product (±)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations, which are promoted by BF3 etherate. β-Aminoesters derived from ester enolates can be converted to the corresponding β-lactams.
Microtubing-Reactor-Assisted Aliphatic C?H Functionalization with HCl as a Hydrogen-Atom-Transfer Catalyst Precursor in Conjunction with an Organic Photoredox Catalyst
Deng, Hong-Ping,Zhou, Quan,Wu, Jie
supporting information, p. 12661 - 12665 (2018/09/20)
Chlorine radical, which is classically generated by the homolysis of Cl2 under UV irradiation, can abstract a hydrogen atom from an unactivated C(sp3)?H bond. We herein demonstrate the use of HCl as an effective hydrogen-atom-transfer catalyst precursor activated by an organic acridinium photoredox catalyst under visible-light irradiation for C?H alkylation and allylation. The key to success relied on the utilization of microtubing reactors to maintain the volatile HCl catalyst. This photomediated chlorine-based C?H activation protocol is effective for a variety of unactivated C(sp3)?H bond patterns, even with primary C(sp3)?H bonds, as in ethane. The merit of this strategy is illustrated by rapid access to several pharmaceutical drugs from abundant unfunctionalized alkane feedstocks.
Palladium-Catalyzed Carbonylative Direct Transformation of Benzyl Amines under Additive-Free Conditions
Li, Yahui,Wang, Zechao,Wu, Xiao-Feng
, p. 738 - 741 (2018/01/17)
In this communication, we developed a new procedure for the direct carbonylative transformation of benzyl amines. Using dimethyl carbonate as the solvent, methyl 2-arylacetates can be produced in good to excellent yields from the corresponding primary, secondary, and tertiary benzyl amines with palladium as the catalyst. Notably, no base or any other additive is required here. In addition, our procedure can also be applied in the preparation of methylphenidate, which is a marketing drug and used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.
This product is a nationally controlled contraband, and the Lookchem platform doesn't provide relevant sales information.