665-66-7

Basic information

• Product Name: 1-Adamantanamine hydrochloride
• Synonyms: TIMTEC-BB SBB003680;TRICYCLODECANE HYDROCHLORIDE;1-ADAMANTYLAMINE HYDROCHLORIDE;1-ADAMANTANAMINE HCL;1-ADAMANTANAMINE HYDROCHLORIDE;1-ADAMANTANEAMMONIUM CHLORIDE;1-AMINOADAMANTANE HYDROCHLORIDE;ADAMANTAN-1-AMINE HYDROCHLORIDE
• CAS NO: 665-66-7
• Molecular Formula: C₁₀H₁₈N*Cl
• Molecular Weight: 187.71
• EINECS: 211-560-2
• Product Categories: Adamantane derivatives;chiral;Adamantanes;Intermediates & Fine Chemicals;Pharmaceuticals;API's;Dopamine receptor;Influenza Viruses;API;SYMADINE;inhibitor
• Mol File: 665-66-7.mol

Chemical Properties

• Melting Point: >300 °C(lit.)
• Boiling Point: 308.63°C (rough estimate)
• Flash Point: 96 °C
• Appearance: White/Fine Crystalline Powder
• Density: 1.0276 (rough estimate)
• Vapor Pressure: 0.085mmHg at 25°C
• Refractive Index: 1.6100 (estimate)
• Storage Temp.: -20°C Freezer
• Solubility: H2O: 50 mg/mL
• Water Solubility: soluble
• Sensitive: Hygroscopic
• Merck: 14,374
• BRN: 4198854
• CAS DataBase Reference: 1-Adamantanamine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Adamantanamine hydrochloride(665-66-7)
• EPA Substance Registry System: 1-Adamantanamine hydrochloride(665-66-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22-40-20/21/22
• Safety Statements: 22-36/37-36-35-20/21
• RIDADR: UN 1759 8 / PGII
• WGK Germany: 3
• RTECS: AU4375000
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 665-66-7(Hazardous Substances Data)

Usage

Uses

1-Adamantanamine hydrochloride is used in various applications across different industries, including:
Used in Pharmaceutical Industry:
1-Adamantanamine hydrochloride is used as an antiviral agent for the prophylactic or symptomatic treatment of influenza A. It is effective in preventing and alleviating the symptoms of the virus.
1-Adamantanamine hydrochloride is used as an antiparkinsonian agent to treat Parkinson's disease and its associated motor symptoms. It helps improve the patient's motor function and quality of life.
1-Adamantanamine hydrochloride is used to treat extrapyramidal reactions, which are drug-induced movement disorders. It helps manage and alleviate these involuntary movements.
1-Adamantanamine hydrochloride is used for postherpetic neuralgia, a painful condition that occurs after a shingles infection. It helps reduce the pain and discomfort associated with this condition.
1-Adamantanamine hydrochloride is used as a selective FP prostanoid receptor agonist and an F-series prostaglandin analog. It is 200 times as potent as Latanoprost, making it a highly effective treatment option.
1-Adamantanamine hydrochloride is used as an NMDA-receptor antagonist, which helps in the treatment of various neurological disorders by modulating the activity of the NMDA receptors in the brain.
Brand names for 1-Adamantanamine hydrochloride include Symadine (Solvay Pharmaceuticals) and Symmetrel (Endo).

Originator

Symmetrel,DuPont (Endo),US,1966

Manufacturing Process

360 ml of 96% sulfuric acid and a solution of 13.6 grams (0.1 mol) of adamantane in 100 ml of n-hexane were emulsified in the apparatus described and provided with an inclined centrifugal stirrer. Then a mixture of 46 grams (1.7 mols) of liquid hydrocyanic acid and 29.6 grams (0.4 mol) of tertiary butanol was added dropwise within 1.5 hours at about 25°C. After 30 minutes of postreaction, the product was poured on ice. The granular mass which precipitated [N-(adamantyl-1)formamide] was sucked off and washed with water. The raw product (37 grams) was then refluxed for 10 hours with a solution of 60 grams of NaOH in 600 ml of diethylene glycol. After cooling, the solution was diluted with 1.5 liters of water and subjected to three extractions with ether. The amine was extracted from the ethereal solution with 2 N HCl and liberated therefrom by the addition of solid NaOH (while cooling). The alkaline solution was extracted with ether and the ethereal solution was dried with solid NaOH. Distillation resulted in 10.6 grams (70% of the theory) of 1-aminoadamantane which, after sublimation, melted at 180°C to 192°C (seal capillary). It is converted to the hydrochloride.

Therapeutic Function

Antiviral, Antiparkinsonian

Biological Activity

amantadine hydrochloride is an antiviral and an antiparkinsonian drug.

Biochem/physiol Actions

Amantadine hydrochloride is effective against influenza viruses both in vivo and in vitro. It is considered as an antagonist of the N-methyl-D-aspartate (NMDA) type glutamate receptor. Amantadine plays an important role in the release of dopamine, preventing dopamine reuptake and blocking microglial activation and neuroinflammation.

Clinical Use

Parkinson’s disease (but not drug-induced extrapyramidal symptoms) Post-herpetic neuralgia Prophylaxis and treatment of influenza A

Safety Profile

Human poison by ingestion. Poison by ingestion, intraperitoneal, and intravenous routes. A human teratogen with developmental abnormalities of the circulatory system. Experimental reproductive effects. Human systemic effects by ingestion: distorted perceptions, euphoria, excitement, hallucinations. When heated to decomposition it emits very toxic fumes of NO, and HCl.

Drug interactions

Potentially hazardous interactions with other drugs Memantine: increased risk of CNS toxicity - avoid; effects of amantadine possibly enhanced.

Metabolism

Amantadine is metabolised in the liver to a minor extent, mainly by N-acetylation. The renal amantadine clearance is much higher than the creatinine clearance, suggesting renal tubular secretion in addition to glomerular filtration. After 4-5 days, 90% of the dose appears unchanged in urine. The rate is considerably influenced by urinary pH: a rise in pH brings about a fall in excretion.

Purification Methods

Dissolve the salt in dry EtOH, add a few drops of dry EtOH saturated with HCl gas, followed by dry Et2O to crystallise the hydrochloride. Dry the salt in a vacuum. [Stetter et al. Chem Ber 93 226 1960.]

InChI:InChI=1/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2/t7-,8+,9-,10-

Synthetic route

1-Adamantanamine (768-94-5) → amantadine hydrochloride (665-66-7)

Conditions	Yield
With hydroxylamine hydrochloride In ethanol for 2h; Reflux;	100%
With hydrogenchloride In water; toluene at 0 - 20℃; for 1h; Product distribution / selectivity;
With hydrogenchloride In diethyl ether

1-Azidoadamantane (24886-73-5) → amantadine hydrochloride (665-66-7)

Conditions	Yield
With propan-1-ol; 2,2'-azobis(isobutyronitrile); phenylsilane; bis(tri-n-butyltin)oxide In benzene Reduction; Heating;	99%

2,2,2-trichloroethyl (adamantan-1-yl)carbamate (17341-91-2) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Stage #1: 2,2,2-trichloroethyl 1-adamantylcarbamate With acetic acid; zinc Stage #2: With acetyl chloride In methanol Heating;	99%

N-(1-adamantyl)acetamide (880-52-4) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Stage #1: N-(1-adamantyl)acetamide With sodium heptadecanoic acid; β‐cyclodextrin; sodium hydroxide In ethanol; water for 20h; Reflux; Stage #2: With hydrogenchloride In water at 70℃;	96.5%
Stage #1: N-(1-adamantyl)acetamide With propylene glycol; potassium hydroxide In water at 125 - 130℃; for 8h; Green chemistry; Stage #2: With hydrogenchloride In dichloromethane; water at 55 - 60℃; for 1h; Temperature; Time; Green chemistry;	82%
Stage #1: N-(1-adamantyl)acetamide With methanol; water; sodium hydroxide at 145℃; for 8h; Autoclave; Stage #2: With hydrogenchloride In dichloromethane; water at 50℃; for 0.5h; Autoclave;	82.2%

N-(1-adamantyl)formamide (3405-48-9) → amantadine hydrochloride (665-66-7)

Conditions	Yield
With hydrogenchloride In ethanol; water at 85 - 90℃; for 1h;	93%

1-nitroadamantane (7575-82-8) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Stage #1: 1-nitroadamantane With iron(III) chloride hexahydrate; hydrazine hydrate In diethyl ether; ethanol at 40℃; Inert atmosphere; Stage #2: With hydrogenchloride In water at 70℃; for 0.5h;	89.5%
Stage #1: 1-nitroadamantane With C36H56Cl3CrN2O; magnesium; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In tetrahydrofuran at 60℃; for 24h; Inert atmosphere; Schlenk technique; Stage #2: With hydrogenchloride In tetrahydrofuran; water; ethyl acetate at 20℃;	83%

adamantylmagnesium bromide (57680-77-0) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Stage #1: adamantylmagnesium bromide With N,N,N,N,N,N-hexamethylphosphoric triamide; copper(I) cyanide*lithium chloride; 4,4'-bis(4-trifluoromethyl)benzophenone O-methylsulfonyloxime In tetrahydrofuran at 0℃; for 1h; Substitution; Stage #2: With hydrogenchloride In water; acetone at 25℃; for 0.5h; Hydrolysis;	82%
Multi-step reaction with 2 steps 1: chlorobenzene; diethyl ether / 0.5 h / 0 °C 2: 334 mg / aq. HCl / ethanol / 10 h / Heating View Scheme
Multi-step reaction with 2 steps 1: CuCN*2LiCl / tetrahydrofuran; hexamethylphosphoric acid triamide / 0.5 h / 0 °C 2: aq. HCl View Scheme

1-Adamantyl bromide (768-90-1) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Stage #1: 1-Adamantyl bromide With urea at 180 - 240℃; Stage #2: With hydrogenchloride In water Temperature;	49.7%

1-(Chloroamino)adamantane (24375-06-2) → N,N-dichloro-adamantan-1-amine (24375-05-1) + amantadine hydrochloride (665-66-7)

Conditions	Yield
silica gel In methanol; dichloromethane disproportionation; Yields of byproduct given;

Adamantan-1-yl-[bis-(4-trifluoromethyl-phenyl)-methylene]-amine → amantadine hydrochloride (665-66-7)

Conditions	Yield
With hydrogenchloride Yield given;

adamantan-1-yl-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-ylidene)-amine → amantadine hydrochloride (665-66-7)

Conditions	Yield
With hydrogenchloride In ethanol for 10h; Heating;	334 mg

adamantane (281-23-2) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: nitric acid / 0.5 h / 25 - 30 °C 2: acetic acid / 0.5 h / 125 °C 3: acetic acid; nitric acid / water / 125 °C 4: sodium hydroxide / water 5: hydrogenchloride / diethyl ether View Scheme
Multi-step reaction with 2 steps 1.1: Nitrogen dioxide; ozone / 0.5 h / -78 - 30 °C 2.1: iron(III) chloride hexahydrate; hydrazine hydrate / ethanol; diethyl ether / 40 °C / Inert atmosphere 2.2: 0.5 h / 70 °C View Scheme

1-nitroxyadamantane (32314-61-7) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid / 0.5 h / 125 °C 2: acetic acid; nitric acid / water / 125 °C 3: sodium hydroxide / water 4: hydrogenchloride / diethyl ether View Scheme

1-(carbamoylamino)adamantne (13072-69-0) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; nitric acid / water / 125 °C 2: sodium hydroxide / water 3: hydrogenchloride / diethyl ether View Scheme
With hydrogenchloride; pyrographite In water at 70℃; for 1h; pH=3 - 4; Industrial scale;	6.4 kg

adamantan-1-amine hydronitrate → amantadine hydrochloride (665-66-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water 2: hydrogenchloride / diethyl ether View Scheme

1-acetyladamantane (1660-04-4) → amantadine hydrochloride (665-66-7)

Conditions	Yield
Stage #1: 1-acetyladamantane With tetrabutylammomium bromide; sodium hydroxide In water; ethylene glycol at 40 - 190℃; for 12h; Autoclave; Stage #2: With hydrogenchloride In water; ethylene glycol pH=4;

adamantane (281-23-2) → amantadine hydrochloride (665-66-7) + adamantan-2-amine hydrochloride (10523-68-9)

Conditions	Yield
Stage #1: adamantane With methanol; cerium(III) chloride; di-tert-butyl-diazodicarboxylate; tetrabutyl-ammonium chloride In acetonitrile at 20℃; for 10h; Irradiation; Inert atmosphere; Sealed tube; Stage #2: With trifluoroacetic acid In dichloromethane at 20℃; for 1h; Reagent/catalyst; Further stages;

Trimethyl orthoacetate (1445-45-0) + amantadine hydrochloride (665-66-7) → N-(1-adamantyl)acetamide (880-52-4)

Conditions	Yield
In methanol at 135℃; for 0.25h; Microwave irradiation;	100%

2,3,4-trifluorophenyl isocyanate (190774-58-4) + amantadine hydrochloride (665-66-7) → 1-(adamantan-1-yl)-3-(2,3,4-trifluorophenyl)urea (1338780-86-1)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; Inert atmosphere;	100%

2,2'-dithiodibenzoic acid dichloride (19602-82-5) + amantadine hydrochloride (665-66-7) → N,N'-bis(1-adamantyl)-2,2'-dithiodibenzamide (847431-86-1)

Conditions	Yield
With triethylamine In dichloromethane for 5.5h;	98%
With triethylamine In dichloromethane at -15℃; for 0.25h;

poly(ethylene glycol)-carboxylic acid, carboxyl content 6.88E-5 mol/g, Mw = 33300, PDI = 1.1 + amantadine hydrochloride (665-66-7) + alpha cyclodextrin (10016-20-3) → poly(ethylene glycol) 3500, bis[N-(1-adamantyl)aminocarbonyl]-terminated, inclusion complex with α-cyclodextrin, prepared with 1-adamantylamine and proton sponge

Conditions	Yield
With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In N,N-dimethyl-formamide at 4℃;	95%

Benzyl isothiocyanate (622-78-6) + amantadine hydrochloride (665-66-7) → 1-(adamantane-2-yl)-3-benzylthiourea (29456-84-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 8h;	95%

1-adamantyl bromomethyl ketone (5122-82-7) + amantadine hydrochloride (665-66-7) → 1-(adamant-1-yl)-2-((adamant-1-yl)amino)ethan-1-one

Conditions	Yield
With sodium carbonate In ethanol for 15h; Heating;	94%

amantadine hydrochloride (665-66-7) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With sodium chloride; sodium hydroxide In water	94%
With sodium hydroxide In water
With sodium hydroxide In dichloromethane; water

4-((3-formyl-4-hydroxyphenyl)diazenyl)benzenesulfonamide (215177-60-9) + amantadine hydrochloride (665-66-7) → C23H26N4O3S

Conditions	Yield
With acetic acid Reflux;	94%

2-hydroxy-5-(p-chlorophenylazo)benzaldehyde (27147-07-5) + amantadine hydrochloride (665-66-7) → C23H24ClN3O

Conditions	Yield
With acetic acid Reflux;	94%

2,4-Dinitrofluorobenzene (70-34-8) + amantadine hydrochloride (665-66-7) → N-(2,4-dinitrophenyl)adamantan-1-amine (149874-11-3)

Conditions	Yield
With triethylamine In acetonitrile for 48h; Reflux; Darkness;	93%
With potassium carbonate; triethylamine In acetonitrile for 48h; pH=8 - 9; Darkness;	50%

Boc-Glu-OBn (30924-93-7) + amantadine hydrochloride (665-66-7) → N-(tert-butyloxycarbonyl)-L-glutamic acid α-benzyl ester γ-(1-adamantylamide) (102651-06-9)

Conditions	Yield
With diphenylphosphoranyl azide; diethylamine In N,N-dimethyl-formamide at 0 - 25℃; for 21h;	92%

amantadine hydrochloride (665-66-7) + phenyl isothiocyanate (103-72-0) → 1-(adamantane-2-yl)-3-phenylthiourea (25444-88-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 8h;	92%

Phenethyl isothiocyanate (2257-09-2) + amantadine hydrochloride (665-66-7) → 1-(adamantane-2-yl)-3-phenethylthiourea

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 8h;	92%

amantadine hydrochloride (665-66-7) → 3-aminoadamantan-1-ol (702-82-9)

Conditions	Yield
With sulfuric acid; nitric acid at 10 - 15℃;	90%
With sulfuric acid; nitric acid at 0 - 10℃; for 2h;	81%
Stage #1: amantadine hydrochloride With sulfuric acid; nitric acid at 0 - 20℃; Inert atmosphere; Stage #2: With sodium hydroxide In water	72%

sodium metavanadate + water (7732-18-5) + amantadine hydrochloride (665-66-7) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4C10H15NH3(1+)*2H(1+)*V10O28(6-)*2HCON(CH3)2*2H2O=(C10H15NH3)4(H2V10O28)*2HCON(CH3)2*2H2O

Conditions	Yield
With aq. HCl In water stirring mixture of adamantane deriv., vanadium compd., water and DMF for few sec. at room temp., adjusting pH to 3 by addn. of 0.1 M aqueous HCl; filtration, keeping in air at room temp. for 2 w, elem. anal.;	90%

(1R)-4-(2-tert-butoxycarbonylamino-2-carboxyethyl)imidazole-1-carboxylic acid tert-butyl ester + amantadine hydrochloride (665-66-7) → N,N'-di(tert-butylcarbamate)adamantylamino-D-histidine amide (1190215-11-2)

Conditions	Yield
With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; trimethylamine In dichloromethane at 20℃; Cooling with ice;	90%

hydrogenchloride (7647-01-0) + 18-crown-6 ether (17455-13-9) + amantadine hydrochloride (665-66-7) + copper dichloride → 2C10H15NH3(1+)*Cu2Cl6(2-)*C12H24O6=(C10H15NH3)2Cu2Cl6(C12H24O6)

Conditions	Yield
In hydrogenchloride; methanol adamantan-1-aminium chloride, 18-crown-6 were dissolved in MeOH, CuCl2 was added followed by concd. aq. HCl; filtered, slow evapd. at room temp., elam. anal.;	90%

Upstream product

• 768-95-6 1-adamanthanol 
• 768-90-1 1-Adamantyl bromide 
• 7575-82-8 1-nitroadamantane 
• 3405-48-9 N-(1-adamantyl)formamide 
• 1660-04-4 1-acetyladamantane 
• 13072-69-0 1-(carbamoylamino)adamantne 
• 32314-61-7 1-nitroxyadamantane 
• 281-23-2 adamantane 
• 880-52-4 N-(1-adamantyl)acetamide 
• 17341-91-2 2,2,2-trichloroethyl ((3s,5s,7s)-adamantan-1-yl)carbamate 
• 768-94-5 1-Adamantanamine 
• 57680-77-0 adamantylmagnesium bromide 
• 24886-73-5 1-Azidoadamantane 
• 24375-06-2 1-(Chloroamino)adamantane 

Downstream Products

• 14973-23-0 N-Adamantan-1-yl-N'-<2-fluor-aethyl>-harnstoff 
• 1145869-17-5 C₂₁H₂₅NO₅ 
• 1145869-18-6 C₂₁H₂₅NO₅ 
• 1145869-19-7 C₂₁H₂₅NO₅ 
• 1145869-20-0 C₂₁H₂₅NO₅ 
• 1145869-16-4 C₂₁H₂₅NO₅ 
• 1426153-00-5 (E)-N-(4-(diethylamino)benzylidene)adamantan-1-amine 
• 1033776-89-4 N-adamantan-1-yl-2-(3-benzyloxyphenyl)-2-hydroxyacetamide 
• 132794-94-6 N-(Tricyclo[3.3.1.13,7 ]dec-1-yl)-2-[bis(4-methoxymethoxyphenyl)methyl]benzylamine 
• 116314-17-1 N-(1-Adamantyl)-3,4-diacetoxy-5-nitrobenzamide 
• 768-94-5 1-Adamantanamine 
• 702-82-9 3-aminoadamantan-1-ol 
• 3717-60-0 2-[N-(1-adamantyl)]aminomethylbenzene 
• 5592-71-2 1-adamantan 

Relevant articles and documents

Preparation method of amantadine

The invention discloses a preparation method of amantadine, which belongs to the technical field of organic chemical synthesis, and is characterized by comprising the following steps: taking a compound adamantane as an initial raw material, generating an intermediate 1-acetamido adamantane in the presence of acetonitrile, a polyion liquid PIL catalyst and sulfuric acid, and then hydrolyzing the intermediate into amantadine in a system of alcohol and alkali. The preparation method is environment-friendly, post-treatment is convenient, the use amount of sulfuric acid and acetonitrile is greatly reduced through the catalyst polyion liquid, and post-treatment is simple. The ionic liquid catalyst can be recycled, so that the cost is greatly saved, and the method is suitable for large-scale industrial production.

Amantadine hydrochloride and preparation method thereof

The invention discloses amantadine hydrochloride and a preparation method thereof, and relates to the technical field of amantadine hydrochloride synthesis. The method aims at solving the problems that the reaction time is too long and the yield of amantadine hydrochloride is not high. The amantadine hydrochloride is prepared from the following components, by weight: 5mmol of nitro compound, 5g ofcatalyst, 15ml of absolute ethyl alcohol, 15ml of concentrated hydrochloric acid, 15ml of hydrazine hydrate and 3ml of sodium hydroxide solution, The preparation method of amantadine hydrochloride comprises the following steps: respectively adding a nitro compound, absolute ethyl alcohol and a catalyst into a 50mL flask; in the production process of the hydrazine hydrate catalytic reduction method, no pollution is caused, the yield is high, the reaction conditions are mild, the yield of the nitro compound is 90%, the conversion rate of the nitro compound subjected to hydrazine hydrate catalytic reduction is 98.5%, the yield of the obtained amantadine hydrochloride is 89.5%, and compared with other processes, the yield is higher, the operation is simple, and the efficiency is high.

Cyclic (Alkyl)(amino)carbene Ligand-Promoted Nitro Deoxygenative Hydroboration with Chromium Catalysis: Scope, Mechanism, and Applications

Transition metal catalysis that utilizes N-heterocyclic carbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for the retention of various reducible functionalities and the compatibility of sensitive groups toward hydroboration, thereby providing a mild, chemoselective, and facile strategy to form anilines, as well as heteroaryl and aliphatic amine derivatives, with broad scope and particularly high turnover numbers (up to 1.8 × 106). Mechanistic studies, based on theoretical calculations, indicate that the CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin; it serves as an H-shuttle to facilitate deoxygenative hydroboration. The preparation of several commercially available pharmaceuticals by means of this strategy highlights its potential application in medicinal chemistry.

Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents

Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.

Synthetic method of amantadine hydrochloride (by machine translation)

Compared, the prior art . the synthesis method: the amantadine hydrochloride has an important clinical value and market value Ritter, and the synthesis process, of the hydrochloric acid adamantanamine, effectively improves the industrial application potential, of the hydrochloric acid adamantane hydrochloride synthesis process as, by adopting a special process and a component, on the one hand for preparation of the medicine, for treating and preventing viral infection, through hydrolysis and purification on the other hand, and effectively solves the problem, of environmental pollution in the synthesis process of the hydrochloric acid adamantanamine by adopting a special process and a component technology; through hydrolysis and purification on an aspect, through hydrolysis and, purification of components . The method mainly, comprises, steps of preparation of an amantadine hydrochloride synthesis process by using a special process and a method. (by machine translation)

Method for continuous production of adamantanamine hydrochloride

The invention aims to provide a method for continuous production of adamantanamine hydrochloride by a high-temperature kneading/spiral propelling reactor. In comparison with a traditional batch reactor, the reaction equipment is small in size and has good reaction stability, helps improve production efficiency by continuous reaction production of amantadine products and more importantly helps avoid the temperature runaway problem of the system, and has good safety. The invention has the prominent characteristics as follows: by using the high-temperature kneading/spiral propelling reactor as the reaction equipment, an aminolysis material can be continuously produced, retention time of the aminolysis material in the equipment can be controlled, side effects are reduced, and the aminolysis material can be removed out of the equipment periodically; in the feeding process, dramatic temperature rise of the system is avoided; and under the condition of high reaction yield, the equipment is small in size, is safe and simple to operate, and has good industrial application value.

Synthetic method of amantadine hydrochloride

The invention discloses a synthetic method of amantadine hydrochloride. The synthetic method comprises the following steps: preparation of 1-acetamido adamantane, preparation of amantadine and preparation of amantadine hydrochloride, wherein the preparation of the 1-acetamido adamantine comprises the steps of dropwise adding acetonitrile into 20 percent of fuming sulfuric acid, adding a nickel-rhodium bimetallic catalyst and adamantane, rising the temperature, slowly and dropwise adding ice salt water for diluting after completing reaction, extracting, washing, drying, and evaporating and removing a solvent, thus obtaining the 1-acetamido adamantine. The synthetic method disclosed by the invention has the beneficial effects that the alumina supported nickel-rhodium bimetallic catalyst is used for catalyzing acetyl ammoniation reaction of the adamantane, nickel and rhodium are in synergistic effect, the catalytic activity is enhanced, reaction is facilitated to proceed, meanwhile, occurrence of side effects is inhibited, and the yield of a target product is increased; a bromine raw material is prevented from being used, corrosion of bromine to equipment and pollution of the bromineto environment can be avoided, the environmental protection property is good, and the synthetic method is mild in condition, simple and feasible in technology and high in product yield.

An Improved Synthesis of Amantadine Hydrochloride

Amantadine hydrochloride 1 is an antiviral drug used in the prevention and treatment of influenza A infections. It has also been used for alleviating early symptoms of Parkinson's disease. Several methods for the preparation of 1 have been reported. These procedures started with adamantane 2 using as many as four reaction steps to produce amantadine hydrochloride with overall yields ranging from 45% to 58%. In this article, we describe a two-step procedure for the synthesis of 1 from 2 via N-(1-adamantyl)acetamide 4 with an improved overall yield of 67%. The procedure was also optimized to reduce the use of toxic solvents and reagents, rendering it more environment-friendly. The procedure can be considered as suitable for large-scale production of amantadine hydrochloride. The structure of amantadine hydrochloride was confirmed by 1H NMR, 13C NMR, IR, and MS.

Process for preparation of amantadine free amine amantadine by use of amantadine hydrochloride

The present invention discloses a process for preparation of amantadine free amine amantadine by use of amantadine hydrochloride, and the process is characterized as follows: in a reaction vessel, water and the amantadine hydrochloride are added in order, the mass ratio of water to amantadine hydrochloride is 1:4, and after even stirring, the pH value is adjusted to 10 with sodium hydroxide or sodium carbonate; and after solid precipitation, the stirring is continued for 0.5h, and a pure free amine amantadine product can be obtained by filtering, washing with water, and drying.