768-90-1Relevant articles and documents
164. The Mild Bromination of Adamantane and (Trimethylsilyl)adamantanes
Grob, Cyril A.,Sawlewicz, Pawel
, p. 1508 - 1510 (1988)
Small amounts of H2O or MeOH catalyze the reaction of Br2 with adamantane and its 1-(trimethylsilyl) and 1,3-bis(trimethylsilyl) derivatives.
H-coupled electron transfer in alkane C-H activations with halogen electrophiles
Fokin, Andrey A.,Shubina, Tatyana E.,Gunchenko, Pavel A.,Isaev, Sergey D.,Yurchenko, Alexander G.,Schreiner, Peter R.
, p. 10718 - 10727 (2002)
The mechanisms for the reactions of isobutane and adamantane with polyhalogen electrophiles (HHal2+, Hal3+, Hal5+, and Hal7+, Hal = Cl, Br, or I) were studied computationally at the MP2 and B3LYP levels of theory with the 6-31G** (C, H, Cl, Br) and 3-21G* (I) basis sets, as well as experimentally for adamantane halogenations in Br2, Br2/HBr, and I+Cl-/CCl4. The transition structures for the activation step display almost linear C···H···Hal interactions and are characterized by significant charge transfer to the electrophile; the hydrocarbon moieties resemble the respective radical cation structures. The regiospecificities for polar halogenations of the 3°C-H bonds of adamantane, the high experimental kinetic isotope effects (kH/kD = 3-4), the rate accelerations in the presence of Lewis and proton (HBr) acids, and the high kinetic orders for halogen (7.5 for Br2) can only be understood in terms of an H-coupled electron-transfer mechanism. The three centered-two electron (3c-2e) electrophilic mechanistic concept based on the attack of the electrophile on a C-H bond does not apply; electrophilic 3c-2e interactions dominate the C-H activations only with nonoxidizing electrophiles such as carbocations. This was shown by a comparative computational analysis of the electrophilic and H-coupled electron-transfer activation mechanisms for the isobutane reaction with an ambident electrophile, the allyl cation, at the above levels of theory.
Nuclear Spin-Spin Coupling via Nonbonded Interactions. 2. γ-Substituent Effects for Vicinal Coupling Constant Involving 13C
Barfield, Michael,Marshall, J. L.,Canada, E. D.
, p. 7 - 12 (1980)
The well-known γ effect on 13C chemical shielding is shown to have a counterpart in vicinal coupling constants 3JCX involving a 13C nuclear spin and a trans-oriented nuclear spin X.Experimental and theoretical results for vicinal 13C1-C2-C3-1H and 13C1-C2-C3-13C coupling constants in a number of C3-substituted aliphatic compounds in the trans arrangement and alicyclic compounds show a substantial decrease relative to the parent compound.By means of modified INDO-FTP molecular orbital procedures, which permit investigation of the importance of nonbonded interactions, it is shown that the γ-substituent effects arise in a complex way from the nonbonded interactions associated with groups bonded to the C3 or γ-carbon atom.A major factor is the positive contribution to 3JCX(180 grad) from the hydrogen atoms on the γ-carbon atom of the parent compound.Methyl groups on C3 make negative contributions; a major factor is the interaction between the hydrogen atoms of the C1 methyl and the hydrogen atoms of the methyl groups on the C3 carbon atom.It is further shown that other substituents also make negative contributions, and that hydrogen atoms on the γ substituents are not essential for the observation of a negative γ effect on vicinal constants.The γ-susbtituent effects on vicinal 13C-X coupling constants appear to be general phenomena of substantial magnitude; their recognition is important for conformational and other coupling-constant studies as they lead to results which appear to be anomalous.
Electrochemical-induced radical allylation via the fragmentation of alkyl 1,4-dihydropyridines
Chen, Xiaoping,Luo, Xiaosheng,Wang, Ping
, (2022/02/02)
Aldehydes are abundant chemical motifs presented in natural products and pharmaceuticals. As a radical precursor, its application is limited. Dihydropyridines (DHPs) can act as masked aldehydes, providing alkyl radicals under the activation of Lewis acid, heat, SET oxidant and light irradiation. Herein, we report the direct activation of 4-alkyl DHPs via single electron transfer at the anode. C–C bond homolysis at the C4-position of DHP generated the corresponding alkyl radical, which was captured subsequently by 2-phenyl and 2-ethoxy carbonyl allyl bromide. The following intramolecular elimination reaction afforded 20 different radical allylation products bearing various alkyl substituents with yields up to 92%.
Method for synthesizing and preparing amantadine dry product
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Paragraph 0057-0063; 0068, (2021/03/13)
The invention discloses a synthesis and preparation method of an amantadine dry product, and relates to the technical field of amantadine preparation. The method mainly comprises adamantane, nitrogendioxide, ozone, hydrazine hydrate, ethanol, diethyl ether, ferric chloride hexahydrate and activated carbon, and comprises the following steps: synthesis of a nitro compound: adding adamantane and dichloromethane into a flask according to a ratio of 1g: 120ml, stirring at a certain temperature, introducing 30 equivalents of nitrogen dioxide under a certain condition, introducing ozone at a low speed, reacting for 30 minutes, adding a sodium bicarbonate solution, washing the organic phase to be neutral, performing drying, and carrying out rotary evaporation to obtain the product 1-nitro adamantane. The dry amantadine product is prepared through a hydrazine hydrate reduction method, corresponding purification is conducted, the whole reaction process is mild, the process steps are simple andconvenient, the requirement for equipment is simple, the conversion rate is very high, and the method has the value of industrial batch production popularization.
Amantadine hydrochloride and preparation method thereof
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Paragraph 0065-0072; 0081-0088, (2021/03/18)
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.
Manganese/bipyridine-catalyzed non-directed C(sp3)–H bromination using NBS and TMSN3
Sneh, Kumar,Torigoe, Takeru,Kuninobu, Yoichiro
supporting information, p. 885 - 890 (2021/05/05)
A Mn(II)/bipyridine-catalyzed bromination reaction of unactivated aliphatic C(sp3)?H bonds has been developed using N-bromosuccinimide (NBS) as the brominating reagent. The reaction proceeded in moderate-to-good yield, even on a gram scale. The introduced bromine atom can be converted into fluorine and allyl groups.
Thiourea-Mediated Halogenation of Alcohols
Mohite, Amar R.,Phatake, Ravindra S.,Dubey, Pooja,Agbaria, Mohamed,Shames, Alexander I.,Lemcoff, N. Gabriel,Reany, Ofer
, p. 12901 - 12911 (2020/11/26)
The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.
Mechanism of Ni-catalyzed oxidations of unactivated C(sp3)-H Bonds
Qiu, Yehao,Hartwig, John F.
supporting information, p. 19239 - 19248 (2020/11/13)
The Ni-catalyzed oxidation of unactivated alkanes, including the oxidation of polyethylenes, by meta-chloroperbenzoic acid (mCPBA) occur with high turnover numbers under mild conditions, but the mechanism of such transformations has been a subject of debate. Putative, high-valent nickel-oxo or nickel-oxyl intermediates have been proposed to cleave the C-H bond, but several studies on such complexes have not provided strong evidence to support such reactivity toward unactivated C(sp3)-H bonds. We report mechanistic investigations of Ni-catalyzed oxidations of unactivated C-H bonds by mCPBA. The lack of an effect of ligands, the formation of carbon-centered radicals with long lifetimes, and the decomposition of mCPBA in the presence of Ni complexes suggest that the reaction occurs through free alkyl radicals. Selectivity on model substrates and deuterium-labeling experiments imply that the m-chlorobenzoyloxy radical derived from mCPBA cleaves C-H bonds in the alkane to form an alkyl radical, which subsequently reacts with mCPBA to afford the alcohol product and regenerate the aroyloxy radical. This free-radical chain mechanism shows that Ni does not cleave the C(sp3)-H bonds as previously proposed; rather, it catalyzes the decomposition of mCPBA to form the aroyloxy radical.
Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents
Sosonyuk, Sergey E.,Peshich, Anita,Tutushkina, Anastasia V.,Khlevin, Dmitry A.,Lozinskaya, Natalia A.,Gracheva, Yulia A.,Glazunova, Valeria A.,Osolodkin, Dmitry I.,Semenova, Marina N.,Semenov, Victor V.,Palyulin, Vladimir A.,Proskurnina, Marina V.,Shtil, Alexander A.,Zefirov, Nikolay S.
supporting information, p. 2792 - 2797 (2019/03/12)
Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents' stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents.
