3074-43-9

Usage

Uses

Used in Pharmaceutical Industry:
1-Methyl-4-phenylpiperazine is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique structure allows it to be a key component in the development of new drugs with specific therapeutic properties.
Used in the Preparation of Phenyl-1,5-anhydro-β-D-glucitol Derivatives:
1-Methyl-4-phenylpiperazine is used as a starting material for the preparation of Phenyl-1,5-anhydro-β-D-glucitol derivatives, which are compounds with potential applications in the treatment of diabetes. These derivatives may help in managing blood sugar levels and improving the overall health of individuals with diabetes.

Synthesis Reference(s)

Synthesis, p. 607, 1975 DOI: 10.1055/s-1975-23854

InChI:InChI=1/C11H16N2/c1-12-7-9-13(10-8-12)11-5-3-2-4-6-11/h2-6H,7-10H2,1H3

Upstream product

• 109-01-3 1-methyl-piperazine 
• 142-04-1 aniline hydrochloride 
• 3651-67-0 N-methylmorpholine hydrochloride 
• 92-54-6 4-phenyl-1-piperazine 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 74-88-4 methyl iodide 
• 105-59-9 N-Methyldiethanolamine 
• 98-80-6 phenylboronic acid 
• 124-38-9 carbon dioxide 
• 51420-33-8 4-phenylpiperazine-1-carboxaldehyde 
• 100-68-5 methyl-phenyl-thioether 
• 591-50-4 iodobenzene 
• 67-63-0 isopropyl alcohol 
• 83991-32-6 1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,3-benzotriazole 

Downstream Products

• 54-77-3 1,1-dimethyl-4-phenylpiperazinium iodide 
• 109-01-3 1-methyl-piperazine 
• 27913-99-1 4-(4-methylpiperazin-1-yl) benzaldehyde 
• 1449714-88-8 C₁₁H₁₂N₂O₂ 
• 7560-86-3 1-cyclohexyl-4-methylpiperazine 
• 175887-81-7 trimethyl(1-methyl-4-phenylpiperazine-N⁽¹⁾)aluminium 
• 130307-08-3 1-bromo-4-(4-methyl-1-piperazinyl)benzene 
• 7556-56-1 1-benzoyl-4-methylpiperazine 
• 5430-77-3 4-methyl-piperazine-1-carbodithioic acid 

Relevant academic research and scientific papers

Mechanistic insights into the Pd(BINAP)-catalyzed amination of aryl bromides: Kinetic studies under synthetically relevant conditions

Kinetic studies using reaction calorimetry were carried out under synthetically relevant conditions to study the mechanism of the amination of bromobenzene with primary and secondary amines using Pd2(dba)3/BINAP mixtures as well as p

Dimenthylphosphine P-Oxide as a Synthetic Platform for Bulky and Chiral Ligands with Dimenthylphosphino Donor Groups

Attaching di(1R)-menthylphosphino fragments (menthyl = Men = 1R,2S,5R-2-isopropyl-5-methylcyclohex-1-yl) to molecular scaffolds turns them into homochiral, bulky, electron-rich phosphine ligands with proven and potential applications in coordination chemistry and transition-metal catalysis. Dimenthylphosphine P-oxide (Men2POH; 1) is established as a platform chemical toward dimenthylphosphino-containing targets via transformation to the known ligand precursors dimenthylchlorophosphine (4) and dimenthylphosphine (6). Transformations of 1 to dimenthylphosphinyl chloride (5) and dimenthylphosphinic acid (8) are elaborated. A phospha-Michael type 1,4-addition of 1 to p-benzo-or 1,4-naphthoquinone gives the corresponding o-hydroxyaryl(dimenthyl)phosphine oxides. Deprotonation of 1 with n-BuLi provides a phosphinyl nucleophile, whose reactions with alkyl halides or 1,n-dihaloalkanes provide tertiary alkyl dimenthylphosphine oxides or 1,n-bis(dimenthylphosphino)alkane bis(P-oxides) 10a-c, respectively. As an example, oxide 10b was deoxygenated to the diphosphine Men2P(CH2)3PMen2 (11) and characterized via the square-planar complex [(Men2P(CH2)3PMen2)PdCl2] (12). A selection of P-aryl dimenthylphosphines, including PhP(Men)2 (19) and 2-ClC6H4P(Men)2 (22), as well as the menthyl analogues Men-JohnPhos (21) and Men-SPhos (24), of the respective Buchwald ligands have been prepared. The combination of the secondary phosphine oxide (SPO) 1 with PdCl2 produces halide-bridged [(Men2POH)2Pd2Cl2] (25), mononuclear [(Men2POH)2PdCl2] (26), or the halide-bridged pseudochelate complex [(Men2PO···H···OPMen2)2Pd2Cl2] (27), depending on the reaction stoichiometry and conditions, all of which have been crystallographically characterized. The new ligands 1, 19, 21, 22, and 24 and complexes 25 and 26 have been evaluated in model palladium-catalyzed C-C-and C-N-fragment coupling reactions and found to display specific reactivity profiles due to the presence of the menthyl groups. Ligand 22 in particular catalyzed an asymmetric biaryl-forming coupling to give 2-methoxy-1,1′-binaphthalene with an er of up to 93:7.

Mechanistic study of nucleophilic fluorination for the synthesis of fluorine-18 labeled fluoroform with high molar activity fromN-difluoromethyltriazolium triflate

The synthesis of fluorine-18 labeled fluoroform with high molar activity has grown in importance for the development of fluorine-18 labeled aryl-CF3radiopharmaceuticals that are useful as diagnostic radiotracers for the powerful technique of positron emission tomography (PET). We designed a strategy of synthesizing fluorine-18 labeled fluoroform fromN1-difluoromethyl-N3-methyltriazolium triflate (1)viaSN2 fluorination without stable fluorine isotope scrambling. Fluoroform was generated at rt in 10 min by fluorination of the triazolium precursor with TBAF (6 equiv.). We propose three routes (a), (b), and (c) for this fluorination. Quantum chemical calculations have been carried out to elucidate the mechanism of experimentally observed nucleophilic attack of fluoride at difluoromethyl groupviaroute (a), notN3-methylviaroute (b).1H and19F NMR studies using deuterium source have been performed to examine the competition between SN2 fluorination (route (a)) and the formation of difluorocarbene (route (c)). The observed superiority of SN2 pathway to formation of difluorocarbene in the reaction of the precursor using CsF in (CD3CN/(CD3)3COD (17.8?:?1)) gives the possibility of preparing the fluorine-18 labeled fluoroform in high molar activity.

New Insights into the Reaction Capabilities of Ionic Organic Bases in Cu-Catalyzed Amination

The application of ionic organic bases in the copper-catalyzed amination reaction (Ullmann reaction) has been studied at room temperature, with sub-mol-% catalyst loadings, and with more challenging amines at elevated temperatures. The cation present in the base has been shown to have little effect on the reaction at standard catalyst and ancillary ligand loadings, whereas the choice of anion is crucial for good reactivity. A substrate scope carried out at room temperature with the best performing bases, TBAM and TBPM, showed both bases to be highly effective under these mild reaction conditions. Moreover, under sub-mol % catalyst loadings and room temperature conditions, TBPM gave good to excellent yields for a number of different amines and functionalized aryl iodides (14 examples). However, reactions involving more challenging amines gave little or no yield. By using more forceful conditions (120 °C) moderate to excellent yields of cross-coupled products containing more challenging amines was achievable using TBPM and to a lesser extent with TBAM. As part of this work a study on the stability of the organic bases at 120 °C was undertaken. TBAM is shown to decompose to give nBu3N and mono-butylmalonate at higher temperatures, and this can be correlated to a decrease in performance in the coupling reaction. The phosphonium cations in TBPM did not undergo analogous reactivity but were shown instead to experience some degree of deprotonation at the α-CH2 to generate phosphonium ylides. This however did not lead to a significantly degradation in the activity of the TBPM in the cross-coupling reaction.

1,4-Dioxane-Tuned Catalyst-Free Methylation of Amines by CO2 and NaBH4

A catalyst-free reductive functionalization of CO2 with amines and NaBH4 was developed. The N-methylation of amines was carried out with CO2 as a C1 building block and 1,4-dioxane as the solvent. Notably, the six-electron reduction of CO2 to form the methyl group occurred simultaneously with formation of the C?N bond to give the N-methylated amine.

Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach

A general iron-catalyzed methylation has been developed using methanol as a C1 building block. This borrowing hydrogen approach employs a Kn?lker-type (cyclopentadienone)iron carbonyl complex as catalyst (2 mol %) and exhibits a broad reaction scope. A variety of ketones, indoles, oxindoles, amines, and sulfonamides undergo mono- or dimethylation in excellent isolated yields (>60 examples, 79% average yield).

n-Butyllithium-mediated synthesis of N-aryl tertiary amines by reactions of fluoroarenes with secondary amines at room temperature

A simple and facile method for the synthesis of aromatic tertiary amines by amination of fluoroarenes with secondary amines in the presence of n-butyllithium at room temperature was reported.

Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions

NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.

C–N cross-coupling on supported copper catalysts: The effect of the support, oxidation state, base and solvent

A series of supported copper catalysts at two different loadings (1 and 2?wt%) have been prepared by deposition precipitation on various supports including TiO2, ZnO, Al2O3 and active carbon and submitted or not to reductive treatments to favor the increase in population of Cu(I). The samples have been characterized by textural measurements, electron microscopy and spectroscopic techniques including EPR and XPS, concluding the presence of dispersed copper oxides on the support with small particle size and contrasting prevalence of Cu(II) or Cu(I). The catalytic activity of all these catalysts for the C–N coupling of aniline and bromobenzene has been evaluated. A strong influence of the support, copper oxidation state, solvent, nature of the base was observed, the optimal conditions being the use of ZnO or TiO2 as supports and toluene/dioxane as solvent and EtOK as base. t-C5H11OK as base in either THF or toluene give rise to the formation of t-C5H11 phenyl ether in some extent. The catalyst undergoes deactivation during the reaction, but about 88% of the activity of the fresh sample could be regained by dioxane washings before reuse. XPS indicates that the most likely origin of catalyst deactivation is adsorption on the copper catalyst surface of KBr and inorganic salts formed as byproducts during the reaction.

Palladium-catalyzed amination of aryl sulfides with aliphatic amines

Conditions for the palladium-NHC-catalyzed amination of aryl sulfides with aliphatic as well as aromatic amines were established. The KHMDS-mediated amination of heteroaryl sulfides could proceed without palladium. Based on the distinct difference in reactivity of C-Br and C-S bonds, a sequential amination of bromothioanisole can take place to install two different alkylamino groups onto the aromatic ring in one pot. A palladium-NHC precatalyst shows high efficiency for C-S bond cleavage for the amination of aryl sulfides with aliphatic amines or aromatic amines.