scholarly journals Direct synthesis of N-methylurethanes from primary amines with dimethyl carbonate

2005 ◽  
Vol 77 (10) ◽  
pp. 1719-1725 ◽  
Author(s):  
Pietro Tundo ◽  
Salima Bressanello ◽  
Alessandro Loris ◽  
Gabriel Sathicq
Keyword(s):  
Aromatic Amines ◽  
Dimethyl Carbonate ◽  
Direct Synthesis ◽  
High Yield ◽  
Primary Amines ◽  
Methyl Derivative ◽  
Acid Base ◽  
One Step ◽  
Soft Acid ◽  
Mechanism Of The Reaction

The mechanism of the reaction between amines with dimethyl carbonate (DMC) has been investigated. Whereas in the absence of bases, they give methylation and carboxymethylation reactions without selectivity (BAl2 and BAc2 mechanisms, respectively), in the presence of bases, the BAc2 mechanism prevails. The carbamate already formed reacts further with DMC via the BAl2 mechanism to give the corresponding N-methyl derivative. Such pronounced double selectivity has been explained in terms of Pearson's Hard-Soft Acid-Base (HSAB) theory.Accordingly, N-methylcarbamates have been prepared from primary aliphatic and aromatic amines, either at reflux temperature of DMC (90 °C) or at 230 °C in autoclave. The reaction can be carried out in one step or through the isolation of the carbamate and the subsequent methylation reaction with DMC. This method is the direct synthesis, in high yield and selectivity, of secondary N-methylamines from the corresponding primary amines.

scholarly journals A Single-Step Synthesis of Azetidine-3-Amines

2020 ◽  
Author(s):  
Brian J Wang ◽  
Matthew Duncton
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Single Step ◽  
Secondary Amines ◽  
High Yield ◽  
Primary Amines ◽  
Privileged Structure ◽  
One Step ◽  
Alternative Procedures ◽  
Approved Drugs

<div> <p>The azetidine group is frequently encountered within contemporary medicinal chemistry where it is viewed as a privileged structure. However, the introduction of an azetidine can be synthetically challenging. Herein, a straight-forward one step synthesis of azetidine-3-amines, starting from a bench stable, commercial material is presented. The reaction tolerates functional groups commonly encountered in biological-, medicinal- and agro-chemistry, and proceeds in moderate-to-high yield with secondary amines, and moderate-to-low yield with primary amines. The methodology compares favorably to recent alternative procedures and can be utilized in “any-stage” functionalization, including late-stage azetidinylation of approved drugs and other compounds with pharmacological activity.</p> </div>

Direct synthesis of dimethyl carbonate from CO2 and methanol over CaO–CeO2 catalysts: the role of acid–base properties and surface oxygen vacancies

2017 ◽  
Vol 41 (20) ◽  
pp. 12231-12240 ◽  
Author(s):  
Bin Liu ◽  
Congming Li ◽  
Guoqiang Zhang ◽  
Lifei Yan ◽  
Zhong Li
Keyword(s):  
Oxygen Vacancies ◽  
Dimethyl Carbonate ◽  
Direct Synthesis ◽  
Surface Oxygen ◽  
Acid Base ◽  
Base Properties

The addition of CaO to the CeO2 catalyst had a significant impact on the acid–base properties and amounts of oxygen vacancies on the surface catalyst.

Nickel peroxide as a selective oxidant in the pyrimidine series. The synthesis of N1-substituted orotic and 2-thioorotic acids

1971 ◽  
Vol 24 (4) ◽  
pp. 785 ◽  
Author(s):  
RN Warrener ◽  
EN Cain
Keyword(s):  
Nickel Complexes ◽  
High Yield ◽  
Carboxyl Group ◽  
Synthetic Route ◽  
Acid Base ◽  
Hydroxymethyl Group ◽  
Oxidative Desulphurization ◽  
Pyrimidine Series ◽  
Soft Acid

A versatile route to the synthesis of iV1-substituted orotic or 2-thioorotic acids is described. The method involves three st>eps: (i) Preparation of 6-hydroxy- methyl-2-thio-1,3-thiazine (24); (ii) conversion of the 1,3-thiazine into the 1- substituted 2-thiouracil by reaction with a primary amine (see Scheme 8); (iii) oxidation of the 6-hydroxymethyl group to a carboxyl group. 3,4-Dihydro-6-hydroxymethyl-4-oxo-2-thio-2H-1,3-thiazine was prepared directly from the reaction of dithiocarbamio acid with ethyl γ-hydroxytetrolate (an improved synthesis of this ester is described). Reaction of the thiazine with primary Bmines was straightforward and produced the related 6-hydroxymethyl-2-thio- uracils in high yield (see Table 2). Similar reactions with O-benzylhydroxylamine formed the 0-benzyl derivative of the Nl-hydroxy-2-thiopyrimidine (40). Nickel peroxide has served as a very selective oxidant in the pyrimidine series. Smoot'h oxidation of the hydroxymethyl group to carboxyl is demonstrated by the conversion of the 6-hyclroxymethyluracils into the corresponding orotic acids. The same products result from the 2-thiouracils on treatment with excess reagent because additional oxidative desulphurization of the 2-thione group occurs. More interestingly, seleotive oxidation of the 6-hydroxymethyl group can be achieved in the presence of the 2-thione group using two equivalents of nickel peroxide, to form a 1-substituted 2-thioorotic acid (Scheme 9). Application of this method to the preparation of I-hydroxyorotic acid mas successful, but only in the presence of excess nickel peroxide reagent. Under other conditions rapid decarboxylation occurred to form either 1-benzyloxyuracil or 1-benzyloxy-2-thiouracil and this has been developed into a useful synthetic route to these products. The role of nickel complexes in this deoarboxylation is discussed in terms of the hard/soft, acid/base theory. P.m.r. data on all compounds are reported.

scholarly journals A Single-Step Synthesis of Azetidine-3-Amines

2020 ◽  
Author(s):  
Brian J Wang ◽  
Matthew Duncton
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Single Step ◽  
Secondary Amines ◽  
High Yield ◽  
Primary Amines ◽  
Privileged Structure ◽  
One Step ◽  
Alternative Procedures ◽  
Approved Drugs

<div> <p>The azetidine group is frequently encountered within contemporary medicinal chemistry where it is viewed as a privileged structure. However, the introduction of an azetidine can be synthetically challenging. Herein, a straight-forward one step synthesis of azetidine-3-amines, starting from a bench stable, commercial material is presented. The reaction tolerates functional groups commonly encountered in biological-, medicinal- and agro-chemistry, and proceeds in moderate-to-high yield with secondary amines, and moderate-to-low yield with primary amines. The methodology compares favorably to recent alternative procedures and can be utilized in “any-stage” functionalization, including late-stage azetidinylation of approved drugs and other compounds with pharmacological activity.</p> </div>

Synthesis of carbonate esters by carboxymethylation using NaAlO2 as a highly active heterogeneous catalyst

2018 ◽  
Author(s):  
Sreerangappa Ramesh ◽  
Kiran Indukuri ◽  
Olivier Riant ◽  
Damien Debecker
Keyword(s):  
Heterogeneous Catalyst ◽  
Dimethyl Carbonate ◽  
Sodium Aluminate ◽  
High Yield ◽  
Solid Catalyst ◽  
Highly Active ◽  
Aromatic Alcohols ◽  
Green Conditions ◽  
Mixed Carbonate

<p>Sodium aluminate is presented as a highly active heterogeneous catalyst able to convert a range of alcohols into the corresponding mixed carbonate esters, in high yield and under green conditions. The reaction is carried out using dimethyl carbonate both as a reactant and solvent, at 90°C. Allylic, aliphatic and aromatic alcohols are converted in good yields. The solid catalyst is shown to be truly heterogeneous, resistant to leaching, and recyclable. </p>

A Simple Synthesis of the Anticancer Drug Altretamine

2020 ◽  
Vol 17 (8) ◽  
pp. 628-630
Author(s):  
Vu Binh Duong ◽  
Pham Van Hien ◽  
Tran Thai Ngoc ◽  
Phan Dinh Chau ◽  
Tran Khac Vu
Keyword(s):  
Aqueous Solution ◽  
Anticancer Drug ◽  
Potassium Hydroxide ◽  
Large Scale ◽  
Synthesis Method ◽  
Practical Method ◽  
Cyanuric Chloride ◽  
Simple Synthesis ◽  
High Yield ◽  
One Step

A simple and practical method for the synthesis on a large scale of altretamine (1), a wellknown antitumor drug, has been successfully developed. The synthesis method involves the conversion of cyanuric chloride (2) into altretamine (1) by dimethylamination of 2 with an aqueous solution of 40% dimethylamine and potassium hydroxide in 1, -dioxan 4in one step to give altretamine (1) in high yield.

α-Ketophosphonates in the Synthesis of α-iminophosphonates

2020 ◽  
Vol 7 (2) ◽  
pp. 226-238
Author(s):  
Petro P. Ony`sko ◽  
Tetyana I. Chudakova ◽  
Vladimir V. Pirozhenko ◽  
Alexandr B. Rozhenko
Keyword(s):  
Bond Cleavage ◽  
Direct Synthesis ◽  
Equilibrium Mixture ◽  
Primary Amines ◽  
Alkyl Amines ◽  
Protic Solvents ◽  
Metallic Salts ◽  
Direct Preparation ◽  
Stage Synthesis ◽  
Aprotic Dipolar Solvent

The potentialities of condensation of α-ketophosphonates with primary amines for direct synthesis of α-iminophosphonates have been revealed. Diesters of α-ketophosphonic acids react with the primary amines by two competitive pathways: with a formation of α-iminophosphonates or a C-P bond cleavage resulting in a hydrogen phosphonate and an acylated amine. In many cases, the latter undesirable pathway is dominant, especially for more nucleophilic alkyl amines. Using metallic salts of α-ketophosphonates avoids the C-P bond cleavage, allowing direct preparation of α-phosphorylated imines by the reaction with primary amines. This strategy provides an atom economy single-stage synthesis of iminophosphonates – precursors of bio relevant phosphorus analogs of α-amino acids. Methyl sodium iminophosphonates, bearing aryl or heteryl substituents at the imino carbon atom exist in solutions at room temperature as an equilibrium mixture of Z- and E-isomers. A configuration of the C=N bond can be controlled by the solvent: changing the aprotic dipolar solvent DMSO-d6 by water or alcohols leads to the change from a predominant Z-isomer to almost an exclusive E-form. In contrast, diesters of the respective iminophosphonates exist in non-protic solvents predominantly in Econfiguration. The solvent effect on E-Z stereochemistry is demonstrated by DFT calculations.

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