Amides, synthetic reactions

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

Although Lehn and his coworkers prepared a large number of cryptands and derived complexes over the years, the synthetic approach to these compounds remained essentially similar for most of them. Details are presented for a number of such compounds in ref. 26. The essential features of these syntheses were use of amide-forming reactions in the absence of templating ions with reliance on a high dilution step to form the second ring. An alternative approach for the synthesis of cryptands was developed by Dye and his coworkers. Their approach involved the use of a flow synthesis to replace the high dilution step. 

The specificity of enzyme reactions can be altered by varying the solvent system. For example, the addition of water-miscible organic co-solvents may improve the selectivity of hydrolase enzymes. Medium engineering is also important for synthetic reactions performed in pure organic solvents. In such cases, the selectivity of the reaction may depend on the organic solvent used. In non-aqueous solvents, hydrolytic enzymes catalyse the reverse reaction, ie the synthesis of esters and amides. The problem here is the low activity (catalytic power) of many hydrolases in organic solvents, and the unpredictable effects of the amount of water and type of solvent on the rate and selectivity. 

This idea is perhaps easiest to illustrate for the oxidation of an amide (Scheme 1). Amide oxidation reactions are of tremendous synthetic interest because they can provide an oxidative alternative to the synthesis of reactive N-acyliminium ion intermediates (3). Such a route would complement well the existing reductive and condensation-based approaches [1-3]. However, because amides... 

Lithium amide is used in synthesis of histamine and analgesic drugs. The compound also is used in many organic synthetic reactions including alkylation of ketones and nitriles, Claisen condensation, and in synthesis of antioxidants and acetylenic compounds. 

Sodium amide is a dehydrating agent. It is used in preparing sodium cyanide and hydrazine, and in many organic synthetic reactions such as Claisen condensations, alkylations of ketones and nitriles, and in ammonoly-sis reactions. 

Common synthetic routes to beryllium amides, which were summarized in Ref. 1, involve the direct or indirect amination of beryllium hydride, beryllium chloride, a beryllium alkyl or amide precursor. Beryllium amides with bulky substituents are generally synthesized via the trans-metallation of beryllium dichloride with the lithium amides. The reaction of beryllium dichloride with secondary amines in the presence of an alkyllithium represents a less common synthetic route to beryllium amides. The formation ofbery Ilium amides via the reaction of an alkyl beryllium as well as beryllium hydride species with amines is also known. ... 

The position of the equilibrium in the overall reaction. An example is provided by the hydrolases that catalyze cleavage of amide, ester, and phosphodiester linkages using water as the entering nucleophile. Because enzymes usually act in an environment of high water content, the equilibrium almost always favors hydrolysis rather than the reverse reactions of synthesis. However, in a nonaqueous solvent the same enzyme will catalyze synthetic reactions. 

However, a useful synthetic reaction can be achieved in the following way. First, the ester anion is formed in the absence of water without causing a Claisen condensation or other carbonyl addition. This can be done with ethyl ethanoate by treating it with lithium bis(trimethylsily])amide in oxacyclopentane solution at -80° ... 

Recent developments in the synthesis, structures, and properties of ionic/covalent ternary nitrides are reviewed. A description, including synthetic conditions, is given of preparative methods reported in the literature. Solid state synthetic reactions from binary nitrides as well as novel synthetic approaches such as amide synthesis and ammonolysis of ternary oxides are described. Examples of common structure types as well as electronic and magnetic properties are discussed. 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

Review. New synthetic reactions based on the onium salts of aza-arenes have been reviewed (75 references). The reactions discussed involve activation of carboxylic acids or alcohols with 2-haIopyridinium, benzoxazolium, benzothiazolium, and pyridinium salts to afford 2-acyloxy or 2-alkoxy intermediates, which can be transformed into esters, amides, thiol esters, (macrocyclic) lactones, acid fluorides, olefins, allenes, carbodiimides, isocyanates, isothiocyanates, and nitriles under appropriate conditions. 

A synthetic route to ( )-0,f>-dimethyltubocurarine iodide (CXXV), via the racemate of 0,0-dimethylbebeerine (CXXIII), was announced in 1959 by Tolkachev and his collaborators (94). It started by the condensation of 3-methoxy-4-hydroxyphenethylamine with 4-benzyloxy-phenylacetic acid to give the amide CXXVI. Reaction of the potassium salt of the latter with the methyl ester of 3-bromo-4-methoxyphenyl-acetic acid in the presence of copper powder gave compound CXXVII. This on condensation with 3-methoxy-4-hydroxy-5-bromophenethyl-amine afforded compound CXXVIII, which was methylated to CXXIX. The latter compound was cyclized with phosphorous oxychloride to the dihydroisoquinoline derivative CXXX. Debenzylation of CXXX followed by intramolecular Ullmann condensation yielded compound CXXXI. The latter was converted to racemic dimethylbebeerine (CXXIII) by reduction with zinc dust in acetic acid followed by methyla-tion. Finally, treatment of ( + )-CXXIII with methyl iodide furnished the dimethyl ether of ( + )-tubocurarine iodide, identified by comparison of its UV-spectrum with that of the dimethyl ether of natural tubo-curarine iodide and by melting-point determination of a mixture of the two specimens. 

The amido ligand is isoelectronic with the alkyl and alkoxo groups and has the possibility to exhibit N-M ir-interactions in order to stabilize the systems they form. Different synthetic reactions are used to prepare mono-Cp titanium derivatives containing amido ligands. These compounds are normally synthesized by (i) the action of the corresponding amide salt on Cp TiCl3, (ii) displacement of amine from a homoleptic amido titanium compound by a Cp reagent, (iii) dehalosilylation reactions, and (iv) elimination of alkane by reaction of an alkyltitanium compound with amine. 

The possibility to tailor-make MIPs towards a desired selectivity in combination with the high stability of the materials under a broad range of conditions has rendered MIPs attractive for the development of synthetic enzymes [243, 244]. A popular strategy has been to imprint a transition state analog to obtain a polymer that reduces the activation energy of the reaction. Catalytically active groups are often included in the polymer network. This approach has been applied towards ester and amide hydrolysis reactions [245, 246]. Examples of other reactions where MIPs have been utilized as enzyme mimics are isomerization [247], transamination [248], Diels-Alder reaction [249], 3-elimination [250] and regioselective cycloaddition [251]. 

N-Halomethyl carboxamides. Chloromethylation of amides is accomplished in one step under anhydrous conditions by heating with (HCHO) and MejSiCl in THF. These products are valuable synthetic intermediates for example, they are converted to (V-acyloxymethyl amides by reaction with sodium carboxylates. A convenient preparation of A-bromomethyl imides is by warming the parent imides with (HCHO) , HBr, and HOAc at 70-80°C for several hours. ... 

The heptanuclear iron carbonyl cluster [Fe3(CO)u(/u-H)]2-Fe(DMF)4 (178) acted as an efficient catalyst in the reduction of carboxamides by l,2-bis(dimethylsilyl)benzene in toluene to the corresponding amines in high yields. Several tertiary and secondary amides including a sterically crowded amide were also reduced smoothly A review of the development of optically active cobalt complex catalysts for enan-tioselective synthetic reactions has addressed the applications of ketoiminatocobalt(II) complexes such as (5)-MPAC (179) and (5)-AMAC (180), transition-state models for borohydride reduction, halogen-free reduction by cobalt-carbene complexes. 

Hydroxyl groups also participate as nucleophiles in a variety of other acid-catalyzed cyclizations of synthetic utility. One example is the Ritter reaction, which normally produces amides upon reaction of olefins or alcohols with nitriles. Cyclization occurs with 1,3-diols, hydroxy alkenes, or epoxides. Examples of each are given in Eqs. (74)-(76). 

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