Amide preparation method

It was found that in spite of the large excess of modifying amine (N-isopropyl-, -diethyl, -dipropyl, -diisopropyl, -n-hexyl, -cyclohexyl, -n-octyl), the extent of substitution did not exceed 5-10 molar %. For the case of the N-isopropyl derivative, i.e. [poly(AAm-co-NiPAAm)], the authors connected such results with the temperature-induced conformational transformation of partially hydrophobized copolymer acquiring the contracted conformation, "... which made it difficult for N-isopropylamine to react further with the amide groups [22], Unfortunately, no data on the solution behaviour of these interesting copolymers have been reported to date, although there is a high probability that they would demonstrate certain properties of the protein-like macromolecules. At least, in favour of similar supposition is supported by the results of our studies [23] of somewhat different PAAm partially hydrophobized derivative, whose preparation method is depicted in Scheme 3. 

Reports regarding selenoamides and selenoureas are less than the corresponding thioamides, thioureas, amides and ureas because of instability of compounds including selenium atom and their difficulty in the preparation. Recently, preparation methods to overcome some difficulties have been developed. Their reactions, preparation, application to heterocycles or biological assay systems have been actively investigated. 

The first peptide amides prepared by solid-phase synthesis were obtained by ammonolysis of resin-bound benzyl esters of peptides in solvents containing methanol (Figure 5.16, A). The method was occasionally employed but was not popular because it was inefficient, producing some ester in addition to the amide. A new variant employing gaseous ammonia will likely rekindle this approach (see Section 8.3). During the early developments of solid-phase synthesis, it was known that the... 

The Mitsunobu reaction has also been applied successfully for the preparation of oxazolines from p-hydroxy amides. This method provides an alternative to the Burgess reagent. Some recent examples are listed in Table... 

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. 

Analogous to the use of chiral enoates (see previous section), a, -unsaturated carboxylic amides, prepared from chiral amines, may be utilized in asymmetric 1,4-additions. When Grignard reagents are added to unsaturated amides (21), derived from (-)-ephedrine (20),25 highly optically active fi-sub-stituted alkanoic acids (22 R and R = alkyl or phenyl) are obtained in a variety of cases, after hydrolysis of the initially formed adducts (Scheme 7). This method was used for the synthesis of the antibiotic (-) malyngolide and its stereoisomers.26 Recrystallization of the intermediate (saturated) amide was necess-... 

Reduction of amides is an important preparative method for the synthesis of primary amines. Reducing agents used for this purpose include lithium aluminum hydride, sodium borohydride, triphenyl-phosphine (Staudinger reduction), and thiols. In the present case it is important to consider the compatibility of the reduction system with the carboxylic and methanesulfonic acid functions. Platinum and palladium arc often used for catalytic reduction. 

This reaction represents the best general method for amide preparation. Cold, concentrated aqueous ammonia is used as in the preparation of iso-butyramide (83%),or the reaction may be carried out by passing dry ammonia into a solution of the acyl halide in anhydrous ether as in the formation of cyclopropanecarboxamide (91%). Separation of the amide from ammonium chloride is usually accomplished by extraction of the amide by organic solvents. Aqueous sodium hydroxide is employed to take up the hydrogen chloride when amine hydrochlorides are used in place of the free amines as in the preparation of N-methylisobutyramide (75%). When phosphorus trichloride is added to a mixture of an amine and a carboxylic acid, phosphazo compounds, RN=PNHR, rather than acyl halides, are believed to be intermediates. These compounds have been shown to react with carboxylic acids to give amides. ... 

A reaction which is applicable to the synthesis of imidazoles substituted at C-4 by sulfur substituents is the interaction of a-chloro-a-phenyl thioketones (prepared from the corresponding diazoketones) with ammonia and carboxylic acids. Although the detailed reaction course is yet uncertain, it bears a close resemblance to the reactions of a-chloro ketones with amides. The method has been used to prepare 2-ethyl-4-methyl-5-phenylthioimidazole (145) using ammonia, propanoic acid and 1-chloro-l-phenylthiopropanone (Scheme 82). 

Preparative Methods Bis[(45)-(l-methylethyl)oxazolin-2-yl]m-ethane is prepared by acylation of L-valinol followed by cy-clization (eq 1). - Thus, transamination of dimethyl mal-onate with 2 equiv of L-valinol afforded the corresponding amide in 72% yield. Chlorination with SOCI2 followed by cy-clization with LiOMe in refluxing MeOH afforded bis[(45)-(l-methylethyl)oxazolin-2-yl]methane in 79% yield. 

Preparative Methods crystalline, enantiomerically pure 10-diisopropyl- and 10-dicyclohexylsulfonamidoisobomeol auxiliaries are readily prepared from the appropriate enantiomer of 10-Camphorsulfonyl Chloride by successive amidation and cxtr selective reduction (eq 1). ... 

Solubility insol H2O sol all common organic solvents. Preparative Methods ligand (1) and related C2-symmetric bisox-azolines are readily prepared from chiral p-amino alcohols using standard methods for the synthesis of 2-oxazolines. This is exemplified by the simple three-step procedure shown in eq 1, involving amide formation, conversion of... 

Preparative Methods The enantiopure sulfonamide la is prepared via sulfonylation of (7 ,7 )-l,2-diaminocyclohexane 2 in the presence of an excess of triethylamine (eq 1). Use of excess amine base is essential for obtaining a high yield of the bis-sulfonamide. Synthesis of related bis-sulfonamides is easily accomplished by substituting the desired sulfonyl chloride in the former procedure. Recrystallization of the bis-sulfonamide la from hexane/ethyl acetate and drying over P2O5 allows for isolation of the analytically pure reagent. Methanesulfonyl chloride and (7 ,/ )-l,2-diaminocyclohexane 2 are commercially available from a number of sources. However it should be noted that racemic 1,2-diaminocyclohexane 2 can be resolved via formation of the tartrate salt. Typically, the diamine can be obtained in >99 1 enantiomeric ratio (er) after two crystallizations from water. Determination of the enantiopurity of the diamine is accomplished via formation of the bis-3-toluyl amide and anal-... 

The procedure below describes the preparation of Uthium bis(trimethylsilyl)amide and its subsequent use in the preparation of tris(trimethylsilyl)amine. Tris(trimethyl-silyl)amine may also be prepared from sodium bis(tri-methylsilyl)amide. The method is described in synthesis 4. 

This article describes further progress in the chemistry of 7r-allylnickel compounds. First, preparative methods for 7r-allylnickel halides, alkoxides, amides, and alkyls are described. Next, some chemical properties of these compounds—e.g., a recently observed disproportionation reaction—are discussed. Then, the use of 7r-allylnickel halides as homogeneous catalysts is discussed. Whereas bis (7r-allyl) nickel is a catalyst for butadiene cyclotrimerization, 7r-allylnickel halides combined with Lewis acids, such... 

As an extension of their chiral aldol and alkylation technology, Evans and cowotkers have reported a variety of methods for cleaving and replacing Ae chiral oxazolidinone auxiliary once chain construction has been completed. Included in this methodology was the direct transformation of a chiral imide to an lV-methoxy-/V-methylamide through the use of aluminum amides (prepared in situ). ° This reaction has been shown to be rather general for complex substrates (Scheme 2). ... 

The thia2olidin-5-one-2-thiones (CLXIII) which can be prepared by refluxing 5-imino thiazohdine-2-thiones (CLXII) with acids (method A), can also be obtained directly from carbon disulfide and a-amino carboxylic acid amides (CLXXVIII) (method B). 

Various preparation methods have been described. Wiley (1945, 1947) converted a-amino acids to acetdmido ketones by reaction with acetic anhydride in pyridine and obtained 2,5-dimethyl-4-substituted oxazoles after dehydration of the enol form of the intermediate. Theilig (1953) applied the reaction of a-bromoketones with the appropriate amides. 

The known preparative methods for the synthesis of imidazo[l,5-a]pyrazines prior to 1983 have been extensively reviewed <84CHEC-I(5)607>. This section will review new methods of syntheses published since 1983. The most common syntheses of this ring system involve closure of the imidazole ring, usually by the conversion of 2-aminomethyl pyrazines, by means of acids or anhydrides, into amides, which are then cyclized to the target heterocycle. The newer methods all involve ring closure of the pyrazine ring. 

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