Aminolysis preparation

Acryhc esters may be saponified, converted to other esters (particularly of higher alcohols by acid catalyzed alcohol interchange), or converted to amides by aminolysis. Transesterification is comphcated by the azeotropic behavior of lower acrylates and alcohols but is useful in preparation of higher alkyl acrylates. 

Reaction of a metal lactate (such as silver lactate) with an alkyl haUde is a classic method of preparation of the ester, but it is too expensive to be of commercial relevance. Lactamide [2043-43-8] is another high yielding condensation product from lactic acid. It can be produced by aminolysis of dilactide or lactate ester such as methyl or ethyl lactate. 

If adipamide reacts with hexarnethylenediarnine, then nylon-6,6 can be prepared by aminolysis of the adipamide this could also be viewed as reverse ammonolysis. 

Mocimycin was prepared from dihydromocimycin (3) by oxidation with selenium dioxide (14,56). 4-Amino-4-dehydroxyefrotomycins were obtained by aminolysis of efrotomycin-4-0-phenylchlorophosphate (57). 

Synthesis. One of the more common routes for the synthesis of aminoboranes involves the aminolysis of the appropriate boron hahde. Trisaminoboranes are most convenientiy prepared by adding BCI3 to an excess of amine in an inert solvent at low temperatures (42). For example for tris(dimetby1amino)borane [4375-83-1]. ... 

Modification of the Erlenmeyer reaction has been developed using imines of the carbonyl compounds, obtained with aniline," benzylamine or n-butylamine. Ivanova has also shown that an A-methylketimine is an effective reagent in the Erlenmeyer azlactone synthesis. Quantitative yield of 19 is generated by treatment of 3 equivalents of 2-phenyl-5(4ff)-oxazolone (2) (freshly prepared in benzene) with 1 equivalent of iV-methyl-diphenylmethanimine (18) in benzene. Products resulting from aminolysis (20), alkali-catalyzed hydrolysis (21), and alcoholysis (22) were also described. 

Conversion of Acid Halides into Amides Aminolysis Acid chlorides react rapidly with ammonia and amines to give amides. As with the acid chloride plus alcohol method for preparing esters, this reaction of acid chlorides with amines is the most commonly used laboratory method for preparing amides. Both monosubstituted and disubstituted amines can be used, but not trisubstituted amines (R3N). 

Very recently, even examples of donor-stabilized bissilylene complexes have been introduced. For instance, the two cyclic systems 13 and 14 are prepared by an aminolysis reaction of the respective bis(chloro)silyl complexes. The x-ray structure analysis of 13 has been performed [39]. 

Note Even from the limited number of recent preparative results that follow, it is evident that the interannular activating effect of a 6/7-nitro group on a 2/3-halogeno substituent is appreciable and that the effect of an adjacent nitro group on a normally unreactive 5-, 6-, 7-, or 8-halogeno substituent is so substantial that aminolysis becomes a practical procedure. 

Over the past years, interest in the preparation of chiral amines and amides by enzymatic ammonolysis or aminolysis reactions [4] has greatly increased for academic and industrial sectors. The role that the enzymatic acylation of amines or ammonia plays for the preparation of some pharmaceuticals is noteworthy [5]. 

Although the aminolysis of esters to amides is auseful synthetic operation, usually it presents some disadvantages in terms of drastic reaction conditions, long reaction times or strong alkali metal as catalyst, which are usually not compatible with other functional groups in the molecule [6]. For this reason, enzymatic aminolysis of carboxylic acid derivatives offers a clean and ecological way for the preparation of different kind of amines and amides in a regio-, chemo-, and enantioselective manner. 

Although, the enzymatic reaction of esters with amines or ammonia have been well documented, the corresponding aminolysis with carboxylic acids are rarer, because of the tendency of the reactants to form unreactive salts. For this reason some different strategies have been used to avoid this problem. Normally, this reaction has been used for the preparation of amides of industrial interest, for instance, one of the most important amides used in the polymer industry like oleamide has been produced by enzymatic amidation of oleic acid with ammonia and CALB in different organic solvents [10]. 

The resolution of racemic ethyl 2-chloropropionate with aliphatic and aromatic amines using Candida cylindracea lipase (CCL) [28] was one of the first examples that showed the possibilities of this kind of processes for the resolution of racemic esters or the preparation of chiral amides in benign conditions. Normally, in these enzymatic aminolysis reactions the enzyme is selective toward the (S)-isomer of the ester. Recently, the resolution ofthis ester has been carried out through a dynamic kinetic resolution (DKR) via aminolysis catalyzed by encapsulated CCL in the presence of triphenylphosphonium chloride immobilized on Merrifield resin (Scheme 7.13). This process has allowed the preparation of (S)-amides with high isolated yields and good enantiomeric excesses [29]. 

The strategy described here explains the different possibilities of enzymatic ammonolysis and aminolysis reaction for resolution of esters or preparation of enantiomerically pure amides, which are important synthons in organic chemistry. This methodology has been also applied for the synthesis of pyrrolidinol derivatives that can be prepared via enzymatic ammonolysis of a polyfunctional ester, such as ethyl ( )-4-chloro-3-hydroxybutanoate [30]. In addition, it is possible in the resolution of chiral axe instead of a stereogenic carbon atom. An interesting enzymatic aminolysis of this class of reaction has been recently reported by Aoyagi et al. [31[. The side chain of binaphthyl moiety plays an important role in the enantiodis-crimination of the process (Scheme 7.14). 

Here, we have selected a few representative examples of the enzymatic resolution of esters by aminolysis or ammonolysis reactions. On the other hand, the enzymatic acylation of racemic amines is also of great utility for the preparation of optically pure... 

Preparation of optically active P-aminoesters, P-aminonitriles, and P-aminocarbox-amides are of special relevance for the synthesis of enantiomerically pure P-aminoacids compounds of special relevance in several areas of medicinal chemistry. The resolution of P-aminoesters can be carried out by acylation of the amino groups or by other biocatalytic reactions of the ester groups, such as hydrolysis, transesterification, or aminolysis. The resolution of ethyl ( )-3-aminobutyrate... 

Rigid polyurethane foams were prepared at room temperature using eommercial polyols and polymerie 4,4 -diphenyl methane diisoeyanate, and used to study their reeyeling by aminolysis. The reaction products obtained by treatment with diethylene triamine at 180 C were evaluated as hardeners for epoxy resins. The exothermie heats of euring were determined over the temperature range 60-80 C by differential scanning calorimetry. A reaction order of 2.2-2.4 was obtained. 8 refs. 

Preparation op Amides from Esters by Aminolysis with Dimethyl-... 

This procedure, which is based on the work of Ishii and co-workers, affords a mild and general method for converting a wide variety of esters to primary, secondary, and tertiary amides (Table 1). While the preparation of the tertiary amide, N,N-dimethylcyclohexanecarboxamide, described here is carried out in benzene, aluminum amides derived from ammonia and a variety of primary amines have been prepared by reaction with trimethylaluminum in dichloromethane and utilized for aminolysis in this solvent. Although 1 equivalent of the dimethylaluminum amides from amines was generally sufficient for high conversion within 5-48 hours, best results were obtained when 2 equivalents of the aluminum reagent from ammonia was used. Diethyl-aluminum amides can also effect aminolysis, but with considerably slower rates. 

Among the routes for preparing phosphinous amides, the most frequently used method is the aminolysis of halophosphanes, most usually chlorophosphanes [32-34], because a number of such halophosphanes are easily accessible from commercial sources. These reactions usually provide the target species, i.e., trisubstituted compounds 1 in Scheme 1, in high yield. The HCl liberated from the reaction forms a salt with an organic base (either excess of the starting amine or externally added as, for example TEA or DBU, sometimes in the presence of DM AP) which is insoluble in the reaction solvent, typically diethyl ether... 

The generalized application of the aminolysis of halophosphanes has been the method of choice for the preparation of a wide variety of chiral phosphinous amides by starting from enantioenriched primary amines [36]. The aminolysis reaction occurs efficiently even when the halophosphane is placed in the coordination sphere of a metal, as in the palladium and platinum complexes of the type ds-M(Ph2PCl2)2Cl (M=Pd, Pt) [37,38]. 

The heterocyclic scaffolds are prepared from pyroglutamic acid [154, 155]. 1-aminoalkyl boronic acid pinanediol esters are readily available through a diastereoselective homologation with dichloromethyllithium, providing (5)-a-chloroboronic esters. Aminolysis of the chloride yielded... 

Thus, the family of azolides represents a versatile system of reagents with graduated reactivity, as will be shown in the following section by a comparison of kinetic data. Subsequent chapters will then demonstrate that this reactivity gradation is found as well for alcoholysis to esters, aminolysis to amides and peptides, hydrazinolysis, and a great variety of other azolide reactions. The preparative value of azolides is not limited to these acyl-transfer reactions, however. For example, azolides offer new synthetic routes to aldehydes and ketones via carboxylic acid azolides. In all these reactions it is of special value that the transformation of carboxylic acids to their azolides is achieved very easily in most cases the azolides need not even be isolated (Chapter 2). 

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

In the preparation of the oxocarboxylic acid imidazolides in ref. [49] and [53], as well as in their aminolysis, the stereochemical integrity was maintained. 

Aminolysis of the corresponding halides is the preferred method for the synthesis of dialkylamino derivatives of boron,1 silicon,2 germanium,3 phosphorus,4 arsenic,5 and sulfur.6 (Dialkylamino) chlorosilanes are prepared stepwise by the reaction of silicon tetrachloride with dialkylamines. This method may be utilized equally well for the conversion of alkyl- or aryl-substituted halides [e.g., (CH3) SiCl4. ] or of oxide and sulfide halides (e.g., POCl3 or PSC13) to the corresponding dialkylamino compounds. 

Tris(dimethylamino)borane has been prepared by dimethyl-aminolysis of boron trichloride, with or without solvent,1-5 and by the reaction of boron trifluoride with dimethylamine in the presence of a suitable Grignard reagent.6 The procedure described here is a modification of the reaction of dimethylamine with boron trichloride in pentane as the solvent. 

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