Esters, ammonolysis hydrolysis

In the first steps, ester condensation to diketo acid, preparadon of oxime and cyclization are completed under standard conditions. Ester ammonolysis is followed by Hofmann rearrangement of amide to heterocyclic amine. Sulfonation of amine under Schotten-Baumann conditions, in a water-organic solvent mixmre, is based on an interesting trick hydroxide is added at a controlled rate to scavenge the hydrochloric acid formed in sulfonation and to maintain the neutral pH of the aqueous solution of heterocyclic amine as a stronger nucleophile than water, avoiding the hydrolysis of sulfonyl chloride ... 

It is, chemically, a point of weakness, being susceptible to hydrolysis, ammonolysis and ester interchange, the first two reactions leading to chain scission. In some cases the reactivity is influenced by the nature of the adjacent groupings. 

Influence of the Monovalent Ions. The addition of ammonium salts retard the course of the deesterification by changing the reaction rate of hydrolysis and ammonolysis. By increasing the concentration of the ions the conversion of the ester groups is reduced from 83.3 % for 0,01 M to 62.8 % for 0.2 M (without added salt this value is 84.05 %), and the ratio hydrolysis ammonolysis is changed correspondingly from 53.8 76.2 to 37.3 62.7 (without added salt this ratio is 57.6 42.4). 

Effect of somme soults on the hydrolysis and ammonolysis of ester groups express Rh nnd Ra... 

By the action of concentrate aqueous ammonia solution upon esters. This process is spokm of as ammonolysis of the ester, by analogy with hydrolysis applied to a similar reaction with water. If the amide is soluble in water, e.g., acetamide, it may be isolated by distillation, for example ... 

Ammonolysis. Reactions involving ammonia. Ammonolysis of esters, acyl chlorides, and anhydrides give amides aniline is produced by ammonolysis of chlorobenzene. The reaction is analogous to hydrolysis, with ammonia substituted for water. 

DinitrobenzenesuIfenic esters were proposed as protecting groups for carboxyl groups.The solvolysis of only a small variety of esters was studied with a high-pressure mercury lamp, and the yields were 88-98% (see Scheme 26). It should be noted, however, that the group is particularly sensitive to hydrolysis and ammonolysis. 

Hydrolysis of carboxylic esters 0-17 Transetherification 0-18 Payne rearrangement 0-23 Transesterification 0-55 Ammonolysis of carboxylic esters 0-68 Cleavage of ethers with concentrated acids... 

Hydrolysis of lactams 0-43 Amination of halo acids 0-55 Ammonolysis of p-lactones 0-94 Alkylation of N-acetylaminomalonic esters (Sorensen)... 

Saponification is the base-mediated hydrolysis of an ester, yielding its component carboxylate salt and alcohol. Ammonolysis of esters gives amides. Esters react with Grignard reagents to give tertiary alcohols. With lithium aluminum hydride, on the other hand, they are reduced to primary alcohols. 

Esterification Using Diazomethane 966 Conversion of an Acid Chloride to an Anhydride 1001 Conversion of an Acid Chloride to an Ester 1001 Conversion of an Acid Chloride to an Amide 1002 Conversion of an Acid Anhydride to an Ester 1002 Conversion of an Acid Anhydride to an Amide 1003 Conversion of an Ester to an Amide (Ammonolysis of an Ester) 1003 Transesterification 1008 Saponification of an Ester 1010 Basic Hydrolysis of an Amide 1012 Acidic Hydrolysis of an Amide 1012... 

Sulphamoyl chloride when reacted with hydroperoxides in the presence of pyridine below — 30 °C leads to the formation of the novel alkyl sulphamoyl peroxides H2NS0200CH2R (R = CH2CH3, CH2CH2CH3) 303 (equation 98)305. Hydrolysis or ammonolysis of these compounds leads to formation of sulphamic acid or sulphamide respectively. 2-Nitrophenylsulphamoyl chloride (304), prepared from the corresponding sulphamic acid by reaction with PC15, has been used to prepare iV-(2-nitrophenyl)-iV -substituted sulphamides (305) and aryl esters (306) (equation 99)306. 

The synthesis of DPP-IV inhibitor Saxagliptin 5 also required (55)-5-amino-carbonyl-4,5-dihydro-lH-pyrrole-l-carboxylic acid, l-(l,l-dimethylethyl)ester 10 (Figure 16.3C). Direct chemical ammonolyses were hindered by the requirement for aggressive reaction conditions, which resulted in unacceptable levels of amide race-mization and side-product formation, while milder two-step hydrolysis-condensation protocols using coupling agents such as 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) [41] were compromised by reduced overall yields. To address this issue, a biocatalytic procedure was developed based on the Candida antartica lipase B (CALB)-mediated ammonolysis of (55)-4,5-dihydro-lH-pyrrole-l,5-dicarboxylic acid, l-(l,l-dimethylethyl)-5-ethyl ester 9 with ammonium carbamate to furnish 10 without racemization and with low levels of side-product formation. 

The effects of changes in structure, temperature, and reaction medium on the kinetics of alkaline hydrolysis of aryl esters of phosphinothioic acids (182 R = R = Me or Ph R = Me, R = Ph X = H, Br, Me, or NO2) have been investigated. The effect of the nature of the leaving group on the kinetics of alkaline hydrolysis of aryl diphenylphosphinates has also been reported on. Indirect evidence has been advanced for the participation of the azaphospholi-dines (183) in the solvolysis of A/-[amino(methyl)phosphinyl]-L-phenylalanine derivatives, and it includes the transfer of the P-amino group to the phenyl-alanyl carbonyl. The products from the hydrolysis or ammonolysis of fosfomycin have the threo structure and have been shown to possess no antibiotic activity. ... 

The simple batch reactor for homogeneous reactions is the most common type. From this kind of reactor, many kinetic data have been obtained. AU the reactants are charged in at the beginning of the reaction, with no mass transfer occurring until the reaction is complete. Examples of batch reactions are the ammonolysis of nitrochlorobenzenes, hydrolysis of esters, and polymerization of butadiene and styrene in aqueous suspension. These will be treated in more detail in later chapters. 

The reaction of the methyl ester of the racemic epoxide 101 with acetone and aluminum chloride gave a 4,S-0-isopropylidene derivative 108. Michael addition of ammonia to the conjugated double bond of 108 with concomitant ammonolysis of the ester group afforded a mixture of 3-amino-2,3,6-trideoxy-4,5-0-isopro-pylidene-OL-arabino- and -r/Z o-hexonamides (109). For the purpose of isolation the mixture was N-acetylated. Acidic hydrolysis of the amide groupings gave a mixture of y- and 8-aminolactone hydrochlorides (110 and 111). Careful N-acetylation and reduction of the lactone carbonyl groups in 112 and 113 afforded N-acetyl-DL-acosamine (115) in 36% yield. The stereoisomeric potential partner of 115, N-acetyl-DL-ristosamine (116), was not isolated in this procedure. 

The anchoring ester bond, that should resist the various operations of the chain-building process, is cleaved at the completion of the procedure by alkaline hydrolysis or better by acidolysis or, when a peptide amide is desired, by ammonolysis. 

---