Hydrolysis derivatives

Alkylation of phthalimide. The Gabriel synthesis (Section 22.8) The potassium salt of phthalimide reacts with alkyl halides to give A/-alkylphthalimide derivatives. Hydrolysis or hydrazinolysis of this derivative yields a primary alkylamine. 

Ethyl 3-oxoalkanoates when not commercially available can be prepared by the acylation of tert-butyl ethyl malonate with an appropriate acid chloride by way of the magnesium enolate derivative. Hydrolysis and decarboxylation in acid solution yields the desired 3-oxo esters [59]. 3-Keto esters can also be prepared in excellent yields either from 2-alkanone by condensation with ethyl chloroformate by means of lithium diisopropylamide (LDA) [60] or from ethyl hydrogen malonate and alkanoyl chloride usingbutyllithium [61]. Alternatively P-keto esters have also been prepared by the alcoholysis of 5-acylated Mel-drum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione). The latter are prepared in almost quantitative yield by the condensation of Meldrum s acid either with an appropriate fatty acid in the presence of DCCI and DMAP [62] or with an acid chloride in the presence of pyridine [62] (Scheme 7). 

Some cyclic AT-Mannich bases have also been reported, for example, the imidazolidin-4-ones (11.116) that were investigated as potential prodrugs of peptides (11.117) [141], The imidazolidin-4-ones, prepared by allowing the peptide to react with acetone under dehydrating conditions, are bases with pKa values of 3 - 4. For most of the derivatives, hydrolysis is spontaneous the protonated form (i.e., at pH < 2) reacts ca. 10 - 30 times slower than does the neutral form (pH > 6). Very large differences in reactivity were noted,... 

Hydrolysis of condensed 1,2,3-triazines results in cleavage of the heterocycUc ring and is in many respects an unexceptional and fully predictable type of reaction. The relative ease with which ring fission takes place, and the products formed, depend almost entirely on the nature of the substituents at the 3- and 4-positions and on the reaction conditions employed. Moreover, hydrolysis under basic conditions normally leads to fission of the N,—C4 bond whereas under acidic conditions most 1,2,3-benzotriazine derivatives behave as masked diazonium compounds, and hydrolysis proceeds with fission of the Nj— N3 bond and transient formation of a diazonium compound, from which the observed products are ultimately derived. Hydrolysis of certain derivatives probably also involves covalent hydration as the key step. 

Kinetic resolutions by means of the selective formation or hydrolysis of an ester group in enzyme-catalyzed reactions proved to be a successful strategy in the enantioseparation of 1,3-oxazine derivatives. Hydrolysis of the racemic laurate ester 275 in the presence of lipase QL resulted in formation of the enantiomerically pure alcohol derivative 276 besides the (23, 3R)-enantiomer of the unreacted ester 275 (Equation 25) <1996TA1241 >. The porcine pancreatic lipase-catalyzed acylation of 3-(tu-hydroxyalkyl)-4-substituted-3,4-dihydro-2/7-l,3-oxazines with vinyl acetate in tetrahydrofuran (THF) took place in an enantioselective fashion, despite the considerable distance of the acylated hydroxy group and the asymmetric center of the molecule <2001PAC167, 2003IJB1958>. 

Adducts have also been obtained by the reaction of methylmagnesium iodide with 3,5-dicyanopyridine and related substrates.138 Their formation involves a shift in the IR spectrum from 1563-1575 cm 1 to 1612-1645 cm"1, for C=C bonds, and from 2230-2248 cm 1 to 2125-2225 cm for the C=N bond, the final values being near the absorbance of the dihydro derivatives. Hydrolysis yields the expected dihydro derivatives. In connection with the nature of metal-nitrogen bond, it is of interest that in the sodium adduct 94 the IR spectrum indicates appreciable electron delocalization relative to the corresponding dihydro derivative (shift toward lower frequency), which suggests a substantial ionic character of the bond due to the low electronegativity of sodium. 

The reduction of a number of pyridazines was treated in Part I1 later electrochemical investigations296 confirmed that the initial reduction consumed two electrons and the primary product was suggested to be 1,2-dihydropyridazine, which tautomerized to the 1,4-dihydro derivative hydrolysis with ring opening followed. 

A general convenient alkyl methyl ketone synthesis, which utilises the /7-keto ester system as an intermediate, involves the acylation of a malonate ester by way of the ethoxymagnesium derivative. Hydrolysis and decarboxylation to the ketone is accomplished by heating in acid solution the synthesis of cyclohexyl methyl ketone is the illustrative example (Expt 5.96). 

Acetamido-5-deoxy-D-ribose has been synthesized from benzyl 2,3-O-isopropylidene-)3-0-ribofuranoside through the sequence of the 5-0-p-tolylsulfonyl, 5-azido, and 5-acetamido derivatives. Hydrolysis of benzyl 5-acetamido-5-deoxy-2,3-0-isopropylidene-j8-D-... 

L(+)-alanine, V-acetyl-, crystals, mp 116C. L(+)-alanine, V-benzoyl-, crystals, mp 152-154C. Derivation Hydrolysis of protein (silk, gelatin, zein), organic synthesis. 

Derivation Hydrolysis of the product obtained when urea is treated with fuming sulfuric acid. 

Derivation Hydrolysis of asparagine, reaction of ammonia with diethyl fumarate. 

Derivation Hydrolysis of bismuth nitrate, filtering and drying. 

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