Barbiturate ions, reactions

Reaction of chloroacetic acid with cyanide ion yields cyanoacetic acid [372-09-8] C2H2NO2, (8) which is used in the formation of coumarin, malonic acid and esters, and barbiturates. Reaction of chloroacetic acid with hydroxide results in the formation of glycoUc acid [79-14-1]. 

Cyanide compounds are classified as either simple or complex. It is usually necessary to decompose complex cyanides by an acid reflux. The cyanide is then distilled into sodium hydroxide to remove compounds that would interfere in analysis. Extreme care should be taken during the distillation as toxic hydrogen cyanide is generated. The cyanide in the alkaline distillate can then be measured potentiometricaHy with an ion-selective electrode. Alternatively, the cyanide can be determined colorimetricaHy. It is converted to cyanogen chloride by reaction with chloramine-T at pH <8. The CNCl then reacts with a pyridine barbituric acid reagent to form a red-blue dye. 

The mechanism of reaction between barbiturate and 1,3-dimethylbarbiturate ions with o-nitro-, j -nitro-, and 2,4-dinitrobenzaldehyde has been explored rate dependence on solvent viscosity is indicative of involvement of a diffusion-controlled proton transfer in the rate-determining step at pH 2-4. Unexpected values of Brpnsted a for the acid-catalysed process have been explained. 

The reaction of barbiturate and 1,3 -dimethylbarbiturate ions with 2- and 4-nitrobenzaldehyde and 2,4-dinitrobenzaldehyde represented generally in Scheme 5 involves a diffusion-controlled (viscosity effects on rates) proton transfer from hydronium ion to an addition intermediate T in the slow step.14 The addition of water and ring-opening reactions of the protonated benzoxazines (14) involves the cyclic intermediate (15). At low buffer concentrations buffer-catalysed collapse of the intermediate is rate limiting but, at high buffer concentrations, the addition of water is the rate-limiting step.15 The anionic tetrahedral intermediate (16) is involved in the hydrolysis of the 2, 2, 2,-trifluoroethyl monoester of 1,8-naphthalic acid (17).16... 

Baeger-Villiger reaction, 311 Barbiturates, 358 Base peak in ms. 248 Bases, soft and hard. 121 Basicity and structure. 43 Basic Red. 428 Beckmann rearrangement. 406 Benzene, resonance structure. 192 structure, 189 Benzenonium ion, 205 Benzhydrol, 269 Benzidine rearrangement. 422 Benzyne. 217 Bicydic compounds. 162 Birch reduction, 200 Bischler-Napieralski reaction, 460 Boat and chair forms. 168 Boiling point, influences on, 212 Bond dissociation, 37 Bond order, 17 Bond stretching. 233 Bonding orbitals, 14 Bredt s rule. 168 Bromonium ion. 100 BrOnsted. 42... 

Several authors pointed out that this relatively simple kinetic model is complicated by some reversible processes. Eriksson presented kinetic evidence for the reversible reaction between the undissociated form of barbiturates and its tetrahedral hydroxide ion complex.339-341 The existence of mono-, di-, and trianionic tetrahedral addition intermediates formed from the monoanionic form of barbituric acid in alkaline medium has been postulated by Khan and Khan.336 Garrett et al. demonstrated, a reversible reaction between the product of hydrolysis 120 and the parent barbiturate 119 in the case of barbital.329 This finding was confirmed342 and also demonstrated for other barbiturates.308,315,330 Reversible reactions have been shown to exist in the hydrolysis of tetrasubstituted barbiturates.314,343 Leslie reported a biexponential degradation rate of 1,3-dimethylphenobarbital in 0.02-0.32 M KOH, but at lower and higher OH- concentrations it approached first-order kinetics.315... 

In photometric titration cyanide ions are transformed into cyanogen chloride in the course of the reaction with chloroamine to form a red-violet compound in the presence of pyridine and barbituric acid at pH 4-5. Absorbance is measured at a wavelength of 580 nm. The method is suitable for the determination of cyanides at concentrations > 0.002 mg 1 [14,19, 63, 64]. 

A test first described by Parri in 1924 in which the barbiturate gives a colored complex with cobalt(II) has been adapted by the pharmacopoeia. The test parameters of the determination have been modified several times through the years, but the presence of a number of elements constitutes the essence of the procedure a ion, normally cobalt(II) or copper(II) an organic solvent, preferably one with a Lewis base character and an alkaline reaction and the absence of water in the test solution. Furthermore ammonia, or an organic amine, is sometimes added. 

This reaction involves an intermediary carbonium ion whose formation is accompanied by an energy gain due to an increase in resonance. Later, the carbonium ion undergoes an attack from a nucleophilic species, with a proton loss. Xanthydrol permits us to obtain characteristic precipitates with bromisoval and sulfalinamide. The xanthydrol reaction may be considered to be relatively selective of amides. With barbiturics, which may be considered diamides, the reaction may occur twice. 

The synthesis of barbiturates is relatively simple and relies on reactions that are now familiar enolate alkylations and nucleophilic acyl substitutions. Starting with diethyl malonate, or malonic ester, alkylation of the corresponding enolate ion with simple alkyl halides provides a wealth of different disubstituted malonic esters. Reaction with urea, (H2N)2C=0, then gives the product barbiturates by a twofold nucleophilic acyl substitution reaction of the ester groups with the -NH2 groups of urea (Figure 22.7). Amobarbi-tal (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal) are typical examples. 

A new tag strategy, termed syndiesis based on affinity separation (SAS) , was developed for high throiq)ut synthesis of organic conq)oimds. In this method, the desired tagged conq)ound was separated from the reaction mixture by solid-phase extraction using specific molecular recognition. The interaction between a crown ether (32-crown-lO) and ammonium ion and the interaction between a barbituric acid derivative and its artificial receptor were used for SAS. 

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