Barbituric acids spectra

Early investigators adduced various kinds of chemical evidence in support of a monohydroxy-dioxo structure for barbituric acid (112) (a) reaction with diazomethane afforded a mono-O-methyl deriva- iye,i59,i6o barbituric acid and its 5-alkyl derivatives are much stronger acids than the 5,5-dialkyl derivatives, and (c) the 5-bromo and 5,5-dibromo derivatives have different chemical properties. - The early physical evidence also appeared to substantiate the monoenol structure, this formulation having been suggested for barbituric acid in 1926 on the basis of its ultraviolet spectrum and again in 1934, In the 1940 s, ultraviolet spectroscopic studies led to the suggestion of other monohydroxy and dihydroxy structures for barbituric acid, whereas its monoanion was assigned structure 113 (a clear distinction between ionization and tautomerism was not made in these papers). 

The approach to the interpretation of the infra-red spectrum of an unknown drug is illustrated by reference to the barbiturates. These are derivatives of malonylurea (barbituric acid) and all of them have two substituents at position 5. In addition, some of them are also substituted at position 1 and in others the oxygen atom attached to position 2 is replaced by sulphur to form thiobarbiturates. 

We still work with an 8 year old LKB-9000 and without a computer. Data acquisition and presentation are done by a multichannel analyzer. The mass spectra are printed out as modulo-14 tables. This can be done on-line (without normalization) or offline (with normalization and listing of the total ion current). Table IV shows a typical example, a barbiturate which had already been indicated by UV-spectrophotometry. The mass spectrum identifies it as the not very common 5-ally 1-5-n-buty 1-barbituric acid. The molecular ion (m/e 224) is not visible. The base jjeak results from the loss of the butyl residue (M -57 = 167). M -29 and M -43 are also visible and so are the ions at m/e 15, 29, 43 and 57 in the vertical column +9. The butyl residue is therefore not branched. Two dominant masses are 41 (allyl residue) and 124 (by ring contraction of the base peak fragment (m/e 167) with elimination of CONH). We are using such modulo-14 tables in place of plots. 

A plethora of weakly acidic pharmaceutical substances may be titrated effectively by making use of a suitable non-aqueous solvent with a sharp end-point. The wide spectrum of such organic compounds include anhydrides, acids, amino acids, acid halides, enols (viz., barbiturates), xanthines, sulphonamides, phenols, imides and lastly the organic salts of inorganic acids. 

Fig. 2. Effect of pH on the ultraviolet spectrum of phenobarb-itone. A, non-ionised barbiturate in 0.1 M hydrochloric acid B, mono-anion in 0.05M borax buffer (pH 9.2) C, di-anion in 0.5M sodium hydroxide (pH 13).

These classes can be further divided depending on whether the substituents in position 5 are alkyl, alkenyl, aryl, or cycloalkenyl. In most common barbiturates, one of the 5-substituents is either ethyl or allyl and the other is either a straight- or branched-chain alkyl or alkenyl group with five or fewer carbon atoms. Some barbiturates are marketed as sodium salts. The infra-red spectrum of a barbiturate will therefore depend on the class of compound, the nature of the substituents, and whether it is the fi ee acid or the sodium salt. 

Chemical derivatives may be used to improve the chromatographic characteristics of polar compounds, e.g. acids may be converted to their methyl esters and barbiturates to their methyl derivatives. This technique may also provide information concerning the number of active sites in a molecule by noting the increase in molecular weight on methylation. In many cases the mass spectrum of tiie derivative may be of more use for identification purposes. 

Barbiturates in micro amounts determined by shift in spectrum going from pH 10.5 to strongly alkaline determined in extracts from blood at 260 m in 1 AT NaOH before and after addition of ethylenediamine dihydrochloride Chloral hydrate in admixture with trichloroacetic acid and trichloroethanol used reaction with pyridine Strychnine (252 m/i) mixed with brucine (262 m ) [ ]. Theobromine and caffeine in cocoa powders (after separa-tion)[ ]. 

---