The ultraviolet spectrum

Determination of structural features. The ultraviolet spectrum has been of value in the determination of the structure of several vitamins. Thus the presence of an a-naphthoquinone system in vitamin K was first detected by this means. Also the 4-methylthiazole and the 2 5-dimethyl-6-aminopyridine system was first identified in vitamin Bj (thiamine), a- and /3-Ionones can be distinguished since the former contains two conjugated chromophores and the latter three conjugated chromophores. 

The ultraviolet spectra of these compounds are similar to those of trans stilbene or of 2- and 4-stilbazole. The effect on the ultraviolet spectrum of various substituents have been found to parallel in many respects the efiects produced by the corresponding group in derivatives of aromatic hydrocarbons (142). 

The infrared spectrum of the l-methoxy-l,4-cyclohexadiene shows the absence of strong aromatic absorption at 1600 cm.the ultraviolet spectrum shows absence of absorption at 270 nm., indicating absence of the conjugated isomer. 

The purity of the 2-cyclohexenone may be assayed by gas chromatography on an 8 mm. x 215 cm. column heated to 125° and packed with di-(2-ethylhexyl) sebacate suspended on ground firebrick. This method of analysis indicates that the 3-cyclo-hexenone in the product amounts to no more than 3%. The fore-run from this fractional distillation contains substantial amounts of 2-cyclohexenone accompanied by ether, ethanol, and minor amounts of other lower-boiling impurities. Additional quantities of pure 2-cyclohexenone can be recovered by redistillation of this fore-run. The preparation of 2-cyclohexenone has been run on twice the scale described with no loss in yield. The ultraviolet spectrum of an ethanol solution of the 2-cyclohexenone obtained has a maximum at 226 m/i (s = 10,400). 

The product may be analyzed by gas chromatography on an 8 mm. x21S cm. column heated to 220-240° and packed with Dow-Corning Silicone Fluid No. 550 suspended on 50-80 mesh ground firebrick. The chromatogram obtained with this column exhibits a single major peak. The ultraviolet spectrum of an ethanol solution of the product has a maxium at 250 m>i (s = 17,200). 

P-Hydroxy-A-norpregn-3(5)-en-2-one (7) A solution of the hydroxy-methylene steroid (5) (24.8 g) dissolved in 240 ml of acetic acid and 240 ml of ethyl acetate is ozonized at — 10° with one molar equivalent of ozone. The resulting solution is diluted with 240 ml. of water and 60 ml of 30 % hydrogen peroxide and allowed to stand overnight. The solution is diluted with 1.5 liters of water and extracted with 3 x 700 ml portions of ethyl acetate. The combined extracts are washed with water, saturated sodium chloride solution, dried over sodium sulfate and concentrated to dryness under vacuum, leaving 23.4 g of a colorless amorphous residue of crude diacid. This material shows a maximum in the ultraviolet spectrum at 224 mp (s 6,400) indicating a 53 % yield of unsaturated acid (6). It is used without further purification. 

The simplest examples of this type of compound are enamines derived from the quinuclidine skeleton (67). The formulation of enamines of qflmuclidine in a inesomeric form would violate Bredt s rule. Actually, the ultraviolet spectrum of 2,3-benzoquinuclidine shows that there exists no interaction of aromatic ring tt electrons and the nitrogen-free electron pair (160,169). The overlap of the olefinic tt orbital and the lone pair orbital on nitrogen is precluded. 

Similar behavior can be observed even in the case of substituted quinuclideines 170). Neostrychnine (68) serves as an example of more complex compounds which show spectra differing from those of other enamines. The ultraviolet spectrum of this compound exhibits no batho-chromic shift and its basicity is considerably decreased 159,171,172) (pK in methylcellosolve at 20° is 3.8, whereas the analogous saturated compound has a pK under the same conditions of 7.45, and a compound with the double bond further removed, strychnine, has a pK of 7.37). As another example, the ultraviolet spectrum of trimethyl conkurchine (69) shows the same absorption maxima as a saturated tertiary amine (A in ether, about 213 m/i). 

According to Dobbie et the ultraviolet spectrum of cotarnine in dilute aqueous or alcoholic solution is identical with that of cotarnine chloride [(1), Ch instead of OH"], but in nonpolar solvents it is identical with that of hydrocotarnine (10a), 1-ethoxy-hydrocotarnine (10b), and cotarnine pseudocyanide (10c). This is in agreement with Decker s view of the structure of cotarnine and with the conclusions of Hantzsch and Kalb. Measurement of electrical conductivity in-... 

The hydrated cation of quinazoline in dilute acid solution becomes dehydrated when the acidity of the solution is progressively increased. At Ho —4.3, the solution consists predominantly of the anhydrous cation with some anhydrous dication ( 7%). The ultraviolet spectrum of the anhydrous cation is similar to that of the neutral molecule (there is a small bathochromic shift) and it is also similar to that of quinazoline in anhydrous dichloroacetic acid. When the acid strength is further increased to Ho —9.4, the quinazoline dication is formed (pKa —5.5). 

Tetrahydroquinazolines are cyclic methylene diamines and are, therefore, readily hydrolyzed by acid to the corresponding o-aminobenzy]amines, 1,2,3,4-Tetrahydroquinazoline is a strong base (pi a 7.65), though it is not as strong as 3,4-dihydroquinazoline because of the absence of amidinium resonance in the cation. The ultraviolet spectrum is only slightly altered on protonation clearly indicating that it takes place on N-3. ... 

The electronic spectrum of a compound arises from its 7r-electron system which, to a first approximation, is unaffected by substitution of an alkyl group for a hydrogen atom. Thus, comparison of the ultraviolet spectrum of a potentially tautomeric compound with the spectra of both alkylated forms often indicates which tautomer predominates. For example, Fig. 1 shows that 4-mercaptopyridine exists predominantly as pyrid-4-thione. In favorable cases, i.e., when the spectra of the two alkylated forms are very different and/or there are appreciable amounts of both forms present at equilibrium, the tautomeric constant can be evaluated. By using this method, it was shown, for example, that 6-hydroxyquinoline exists essentially as such in ethanol but that it is in equilibrium with about 1% of the zwitterion form in aqueous solution (Fig. 2). 

Ultraviolet spectra have long been used to study systems of this type. In 1889, comparison of the ultraviolet spectrum of 2-hydroxy-quinoline with those of its O- and A -methylated derivatives led... 

Attempts have been made to deduce the structure of the predominant form of a potentially tautomeric compound from the shifts which occur in the ultraviolet spectrum of the compound in question on passing from neutral to basic or acidic solutions. The fact that no bathochromic shifts were observed for 2- and 4-hydroxy quinoline and 1-hydroxyisoquinoline under these conditions was taken as evidence that they existed in the oxo form [similar work on substituted quinol-4-ones led to no definite conclusions ]. A knowledge of the dissociation constants is essential to studies of this type, and the conclusions can, in any case, be only very tentative. A further dif-... 

Many of the properties oj -hydroxypyridines are typical of phenols. It was long assumed that they existed exclusively in the hydroxy form, and early physical measurements seemed to confirm this. For example, the ultraviolet spectrum of a methanolic solution of 3-hydroxypyridine is very similar to that of the 3-methoxy analog, and the value of the dipole moment of 3-hydroxypyridine obtained in dioxane indicates little, if any, zwitterion formation. However, it has now become clear that the hydroxy form is greatly predominant only in solvents of low dielectric constant. Comparison of the pK values of 3-hydroxypyridine with those of the alternative methylated forms indicated that the two tautomeric forms are of comparable stability in aqueous solution (Table II), and this was confirmed using ultraviolet spectroscopy. The ratios calculated from the ultraviolet spectral data are in good agreement with those de-... 

The ultraviolet spectrum of vitamin Be, or pyridoxine, measured in aqueous ethanol varies with the composition of the solvent indicating that this compound is in equilibrium with the zwitterion form 38. The equilibrium constant in pure water was obtained by extrapolation. Prior to this, equilibria which involved tautomers of type 39 had been suggested for vitamin Be, but see Section VI,A. In the case of pyridoxal, an additional equilibrium, 40 41, occurs (cf. Section VIII) other pyridoxal analogs have also been studied (Table II). 

Between 1951 and 1953 investigations by three English groups clearly demonstrated the preponderance of the oxo forms of pyrimidin-2- and -4-ones by comparing the ultraviolet spectra of these compounds with those of the N and 0-alkylated derivatives, The o-quinonoid form 91 (R = H) is favored by the evidence that A -methylation of the 6-methyl derivative of 89a does not cause a bathochromic shift in the ultraviolet spectrum (A -methylation of pyrid-4-one causes a bathochromic shift, but this is not observed for pyrid-2-one) The isomeric A -methyl derivatives of pyrimidin-4-ones [e.g., 91 (R = Me) and 90 (R = Me)] form similar cations (e.g., 92 and 93), and hence the equilibrium constant between... 

Trihydroxypteridine exists predominantly in the dioxo-mono-hydroxy form 191(R = H), its ultraviolet spectrum closely resembling those of both the 1- and the 3-methyl derivatives and that of l,3-dimethyl-7-methoxypteridine-2,4-dione (191, R = Me). These spectra are quite different from those of 8-methyl- (192, R = H) and l,3,8-trimethyl-pteridine-2,4,7-trione (192, R = Me), which are similar to each other and to those of other 8-substituted pteridine-2,4,7-triones. However, the ultraviolet spectrum of 2,4,7-trihydroxypteri-dine does, indeed, show that a small proportion of the trioxo form is present at equilibrium. A somewhat larger proportion of the 6-methyl derivative exists in the trioxo form, although structure 193 predominates. The trioxo form (194) of 2,4,7 trihydroxy-l,3,6-trimethyl-pteridine is the most important tautomer, but the corresponding 6-carboxylic acid exists entirely in the monohydroxy-dioxo form 195. 

In 1939, the ultraviolet spectrum of 4-methylquinol-2-thione was reported to differ from that of the 2-alkylthio analog, and the former compound was concluded to exist in the thione form. However, other investigators were unable to reach any conclusions from ultraviolet and infrared spectral data concerning the tautomerism of quinol-2- and -4-thione. A definitive pK and ultraviolet spectral investigation by Albert and Barlin has recently established that the thione forms of quinol-2- and -4-thione and of isoquinol-1- and -3-thione (cf. 202) greatly predominate (Table V). The infrared... 

The ultraviolet spectrum of 4-aminoquinazoline has been interpreted to support the amino structure. ... 

In contrast to these findings, two independent reports have appeared in which the ultraviolet spectrum of 2-amino-l,3,5-triazine has been interpreted to indicate that this compound exists in the imino form, but the correctness of these conclusions appears doubtful, especially since comparisons were not made with the spectra of the alkylated derivatives. Other investigators have interpreted the ultraviolet spectra of a series of amino- and diamino-1,3,5-triazines to indicate that the amino forms of these compounds predominate. ... 

The ultraviolet spectrum of 2-aminopteridine (265, R = H) is similar to that of its dimethylamino derivative (265, R = Me) suggesting that it exists in the amino form, and similar evidence is available for 4- and 6-aminopteridine. Basicity values show that the amino form of 4-aminopteridine is preferred to the imino form (266) by a factor of about 4-Aminopteridine is preferentially... 

The ultraviolet spectrum of the tautomeric compound 290 (R = H) 291 is qualitatively similar, but quantitatively dissimilar, from that of the methyl derivative (290, R Me), and it may be tentatively concluded that both forms 290 (R = H) and 291 are present... 

The spectral changes which occur in increasingly acid solutions of polyaza-heterocycles may indicate a second ionization. This event, however, can readily be distinguished from dehydration by measuring the spectra in anhydrous dichloroacetic acid, provided that the pKa value for the anhydrous species is above 1. Anhydrous dichloroacetic acid has a Hammett acidity function (Hq) of — 0.9 (as determined using o-nitroaniline as the solute), and the ultraviolet spectrum of a base with a p > 1 would be that of the anhydrous cation in this 2 A. Albert and W. L. F. Armarego, J. Chem. Soc. 4237 (1963). 

The anomalous behavior of quinazoline was first discovered by Albert et who made the surprising observation that 4-methyl-quinazoline 2.5) was a weaker base than quinazoline (pA 3.5). Mason then observed that the ultraviolet spectrum of the quinazoline cation was abnormal but that the spectrum of 4-methylquin-azoline was normal (see Fig. 2). These anomalies led to the suggestion that water adds covalently to the cation of quinazoline to give 12 (R = H). The occurrence and position of hydration were confirmed by a detailed study of the ultraviolet and infrared spectra of the anhydrous and hydrated hydrochlorides and by mild oxidation of the cation to 4(3 )-quinazolinone. Using the rapid-reaction technique (the continuous-flow method), the spectrum of the unstable... 

The cation of 4,4 -biquinazolinyl and its 2,2 -dimethyl derivative readily add water across the 3,4- and 3, 4 -double bonds, but the cation of 2,2 -biquinazolinyl is not hydrated. Hydration in the 4,4 -isomers has been attributed to restricted rotation about the 4,4 -bond, a steric effect which is relieved by hydration. The ultraviolet spectrum of 2,2 -biquinazolinyl (neutral species and cation) shows that there is considerable conjugation between the quinazoline groups. Covalent hydration is absent from the latter compound because it would otherwise destroy the extended conjugation present. 

The infrared spectrum of 2-hydroxythiophene was originally interpreted as showing both vOH and vC=0 peaks indicating that it exists as a mixture of the hydroxy form 39 (R — H) and at least one of the 0X0 forms, 40 and/or 41. The ultraviolet spectrum of 2-hydroxythiophene is different from that of the corresponding methyl ether (39, R = Me) suggesting the presence of the chromophore contained in structure 40. The facts that this compound gives a positive... 

The chemical reactions of this compound were recently reconsidered, and both structures 64 and 65 were rejected in favor of the zwit-terion formulation 66, which is supported by the presence of a band at S.lfx (3226 cm ) in the infrared spectrum and is merely an alternative canonical form of 64. On the other hand, the ultraviolet spectrum of 4-hydroxypyrrole-2-carboxylic acid (67) resembles that of its ethyl ether, possibly indicating that the 2-acid exists in the hydroxy form. -... 

In 1882 Baeyer and Oekonomides advanced formula 72 (R = H) for isatin on chemical grounds, but shortly thereafter the dioxo structure 73 (R H) was proposed since the ultraviolet spectrum of isatin resembled that of the N—Me derivative (73, R Me) and not that of the O—Me derivative (72, R = Me). " It was later shown, despite a conflicting report, that the ultraviolet spectrum of isatin is very similar to the spectra of both the O— and N—Me deriva-tives - the early investigators had failed to take into consideration the facile decomposition of the O—Me derivative. Although isolation of the separate tautomers of isatin has been reported, - these claims were disproved. A first attempt to determine the position of the mobile hydrogen atom using X-ray crystallographic techniques was inconclusive, but later X-ray work," dipole moment data, and especially the infrared spectrum demonstrated the correctness of the... 

Comparison of the ultraviolet spectrum of benzotriazole with those of the alkyl derivatives of both forms (cf, 6 and 7) showed that the IH-form (6) was the predominant tautomer - dipole momenU ... 

The similarity of the ultraviolet spectrum of 4,5-diphenyloxazol-2-one (91) with those of both alternative methyl derivatives preclude application of the spectral comparison method to the elucidation of their structures, but the fluorescence spectra of these compounds indicate that 91 exists in the oxo form. ° Infrared data for a number of substituted oxazol-2-ones support this conclusion. ... 

---