Pyridazines spectra

The H NMR spectrum of pyridazine shows two symmetrical quartets of an A2X2 or A2B2 type dependent on the solvent and concentration. The satellites have been used to obtain all coupling constants. Spectra of C-substituted pyridazines, methylthio- and methylsulfonyl-pyridazines, both as neutral molecules and as cations, N-1 and N-2 quater-nized species, pyridazinones, hydroxypyridazinones, A-oxides and 1,2-dioxides have been reviewed (b-73NMR88> and are summarized in Tables 6, 7 and 8. 

The mass spectrum of pyridazine is simple and high resolution measurements have shown that the ion at m/e 52 is composed of both (73.5%) and C3H2N (26.5%) ions ... 

The ESR spectrum of the pyridazine radical anion, generated by the action of sodium or potassium, has been reported, and oxidation of 6-hydroxypyridazin-3(2//)-one with cerium(IV) sulfate in sulfuric acid results in an intense ESR spectrum (79TL2821). The self-diffusion coefficient and activation energy, the half-wave potential (-2.16 eV) magnetic susceptibility and room temperature fluorescence in-solution (Amax = 23 800cm life time 2.6 X 10 s) are reported. 

The photoelectron spectra of pyridazine have been interpreted on the basis of many-body Green s function calculations both for the outer and the inner valence region. The calculations confirm that ionization of the first n-electron occurs at lower energy than of the first TT-electron (79MI21201). A large number of bands in the photoelectron spectrum of 3,6-diphenylpyridazine in stretched polymer sheets have been assigned to transitions predicted... 

The NMR spectra of the parent compounds of the pyrido-[2,3-d]- and -[3,4- f]-pyridazine systems have been studied, together with those of some closely related derivatives parent compound, 282). In the pyrido[4,3-c]pyridazine series, only the spectrum of the dihydro compound (302) has been recorded <79X2027). 

Amino-pyrazines and -pyridazines have been shown to exist predominantly in the amino form by infrared spectroscopic studies (cf. Table VI). Ultraviolet spectral data have been interpreted to indicate that 4-aminocinnoline exists predominantly in the imino form 256, but this conclusion, which was based on comparison of its spectrum with those of cinnolin-4-one and 4-ethoxycinnoline, is probably incorrect. Ultraviolet spectroscopic data strongly support the predominance of amino structures for 2-aminopyrazine (257) and 2-aminoquin-oxaline how ever, the former compound was at first erroneously concluded to exist in the imino form from ultraviolet spectral evidence. Isolation of two isomers of 2-amino-8-dimethylamino-3-methylphenazine, assigned the amino and imino structures 258 and 259, respectively, has been claimed, but it is very unlikely that these assignments are correct. 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

In search of novel and more effective antibacterial agents, numerous /1-lactam antibiotics bearing a pyridazine core have been synthesized mainly in Japan. Thus, the penicillin derivative (125) characterized by a 3-hydroxypyridazine-4-carboxamido subunit has been patented as a broad-spectrum bactericide [342-345] likewise, the corresponding cephalosporin analogue has been claimed in a patent [346]. 

With this in mind, the coordination chemistry of 52 with different diazine structural isomers was investigated. There were no detectable changes in the H NMR spectrum of 52 in a THF-Jg solution when either pyrazine or pyrimidine were added in 1 1 or 1 2 molar ratios, which suggested that only weak interactions might occur between 52 and these bases. In contrast, incremental addition of pyridazine or phthalazine to a THF-Jg solution of 52 at 25 °C resulted in an upheld shift of the aromatic NMR resonances of the diindacycle 52 thus reflecting the formation of complexes between 52 and the 1,2-diazines. Analysis of the tritration data clearly indicated the formation of 1 1 Lewis acid-diazine complexes 52-pyridazine-(THF)2 and 52-phthalazine-(THF)2 whose stability constants are equal to 80 ( 10) and 1000 ( 150) M respectively (Scheme 29). These data, as a whole, indicate that 52 is a selective receptor for 1,2-diazines. 

Of the six possible conformers containing chair rings, two tra/j5-fused conformers 18 and 19, with a slight excess of 18, could be identified as major conformers, with one a>-fused conformer as a minor constituent in the C NMR spectrum of l-methylperhydropyrido[l,2-h]pyridazine in acetone-dfi in the temperature range -75 to -89°C (78JA4012). The low intensity of the signal of the c -fused conformer did not allow determination of the exact structure of this component. The results of low-temperature cyclic voltammetry experiments supported the NMR findings. 

Nuclear Overhauser effect (NOE) difference measurements were used to assign structure 79 for the product of reaction of diphenylnitrile imine with 5-ethylsulfonyl-2-methyl(27/)pyridazinone. Thus in the H NMR spectrum the ot/, o-protons of the arylhydrazino moiety (which were identified by two-dimensional heteronuclear multiple quantum correlation (2-D HMQC) spectroscopy) were shown in differential NOE (DNOE) experiment to be significantly enhanced on irradiation of pyridazine hydrogen H-7, proving their steric proximity <2000JST13>. 

In the ultraviolet photoelectron spectrum, the most readily ionized level of pyridine is the nonbonding orbital (with contributions from the o -framework). The three diazines show two lone-pair levels, with the greatest splitting in the case of pyridazine but considerable also in pyrimidine and pyrazine. These long-distance splittings are attributed to both through-space and through-bond interactions, particularly the latter. 

The NMR spectrum for the parent unsubstituted heterocycle gives absorptions at S 8.17 (H-4), 9.78 (H-5), 9.88 (H-3) and 10.20 (H-8), /3,4 = 6Hz (73JHC1081). H NMR, IR and UV spectral data have also been reported for several pyridazino[4,5-c]pyridazine derivatives (67JHC393). Hiickel MO calculations have been made for this ring system (66JSP(19)25). 

The IR spectra of several hydroxypyridazino[4,5-cf]pyridazines have also been used to determine predominant tautomeric structures. These data confirm the HNMR data which have already been discussed (72G169). The IR spectrum of the parent unsubstituted heterocycle reveals a high molecular symmetry, showing a limited number of sharp absorptions at 3065, 3020,1530,1445,1308,1290,1250,1170,953,892,680, 668 and 478 cm" (67CC1006). 

UV spectroscopy has been used to study tautomerism in hydroxypyridazino[4,5-(i]-pyridazines (68JCS(C)2857). The spectrum of l-hydroxypyridazino[4,5-different from that of l-methoxy-5,8-dimethylpyridazino[4,5-cf]pyridazine to support the oxo structure as the predominant tautomeric form for these two compounds (72G169). 

The H NMR spectrum of 2-methylpyrazino[2,3-d]pyridazine reveals a singlet at 5 9.76 for both the H-5 and H-8 protons. The H-2 proton absorbs at 5 9.17. The HNMR spectrum for 5,8-dichloropyrazino[2,3-d]pyridazine exhibits a singlet at 5 9.42 for both the H-2 and H-3 protons. Spectral data for several other 5,8-disubstituted derivatives of this ring system all give a singlet for the two H-2 and H-3 protons at 5 9.1-9.4 (66JHC512). 

The UV spectrum for the parent pyrazino[2,3 -d]pyridazine shows absorptions at Amax 219 (e 13 300), 284 (1330) and 295 (980). Hiickel MO calculations have also been reported... 

IR spectral data for most known 1,2,4-triazines have been published. The absorption of the 1,2,4-triazines in the IR region are those expected for this system. The IR spectrum of the parent compound (1) shows three absorption bands for the C—H stretching vibrations at 3090, 3060 and 3030 cm-1, five bands for C=N and C=C stretching vibrations at 1560, 1529,1435,1380 and 1295 cm-1, three for the C—H in-plane deformations at 1163,1135 and 1113 cm-1, two for the characteristic ring skeleton vibrations at 1050 and 995 cm-1 and three bands for the C—H out-of-plane deformation vibrations at 851,768 and 713 cm-1 (68CB3952). These values are in good agreement with similar bands for pyridine, pyridazine, pyrimidine and pyrazine. Alkyl and aryl derivatives of 1,2,4-triazine show similar bands in their IR spectra, with additional bands from the substituents. 

It must be also emphasized that UV-vis irradiation favors the formation of the thiol conformer. A typical example is provided by 3-pyridazine, which, as we have mentioned above, is found exclusively in the thione form. However, one hour of UV-vis irradiation (A, > 330 nm) of matrix-isolated 3-thiopyrazine caused a nearly complete disappearance of the initial IR spectrum and the new observed spectrum fits well with the predicted spectrum of the thiol form, which was taken123 as evidence that the photoproduct is the thiol tautomer. A similar conversion of the thione tautomeric form into the thiol tautomer upon UV-vis irradiation was also observed for 2-thiopyridine63 and for 4-thiopyrimidine123. 

The IR spectrum of allopurinol (53), the 6-thioxo and the 6-oxo derivative reveal strong carbonyl absorption and an absence of any absorption for enol forms <76ACHS533>. The hydroxypyrazolo[3,4-djpyrimidine derivatives (90) exist mainly in the hydroxy form as shown by the absence of a carbonyl band in the IR spectrum <6iJOC451>. 4,7-Dioxopyrazolo[3,4-d]pyridazines exist in dioxo form <77JHC375>. 

In a second investigation of the microwave spectrum of 1,3,4-thiadiazole, 14N quadrupole coupling and centrifugal distortion for lines with J = 5 and / 50, respectively, are determined. These are compared with results obtained from 1,3,4-oxadiazoles and pyridazine. Comprehensive tables showing microwave transitions, the microwave spectrum and the a and n population from 14N quadrupole coupling data for 1,3,4-thiadiazole are also given (71JST(9)163> (see also Sections 4.01.3.2, 4.01.4.2.2.(i) and (iii), and 4.01 Table 2). 

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