Heterocyclic compounds, aromatic triazines

A rich coordination chemistry of aromatic diazine (N-N), especially pyridazine and phthalazine related ligands has emerged over the last three decades,1-72 and recently open-chain diazine (N-N) coordination chemistry has been well developed, especially by Thompson and others.62-113 Many types of aromatic heterocyclic compounds contain a 1,2-diazine (N-N) moiety, e.g., pyridazine and its 3,6-disubstituted derivatives (Scheme 1, Type 1), phthalazine, condensed phthalazines and their substituted derivatives (Scheme 1, Type 2), and other compounds such as pyrazole, triazole, thiadiazole, tetrazole, indazole, 1,2,4-triazine, 1,2,4,5-tetrazine, and thiadiazepines. Alternatively, the 1,2-diazine (N-N) moiety also exists as an open-chain entity in some related compounds, e.g., A-substituted-amide hydrazonimidates (Scheme 1, Type 3), A-substituted-amide hydrazonidates (Scheme 1, Type 4), A-substituted hydrazides (Scheme 1, Type 5), A-substituted amidrazones (Scheme 1, Type 6), and A-sub-stituted hydrazidates (Scheme 1, Type 7). 

In 1975 the anion of T was observed in a mass spectrometer, indicating a positive valence-state Ea for T. In 1990 the Ea of AGCUT were predicted using substitution, replacement, and conjugation effects [10-14], In order to estimate the Ea of substituted compounds, that of the parent compounds is required. In 1974 I. Nenner and G. J. Schulz estimated the AEa of quinoline (0.36 eV), pyradazine (0.40 eV), pyrimidine (0.00 eV), pyrazine (0.40 eV), and s-triazine (0.45 eV) from electron transmission spectra and half-wave reduction potentials [15]. No adiabatic electron affinities of aromatic nitrogen heterocyclic compounds were measured in the gas phase before 1989 [16]. 

Aromatic rings are characterized by sharp bands near 1600, 1580, 1500, and 1460 cm which may vary in intensity with different substituents. Pyridines are closely related to the benzene compounds. Triazines have strong bands in the 1600-1500 cm region. Heterocyclic compounds with two double bonds in a five-membered ring usually absorb at 1600-1530 and 1500-1430 cm"L... 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

H(65)1889, 2005EJO3553>. Starting dihydro[l,2,4]triazolo[3, 4-4]benzo[l,2,4]triazines 482 readily react with aromatic aldehydes to yield iminium salts 483. These salts treated with a base (e.g., triethylamine) are deprotonated to reactive 1,3-dipolar azomethine imines 484. In contrast to related five-membered heterocycles, these compounds are relatively unstable on storage in the solid form and particularly in solution. Fortunately, this obstacle can be easily circumvented by their in situ preparation and subsequent 1,3-dipolar cycloaddition. These compounds can participate in 1,3-dipolar cycloadditions with both symmetric and nonsymmetric dipolarophiles to give the expected 1,3-cycloadducts in stereoselective manner. Selected examples are given in Scheme 82. 

Modern life and civilization opened the way to other important practical applications of heterocycles, for example dyestuffs, copolymers, solvents, photographic sensitizers and developers, and in the rubber industry antioxidants and vulcanization accelerators. Some of the sturdiest polymers, such as Kevlar, have aromatic rings. Melamines (2,4,6-triamino-substituted s-triazines) are monomers with numerous applications as both homopolymers and copolymers. Scheme 9 shows a few examples of compounds with various applications in our daily life, having in common the same building block, the aromatic s-triazine. 

The most widely used herbicides today are triazine compounds (three nitrogens in the heterocyclic aromatic ring). Atrazine is used especially on com but also on pineapple and sugarcane. It is synthesized by reacting cyanuryl chloride successively with one equivalent of ethylamine and one equivalent of isopropylamine. Cyanuryl chloride is made in one step from... 

As aromatic compounds have been exhausted as building blocks for life science products, A-heterocyclic structures prevail nowadays. They are found in many natural products, such as chlorophyll hemoglobin and the vitamins biotin (H), folic acid, niacin (PP), pyridoxine HCl (Be), riboflavine (B2), and thiamine (Bi). In life sciences 9 of the top 10 proprietary drugs and 5 of the top 10 agrochemicals contain A-heterocycIic moieties (see Tables 11.4 and 11.7). Even modern pigments, such as diphenylpyrazolopyrazoles, quinacri-dones, and engineering plastics, such as polybenzimidazoles, polyimides, and triazine resins, exhibit an A-heterocydic structure. 

More than 130 different organic chemicals are currently employed as herbicides in the U.S. All of the main families of organic compounds are represented aromatic, aliphatic, and heterocyclic. Herbicidal activity is found in a variety of classes of compounds haloaliphatic, phenoxy, and benzoic acids carbamates dinitroanilines acetanilides amino triazines quaternary pyridinium salts uracils and ureas. A few selected key examples are reviewed below. 

Various perhalo aromatic compounds as well as a series of heterocyclic precursors, such as, for instance, chloro-pyridazine or -triazine derivatives, gave rise to the corresponding azides, too." -" -" ... 

Simple uncharged six-membered aromatic heterocycles cannot contain a divalent heteroatom. The azines are numbered to indicate the relative positions of the nitrogen atoms. 1,2,3,4-Tetrazine, pentazine and hexazine are unknown, however, a number of fused 1,2,3,4-tetrazines, primarily A -oxides and A -aryl quaternary salts, are known, but of monocycUc compounds, only a few di-A -oxides have been prepared. Of the other systems, 1,2,3,5-tetrazine is unknown, although theoretically it could be moderately stable, but fused derivatives include the drug temozolomide (see 33.7). Derivatives of 1,3,5-triazine are very well known and available in large quantities, indeed they are amongst the oldest known heterocycles the trioxy-compound ( cyanuric acid ) was first prepared in 1776 by Scheele by the pyrolysis of uric acid. 

Certain heteroaromatic compounds that have acidic methyl groups are effective in the Knoevenagel condensation. 6-Methyl-1,3,5-triazine (156), 2-methylpyridine V-oxides (157), quinolines and pyrimidines all condense with aromatic aldehydes in the presence of the usual catalysts. An example of a doubly activated methylene compound in which one activation group is a heterocycle is the 2-oxopro-pylthiazole (158), which condenses with a number of aldehydes. " ... 

The MM3 force field has been extended by Allinger and co-workers to cover aromatic heterocycles of the pyridine and pyrrole types <93JA11906>. Structures (32 compounds), dipole moments (35 compounds), heats of formation (35 compounds), and vibrational spectra (11 compounds) were examined. The results are good for structure and fair for the other items resonance energies were reported for the series benzene (17.79 kcal mol ), pyridine (17.02 kcal mol ), pyridazine (14.35 kcal mol ), pyrazine (17.01 kcal mol ), pyrimidine (15.60 kcal mol ), 1,3,5-triazine (13.51 kcal mol ), and 1,2,4,5-tetrazine (17.72 kcal mol ). Finally, ab initio studies of the dipole polarizabilities of conjugated molecules have been reported in which monocyclic azines (pyridine, pyridazine, pyrimidine, pyrazine, 5-triazine, and 5-tetrazine) are compared <94JST(304)109>. 

Condensation of substituted aromatic or heterocyclic amines with formaldehyde and urea or phenylthioureas under MWI in an aqueous medium gave 2-(oxo)thioxo-hexahydro-l,3,5-triazines 778 in 92-98% yields within 45-120s, but conventional heating gave 50-58% yields within 10-12 h. Triazines 778 further reacted with chloroacetic acid or hydrazine hydrate to give 779 and 780, respectively. Compounds 780 were obtained in 86-90% yields within 1.5-2.0 min under MWI, but classically... 

Other substituents, such as the pseudohalo groups (CN, NCO, OCN, NCS, SCN) and carboxyl groups, can be attached to the --C(X)=N— system, and compounds of this type are discussed within the outlined scheme. Likewise, O-substituted derivatives of hydroxamoyl halides are included in Chapter 6. Since the imidoyl halides can be part of a heterocyclic system, the cyclic homologs are treated separately in the last chapter. The fully aromatic compounds, such as halopyridines, halopyrimidines, and halo-1,3,5-triazines, are discussed only briefly in Chapter 8, as their chemistry is somewhat different. 

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