Azomethine type compounds

A few nitrofuran azomethine compounds are soluble in water. But guanofuracin and furaltadone are soluble only in acidic solution by salt formation. The free base precipitates rapidly by addition of alkali to the solution. It is known that the water solubility of nifuroxime and nitrofurantoin increases by adding alkali, and a sodium salt of nitrofurantoin can be prepared for practical purposes. Most of the nitrofurans are readily soluble in polyethyleneglycols and in dimethylformamide. A solution of the desired concentration of nitrofurans can sometimes be prepared by dissolving the compound 

Compound number M.wt. Appearance m.p. Ultra-violet Approx, solubility (mg/1)  

I 5-Nitro-2-furfuraldehyde semicarbazone (nitrofurazone, nitrofura], NF-7, Furacin, Sanfuran). 

II 5-Nitro-2-furfurylideneaminoguanidine hydrochloride (guanofuracin hydrochloride) (NF-56 is the sulphate). 

Ill i-(5-Nitro-2-furfurylideneamino)hydantoin (nitrofurantoin, NF-153, Furadantin, Furantoin). ly 3-(5-Nitro-2-furfurylideneamino)oxazolidin-2-one (furazolidone, NF-180, Furoxone, Medaron, Puradin, Trifurox). 

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The formation of tertiary amines is also explained by the analogous reactions shown in eqs. 7.7 and 7.8. In this case, however, elimination of ammonia from the addition product 4 to form an azomethine type compound is not possible, but tertiary amines may be formed either by direct hydrogenolysis of 4 or through the formation of an enamine 5 followed by hydrogenation. 

The clinically used nitrofuran compounds may be divided into four groups (1) azomethine type nitrofurans (2) di-(nitrofuran) compounds ... 

The following is a selection of papers which have appeared since the main part of this review was completed. Further variants of the azomethine type of compound (p. 322) have been prepared, for example, those of general formula 5-02N-Fur-GH=NR in which R is a 5-substituted 3-rhodanine, ... 

Methine isoindolinones of generic structure 23 can be prepared by the reaction of active methylene compounds with either phthalimides [e.g., 22], or iminoisoindoli-nones [e.g., 23], or a-cyanobenzoates by analogy with the methods described above for azomethine type isoindolinones. 

Interesting structures can be formed by combinations of ring and side-chain substituents in special relative orientations. As indicated above, structures (28) contain the elements of azomethine or carbonyl ylides, which are 1,3-dipoles. Charge-separated species formed by attachment of an anionic group to an azonia-nitrogen also are 1,3-dipoles pyridine 1-oxide (32) is perhaps the simplest example of these the ylide (33) is another. More complex combinations lead to 1,4-dipoles , for instance the pyrimidine derivative (34), and the cross-conjugated ylide (35). Compounds of this type have been reviewed by Ramsden (80AHCl26)l). 

The additional protection given to nylon by antioxidants has already been mentioned. Since the need is to protect against oxidation by free radicals, antioxidants are essentially of two types peroxide decomposers and radical scavengers. Reviews of these products are available [409,410,413] these should be consulted for details of the mechanisms involved. Peroxide decomposer types include compounds of manganese (II) or copper(I) and copper(II) complexes, such as azomethine bridge derivatives of the type represented by 10.160, of which numerous water-soluble or water-insoluble variants are possible [409]. These products have a catalytic action and are therefore used in very small amounts. 

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

Pyridones, as exemplified by ABT-719 (154, Figure 3.8), represent a new class of DNA gyrase inhibitors possessing a broad spectmm of antibacterial activity and, in studies toward such compounds, it was revealed that the C(8) functionality was an important part of the DNA binding action. Azomethine ylide cycloadditions were employed to give a range of proline-type derivatives in order to study stmcture-activity relationships (39). 

The orientation of the CH=CH2 in 2-vinylfuran and 2-vinylthiophene is of the X,C-cis type (81RCR336), as expected from conjugative interactions which should largely prevail over dipole composition in these compounds. It is also worthy to note that in the radical anion of trans-1,2-di(2-thienyl)ethylene (71G10), the preferred conformation is the one with both the thienyl rings in the S,C-cis orientation (155). The azomethines of five-membered rings retain the X,N-cis conformation (156), like the... 

When the aziridine nitrogen is substituted, Michael-type addition to the acetylene is not possible. Reactions are then usually preceded by ring cleavage with the formation of an azomethine ylid. The product obtained depends on the nitrogen substituent. Heine and co-workers 45,46 used m-l,2,3-triphenylaziridine (27) with DMAD, DEAD, EP, and EPP. The DMAD gave 98% of compound 28 after refluxing in toluene... 

Azomethines bear a formal resemblance to azo compounds and many parallels exist in the coordination chemistry of the two series of compounds. Thus the bidentate azomethines (191) behave in a strictly comparable manner to the bidentate azo compounds (20) (Section 58.2.2.1). The isomeric, bidentate azomethines (192), however, form metal complexes which undergo very facile hydrolysis as a result of polarization of the azomethine linkage. The difference between the two types of complex is dramatically illustrated by the results of a study135 of metal complex formation by the bis(azomethine) (193). This cannot function as a tetradentate ligand for steric reasons and reacts with copper, nickel and cobalt halides in cold ethanolic solution to form the five-coordinate complexes (194). Crystallization of these products from ethanol gives the five-... 

In general, the stability of metal complexes of bidentate azomethines of the type (191) is comparable to that of metal complexes of the analogous bidentate azo compounds (14) and is inadequate for practical application in the dyestuffs field. Limited numbers of such complexes have, however, been claimed to be suitable for pigment applications. 

Thus, FUB 307 (42) may be regarded as a kind of retard prodrug and represents the first reported compound of the azomethine prodrug type and particularly the first histamine H3 receptor agonist to possess such prolonged in vivo pharmacokinetics [45],... 

From the viewpoint of stereochemistry the most interesting metal complexes are the octahedrally coordinated 1 2 chromium and cobalt complex dyes, which are medially metallized azo and azomethine compounds with functional groups in the o- and o -positions. Three types of isomerism can be discriminated geometrical, N-a, 3, and that arising from azo-hydrazone tautomerism. 

Precursors of azomethinic complexes with live-member metal-cycles, of the type MN2S2, are the benzothiazoline compounds represented by structure 461 [337a,805,823,824] they can easily be transformed into chelates of type 462 [806-812] under proper conditions for complex formation (2.12) [9,269,804,823,824] ... 

Complex compounds of azomethines containing a six-member N,S-ligand environment are represented by numerous chelates, whose synthesis, physical, and chemical properties, and molecular structures, are reported in a number of reviews [269,270,448,804,823]. Compounds of the types 467 and 468 are the most propagated amongst this kind of complex ... 

Additionally to nickel ICC, chelates of the types 467, 468, 472, and 473, containing either cobalt, iron, copper, palladium, zinc, cadmium, or mercury, have also been obtained [269,270,804]. Special interest amongst them is provoked by copper ICC containing an azomethinic N,S-ligand environment. These compounds are one of the several biomimetic models of nonporphyrine metal proteins [448,804,834]. The majority of these ICC have trimetallocyclic structures of the types shown by struc-... 

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