Saturated heterocyclic

Despite the inconveniences, a certain number of studies have been carried out, particularly concerning dyes containing azomethine groups. Such as hydrazones, pyrazolones, formazans, and selenazoles quinoids. Saturated heterocycles, that is, selenazolines and selenazolidines. have also been tackled. Selenium derivatives for pharmacological or physiological applications are little developed by comparison with their thiazole homologs. 

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

Many studies have been made of substituent effects in saturated heterocyclic six-membered rings. For a detailed discussion the review of Eliel and Pietrusziewicz should be consulted [Pg.15]

The spectra of saturated heterocycles are generally fairly featureless, with amine n —>a absorptions and those transitions associated with sulfur showing up weakly, while saturated ethers are usually transparent down to 210 nm. 

PE spectroscopy has also been applied to the study of the conformational equilibria of saturated heterocyclic six-membered rings, and in particular of hexahydropyridazines. The... 

Information on partially and fully saturated heterocycles is much more limited and is summarized in Figure 3. As would be expected, the downfield shift of the a-carbon atom decreases with decreasing electronegativity of the heteroatom in the sequence O < NH < S < CH2. 

Calculation of group increments for oxygen, sulfur and nitrogen compounds has allowed the estimation of conventional ring-strain energies (CRSE) for saturated heterocycles from enthalpies of formation. For 1,3-dioxolane, CRSE is about 20 kJ mol . In 2,4-dialkyl-l,3-dioxolanes the cis form is always thermodynamically the more stable by approximately 1 kJ mol" . 

For the antiaromatic three-membered heterocycles, experimental data are available only for thiirenes (and there is some doubt about the true antiaromaticity of thiirenes). Bond lengths have been calculated, however, for these antiaromatic 47r-systems (80PAC1623). In comparison with the corresponding saturated heterocycles, the C—X bond lengths are increased by 0.05 to 0.17 A and the C—C bond length is decreased by 0.2 A. 

Compounds of type (6), (7), (8) and (9), although not strictly derivatives of a saturated heterocyclic system, will be discussed in this chapter. Our discussion of (7) begins and ends here, since oxiranethiones or a-thiolactones are apparently unknown (80AG(E)276). Little is known of (8) and its derivatives, oxiranimines or a-iminolactams. They have been postulated as intermediates in the thermal decomposition of aziridinones (a-lactams) (Scheme 1) but there is no well-established case of the isolation of an oxiranimine (80AG(E)276). 

Fig. 12.23c) and many other saturated heterocycles featuring either or have been... 

In a saturated heterocyclic compound the situation is very different from that in an aromatic compound. The volume requirement of a... 

Each section has the following structure synthesis of target structures, properties including spectral properties (meaning anomalous or confirming structure), reactions on ring atoms, reactions on substituents, partially saturated heterocycles, applications, and biological properties. 

Palladium(II)-catalyzed cyclization of N-alkylation of allyl alcohols by ure-tanes and its application to the synthesis of natural saturated heterocycles 98YGK34. 

Heterocyclization by catalytic formation of N—Car bond to give indoles, amino-pyridines, and N-aryl-substituted saturated heterocycles 98ACR805. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Data are given in Table IV for heterocyclic compounds. For piperidine there is no difference between E and E, showing that the bond energies used are applicable to saturated heterocyclic molecules. Pyridine and quinoline differ from benzene and naphthalene only by the presence of one N in place of CH and, as expected, the values 1.87 v.e. and 3.01 v.e., respectively, of the resonance energy are equal to within 10 percent to the values for the corresponding hydrocarbons. 

Strategy XIII Introduction to Ring Synthesis Saturated Heterocycles... 

Over the years, many spiropyran structures have been prepared. The pyran component consists of benzopyran or naphthopyran and the heterocyclic part consists of indoline, benzothiazoline, benzoxazoline, benzoselen-azoline, phenanthridine, acridine, quinoline, benzopyran, naphthopyran, xanthene, benzodithiole, benzoxathiole, and saturated heterocyclic rings such as pyrolidine and thiazolidine. 

Absorption maxima for a wide range of heterocyclic systems are shown in Figure 1.5.2 When the indolyl residue 8a is replaced by other heterocyclic residue, a somewhat small shift in the Xmax occurs. Replacement with a benzothiazoline residue, 8c, results in a bathochromic shift. Comparison between saturated heterocycles 8d-8f and the corresponding benzoderiv-atives 8a-8c shows that the conjugation produced by the benzene nuclei causes a bathochromic shift (ca. 20-50 nm). Replacement of saturated five-membered heterocycles by saturated six-membered heterocycles results in a hypsochromic shift. In the case of the piperidine series (8g) a significant hypsochromic shift occurs, due to steric hindrance in the colored form. 

The same pattern of activity is maintained in a closely related analogue. Condensation of amino-sulfonamide 201 with aldehyde 202 affords the saturated heterocyclic system (203) oxidation with silver nitrate leads to the antihypertensive agent pazoxide (204). 49... 

Chemical libraries of /3-turn mimetics, among them highly saturated pyrazino[l,2-tf]pyrazines, were synthesized and patented as biologically useful compounds <2001W02001/000210>. Solid-phase syntheses starting from substituted a,/3-unsaturated ester templates provided differently substituted saturated heterocyclic systems, among them saturated 2,4,8-trisubstituted-pyrazino[l,2- ]pyrazine-l,6-diones <2003W02003/013740>. 

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

A Greek team also reported on oxidation of partially saturated heterocycles to fully heteroaromatic rings <1996JHC599> 5-/>-anisyl-4,5-dihydro[l,2,3]triazolo[5,l-/][l,2,4]triazine 91, when treated with cerium ammonium nitrate, underwent an oxidative hydrolysis giving heteroaromatic product 92 in poor yield (20%). 

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