Heterocyclic compounds five-membered-ring

The Srn 1 reaction has been applied to heterocycles. Among five-membered ring compounds, halothiophenes have been the most studied they have been shown to be susceptible to both electron-stimulated and photostimulated reactions, and have been converted to the corresponding acetonitriles [150], acetones [151], and phenyl-sulfides [ 152] in low to medium yields. In the study with the benzenethiolate anion it has been shown that the yield is low because of fragmentation of the adduct radical anion it can be increased by adding an electron acceptor, e.g. benzonitrile which prevents decomposition. Further applications include the thermally activated SrnI reaction between 3-iodobenzothiophene and enolates [153] and the photo-stimulated reaction of 3-halo-2-aminobenzothiophenes [154]. 

During experiments to trap a reaction product of a nitroso compound and isonitrile with an alkyl isocyanate, an additional way of formation of diaziridinimines was discovered. Besides some other heterocycles the five-membered ring compound 138 was formed, which yielded 133 by extrusion of carbon dioxide at 150°. ... 

Pyrrole, fiiran, and thiophene are heterocycles with five-membered rings. We have seen that these compounds are aromatic because they are cyclic and planar, every atom in the ring has a p orbital, and the tt cloud contains three pairs of tt electrons (Sections 8.8 and 8.10). 

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

Phosphorus heterocyclic compounds, 1, 493-538 five-membered ring systems, 1, 513-523 nomenclature, 1, 496 six-membered ring systems, 1, 497-513 Photoaromatization oxirenes from, 7, 125-126 Photobleaching chromenes in, 3, 880 Photochemical reactions heterocyclic compound synthesis from, 5, 159 reviews, 1, 56 heterocyclic compounds reviews, 1, 71, 72... 

Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

Conditions more accessible to rate measurements and, possibly, more favorable to a normal course of substitution (Section II, A) make the use of activated compounds such as nitro- and aza-sub-stituted derivatives desirable. In both cases, the activated halogeno-substituted five-membered ring heterocycle is also more reactive than a similarly activated six-membered ring compound. This... 

This tendency is especially significant in compounds containing functional groups capable of addition with the formation of both five- and six-membered rings. It has been shown that for amides and hydrazides of azolecarboxylic acids, selectively, and for the acids with any arrangement of a function and triple bond, heterocyclization always leads to the closure of the six-membered ring. Similar reactions in the benzoic series mainly lead to the formation of five-membered rings. 

Relatively little data are available on sulfonamido derivatives of heterocyclic systems with five-membered rings. The tautomeric equilibrium between structures 222 and 223 has been shown to favor the imine form by about 10 1 by comparison of the ultraviolet spectrum of the parent compound with those of both methylated forms." ... 

Aromatic sextets can also be present in five- and seven-membered rings. If a five-membered ring has two double bonds and the fifth atom possesses an unshared pair of electrons, the ring has five p orbitals that can overlap to create five new orbitals— three bonding and two antibonding (Fig. 2.6). There are six electrons for these orbitals the four p orbitals of the double bonds each contribute one and the filled orbital contributes the other two. The six electrons occupy the bonding orbitals and constitute an aromatic sextet. The heterocyclic compounds pyrrole, thiophene, and... 

Grubbs and coworkers [238] used the ROM/RCM to prepare novel oxa- and aza-heterocyclic compounds, using their catalyst 6/3-15 (Scheme 6/3.9 see also Table 6/3.1). As an example, 6/3-35 gave 6/3-36, by which the more reactive terminal alkene moiety reacts first and the resulting alkylidene opens the five-membered ring. In a similar reaction, namely a domino enyne process, fused bicyclic ring systems were formed. In this case the catalyst also reacts preferentially with the terminal alkene moiety. 

Many versatile approaches to the construction of fused heterocyclic systems (6 5 6) with ring junction heteroatoms have been reported. More general reactions which can be used for synthesis of derivatives of several tricyclic systems, and transformations which have potential for use in the preparation of a series of substituted compounds, are discussed in this section. Formation of the five-membered ring is presented first because it is a conceptually simple approach. It should be noted, however, that the addition of a fused six-membered ring to a bicyclic component offers much more versatility in the construction of a (6 5 6) system. Each subsection below starts with intramolecular cyclization of an isolated intermediate product. Reactions which follow are one-pot intermolecular cyclizations. 

As might be expected of a reactive dienophile, ADC compounds react readily with a variety of 1,3-dipoles to give five-membered ring heterocycles. These reactions are discussed in detail in Section IV,C. 

Five-membered ring heterocycles can be the result of cycloaddition reactions of ADC compounds acting as 2n components with 1,3-dipoles, or as 47t components in cheletropic reactions. They can also result from nucleophilic attack on the ADC compound, followed by ring closure of the initial adduct. 

The concept of five-membered ring heterocyclic synthesis by transformation of the initial adduct of the ADC compound and substrate is not limited to cyclization of substitution products. l,3,4-Oxadiazol-2-ones (30, Scheme 3) result from heating the initial DEAZD-dichlorocarbene adduct.72 Treatment of the Diels Alder adducts 96 with zinc in acetic acid gives pyrroles in good yield (Eq. 17).151 The reaction has been extended to the synthesis of dipyrroles from the appropriate Diels-Alder adduct (96, R = pyrrol-2-yl). 

As with five-membered ring formation, the reactions of ADC compounds which lead to six-membered ring heterocycles can be classified according to how the ADC compound reacts in the initial step. Most common is the Diels-Alder reaction, with the ADC compound acting as dienophile. Six-membered rings also result from the reaction of monoenes with ADC compounds acting as the 4n component, and by cyclization or other transformation of an initial adduct. 

A lot of methods are available for the synthesis of this heterocycle, and most of them rely on the formation of the five-membered ring. In this section, only the methodologies of reasonable scope will be reported. The most classical method involves the cyclocondensation of 2-aminopyridine with an a-halo carbonyl compound. Due to the broad availability of the required substrates and the efficiency of this cyclocondensation, it continues to be the method of choice to prepare this heterocycle. New examples highlighting the generality of this reaction are collected in Table 14. 

A number of other ring systems have been prepared by intramolecular bis-annulation procedures. Pyrrolothiadiazolines 174 were prepared by condensation between hydrazides and compound 173 (Equation 14) <1998JPR676>. The thermally induced intra-intermolecular criss-cross cycloaddition of azine 175 in the presence of phenyl isocyanate leads to heterocyclic compound 176 containing three fused five-membered rings (Equation 15) <2002TL6431>. 

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