Compounds Containing Two Heteroatoms

A fuUy unsaturated imidazop5Tidine acts as a platelet-aggregation inhibitor. The presence of the fatty acid side chain suggests a possible interaction with arachidonic 

Condensation of a 2-aminopyridine with an a-haloketone provides an alternative method for budding the imidazopyiridine. For example, reaction of 2-aminopicoline (9-1) with para-methylphenacyl bromide (9-2) leads directly to the imidazopyridine (9-4). The overall transformation can be rationalized by assuming an initial alkylation on ring nitrogen (9-3) imine formation followed by bond reorganization then forms 

The first published scheme for the preparation of the platelet-aggregation inhibitor ticlopidine describes the alkylation of the thienopyridine (10-1) with 2,a-dichoro-toluene (10-2) to give the ternary salt (10-3). Reaction of that product with sodium borohydride selectively reduces the charged ring to give ticlopidine (10-4) [10]. 

An alternate method for building the partly saturated fused heterocyclic system for ticlopidine (10-4) starts by formation of the mesylate (11-2) from cyanopyridone (11-1) by treatment with methanesulfonyl chloride. The reaction of that with butyl thioglycolate can be envisaged as involving, first, the addition of the thiol group to 

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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. 

Such compounds contain two or three pyridine-like heteroatoms. For the symmetrical systems (73) and (74), no ambiguity occurs, but for systems (75)-(78) there are at least two alternative reaction sites. It appears that reaction takes place at the nitrogen atom furthest away from the pyrrole-like heteroatom, as shown in (75)-(77) where evidence is available from reactions with alkylating reagents (Section 4.02.1.3.8). 

Another example of resort to heteroatoms to obtain both oral potency and a split between androgenic and anabolic activities Ls tiomestrone (99). Trienone, 98, prepared in much the same way as 23, undergoes sequential 1,6 and 1,4 conjugate addition of thioacetic acid under either irradiation or free radical catalysis to afford the compound containing two sulfur atoms. 

There are an increasing number of compounds being prepared that contain two heteroatoms attached to a CF2 group, in particular halodi-... 

The aromatic 7r-electron system of thienothiophenes and related compounds containing two condensed rings comprises electrons from three carbon-carbon double bonds and unshared electron pairs from two heteroatoms, and thus is similar to that of naphthalene. 

There are few examples of the preparations of heterocyclic compounds containing two or more heteroatoms which involve cyclization with formation of a bond between two heteroatoms. The best known instances of this type of reaction, all of which are [6 + 0] reactions, are the preparations of benzocinnolines as outlined in equations (l)-(4). A similar type of approach to that outlined in equation (4) has been used for the direct preparation of the di-N-oxide (2) from the dioxime (1 equation 5). The naphthotriazine betaine (4) is obtained as one of the products of the thermal decomposition of the azidoazo compound (3 equation 6). 1,2-Dithiins and their dibenzo derivatives have been prepared by oxidation of appropriate dithiols and related starting materials as outlined in equation (7). All of these reactions are, however, somewhat specialized and there has been essentially no systematic study of the preparation of six-membered heterocycles via formation of a bond between two heteroatoms. 

The structural diversity associated with bicyclic 5-5 fused heterocyclic systems containing two heteroatoms in each ring has been noted previously in both CHEC(1984) <1984CHEC(6)1027> and CHEC-II(1996) <1996CHEC-11(7)115>. In recent years this diversity has also been reflected in the number of applications that have been found for these compounds which include organic metals, molecular clips and receptors and molecular magnets. These fields will be examined in due course through this chapter. 

The 8 and p values that are not given in the survey have the standard values of 8 = 0 and p = 1. In the case of compounds containing two sulfur atoms and/or other heteroatoms, the values given in Table III have also been used frequently. For the sake of brevity, we shall call this set of parameters Model C. It is easily seen that some of these values are not fully adequate, especially the parameters for oxygen. 

Compounds with two heteroatoms are illustrated in Scheme 5. The oxazines and thiazines contain a saturated carbon atom the corresponding aromatic cations are oxazinium and thiazinium. 

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