Aminoazines

A variety of anellated 1H- and 4//-[l,4,2]diazaphospholes could be obtained by our research group via [3+2] cyclocondensation and [4+1] cyclocondensation routes [7-9], Condensation of 2-aminoazines (68) with chloromethyldichlorophosphine (65) proceeds with complete regioselectivity to afford 3-unsubstituted [4,5]-anellated... 

By carrying out the Ugi-reaction with a large number of isonitrils, aldehydes, carboxylic acids, and amines, it was found that formation of different products of the reaction occurred depending on the structure of the amines used. Thus, 3-aminoimidazoles 88 were isolated when aldehyde reacted with isocyanide and heterocyclic aromatic 2-aminoazine as primary amine (Scheme 38). 

An extensive study has been performed concerning the basicity of aminoazines using the SCF MO LCAO method.165 Moreover, attention has been paid to the influence of various factors influencing the basicity of azines196 and to the relationship between the protonation and solvation entropy.167... 

With an aminoazine, the size of an alkylating agent may influence the site of reaction. For example, both 4- and 5-aminoquinolines react predominantly at the side chain with a bulky reagent such as benzhydryl... 

Reaction of aminoazines with electrophiles at the amino group... 

Two effective tin reagents, triethylammonium triphenyltin and dibuthyltin dihydride have been offered for reduction of fused tetrazoloazines to aminoazines (87TL5941). The reaction was interpreted to proceed via ring opening to an azide and subsequent reduction. 

Imidazo[l,2-fl]pyridines are formed upon treatment of isonitriles with aldehydes and 2-aminopyridines (Entry 14, Table 15.14). 2-Aminoazines other than 2-aminopyr-idine can also be used in this multicomponent reaction, yielding the corresponding fused imidazoles [179-183]. 

Reactions of a,(3-unsaturated ketones with various aminoazines are also described in the literature. Treatments involving 6-aminouracils and chalcones or their analogues are the most investigated among them [229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241]. 

Multicomponent reactions of aminoazines with pyruvic acid have not been described in literature at the present time. 

Treatment of aminoazines, in particular, 6-aminouracil 305, with cyclic oc,(3-unsaturated ketones was described in [235]. The authors showed that 1,3-dimethyl-6-aminouracil reacts easily with cyclooct-2-enone 313, cyclonon-2-enone 316 and other cyclic unsaturated carbonyls (cyclododec-2-enone, cycloundec-2-enon, etc.), forming the appropriate tricyclic compounds 314, 317 or analogues (Scheme 3.86). The interaction of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) with compound 314 leads to a rearrangement of the carbon skeleton and formation of another tricyclic structure 315, while in the... 

Azine approach. The fused pyrimidines can be synthesized in the same way as the pyridines, e.g. by the cyclization of vicinal aminothiocyanates (70JCS(C)2478>. Another useful method for aminoazines is the reaction with chlorocarbonylsulfenyl chloride, e.g. with the aminopyrimidine (440) (73LA1018). The reaction can be rationalized by initial acylation of the amino group which is then cyclized with formation of the 2(3//)-one (441). Another case is the reaction of the 6-aminouracil (442) with thionyl chloride (69JOC3285). The reaction is rationalized as an initial electrophilic substitution at the 5-position of the activated pyrimidine. Subsequently the chlorosulfinyl derivative (443) is cyclized to a thiazoline S-oxide which loses water to yield the thiazole. 

Proton loss. The side-chain anions from 2- and 4-aminopyridines are stabilized by resonance 761. Aminoazines are thus weak acids their anions react with electrophilic reagents preferentially at the amino nitrogen. 2-Aminopyridine 745 is thus converted by NaNH2/MeI to the 2-methylamino- 763 or 2-dimethylamino-derivatives 764. With EtONO/NaOEt, a sodium diazotate 762 is formed which will couple with phenols. 

The peri derivatives, 1-aminoacridine, 8-aminoquinoline, and 8-aminoquinazoline, are anomalous. This correlation for derivatives in the adjoining ring is free from the field effect or charge repulsion which can contribute to the relatively low base-strengthening in 2-aminoazines. The lack of interaction of a 1-aza moiety with the... 

The inductive and resonance constants obtained can serve as a basis for estimating the generalized Hammett constants for azinyl groups. The values of ff p constants are found to satisfactorily describe the equilibrium CH acidity of methyl- and acetylazines, as well as the NH acidity of aminoazines estimated in the medium of dipolar aprotic solvents (82ZOR9 83ZOR465). The respective correlations are shown in Fig. 1. 

Fig. I. Plot of pK values of azine derivatives versus for azinyl groups. O, Acetylazines, DMSO 0, aminoazines, DMSO A, methylazines, DME.

Dinitrogen nucleophiles, such as 2-aminoazines 194 and 195, react with CSI to afford fused thiatriazinone derivatives 139 and 138 (79H815). Similarly 2-aminothiazoline 196 reacts with CSI to give a single adduct 197 (Scheme 71). 

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