2- Amino-4H-pyrans

Synthesis, Structure, Chemical Reactivity, and Practical Significance of 2-Amino-4H-pyrans... 

Synthesis of 2-amino-4H-pyrans, annulated with five- 201 to seven-membered carbocycles... 

The class of 2-amino-4H-pyrans has been known for several decades. The first representatives 1 and 2 are from the late 1950s to the early 1960s. Spiro-conjugated pyranopyrazole 1 was obtained in studies on pyrazolone dyestuffs (56ACS587), while pyranopyranone 2 served as a precursor for the blood anticoagulant warfarin (62JOC3086). 

Most of the 2-amino-4H-pyrans are colorless, pale-yellow, or pale-cream crystals with high melting points. They are readily soluble in aromatic hydrocarbons, alcohols, acetone, acetonitrile, chloroform, DMF, and DMSO, and nearly insoluble in hexane and water. 

NMR spectroscopy is the main method for characterization of 2-amino-4H-pyrans. Most NMR data were obtained using DMSO-ds and CDCI3. The spectra always contain a signal for NH2 protons (br. s, 2H), but its chemical shift strongly depends on the nature of a 3-substituent and conditions (Table 1). 

For the synthesis of nonannulated 2-amino-4H-pyrans, acyclic carbonyl compounds 24 are used in Methods 1,2, and 3. Generally, readily accessible ketones 24, as well as unsaturated nitriles 25 contain electron-withdrawing substituents (R, X). Consequently, densely functionalized pyrans 22 are formed. UNs, widely used for aminopyran preparation, include 30-34... 

Figure 1 General methods of 2-amino-4H-pyran synthesis.

Most probably, the last stage in the synthesis of 2-amino-4H-pyrans involves base-catalyzed nucleophilic addition of the enolic oxygen to a C=N group, which can be regarded as a hetero-Thorpe-Ziegler reaction (Scheme 21). 

Heterocyclic methylene-active carbonyl compounds (or their tautomers) with arylidenemalononitriles yield 2-amino-4H-pyrans condensed with... 

The reactivity of 2-amino-4H-pyrans as well as their chemical properties has been poorly studied because of their weak stability toward many reactants. They undergo ring opening and recyclizations in the presence of strong acids and bases, nucleophiles, and so on. But this feature can be turned to advantage in the synthesis of various heterocycles via recyclizations. Thus, the enamino moiety in 2-amino-4H-pyran-3-carbonitriles and 2-amino-4H-pyran-3-carboxylic esters provides access to diverse derivatives, including fused pyrans. The available data on the chemical properties of 2-aminopyrans are not systematic, and, in certain cases, are contradictory. 

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