2-amino-2-chromene derivatives

The Michael addition of malononitrile and/or ethyl cyanoacetate (386) to nitrostyrenes has been reported to proceed in water at 80 C over 3h. In the presence of an orthohydroxy group, as in (385), the reaction is complete within 12 h at 40 C and gives rise to 2-amino-2-chromene derivatives (387) as a result of the subsequent cyclization. ... 

Mondal et al. reported the synthesis of a new robust, non-air-sensitive, metal-free triazine-functionalized mesoporous organocatalyst TFMO-1 (Figure 1.5) and successfully used this material as an excellent catalyst in the one-pot three-component condensation reactions for the syntheses of 2-amino-chromene derivatives under solvent-free conditions (Mondal et al., 2012). TFMO-1 is an easily separable heterogeneous organocatalyst devoid of metal ions and thus is highly desirable to address industrial and environmental concerns. 

Among different active methylene compounds (malononitrile, ethyl cyanoacetate, and diethyl malonate), only malononitrile showed a high product yield, suggesting that it was the best-suited active methylene compound for the synthesis of 2-amino-chromene derivatives over TFMO-1. 

In recent years, interest in substituted 2-amino-4//-chromene derivatives has been continuously increasing these molecules have several important pharmacological properties, such as antimicrobial (Khafagy et al., 2002), antiviral (Martmez-Grau and Marco, 1997 Smith et al 1998), mutagenic (Hiramoto et al., 1997), antiproliferative (Dell and Smith, 1993a,b), antitumor, and central nervous systan activities (Mohr et al 1975 Eiden and Denk, 1991). 

Synthesis of 2-Amino-4H-Chromene Derivatives Catalyzed by TFMO-1 ... 

Chromene frameworks are commonly found in natural products [69]. Due to their useful biological activities and pharmacological properties [70], such as pro-apop-totic activity against cancer cells, anticoagulant, and spasmolytic, the synthesis of chromene derivatives, especially 2-amino-4/f-chromene, has attracted much attention. 

An easier, practically convenient, and eco-friendly green synthesis of snbstitnted 2-amino-4H-chromene and benzo[e]chromene derivatives has been developed that avoids the use of harsh and highly environment-contaminating conditions, viz., classical heating, use of expensive and toxic reagents, solvents, and catalyst [8] (Scheme 8.8). 

A variety of substituted 2-amino -aryl-4H-benzo[/f]chromene derivatives were synthesized from one-pot multicomponent reaction of aromatic aldehydes, malononitrile, and 1-naphthol in aqueous media. In 2004, Maggi and coworkers [79] explored the use of basic alumina as a useful heterogeneous and reusable catalyst for the synthesis of 2-amino-4H-chromenes (8) from the reaction of these substrates in water under reflux condition (Scheme 3). Only a-naphthol was found to be capable of xmdergoing this reaction as an activated phenol although, the easy purification of products simply by crystallization, the use of water as solvent, and of y-alumina as a heterogeneous and reusable catalyst suggest good prospect for the industrial applicability of this process. A simple, clean, and environmentally... 

A novel kind of thiophosphonodiamide (637) derived from L-valine has been developed as an efficient hydrogen bond donor catalyst in the tandem Michael addition/cyclization reaction between 2-( )-2-nitrovi-nylphenols (634) and malononitrile (635). In the presence of (637), a wide range of highly functionalized 2-amino-4//-chromene derivatives (636) have been obtained in high yields (up to >99%) and with good to excellent enantioselectivities (up to 95% ee) (Scheme 185). ... 

The compound 3-(2-Bromoacetyl)-4-hydroxychromen-2-one (18) reacts with thiourea to afford 3-(2-amino-thiazol-4-yl)-4-hydroxychromen-2-one hydrobromide (19a). This reaction was carried out in boiling ethanol for 30 min. Compound 19a also gave positive coloration with iron(III) chloride solution (Scheme 7). In the reaction of compound 18 with 1-methylthiourea under identical experimental conditions as above, 4-hydroxy-3-(2-methyl-aminothiazol-4-yl)chromen-2-one (19b) in 67% yield was obtained. In a similar manner, 18 reacted with three arylthiourea derivatives affording the corresponding 3-(2-arylthiazol-4-yl)chromen-2-ones (19c-e) in different yields (70, 63 and 74%, respectively). The derivatives formed in these reactions were identified as 4-hydroxy-3-(2-phenylaminothiazol-4-yl)chromen-2-one(19c), 4-hydroxy-3-(2-p-tolylaminothiazol-4-yl)chromen-2-one (19d) and 4-hydroxy-3-2-(4-methoxyphenylamino)thiazol-4-yl)chromen-2-one (19e). The identities of these compounds were established by spectral data and elemental analysis. 

The carbon chain functionalised with the chromone nucleus characterises the patented saccharin derivatives 412 as agents for treating disorders of the central nervous system. As an example, the synthesis of (R)-(-)-[2-[4- (benzyl [7-(benzyloxy)-6-methoxy-3,4-dihydro-2ff-chromen-2-yl]methyl-amino)-2-butynyl]-l,2-benzisothiazol-3(2ff)-one S,S-dioxide (412 = H,... 

When salicylaldehyde is heated with a 2-nitrovinylamine (122), 2-amino-3-nitro-2/f-chromenes (123) are formed. A number of cannabichromene-type compounds have been synthesized, in moderate yields, by condensing citral with the 2-lithio-derivative of a 3-methoxyanisole (124 R = H or alkyl). ... 

However, when 36 was heated with a-amino heterocycles or with cyclic 1,3-dicarbonyl or potential 1,3-dicarbonyl compounds, 3-heteroarylp)rr-azol derivatives were obtained. In this manner 36 afforded, when heated with 2-aminopyridine and 3-amino-lH-pyrazol in acetic acid under reflux for 2 h and 5 h, respectively, 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-4H-pyrido[l,2-fl]pyrimid-4-one (38) and 6-(5-ethoxy-l-phenyl-lH-p5rrazol-3-yl)pyrazolo[l,5-fl]pyrimid-7(lH)-one (39) in 70% and 77% 5deld, respectively. Similarly, 36 afforded with cyclicjS-dicarbonyl compounds, such as 4-hydroxy-6-methyl-2H-pyran-2-one and 5,5-dimethylcyclohexane-l,3-dione by heating in acetic acid for 4 h and 8 h, respectively, the corresponding 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-7-methyl-2H,5H-pyrano[4,3- 7]pyran-2,5-dione (40) and 3-(5-ethoxy-l-phenyl-IH-pyrazol-3-yl)-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5-dione (41) in 26% and 82% yield, respectively (Scheme 15). 

The iron-catalyzed synthesis of dihydro-2H-pyrans, 2H- and 4H-chromenes, chromones, isocoumarins and xanthenes were described in a broad review on the synthesis of heterocycles (14T4827), while the synthesis of 2H-pyran and chroman derivatives, coumarins and xanthone-type compounds was described in a review of recent progress on the chemistry of dimethyl acetylenedicarboxylate (14S537). The synthesis of several polysubstituted spirooxidole-2-amino-4H-pyrans, mainly through three-component reactions, was also described in a review on the synthesis of biologically active spirooxindoles (14T9735). 

The tandem Michael addition-cyclization reaaions of ( )-2-(2-nitrovi-nyl)phenols with malononitrile using a chiral thiophosphonodiamide as catalyst deliver 2-amino-3-cyano-4H-chromenes in high yields (14T181). Other derivatives are obtained from a two-step reaction of benzaldehydes... 

Further designs based on AUDA lead to the preparation of photochromic organogelators [15]. The covalent attachment of a photostimulable chromene unit at the amino terminus of AUDA giving a urethane (13) or amide derivative (15) was accomplished by using an appropriate isocyanate or by DCC condensation of AUDA methyl ester and 3,3-diphenylnaphthopyran-8-carboxylic acid 14 (Scheme 4). 

Kumaravel K, Vasuki G (2009) Four-component catalyst-fiee reaction in water combinatorial library synthesis of novel 2-amino-4-(5-hydroxy-3-methyl-177-pyrazol-4-yl)-47/-chromene-3-carbonitrile derivatives. Green Chem 1 1945-1947... 

Keywords Hydrazine hydrate, ethyl acetoacetate, 2-hydroxy benzaldehydes, malononitrile, water, room temperature, one-pot multicomponent synthesis, 2-amino-4-(5-hydroxy-3-methyl-l//-pyrazol-4-yl)-4//-chromene-3-carbonitrile derivatives... 

Rao Kolia, S., and Lee, Y. R. (2012). Efficient one-pot synthesis of p-phosphono malonates and 2-amino-4//-chromen-4-ylphosphonate derivatives by ethylenediamine diacetate-catalyzed three-component reactions. Tetrahedron, 68, 226-237. 

The quinine-derived thiourea (288b) has been reported to exhibit the highest enantio-selectivity (94% ee) in the addition of malonates RCH(C02R )2 to 2-imino chromenes, affording 2-amino-3-nitrile-chromene (405) with 82-96% ee ... 

The 1,3-dipolar cycloaddition reaction of non-stabilized azomethine ylides, derived from A-alkyl-cf-amino acids, with 3-nitro-2-trifluoro(trichloro)methyl-2//-chromenes produced l-benzopyrano[3,4-c]pyrrolidines in good yields." AgOAc-catalysed asymmetric 3 + 2-cycloaddition reactions of azomethine ylides with e-deficient alkenes yielded enr/o-adducts with up to 99% ee. New chiral ferrocenyl P,N-ligands possessing a benzoxazole ring as the Af-donor (35) are effective asymmetric catalysts... 

For synthesis of pyrayaquinone A and pyrayaquinone B 42) 7-Amino-2,2-dimethyl-chromene (122) prepared from m-hydroxyacet-amide (123) gave on condensation with 2-methylbe(nzoquinone (124) diphenylamine (125) which on cyclisation with pall ium acetate afforded pyrayaquinone A (25). Similarly 5-amino-2,2-dimethylchromene (126) on condensation with 2-methylbenzoquinone (124) afforded the diphenylamine derivative (127) which on cyclisation by the above method furnished pyrayaquinone B (26). 

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