Chromene phosphonates

Keywords Chromene phosphonic acid diethyl ester, salicylaldehydes, malononitrile, triethyl phosphate, ethanol, room temperature, one-pot multicomponent synthesis... 

Table 3.20 lists examples of the preparation of oxygen-containing heterocycles by RCM. Further examples, including lactones [895], pyrans [896,897], chromenes [839], tetrahydrofurans [838], phosphonates [898], and oxepines [856,899-902], have been reported. For references to macrocyclizations see Scope and Limitations in this section. 

Budzisz et al. have described the synthesis and the antimicrobial properties of chromone derivatives (01APPMC381). These compounds were synthesized and tested for their antimicrobial activity against Gram-positive and Gramnegative bacteria using naHdixic acid as reference. (NaHdixic acid is one the first synthetic quinolone antibiotic.) The first cycHc phosphonic analogs of chromone 139 were obtained by the reaction of dimethyl 2-methyl- and dimethyl 2-phenyl-4-oxo-4H-chromen-3-ylphosphonate 138 with primary amines (99T4815) (Scheme 31). 

Cyclic (hetero- and carbocyclic) vinyl sulfoxides have been prepared by a tandem Michael addition/Homer olefination reaction of a-phosphorylvinyl sulfoxides and carbonyl compounds bearing a nucleophilic center. Using optically active a-phosphorylvinyl sulfoxides a series of enantiomeric cyclic vinyl sulfoxides in which the chiral sulfinyl group is bonded to a chromene, pyrrazolyne, quinoline or cyclopen-tene ring, has been obtained. The H-W-E reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates (228) represents a new method for the asymmetric synthesis of ring-functionalized cw-2,5-disubstituted 3-oxo pyrrolidines (229) (Scheme 90). ... 

Diethyl (2-amino-3-cyano-8-ethoxy-4//-chromen-4-yl)phosphonate (4a) Reaction tune 35 min yield 82%... 

To a stirred mixture of arylaldehyde (1 1.0 mmol) or salicylaldehyde (1.0 mmol) and malono-nitrile (2 1.0 mmol) in ethanol, triethyl phosphite was added followed by addition of InCls (20 mol%). The reaction mixture was stirred at room temperature until the reaction was completed as monitored by TLC (25-35 min). After completion of the reaction, the mixmre was poured into ice and extracted with EtOAc. The organic extracts were washed with brine solution, dried over Na2S04, and concentrated under vacuum to yield pure diethyl (2-amino-3-cyano-4//-chromen-4-yl) phosphonate (4) in good to excellent yield (70-86%). All the products were characterized from their analytical and detailed spectral studies including IR, NMR, NMR, NMR and MS. 

Jayashree, P., Shanthi, G., and Pemmal, P. T. (2009). Indium trichloride catalyzed one-pot synthesis of new (2-amino-3-cyano-4//-chromen-4-yl) phosphonic acid diethyl ester. Synlett, 917-920. 

Diethyl (2-amino-6,8-dibromo-3-cyano-4//-chromen -yl)phosphonate (4a) Solid, mp 198-200 °C, reaction time 3 h yield 80%... 

Brahmachari, G., and Laskar, S. (2014). Nano-MgO-catalyzed one-pot synthesis of phosphonate ester functionalized 2-amino-3-cyano-4//-chromene scaffolds at room temperature. Phosphorus, Sulfur, and Silicon and the Related Elements, 189, 873-888. 

In 2011, Pore and his group reported a room temperature method for the rapid and efficient synthesis of (2-amino-3-cyano-4//-chromen-4-yl) phosphonic acid diethyl esters (34) via a single-step multi-component reaction of structurally diverse salicylaldehydes (32) with malononitrile (33) and triethyl phosphite, using a catalytic amount of potassium phosphate, in ethanol (Scheme 14). Use of potassium phosphate as an inexpensive catalyst, mild reaction conditions, and a simple work-up procedure are the added advantages of the present method. 

In the following year (2012), Rao Kolia and Lee extended the reaction for the synthesis of such biologically relevant 2-amino-4//-chromen-4-ylphosphonate derivatives (35) from the one-pot three-component condensation of substituted salicylaldehydes, malononitrile (or ethylcyanoacetate) and triethylphosphite in the presence of ethyle-nediamine diacetate (EDDA) as a catalyst in alcohol under room temperature conditions (Scheme 15). Recently, Brahmachari and Laskar (2014) have also developed an energy-efficient multicomponent one-pot procedure for the facile synthesis of a wide range of diverse (2-amino-3-cyano-4/f-chromen-4-yl)phosphonic acid diethyl esters at room temperature from the reaction of salicylaldehydes, malononitrile (or ethyl cyanoacetate) and triethylphosphite on the surface of a reusable heterogeneous MgO-nanocatalyst in aqueous ethanolic... 

Diethyl (2-amino-3-cyano6-methoxy-4H-chromen-4-yl)- Diethyl (2-amino-6.8-dichloro-3-cyano-4H-chroinen-4-yl)-phosphonate (34a solid, mp 172-174 °C yield 88%) phosphonate (34b solid, mp 169-170 °C yield 89%)... 

Scheme 14 Synthesis of (2-amino-3-cyano-4/-/-chromen-4-yl) phosphonic acid diethyl esters using potassium phosphate as catalyst.

Diethyl (2-amino-6,8-dibromo-3-< ano-4H-chromen-4-yl)- Ethyl 2-amino<4-(diethoxyphosphoryl)-6-methyl-phosphonate (35a solid, mp 198-200 X yield 80%) 4H-chromene-3-cart)oxylate (35b oil yield 65%)... 

Scheme 17 Proposed mechanism for the synthesis of 2-amino-3-cyano-4H-chromen-4-yi)phosphonic acid diethyi esters cataiyzed by nano-MgO.

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