Ethylenediamine diacetate

As early as 1996, Nelson and Miller (1996) reported initial successful experiments. They synthesized AEG and small amounts of ethylenediamine diacetic acid from mixtures containing ethylenediamine, formaldehyde and HCN thus the formation of AEG (Fig. 6.12) is possible via the Strecker synthesis (see Sect. 4.1). 

As discussed in Section 7.1.4, polymer-bound acetoacetates can be used as precursors for the solid-phase synthesis of enones [33], For these Knoevenagel condensations, the crucial step is to initiate enolization of the CH acidic component. In general, enolization can be initiated with a variety of catalysts (for example, piperidine, piperidinium acetate, ethylenediamine diacetate), but for the microwave-assisted procedure piperidinium acetate was found to be the catalyst of choice, provided that the temperature was kept below 130 °C. At higher reaction temperatures, there is significant cleavage of material from the resin. 

Namely, the reaction of 2-thioxothiazolidin-4-one N-hexanoic acid (116) with 2,5-dimethyl-l-phenylpyrrol-3-carboxaldehyde (117) in methanol under the catalytic action of ethylenediamine diacetate (EDDA) yields 5-[(2,5-dimethyl-l-phenylpyrrol-3-yl)methylidene]-2-thioxothiazolidin-4-one N-hexanoic acid (118) in 79% yield. The hydroxamate derivative of 118 is prepared by reacting this compound with 0-(tetrahydro-2H-pyran-2-yl)hydroxylamine followed by treatment with p-toluenesulfonic acid in methanol to afford compound 121 in 60% yield. Esterification of compound 118 is carried out by using methyl iodide in acetonitrile in the presence of sodium carbonate to give compound 120. The 5-(cyclohexyl)methylidene analogue (119) is obtained in 42% yield by direct reaction of compound 116 with cyclohexanecar-boxaldehyde in methanol under the catalytic action of EDDA. 

Solutions of chromium bis(ethylenediamine)diacetate complex in methanol are capable of reducing simple a,p-unsaturated ketones to the corresponding saturated ketones. Useful yields are obtained provided a proton donor (AcOH) and a good hydrogen donor (BuSH) are present in the reaction mixture (Scheme 16). ... 

The reaction of resorcinols with a,P-unsaturated aldehydes and ketones catalysed by ethylenediamine diacetate has been used to synthesise the naturally occurring chromenes confluentin and daurichromenic acid <05OBC3955, 05TL7539>. 2-Hydroxynaphthoquinone behaves similarly providing a useful route to pyranonaphthoquinones <05S3026>. 

Tietze et al. (88LA9) (Scheme 77) alkylated 2-hydroxybenzaldehyde with 5-bromo-2-methylpent-2-ene and 1 //-pyrrole-2-carbaldehyde with l-bromo-3-methyl-but-2-ene and obtained the corresponding aryl aldehydes 246 and 248. Condensation of the latter with pyrazol-3-one 262 in acetonitrile containing ethylenediamine diacetate as a catalyst provided (7 /Z)-4- 2-[(4-methylpent-3-enyl)oxy]benzylidine -pyrazol-3-one 247 and ( /Z)-4- [l-(3-methylbut-2-enyl)-177-pyrrol-2-yl]methylene -pyrazol-3-one 249, in 67 and 99% yield, respectively. 

EDMA - Ethylenediamine monacetic Acid EDDA - Ethylenediamine diacetic Acid... 

Quinazolines and their spiro derivatives are also available via MCRs in water. The three-component condensation of isatoic anhydride, primary amines and aromatic aldehydes or isatin to give 2,3-dihydroquinazolin-4(l/f)-ones 67 or spiroox-indole derivatives 68 (Scheme 1.36) was performed in water using ethylenediamine diacetate (HDDA) as catalyst [56]. 

Narasimhulu N, Lee YR (2011) Ethylenediamine diacetate-catalyzed three-component reaction for the synthesis of 2,3-dihydroquinazolin-4( 17/)-ones and their spirooxindole derivatives. Tetrahedron 67 9627-9634... 

Types of reaction C-P bond formation Reaction conditions Alcohol, room temperature Synthetic strategy One-pot multicomponent Catalyst Ethylenediamine diacetate (EDDA)... 

Keywords Chromene phosphonates, salicylaldehydes, malononitrile, ethyl cyanoacetate, triethyl phosphate, alcohol, ethylenediamine diacetate (EDDA) room temperature, one-pot multicomponent synthesis... 

To a stirred mixture of arylaldehyde (1 1.0 mmol) or saUcylaldehyde (1.0 mmol), malononi-trile (or ethyl cyanoacetate 2 1.0 mmol) and triethyl phosphite (or phosphite derivative 3 1.0 mmol) in 5 mL of ethanol (or other alcohol), ethylenediamine diacetate EDDA (0.2 mmol) was added. The resulting mixture was stirred at room temperature until completion of the reaction, as indicated by TLC. The reaction mixture was evaporated under reduced pressure and the crude product was purified by silica gel column chromatography using EtOAc/ -hexane as the eluent to give the desired products (4) in good yields. AU the products were characterized from their detailed spectral studies including IR, NMR, NMR, and El- and HR-MS. 

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 tandem Knoevenagel-Diels-Alder sequence is well known, and has been extensively studied by Tietze and others. The Knoevenagel products have been shown to be active as dienophiles in normal-electron-demand Diels-Alder reactions, as well as heterodienes in inverse-electron-demand hetero-Diels-Alder reactions. One of the most elegant examples of a tandem Knoevenagel-hetero-Diels—Alder sequence is Tietze s synthesis of hirsutine 76. In this sequence, a mixture of aldehyde 70, Meldrum s acid 71, enol ether 73 (a mixture of isomers) and a catalytic amount of ethylenediamine diacetate were sonicated in Benzene for 12 h at 60 °C. This effected a cascade sequence that began with Knoevenagel condensation to form the heterodiene 72, followed by intermolecular hetero-Diels-Alder reaction with enol ether 73 to lead to 74, which underwent in situ hydrolysis and decarboxylation to yield intermediate 75 in 84% yield. 

Scheme 15 Synthesis of 2-amino-4H-chromen-4-ylphosphonate derivatives using ethylenediamine diacetate as catalyst.

Recently, Wang and Lee developed a series of reactions involving the ethylenediamine diacetate-catalyzed reactions for the highly efficient synthesis of the biologically interesting poly cycles bearing citran [118], They successfiiUy applied these cyclization reactions to the synthesis of three... 

For the synthesis of desbenzylidenembramin 267, treatment of 148 with 1.2 equiv of citral at 100 °C in the presence of 20mol% ethylenediamine diacetate for 10 h in DMF afforded tetracyclicmonoterpenoid target product 267 in 66% yield [118a]. 

AT-silylated a-substituted a-aminophosphonates (239a) and a,a-di-substituted a-aminophosphonates (239b) have been obtained from aldehydes or ketones, hexamethyldisilazane and diethylphosphite in the presence of ytterbium(III) triflate under mild conditions (Scheme 83). One-pot reaction of arylaldehydes with malononitrile and triethyl phosphite has been carried out in the presence of ethylenediamine diacetate (EDDA) as a catalyst. Thus, the biologically interesting phospho-nates (240) have been obtained in good yields, under mild reaction conditions (Scheme 84). ... 

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