Potassium Trimethylsilanolate-Mediated Conversion of Dialkyl Phosphonates to Their Anhydrous Potassium Monoalkyl Phosphonates Under Mild, Non-Aqueous Conditions

Abstract

Anhydrous potassium monoalkyl phosphonates have been prepared from the corresponding dialkyl phosphonates and potassium trimethylsilanolate under non-aqueous conditions in good to excellent yields. Simple workup procedure has been developed to afford high purity products.Potassium trimethylsilanolate is a common equivalent of hydroxide anion. It has two unique advantages over hydroxide anion: (i) It has appreciable solubility in organic solvents and (ii) the oxygen silicon bond can be very often easily cleaved under mild reaction conditions. Despite these unique properties, trimethylsilanolates have been mainly reported in a narrow range of reaction, e.g. as polymerisation initiators, 1 as bases to promote elimination of MeOH from b-methoxyketones, 2 in the deprotection of propyne iminium salts, 3 and as a hydroxyl synthon for fluoride S N Ar-type displacement from certain activated aromatics. 4 The most valuable synthetic applications of alkali trimethylsilanolates were reported by Merchant for conversion of nitriles to primary amides, 5 by Laganis and Chenard for preparation of anhydrous carboxylate salts from the corresponding esters and acid chlorides. 6 We have found that potassium trimethylsilanolate is very effective in the conversion of esters with large steric hindrance to corresponding carboxylate salt or acid. 7 Here, we report the use of potassium trimethylsilanolate (KOTMS) to convert dialkyl phosphonates to their anhydrous potassium monoalkyl phosphonates.Base-mediated hydrolysis of dialkyl phosphonates to their monoalkyl phosphonic acid alkali metal salts requires drastic experimental conditions (high pH and prolonged heating times). This method cannot be applied to compounds possessing other base-sensitive functional groups. We have found that treatment of wide range of dialkyl phosphonates with potassium trimethylsilanolate in either anhydrous THF, Et 2 O or CH 2 Cl 2 affords corresponding potassium monoalkyl phosphonates with high purity and yield (Scheme 1). Scheme 1The developed method has two major advantages: firstly, the reaction can be performed in the presence of other functional groups and secondly, as the potassium salts precipitate from Et 2 O, any impurities can be conveniently washed away. The results are summarized in the Table 1.The reaction of calix[4]arene phosphonates with potassium trimethylsilanolate (Table 1, entries 1-4) afforded corresponding potassium monomethyl calix[4]arene phosphonates in excellent yields (84-98%). In contrast, the aqueous basic hydrolysis gave complicated mixture of mono-and dimethyl phosphonates and purification could not be accomplished.The presence of a-protons does not interfere with the desired reaction (entries 5 and 9-16). In particular, we were concerned with proton abstraction from triethyl phosphonoacetate (pK a 11.89, lit. 8 ), but in this case (entries 11-14) KOTMS behaves as a nucleophile rather than a base.The treatment of dimethyl dithiophosphonates (entries 7 and 8) afforded corresponding potassium thiophosphonates in very good yield. T...

Design & Synthesis of Novel Nitrofuranyl Indole Carboxylates as Potential Antibacterial Drug Conjugates

“…Modern reagents have been highly successful in a wide variety of hard to achieve ester hydrolyses, 28,29 not least in accounting for chemoselectivity under mild conditions, 30 however, attempts at hydrolysing 18 via some of the fanciest and most fable ester hydrolysis procedures of the literature, were all nothing but futile (ESI S3 †).…”

Design & Synthesis of Novel Nitrofuranyl Indole Carboxylates as Potential Antibacterial Drug Conjugates

“…Perhaps the most referenced ester hydrolysis under anhydrous conditions in the literature is described by various silyl reagents such as potassium trimethylsilanolate, 34 and trimethylsilyl trifluoromethanesulfonate. 35 However, upon addition of such silyl reagents to carefully dried solutions of 18 in strictly anhydrous organic solvents, a spontaneous decomposition was observed on each and every single occasion, and the clear ruby in colour anhydrous mixtures of 18 all turned completely pitch-black upon addition of silyl reagents thereto.…”