Microwave-assisted alcoholysis of dialkyl phosphites by ethylene glycol and ethanolamine

Introduction

Within green chemistry, the use of the microwave (MW) technique is an important tool that offers advantages [1]. The most common benefit is that the reaction times become shorter and the yields are higher. A major advantage is, when a reaction resisting to proceed on thermal heating takes place on MW irradiation. Such reaction is the direct esterification of phosphinic acids [2–4]. There are cases, when MW irradiation may substitute catalysts. This may be exemplified by the MW-assisted alkylation of CH acidic compounds in the presence of K₂CO₃ under solvent-free conditions, when the phase transfer catalyst may be omitted [5–8]. Another good example is the catalyst-free Kabachnik–Fields condensation of aldehydes, amines and dialkyl phosphites under neat conditions to afford α-aminophosphonates [9]. It is also a valuable observation that MW irradiation may make possible the simplification of catalytic systems. This is well demonstrated by the P-ligand-free Hirao reaction in the presence of Pd(OAc)₂ [10, 11]. It was also observed that in phase transfer catalyzed O-alkylations, the effect of the catalyst was synergized by the MW irradiation [12–14].

MW-assisted syntheses proved to be especially useful within organophosphorus chemistry [15–18]. Within acylation, not only the direct esterification of phosphinic acids mentioned above was studied [2–4], but also the thioesterification [19], the amidation [20] and the alcoholysis of phosphinic and phosphonic esters [21].

As a continuation of this project, we aimed at the synthesis of difunctionalized P-intermediates that could be utilized in the preparation of phosphorus-containing macromolecules. The P-functionalized polymers form a representative group within plastics [22, 23]. Utilizing alcoholysis (transesterification), the thermal polycondensation of ethylene glycol, diethylene glycol, triethylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,10-decanediol, resorcinol, hydroquinone, glycerol and pentaerythritol with dialkyl phosphites, especially dimethyl phosphite [24, 25] and the MW-assisted reaction of poly(ethylene glycol) with dimethyl phosphite were described [26]. The potential of the MW technique in the synthesis of polymers was also demonstrated [27].

In this article, we share our results on the MW-assisted reaction of diethyl phosphite with ethylene glycol and ethanolamine. The thermal alcoholysis of dimethyl phosphite with a few diols was described, but no evidence for the structure of the products was presented [28]. In two other articles, the alcoholysis of nucleoside H-phosphonates was investigated [29, 30]. It was shown that the alcoholysis with aminoethanol is catalyzed by the amino-function of the bis-nucleophile [30].

Experimental

The alcoholyses were carried out in a CEM Discover microwave reactor equipped with pressure controller using a ca. 20–30 W irradiation. Standard reaction vessels were used. The ³¹P NMR spectra were recorded on a Bruker DRX-500 spectrometer operating at 202.4 MHz [with a 90° pulse (7.55 μs pulse length) and with a repetition time of 3.08 s]. LC-MS experiments were carried out with an Agilent 1100 liquid chromatography system coupled with a 6120 quadrupole mass spectrometer equipped with an ESI ion source (Agilent Technologies, Palo Alto, CA, USA). Analysis was performed at 40 °C on a Kinetex-XB C18 column (5 cm ∼ 2.1 mm, 2.6 fμm; Phenomenex, Torrance, CA, USA) with a mobile phase flow rate of 0.75 mL/min. Composition of eluent A was 10 mM ammonium-acetate in water (pH 6.5); eluent B was acetonitrile. An isocratic elution was applied with 5 % B for 7 min. The injection volume was 1 μL. The chromatographic profile was registered at 240 nm. The MSD operating parameters were as follows: positive ionization mode, scan spectra from m/z 100 to 1000, drying gas temperature 350 °C, nitrogen flow rate 12 L/min, nebulizer pressure 60 psi, capillary voltage 2500 V.

Results and discussion

The first model to be investigated was the alcoholysis of diethyl phosphite with ethylene glycol under MW conditions. In principle, this reaction may lead to the mixed phosphite (1), the fully transesterified product (2), the bis(phosphonylated)ethylene glycol (3) (Scheme 1) and the cyclic phosphite (CH₂O)₂P(O)H. To find the optimum conditions for the formation of species (2), the alcoholysis was performed using different molar ratios and at different temperatures for different times (Table 1).

Scheme 1

MW-assisted alcoholysis of diethyl phosphite with etylene glycol.

It can be seen that the phosphinate with different substituent (1) was the main component if diethyl phosphite and ethylene glycol was used in a molar ratio of 1:1 at 120–140 °C (Table 1/Entries 1–3). At 120 °C, the maximum conversion was 55 %, while at 140 °C, this number was 67 %, but in the latter case a prolonged heating led to the formation of by-products including the oligomers formed from ethylene glycol. Increasing the previous molar ratio to 1:2, somewhat more (23 %) of the fully transesterified product (2) was formed at 140 °C (Table 1/Entry 4) than in the earlier cases (11–15 %). Applying 4, 6 and 8 equivalents of the ethylene glycol at 140 °C, the proportion of the target compound (2) was 41, 47, and 59 %, respectively (Table 1/Entries 5–7). At the same time, carrying out the alcoholysis at 140 °C with a 2:1 molar ratio of the components, only the mixed ester (1) and the bisphosphorylated ethylene glycol (3) were present in the mixture. Their ratio was 75:25 (Table 1/Entry 8).

The spectral data on which basis the products (1–3) were identified are shown in Table 2.

The next bifunctional nucleophile was ethanolamine in the transesterification of diethyl phosphite. As in earlier cases [30], ethanolamine reacted as an O-nucleophile [Scheme 2/(1)]. The best experiment was, when ethanolamine was used in a 10 equivalents quantity at 140 °C, as in this case, the mixed phosphinate (4) was formed in a proportion of 15 %, while the fully transesterified product (5) in 85 %. In this instance, the conversion was 100 % after 20 min. (Table 3/Entry 4). Decreasing the quantity of ethanolamine to 8, 6 and 4 equivalents, the proportion of target-compound 5 was decreased to 78, 70, and 55 %, respectively (Table 3/Entries 1–3). It is worth mentioning that if the ethanolamine was applied in only a 1–2 equivalents quantity, diethyl phosphite acted as an alkylating agent to furnish ethylaminoethanol (7) and diethylaminoethanol (8) along with ethyl H-phosphonic acid 6 [Scheme 2/(2)]. It is interesting that with this model, the concentration of diethyl phosphite in the mixture has such a great impact on the outcome.

Scheme 2

MW-assisted alcoholysis of diethyl phosphite with ethanolamine.

Table 4 contains the spectral data of species 4–8 on which basis they were characterized.

It was observed that methylaminoethanol failed to react with diethyl phosphite under MW conditions.

It can be said that monomer (H₂NCH₂CH₂O)₂P(O)H can be prepared better than monomer (HOCH₂CH₂O)₂P(O)H by the MW-assisted alcoholysis of diethyl phosphite with the corresponding nucleophile.

It seems to be probable that the alcoholyses take place via 4-membered transition state (TS) coming from the attack of the alcohol on the P=O function of the diethyl phosphite. Such an intermediate (A) was substantiated for the transesterification of dialkyl phosphites by theorethical considerations [32, 33] and by AM1 semiempirical calculations [34]. Similar TSs were suggested in the direct esterification of phosphinic acids (see TS B) by us, where the latter species is autoprotonated by another molecule of phosphinic acid [2], as well as in the non-catalyzed hydrolysis of phosphinate and phosphate esters by thermodynamic calculations [35] (see TS C) and by a comparative ab initio study [34].

The (YCH₂CH₂O)₂P(O)H type intermediates (where Y = OH or NH₂), or the species (YCH₂CH₂O)₂P(O)OH obtained by oxidation of the previous one may be used as starting materials in the synthesis of P-containing polymers. The latter phosphorus acid derivatives may also be prepared by the reactions of phosphoroxychloride with two equivalents of YCH₂CH₂OH followed by hydrolysis.

Conclusion

It was found that under suitable conditions, the MW-assisted alcoholysis of diethyl phosphite with ethylene glycol and ethanolamine may lead to the fully transesterified product (YCH₂CH₂O)₂P(O)H (where Y = OH or NH₂), although the mixed phosphite may also be formed as a minor component and the conversion is quantitative only in the second instance.