Triton-X-100 as an Organic Catalyst for One-Pot Synthesis of Arylmethyl-H-phosphinic Acids from Red Phosphorus and Arylmethyl Halides in the KOH/H2O/Toluene Multiphase Superbase System
, Svetlana F. Malysheva, Natalia A. Belogorlova, Ruslan I. Fattakhov, Alexander I. Albanov and Boris A. Trofimov *
Round 1
Reviewer 1 Report
The authors reported a simple and mild protocol for the one-pot selective synthesis of arylmethyl-H-phosphinic acids. The micellar catalysis with alkylaryl ether of poly- 101 ethylene glycols could be used for the alkylation/oxidation of red phosphorus in the multiphase aryl- 102 methyl halides/aq.KOH (50-55%)/toluene system. The possible mechanism of this phosphorylation reaction was also proposed. Therefore, this work should be plausible to publish as a research article in Catalysts only after addressing the following issue:
The substrate scope of arylmethyl chlorides in this reaction is very limited. The authors should add some examples bearing different functional groups such as NO2, CN, NMe2, OMe and COR.
Author Response
The substrate scope of arylmethyl chlorides in this reaction is very limited. The authors should add some examples bearing different functional groups such as NO2, CN, NMe2, OMe and COR.
We acknowledge the advice of the respected reviewer to extend the scope of the substrates involved in the phosphorylation reaction. Unfortunately, the strongly basic reaction conditions do not allow the substrates with substituents sensitive to aqueous strong bases to be employed in the process. Nevertheless, to follow the reviewer recommendation, we have tried 4-methoxybenzylchloride as a substrate, which might tolerate the reaction conditions. In this case, the expected 4-methoxybenzyl-H-phosphinic acid was formed in about 10% yield, while the major products were tris(4-methoxybenzyl)phosphine oxide in 26% yield, the small amounts of the corresponding primary 4-benzylphosphine and dibenzylphosphine oxide being also detected. Such a low yield of 4-methoxybenzyl-H-phosphinic acid is explained by very high reactivity of 4-methoxybenzylchloride, which is prone to polycondensation to form oligomers (“Organic Process Research & Development, 2005, vol.9, p.1009-1012, doi:10.1021/op050183f”). It was reported that this methoxybenzyl chloride polymerizes upon storage. The same is true for 4-(N,N-dimethylamino)benzyl chloride, which is, besides, highly toxic.
We also tried 3-acylbenzylchloride, which in the presence of strong bases could undergo aldol/crotone condensation over the ketone function accompanied by solvolysis of the chloromethyl group. Probably these processes indeed took place here because the only product isolated in this case was a polymer containing no phosphorus. Thus, to our regret, we should agree with the respected reviewer that the substrate scope of this reaction is somewhat limited. But at the same time, we would like to draw attention that the synthesis of benzyl-H-phosphinic acids developed by us covers the most practically available substrates and hence may find a wide application. It should also be noted that another major goal of the paper, apart from the synthesis of practically useful compounds, is to promote a commercially available surfactant (Triton-X-100) as an active catalyst, in principle, recyclable for phosphorylation of benzyl chlorides with red phosphorus.
In the light of additional experimental results, the following explanation was included into the manuscript.
Also, the relevant experimental details were added to SI.
For instance, the above side processes were typically expressed in the case of 4-methoxybenzyl chloride: the expected 4-methoxybenzyl-H-phosphinic acid was formed in about 10% yield, while the major products were tris(4-methoxybenzyl)phosphine oxide (δP = 40,8 ppm) in 26% yield, the small amounts of the corresponding primary 4-benzylphosphine (δP = -122 ppm, 1JPH= 194 Hz) and dibenzylphosphine oxide (δP = 36.7 ppm, 1JPH= 469 Hz) being also detected. Such a low yield of 4-methoxybenzyl-H-phosphinic acid is explained by very high reactivity of 4-methoxybenzyl chloride, which is prone to polycondensation to form oligomers (“Organic Process Research & Development, 2005, vol.9, p.1009-1012, doi:10.1021/op050183f”).
Reviewer 2 Report
To
Editor in Chief
Catalysts
Subject- Comments regarding the review of manuscript
Dear Sir,
I have reviewed the manuscript entitled “Triton-X-100 as an Organic Catalyst for One-Pot Synthesis of Arylmethyl-H-phosphinic Acids from Red Phosphorus and Arylmethylhalides in the KOH/H2O/toluene multiphase superbase system”. This research work is written in well manner and covers an important method to synthesize Arylmethyl-H-phosphinic Acids. They studied catalytic activities of several catalysts towards this synthesis and proposed Triton-X-100 as best suitable catalyst. This literature added valuable content toward this topic for further research.
I suggest that some minor corrections that need to be corrected before the publication in your esteem journal and that are as follows-
1. The references cited in the manuscript are outdated. The latest references published within the last five years are strongly required and should account for a maximum of the total references.
2. I believe that, in order to enhance the substrate scope, heterocyclic aromatic compounds should also be used in this synthesis.
3. There are so many typographical errors. Please correct them.
Author Response
I suggest that some minor corrections that need to be corrected before the publication in your esteem journal and that are as follows.
- The references cited in the manuscript are outdated. The latest references published within the last five years are strongly required and should account for a maximum of the total references.
Done as recommended. The references were updated.
- I believe that, in order to enhance the substrate scope, heterocyclic aromatic compounds should also be used in this synthesis.
To meet the reviewer suggestion, we tried in the synthesis 2-chloromethylthiophene, which under optimum conditions gave 2-thienylmethyl-H-phosphinic acid in 6% yield only, while the major product was tris(2-thienylmethyl)phosphine oxide (40% yield). This indicates that the chloromethyl group in this case is more electrophilic compared to that in benzyl chloride and hence nucleophilic substitution of chlorine atom with P-centred anions becomes preferable.
Correspondingly, the following sentences were included in the manuscript
In an attempt to extent the catalytic process studied over heterocyclic analogues of benzyl chlorides, we tried in this synthesis 2-chloromethylthiophene, which under optimum conditions gave 2-thienylmethyl-H-phosphinic acid in 6% yield only, while the major product was tris(2-thienylmethyl)phosphine oxide (40% yield). This indicates that the chloromethyl group in this case is more electrophilic compared to that in benzyl chloride and hence nucleophilic substitution of chlorine atom with P-centred anions becomes preferable. Thus it is obvious that to extend the synthesis over the heterocyclic representatives, a special systematic exploration is required.
- There are so many typographical errors. Please correct them.
Done as recommended
Reviewer 3 Report
The author describes a one-step process for producing arylmethyl-H-phosphinic acids using a KOH/H2O/toluene superbase system and red phosphorus. This process involves the direct phosphorylation of arylmethylhalides through the alkylation/oxidation of red phosphorus with aryl methyl halides mediated by super base hydroxide anions. The micellar organic catalyst Triton-X-100 used in the process demonstrated good recoverability. This paper could be a potential fit for Catalysts due to its synthetic usefulness and innovative approach for one-step synthesis of arylmethyl-H-phosphinic acids. However, several issues will need to be addressed prior to acceptance, as outlined below:
Point 1: On page 2, Scheme 1, please add yield ranges like "32%" to show how the yields of arylmethyl-H-phosphinic acids obtained by different synthesis methods could directly reflect the reaction effect.
Point 2: On page 3, Scheme 4, the product of this example is phosphoric acid, not arylmethyl-H-phosphinic acids. Please explain why it is listed here.
Point 3: On page 5, Table 2, the time unit "h" in "Feeding time of BnCl, h" repeats the expression in the table. Please explain how the feeding time of BnCl affects the reaction. Also, how can you explain that shorter time caused higher conversion of Pred and yield of 2a in entries 8 and 9?
Point 4: Arylmethyl-H-phosphinic acid is formed in the reverse micellar structure of the organic phase. Please explain the source of hydrogen.
Author Response
However, several issues will need to be addressed prior to acceptance, as outlined below:
Point 1: On page 2, Scheme 1, please add yield ranges like "32%" to show how the yields of arylmethyl-H-phosphinic acids obtained by different synthesis methods could directly reflect the reaction effect.
Done as recommended
Point 2: On page 3, Scheme 4, the product of this example is phosphoric acid, not arylmethyl-H-phosphinic acids. Please explain why it is listed here.
In scheme 4, there is shown benzylphosphonic acid (not phosphoric). This scheme is given here just to mention that red phosphorus was previously used (though under acidic conditions) in the synthesis of organophosphorus acids, albeit not those, which are synthesized in this work.
To make the presence of Scheme 4 in text more logic, we re-edited the paragraph related to this Scheme.
Point 3: On page 5, Table 2, the time unit "h" in "Feeding time of BnCl, h" repeats the expression in the table. Please explain how the feeding time of BnCl affects the reaction. Also, how can you explain that shorter time caused higher conversion of Pred and yield of 2a in entries 8 and 9?
To avoid the confusion and to improve understanding the data of Table 2, line 8 was deleted.
Point 4: Arylmethyl-H-phosphinic acid is formed in the reverse micellar structure of the organic phase. Please explain the source of hydrogen.
The source of hydrogen is the isomerization P-P-OH → P(HP=O) occurred in the intermediate E (Scheme 9), in other words, the transformation of tri-coordinated phosphorus to four-coordinated one.
