Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent
Butyl phenyl-<i>H</i>-phosphinate that is not available commercially was prepared from phenyl-<i>H</i>-phosphinic acid by three methods: by alkylating esterification (i), by microwave-assisted direct esterification (ii), and unexpectedly, by thermal esterification (iii). Cons...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/2/339 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587895402135552 |
|---|---|
| author | Bence Bajusz Dorka Nagy Regina Tóth Zsuzsanna Szalai Ágnes Gömöry Angéla Takács László Kőhidai György Keglevich |
| author_facet | Bence Bajusz Dorka Nagy Regina Tóth Zsuzsanna Szalai Ágnes Gömöry Angéla Takács László Kőhidai György Keglevich |
| author_sort | Bence Bajusz |
| collection | DOAJ |
| description | Butyl phenyl-<i>H</i>-phosphinate that is not available commercially was prepared from phenyl-<i>H</i>-phosphinic acid by three methods: by alkylating esterification (i), by microwave-assisted direct esterification (ii), and unexpectedly, by thermal esterification (iii). Considering the green aspects, selectivity and scalability, the thermal variation seemed to be optimal. However, there was need for prolonged heating. The butyl phenyl-<i>H</i>-phosphinate, along with the ethyl analogue, was utilized in the synthesis of alkyl (α-alkylamino-arylmethyl-)phenyl phosphinates in the aza-Pudovik reaction with imines obtained from primary amines and substituted benzaldehydes. The aminophosphinates were obtained as diastereomeric mixtures in 65–92% yields. The aza-Pudovik approach was more efficient than the Kabachnik–Fields condensation. Interestingly, one aminophosphinate, the butyl (α-butylamino-benzyl-)phenylphosphinate, was of significant cytotoxic activity on the PANC-1 pancreas cell line. Another derivative, ethyl (α-benzylamino-benzyl-)phenylphosphinate, revealed a selective toxic activity on U266 myeloma cells. |
| format | Article |
| id | doaj-art-faadcba6f6b0407798a1d362ea9ac453 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-faadcba6f6b0407798a1d362ea9ac4532025-01-24T13:43:41ZengMDPI AGMolecules1420-30492025-01-0130233910.3390/molecules30020339Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-ReagentBence Bajusz0Dorka Nagy1Regina Tóth2Zsuzsanna Szalai3Ágnes Gömöry4Angéla Takács5László Kőhidai6György Keglevich7Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, HungaryMS Proteomics Research Group, Research Centre for Natural Sciences, 1117 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, HungaryButyl phenyl-<i>H</i>-phosphinate that is not available commercially was prepared from phenyl-<i>H</i>-phosphinic acid by three methods: by alkylating esterification (i), by microwave-assisted direct esterification (ii), and unexpectedly, by thermal esterification (iii). Considering the green aspects, selectivity and scalability, the thermal variation seemed to be optimal. However, there was need for prolonged heating. The butyl phenyl-<i>H</i>-phosphinate, along with the ethyl analogue, was utilized in the synthesis of alkyl (α-alkylamino-arylmethyl-)phenyl phosphinates in the aza-Pudovik reaction with imines obtained from primary amines and substituted benzaldehydes. The aminophosphinates were obtained as diastereomeric mixtures in 65–92% yields. The aza-Pudovik approach was more efficient than the Kabachnik–Fields condensation. Interestingly, one aminophosphinate, the butyl (α-butylamino-benzyl-)phenylphosphinate, was of significant cytotoxic activity on the PANC-1 pancreas cell line. Another derivative, ethyl (α-benzylamino-benzyl-)phenylphosphinate, revealed a selective toxic activity on U266 myeloma cells.https://www.mdpi.com/1420-3049/30/2/339alkyl phenyl-<i>H</i>-phosphinatesaza-Pudovik reactionKabachnik–Fields reactionα-aminophosphinatesmicrowavecytotoxic activity |
| spellingShingle | Bence Bajusz Dorka Nagy Regina Tóth Zsuzsanna Szalai Ágnes Gömöry Angéla Takács László Kőhidai György Keglevich Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent Molecules alkyl phenyl-<i>H</i>-phosphinates aza-Pudovik reaction Kabachnik–Fields reaction α-aminophosphinates microwave cytotoxic activity |
| title | Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent |
| title_full | Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent |
| title_fullStr | Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent |
| title_full_unstemmed | Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent |
| title_short | Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl-<i>H</i>-phosphinate Starting P-Reagent |
| title_sort | synthesis of alkyl α amino benzylphosphinates by the aza pudovik reaction the preparation of the butyl phenyl i h i phosphinate starting p reagent |
| topic | alkyl phenyl-<i>H</i>-phosphinates aza-Pudovik reaction Kabachnik–Fields reaction α-aminophosphinates microwave cytotoxic activity |
| url | https://www.mdpi.com/1420-3049/30/2/339 |
| work_keys_str_mv | AT bencebajusz synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT dorkanagy synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT reginatoth synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT zsuzsannaszalai synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT agnesgomory synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT angelatakacs synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT laszlokohidai synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent AT gyorgykeglevich synthesisofalkylaaminobenzylphosphinatesbytheazapudovikreactionthepreparationofthebutylphenylihiphosphinatestartingpreagent |