Selective and clean synthesis of aminoalkyl-H-phosphinic acids from hypophosphorous acid by phospha-Mannich reaction

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F20%3A10413846" target="_blank" >RIV/00216208:11310/20:10413846 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gO5~VBYlSO" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gO5~VBYlSO</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d0ra03075a" target="_blank" >10.1039/d0ra03075a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Selective and clean synthesis of aminoalkyl-H-phosphinic acids from hypophosphorous acid by phospha-Mannich reaction

Popis výsledku v původním jazyce

Aminoalkyl-H-phosphinic acids, also called aminoalkylphosphonous acids, are investigated as biologically active analogues of carboxylic amino acids and/or as valuable intermediates for synthesis of other aminoalkylphosphorus acids. Their synthesis has been mostly accomplished by phospha-Mannich reaction of a P-H precursor, an aldehyde and an amine. The reaction is rarely clean and high-yielding. Here, reaction of H(3)PO(2)with secondary amines and formaldehyde in wet AcOH led to aminomethyl-H-phosphinic acids in nearly quantitative yields and with almost no by-products. Surprisingly, the reaction outcome depended on the basicity of the amines. Amines with pK(a)&gt; 7-8 gave the desired products. For less basic amines, reductiveN-methylation coupled with oxidation of H(3)PO(2)to H(3)PO(3)became a relevant side reaction. Primary amines reacted less clearly and amino-bis(methyl-H-phosphinic acids) were obtained only for very basic amines. Reaction yields with higher aldehydes were lower. Unique carboxylic-phosphinic-phosphonic acids as well as poly(H-phosphinic acids) derived from polyamines were obtained. Synthetic usefulness of the aminoalkyl-H-phosphinic was illustrated in P-H bond oxidation and its addition to double bonds, and in selective amine deprotection. Compounds with an ethylene-diamine fragment,e.g.most common polyazamacrocycles, are not suitable substrates. The X-ray solid-state structures of seventeen aminoalkyl-phosphinic acids were determined. In the reaction mechanism,N-hydroxyalkyl species R2NCH2OH and [R2N(CH2OH)(2)](+), probably stabilized as acetate esters, are suggested as the reactive intermediates. This mechanism is an alternative one to the known phospha-Mannich reaction mechanisms. The conditions can be utilized in syntheses of various aminoalkylphosphorus compounds.

Název v anglickém jazyce

Selective and clean synthesis of aminoalkyl-H-phosphinic acids from hypophosphorous acid by phospha-Mannich reaction

Popis výsledku anglicky

Aminoalkyl-H-phosphinic acids, also called aminoalkylphosphonous acids, are investigated as biologically active analogues of carboxylic amino acids and/or as valuable intermediates for synthesis of other aminoalkylphosphorus acids. Their synthesis has been mostly accomplished by phospha-Mannich reaction of a P-H precursor, an aldehyde and an amine. The reaction is rarely clean and high-yielding. Here, reaction of H(3)PO(2)with secondary amines and formaldehyde in wet AcOH led to aminomethyl-H-phosphinic acids in nearly quantitative yields and with almost no by-products. Surprisingly, the reaction outcome depended on the basicity of the amines. Amines with pK(a)&gt; 7-8 gave the desired products. For less basic amines, reductiveN-methylation coupled with oxidation of H(3)PO(2)to H(3)PO(3)became a relevant side reaction. Primary amines reacted less clearly and amino-bis(methyl-H-phosphinic acids) were obtained only for very basic amines. Reaction yields with higher aldehydes were lower. Unique carboxylic-phosphinic-phosphonic acids as well as poly(H-phosphinic acids) derived from polyamines were obtained. Synthetic usefulness of the aminoalkyl-H-phosphinic was illustrated in P-H bond oxidation and its addition to double bonds, and in selective amine deprotection. Compounds with an ethylene-diamine fragment,e.g.most common polyazamacrocycles, are not suitable substrates. The X-ray solid-state structures of seventeen aminoalkyl-phosphinic acids were determined. In the reaction mechanism,N-hydroxyalkyl species R2NCH2OH and [R2N(CH2OH)(2)](+), probably stabilized as acetate esters, are suggested as the reactive intermediates. This mechanism is an alternative one to the known phospha-Mannich reaction mechanisms. The conditions can be utilized in syntheses of various aminoalkylphosphorus compounds.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/GA19-17380S" target="_blank" >GA19-17380S: Selektivní komplexace kovů polytopickými ligandy jako cesta k biomedicinským próbám se dvěma kovy v jedné molekule</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

RSC Advances

ISSN

2046-2069

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

36

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

21

Strana od-do

21329-21349

Kód UT WoS článku

000542722900032

EID výsledku v databázi Scopus

2-s2.0-85086514909