Direct estirification and amidation of phosphinic acids under microwave conditions

Article abstract of DOI:10.1080/10426507.2012.743542

Phosphinic acids may be efficiently esterified in microwave-assisted reactions with alcohols. Especially alcohols with longer alkyl chain are suitable reagents for direct esterifications. At the same time, the direct amidation cannot be complete under such conditions. Hence, the tradional amidations via the phosphinic chloride intermediates have to be applied. The values of activation enthalpies and reaction enthalpies obtained by quantum chemical calculations justified the experimental observations. Microwave has a potential in overcoming relatively high activation enthalpies.

Full text of DOI:10.1080/10426507.2012.743542

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Phosphorus, Sulfur, and Silicon and the
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Direct Estirification and Amidation of
Phosphinic Acids Under Microwave
Conditions
György Keglevich a , Nóra Zsuzsa Kiss a , Tamás Körtvélyesi b &
Zoltán Mucsi a
a Department of Organic Chemistry and Technology , Budapest
University of Technology and Economics , Budapest , Hungary
b Department of Physical Chemistry and Material Science , University
of Szeged , Szeged , Hungary
Accepted author version posted online: 14 Nov 2012.Published
online: 08 May 2013.
To cite this article: György Keglevich , Nóra Zsuzsa Kiss , Tamás Körtvélyesi & Zoltán Mucsi (2013):
Direct Estirification and Amidation of Phosphinic Acids Under Microwave Conditions, Phosphorus,
Sulfur, and Silicon and the Related Elements, 188:1-3, 29-32
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Phosphorus, Sulfur, and Silicon, 188:29–32, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.743542
DIRECT ESTIRIFICATION AND AMIDATION OF
PHOSPHINIC ACIDS UNDER MICROWAVE CONDITIONS
Gyo¨rgy Keglevich,1 No´ra Zsuzsa Kiss,1 Tama´s Ko¨rtve´lyesi,2
and Zolta´n Mucsi1
1Department of Organic Chemistry and Technology, Budapest University of
Technology and Economics, Budapest, Hungary
2Department of Physical Chemistry and Material Science, University of Szeged,
Szeged, Hungary
GRAPHICAL ABSTRACT
MW
ROH
MW
H2NR
O
O
O
P
P
P
− H2O
− H2O
NHR
OR
OH
Abstract Phosphinic acids may be efficiently esterified in microwave-assisted reactions with
alcohols. Especially alcohols with longer alkyl chain are suitable reagents for direct esteri-
fications. At the same time, the direct amidation cannot be complete under such conditions.
Hence, the tradional amidations via the phosphinic chloride intermediates have to be applied.
The values of activation enthalpies and reaction enthalpies obtained by quantum chemical
calculations justified the experimental observations. Microwave has a potential in overcoming
relatively high activation enthalpies.
Keywords Phosphinic derivatives; esterification; amidation; microwave; quantum chemical
calculations
The usual way for the preparation of phosphinic esters (2) and amides (3) involves
the reaction of phosphinic chlorides (1) with alcohols and amines, respectively.1
O
O
O
H2NR
ROH
P
3
P
2
P
1
− HCl
− HCl
OR
Cl
NHR
However, it is a disadvantage that the phosphinic chlorides are relatively expensive,
the reactions are not atomic efficient and hydrochloric acid is formed as the by-product. It
is known that phosphinic acids (4) do not undergo direct esterification and amidation.
Received 16 July 2012; accepted 14 October 2012.
Address correspondence to Gyo¨rgy Keglevich, Department of Organic Chemistry and Technology, Budapest
University of Technology and Economics, 1521 Budapest, Hungary. E-mail: gkeglevich@mail.bme.hu
29

30
G. KEGLEVICH ET AL.
Δ
ROH
Δ
H2NR
O
2
P
4
3
OH
It was a challenge for us to attempt the direct derivatization of phosphinic acids
under microwave (MW) conditions. Recent studies showed the potential of MW in organo-
phosphorus chemistry. MW irradiation was successfully applied in C-alkylations, additions,
cycloadditions and condensations.2–4 Cyclic phosphinic acids (5), such as 1-hydroxy-3-
phospholene oxides, 1-hydroxyphospholane oxides and 1-hydroxy-1,2,3,4,5,6-hexahydro-
phosphinine oxides were irradiated in the presence of ca. 15 equivalents of alcohols at
200–230◦C in sealed tubes. The over-pressure developed depended on the volatility of the
alcohols used and falls in the range of 0–14 bar. The phosphinates (6), with one exception,
were obtained in yields of 45–95% (Table 1).5–7
Using longer chain alcohols and applying ca. 210◦C, the esterifications were quanti-
tative. Comparative thermal experiments showed reluctancy of the direct esterifications; in
the best case a conversion of 11% was achieved.
Table 1 Direct esterification of cyclic phosphinic acids
MW
200−230 °C
≤ 14 bar
2−4 h
ROH
(~15 equiv.)
+
P
P
− H2O
O
O
OH
OR
5
6
R
Yield of 6 (%)
Ref.
nBu
58
71
95
7
8
8
Me
C8H17
12H25
(a)
C
nBu
iBu
C8H17
12H25
60
30
95
95
7
7
8
8
Me
Me
(b)
C
Me
nBu
45
74
7
8
(c)
C8H17
nBu
54
70
7
8
Me
Me
(d)
C8H17
Me
nBu
45
7
(e)

DIRECT ESTIRIFICATION AND AMIDATION OF PHOSPHINIC ACIDS
31
Alkylating esterification of the phosphinic acids (5) by alkyl halides was a good alter-
native to prepare the phosphinates (6). These reactions were performed under phase transfer
catalytic (PTC) conditions in the presence of K2CO3 without any solvent (Scheme 1).6,8 In
particular the reactions with alkyl halides of normal reactivity were enhanced by the use of
MW.
MW
100−120 °C
PTC
5 + RX
6
K2CO3
no solvent
(73−98%)
RX = EtI, nPrBr, nBuBr, BnBr
Scheme 1
Regarding the direct amidations of phosphinic acids 5a,c,d our results were more
modest. Under MW conditions the phosphinic amides (8) were formed only in conversions
of ca. 30% (Scheme 2/Route A). Obvious intermediates of these amidations are the corre-
sponding ammonium salts (7) formed from the phosphinic acid (5) and the amine. For the
synthesis of phosphinic amides 8 the traditional method remains which applies phosphinic
chlorides 9 as the starting material (Scheme 2/Route B).
H2NY
MW
5a,c,d
(as above)
+
H2NY
H3NY
− H2O
P
P
P
− HCl
Route B
O
O
O
NHY
O
Cl
Route A
7
8
9
Y = nhexyl, chexyl, Bn
(~84% by Route B)
Scheme 2
However, it was observed that the reaction of phosphinic chlorides 9 with primary
amines was accompanied by the formation of bis(phosphinic) derivatives 10. Moreover,
the reaction could be directed so that the bis(phosphinic) amide 10 was the predominant
product.9
Y = as above
P
P
O
O
N
Y
10
The question arises how it is possible that while the direct esterification of phosphinic
acids 5 is quite efficient under MW conditions, the amidations can only be performed
in low conversions. This experience is the consequence of the thermodynamics of the
reactions. B3LYP/6–31++G(d,p) calculations suggestedthat while the direct esterifications
are thermoneutral, as shown by the reaction enthalpies, the direct amidations are by ca.
30–40 kJ/mol endothermic.

32
G. KEGLEVICH ET AL.
The mechanism of the esterifications and amidations was also investigated by
B3LYP/6–31++ G(d,p) calculations. It was found that both the esterifications and the
amidations take place via four-center transition states like 11 and 12. The activation en-
thalpy leading to them is rather high (ca. 70–160 kJ/mol for the esterifications and ca. 60–90
kJ/mol for the amidations).
HO
P
H
HO
P
H
OR
NHR
OH
11
OH
12
It may be concluded that the esterifications are kinetically controlled and the high
barrier can be overcome by the beneficial effect of MW.
Further evidences have been collected and show that the esterifications are indeed
phosphorylations (acylations) and do not involve alkylations taking place via the SN2 or
SN1 mechanism or via the formation of olefins from the alcohols under the circumstances
of the reaction.
In summary, MW irradiation promotes highly the direct esterification of phosphinic
acids, while the analogous amidations are enhanced only moderately by MW. The practice
and theory are in full agreement.
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R.; Fehe´rva´ri, A.; Csontos, I. Phosphorus, Sulfur Silicon Relat. Elem. 2011, 186, 613-620.
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