Mixed anhydrides: Key intermediates in carbamates forming processes of industrial interest

Article abstract of DOI:10.1002/1521-3765(20020201)8:3<685::AID-CHEM685>3.0.CO;2-1

Mixed anhydrides of carbonic acid with phosphonic or carbamic acid, are mimic of relevant biological systems, and behave as key intermediates in transesterification processes that afford carbamates of industrial interest. They are formed in the phosphonic acids mediated or direct transesterification reaction of organic carbonates with amines to afford carbamates and have been isolated and characterised in the solid state and solution. Their conversion into the products has been demonstrated to occur with high regioselectivity. The application of such intermediates in some synthetic processes is discussed.

Full text of DOI:10.1002/1521-3765(20020201)8:3<685::AID-CHEM685>3.0.CO;2-1

FULL PAPER
Mixed Anhydrides: Key Intermediates in Carbamates Forming Processes
of Industrial Interest[=]
Michele Aresta* and Angela Dibenedetto[a]
Abstract: Mixed anhydrides of carbonic acid with phosphonic or carbamic acid, are
mimic of relevant biological systems, and behave as key intermediates in trans-
esterification processes that afford carbamates of industrial interest. They are formed
in the phosphonic acids mediated or direct transesterification reaction of organic
carbonates with amines to afford carbamates and have been isolated and
characterised in the solid state and solution. Their conversion into the products
has been demonstrated to occur with high regioselectivity. The application of such
intermediates in some synthetic processes is discussed.
Keywords: anhydrides ¥ carbamates
¥
carbonates ¥ industrial processes ¥
intermediates
Introduction
processes as active form of otherwise much less reactive
species. However, one of the most interesting compounds is
Mixed anhydrides, compounds of general formula
carboxyphosphate (see below)which represents the active
À
X (O)EOE'(O)Y , play an important role as intermediates
form of hydrogencarbonate anion, HCO , used instead of
n
m
3
in biological[ and chemical processes. According to the
nature of E and E' they can be categorized as reported in
Figure (1).
1]
[2]
CO in some natural carboxylation reactions.
[1]
2
In this paper we report the characterisation and reactivity
of mixed anhydrides of formula MAA and MAB which have a
key role in transesterification reactions which convert amines
and organic carbonates into organic carbamates.
O
E
O
organic
E = E' = C (organic)
E'
X, Y = alkyl, aryl, other
X
X
O
O
Y
O
P
O
C
O
C
O
C
O
E
O
R
X
O
OR'
N
O
OR''
organic/
inorganic
E = C (organic)
Y
E'
E' = N, P, S, C (carbonic acid)
X = alkyl, aryl, other; Y = OH, OM, OR, R
m = 1, 2; M = metal ion
R'
Ym
MAA
MAB
O
E
O
inorganic
E = C (carbonic acid)
E, E' = N, P, S
The conversion of the mixed anhydride into the final
product is 100% regioselective, which ensures that mixed
anhydrides react in very selective processes in vitro as they do
in biosystems.
E'
Xn
O
Ym
X, Y = OH, OM, OR, R
n, m = 1, 2; M = metal ion
Figure 1. Categorization of mixed anhydrides.
[
3]
Although they are common intermediates in organic,
Results and Discussion
organometallic,[ and inorganic reactive processes, they
have only seldom been used for solving synthetic problems.
Their role is rarely emphasized and the only review available
in the literature dates back to early sixties.[ In biochemical
systems, mixed anhydrides play a key role in synthetic
4]
[5]
Organic carbamic esters, RR'NCOOR'', find a large utilisa-
tion in the chemical,[ pharmaceutical, and agrochemical
6]
[7]
[8]
2a]
industry. Presently, they are synthesized from phosgene,
mainly as in Equation (1), but also by alternative synthetic
routes if necessary to meet environmental and raw material
diversification issues.
[
a] Prof. M. Aresta, Dr. A. Dibenedetto
Department of Chemistry, University of Bari, and Centro METEA
via Celso Ulpiani 27, 70126 Bari (Italy)
Fax : (‡39)080 544 2429
B
(1a)
ROH + COCl2
ROCOCl + BHCl
E-mail: aresta@metea.uniba.it
[
=] Supported by MURST, Project MM 03027791.
ROCOCl + R'R''NH
B
R'R''NCOOR + BHCl
(1b)
Chem. Eur. J. 2002, 8, No. 3
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685

M. Aresta and A. Dibenedetto
FULL PAPER
Innovative synthetic pathways are reported in Equa-
tions (2)and (3).
However, in order to evaluate the potential of such mixed
anhydrides in synthetic chemistry, we have prepared such
compounds and treated them with amines. XYP(O)ONa, the
B
(
2)
sodium salts of the commercially available acids Ph P(O)OH,
2
RR'NH + CO2 + R''X
RR'NH + (R''O)2C=O
RR'NC(O)OR'' + BHX
RR'NC(O)OR'' + R''OH
(
PhO) P(O)OH, (BuO) P(O)OH, promptly react with organ-
2 2
(3)
ic chloroformates ClC(O)OR to afford mixed anhydrides of
general formula MAA [Eq. (8b)]. The latter then easily
reacts with aliphatic and aromatic amines to afford organic
carbamates [Eq. (9)] and ammonium phosphonate:
which also correspond to the atom economy principle and
reduction of waste.[ These reactions could find an industrial
exploitation, given that fast and selective reactions were to be
developed.
9]
O
P
O
C
In particular, Reaction (3)is attractive, as routes alternative
to phosgene are now available for the synthesis of organic
+ 2 R'R''NH
XYP(O)OR'R''NH2 + R'R''NC(O)OR
X
O
OR
(9)
Y
carbonates as the ENIChem[ [Eq. (4)] and Ube processes
10]
[11]
MAA
[Eq. (5)]:
Thus, MAA acts as an active organic carbonate in a
transesterification process, a reaction of great potential
interest [Eq. (3)] that can be implemented as alternative to
the phosgene amination/alcoholation for the synthesis of
carbamates. However, the synthetic strategy based on the use
of sodium salts of phosphonic acids and chloroformates
[Eq. (8b)] is not economically viable, although it is interesting
for the easy synthesis of MAA. Therefore, we have inves-
tigated alternative ways to the synthesis of the mixed
anhydride MAA. As the acid XYP(O)OH itself promptly
reacts with amines to afford the corresponding ammonium
salt [Eq. (10)], the question arose whether the latter would
efficiently substitute the sodium salt used in our first attempts
or not.
I
II
Cu /Cu
(
(
4)
5)
2
CH3OH + CO + 1/2 O2
CH3OH + CO + 1/2 O2
(CH3O)2CO + H2O
(CH3O)2CO + H2O
II
Pd /NO
2
Reaction (3)requires a catalyst which is often a transition
metal system.[ The major drawback is the concurrent
alkylation/arylation reaction of the amine [Eq. (6), R'' ˆ alk-
yl, aryl].
12]
RR'NH + (R''O)2CO
RR'R''N + R''OH + CO2
(6)
Therefore, the ideal catalyst should not promote the amine
alkylation/arylation [Eq. (6)], while enhancing the carbama-
tion reaction, at moderate temperature, as this parameter may
also play an important role in the byproduct formation.
As we have anticipated, biological systems use mixed
anhydrides in processes related to those described above. A
XYP(O)OH + R'R''NH
XYP(O)O R'R''NH2
(10)
The discovery that the ammonium salts of phosphonic and
phosphinic acids react with organic carbonates [Eq. (11)]
relevant case is represented by the enzyme carboxyphosphate
CP)[ in the carbamation of ammonia or amines [Eq. (7)].
13]
(
(11)
O
P
O
C
+
+
NH3
( O)2P(O)OH + H2NCOO
( O)2P(O)OH + RHNCOO
opened the way to the exploitation of phosphonic acids as
catalysts in the transesterification reaction described in
Scheme 1, which shows how a catalytic cycle can be run based
O
O
O
(7)
O
RNH2
CP
À
CP represents the active form of HCO3 from which it is
generated by reaction with ATP [Eq. (8a)].
O
P
O
P
O
P
O
P
O
C
(8a)
+ HCO3
ADP +
AO
O
O
O
O
O
O
O
O
O
O
Despite several attempts, CP has not yet been synthesized
À
in vitro starting from phosphate and HCO3 or CO . Thus, it
2
has not been possible to demonstrate so far and exploit its
peculiar properties [Eq. (7)] nor those of relevant species.
Mixed anhydrides (MAA)derived from phosphoric/phos-
phonic acids and organic carbonates have structural proper-
ties similar to CP. They can be easily synthesized starting from
the sodium salt of the commercial phosphonic acid, XY-
Scheme 1. Use of phosphonic acids as catalysts in transesterification
reactions for the selective synthesis of carbamates from amines and organic
carbonates.
P(O)OH, and an alkyl ester of the chlorocarbonic acid,[
14]
on the reactions described in Equations (10), (11) and (9),
respectively.
However, the net reaction is represented by Equation (12):
ClC(O)OR [Eq. (8b)].
O
P
O
C
XYP(O)ONa + ClCOOOR
(8b)
X
O
OR
(RO) CO + R'R''NH2
R'R''NC(O)OR + ROH
(12)
2
Y
686
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Chem. Eur. J. 2002, 8, No. 3

Mixed Anhydrides
685±690
The practical interest of such a reaction is demonstrated by
the fact that phosphonic acids have been used as efficient
catalysts in the carbamation of industrially relevant amines
such as TDA and MDA.[
Although all routes described in Reactions (14 a ± c)have
been proven to occur independently, Reaction (14c)is most
likely to be operative under the reaction conditions at least
until a low concentration of free alcohol is present in the
reaction medium. The direct deactivation of the MAA
undergoes an intramolecular rearrangement, and the rate of
deactivation depends on the alcohol used. In the case of
PhOH or MeOH, we have observed that it occurs that the rate
is MeOH > PhOH. It may be worth to note that the rate of the
intramolecular rearrangement reaction follows the trend of
the acidity of the alcohol (pKaPhOH 9.89, pKaMeOH 16), that
means that Reaction (14b)may be operative when the
concentration of free alcohol increases in the medium.
We have found that the species XYP(O)OR is not active in
catalysis when R ˆ Me, while with R ˆ Ph it still has a catalytic
activity. However, the deactivation of the catalyst has been
observed essentially when DMC or MPC is used, while DPC
does not produce any negative effect on the catalyst.
15, 16]
CH3
NH2
H2N
CH2
NH2
NH2
TDA
MDA
The transesterification reaction is carried out treating the
diamine with the organic carbonate under mild conditions
(
360 K)using the carbonate itself as the solvent. The reaction
seems to be of general application. In fact, we have used either
dimethylcarbonate (DMC)or diphenylcarbonate (DPC)or
methylphenylcarbonate (MPC)for the carbamation of both
mono-aromatic amines as aniline or naphthylamine, and the
diamines reported above.
The reaction is very selective (see Experimental Section)
and the alkylation/arylation of the amine is not observed
under the experimental conditions reported above. The
reactivity of carbonates is in the order DPC > MPC > DMC.
Interestingly, MPC behaves as a very selective carboxy-
methylating reagent for aromatic amines with selective
release of phenol instead of methanol [Eq. (13)].
Reaction (14c)is an example of CO 2 elimination from a
mixed anhydride. The process takes place with high regiose-
lectivity. Two pathways are possible for the CO expulsion, as
2
depicted in Scheme 2: a)nucleophilic attack at the P atom by
the RO group; b)electrophilic
O
O
attack by R at the bridging O
atom. Path a)is actually ob-
served as was demonstrated by
labeling the O atoms.
P
C
X
O
OR
b)
Y
a)
Scheme 2. Possible pathways
for CO elimination from the
mixed anhydrides.
Carbamates of TDA and
MDA find an industrial use as
precursor of isocyanates (TDI
O
2
a)
Ar
+
+
PhOH
MeOH
O
N
N
OMe
OPh
H
(
13)
ArNH2 + PhO
OMe
and MDI)which are formed upon controlled thermal treat-
ment of the relevant carbamates.
O
b)
Ar
H
The purity of the carbamates is, thus, of crucial importance
in order to avoid side reactions (for example, ureas formation)
and the reaction based on mixed anhydrides has a good
potential for application purposes.[
Thus, MPC is more reactive and selective than DMC[16] in
the synthesis of the methylcarbamate, and neither the
alkylation nor the arylation of the substrate is observed. The
fact that the carbonate itself can be used as solvent, either
liquid or low melting solid, makes the reaction and recycling
of the catalyst easier as the phosphonic acid can be easily
17]
The high regioselectivity of CO elimination has been also
2
demonstrated using mixed anhydride MAB, which is formed
by reacting ammonium carbamates with organic carbonates.
Mixed anhydrides of the MAB type are known since time.[
According to the amine used, they have been shown to have a
18]
separated as ammonium phosphate and, thus, does not
contaminate the product.[9a, 15]
different stability at room temperature, undergoing CO
2
The catalyst runs for hours, with a 1 ± 3% load with respect
to the amine, the carbonate being both reagent and solvent.
The intermediacy of the mixed anhydride is of crucial
importance in the overall reaction. The deactivation of the
catalyst is caused by the formation of esters of the acid which
can, in principle, be produced either by an intramolecular
rearrangement of the mixed anhydride as in Reaction (14c)or
by reaction of the acid or the mixed anhydride with the
alcohol present in the reaction medium as in Reactions
elimination.[
19]
For a complete characterisation of the system we have
synthesized[ MAB by reacting sodium N-alkylcarbamates
with ClC(O)OMe [Eq. (15), R ˆ benzyl, cyclohexyl, allyl].
19]
RNHCO2Na + ClC(O)OMe
RNHC(O)OC(O)OMe + NaCl
(15)
Either aliphatic or aromatic amine derivatives can be
synthesized in this way and characterized.[ The subsequent
19]
(
14a, b)].
elimination of CO affords organic carbamates as in Equa-
2
tion (16).
XYP(O)OH + ROH
XYP(O)OR + H2O
(14a)
(14b)
(14b×)
(14c)
RNHC(O)OC(O)OMe
RNHC(O)OMe + CO2
(16)
XYP(O)OC(O)OR + ROH
XYP(O)OR + HOC(O)OR
HOC(O)OR
H2O + CO2 + ROH
Again, the reaction per se may have a synthetic interest, but
the reagents used in Reaction (15)render it of no economic
interest.
XYP(O)OC(O)OR
XYP(O)OR + CO2
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687

M. Aresta and A. Dibenedetto
FULL PAPER
However, Reaction (15)provides a means for the isolation
of various MAB, which have been studied for the elimination
mechanism. By using labelled *CO , the reaction has been
2
shown to occur according to the mechanism presented in
Scheme 3a, which represents a quite unique CO -catalyzed
2
1
3
transesterification process. In fact, CO has been recovered
2
Figure 2. Formation trend of aliphatic carbamates.
CO and why it can be accelerated under nitrogen by using
2
ammonium salts, which can speed up the formation of CO2
according to Reaction (17).
Scheme 3. CO
reactivity.
2
catalysis in the formation of mixed anhydrides and their
RNH3Cl + (R'O)2CO
RNH2 + R'OH + CO2 + R'Cl
(17)
at the end of the cycle and 13C NMR experiments have clearly
shown that no C was incorporated into the methylcarbamate
isolated in quantitative yield. This estimate is easily done by
comparing the intensity of the peaks for the carbamic C in
However, also if CO is not added to the amine/carbonate
2
13
system, there may be a CO catalysis, but obviously much less
2
important, due to the limited amount of CO2 formed
concurrently with the alkylation/arylation of the amine by
the organic carbonate.
reactions with labelled and unlabelled CO by allowing the
2
Noteworthy under CO catalysis the alkylation/arylation of
decomposition reaction to occur in an NMR tube. The
reaction clearly takes place through a nucleophilic attack of
carbamic N at carbonic C (path a), Scheme 4) with expulsion
2
the amine proceeds at a much less extent with respect to a
metal catalysed reaction, with a benefit for the whole process.
The usefulness of such synthetic methodology is demonstrat-
ed by the fact that it can be applied to the conversion of
1
3
of CO . The nucleophilic at-
2
1
3
O
O
tack by OR at C would also
have generated the carbamate,
but with C incorporation.
R
13C
12C
functionalized amines, such as silylamines, into carbamates.
N
O
OR
b)
We have reported in a preliminary note[
20, 21]
that silylamines
R'
13
a)
of formula H N(CH ) Si(OMe) , H N(CH ) Si(OEt) , H N-
The global reaction is repre-
sented in Scheme 3a. A better
exploitation of this reaction to
a synthetic end is achieved by
performing the reaction of
2
2
3
3
2
2
3
3
2
Scheme 4. Elimination of CO
from the mixed anhydride to
afford an organic carbamate.
2
(
(
CH ) NH(CH ) Si(OMe) , and H NC(O)NH(CH ) NH-
2 2 2 3 3 2 2 2
CH ) Si(OMe) can be selectively converted into the
2
3
3
corresponding carbamates MeO(O)CNH(CH ) Si(OMe) ,
2
3
3
MeO(O)CNH(CH ) Si(OEt) ,
MeO(O)CNH(CH ) NH-
2 2
2
3
3
(
CH ) Si(OMe) , MeO(O)CNHC(O)NH(CH ) NH(CH ) -
amines with organic carbonates under a CO atmosphere.
2 3 3 2 2 2 3
2
Si(OMe) under mild conditions. The CO catalysis, which
As shown in Scheme 3b, CO behaves as a catalyst and mixed
3
2
2
bears to the formation of mixed anhydrides, appears to be
useful for substituting more drastic conditions and harsh
catalysts.
anhydride MAB has a crucial importance in the formation of
the carbamates from amines and organic carbonates. The
catalytic property of CO is clearly demonstrated by kinetic
2
Mixed anhydrides MAA and MAB are, thus, quite useful
intermediates in a chemistry which is relevant to industrial
processes. They can be used for developing innovative
synthetic methodologies with both waste elimination at the
source and energy-saving costs.
studies which have shown that in absence of CO the reaction
of amines with organic carbonates has an induction time
2
(
Figure 2)of a few hours (c.) The marked difference of
reactivity in presence (a)and absence of CO (c)stimulated us
2
to investigate and explain the reason for such behaviour.
We have shown that in absence of CO , the organic
2
carbonate primarily acts as an alkylating/arylating (depending
[
19]
on the nature of R)agent for the amine [Eq. (6 )] .
Conclusion
This reaction eventually releases CO , which is formed and
2
can be detected in the reaction medium. Once CO is formed,
We have shown that mixed anhydrides of formula XYP(O)O-
C(O)OR and RR'NC(O)OC(O)OR'' can be easily formed
under different conditions in which amines, an organic
2
it reacts with the amine and generates the carbamate, which,
in turn, produces MAB according to Scheme 5b. This explains
why the carbamation reaction starts with a long delay under
carbonate and a phosphonic acid and/or CO are present.
2
N with respect to the case of the reaction carried out under
2
They have an important role as intermediates in chemical
688
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Chem. Eur. J. 2002, 8, No. 3

Mixed Anhydrides
685±690
syntheses, recalling the role of similar compounds in bio-
logical systems. Their formation represents the key step for
evolving selective synthesis of organic carbamates from
amines and organic carbonates in transesterification reactions
to be useful in obtaining industrially relevant compounds.
(1.170 g, 50%). IR (Nujol, KBr disks): nÄ ˆ 3321 (ms, br, nNH), 1715 (s,
n
CO), 1597 (m-s), 1590 (m), 1530 (s), 1488 (m-s), 1443 (s), 1317 (m-s), 1260
À1
1
(
(
(
m), 1223 (s), 1201 (s), 790 (m-s), 755 (s), 724 (m), 694 cm (s); H NMR
CD Cl
, 200 MHz, 293 K): d ˆ 7.46 (m), 7.42 (m), 7.38 (m), 7.34 (m), 7.29
m), 7.26 (m), 7.21 (m), 7.18 (m), 7.15 (tt). Addition of D O reveals the NH
, 50.3 MHz, 293 K): d ˆ
51.79 (br, C(O)O), 150.53 (Cipso, OPh), 137.36 (br, Cipso, NHPh), 129.43/
29.15 (Cmeta, OPh/Cmeta, NHPh)), 125.74 (Cpara, OPh), 123.91 (br, Cpara
2
2
2
1
3
proton at around d ˆ 7.1 ; C ATP NMR (CDCl
3
1
1
,
NHPh), 121.68 (Cortho, OPh), 118.78 (br, Cortho, NHPh); elemental analysis
calcd (%)for C 13 11NO : C 73.22, H 5.20, N 6.57; found: C 73.52, H 5.24, N
.40.
H
2
Experimental Section
6
All reactions and manipulations were carried out under an inert
The same methodology has been used for the synthesis of mono- and
dicarbamates of MDA and TDA.[
15]
atmosphere, by using vacuum line techniques. All solvents were dried as
described in the literature[ and stored under N
22]
.
2
Synthesis of PhCH
2 2 2
NHC(O)OC(O)OMe: A solution of PhCH NH
1
IR spectra were obtained with a Perkin ± Elmer 883 spectrophotometer. H
(1.0 mL, 0.981 g, 9.15 mmol)in diethyl ether (40 mL)was saturated with
1
3
À‡
and C NMR spectra were recorded with a Varian XL-200 spectrometer.
CO
NCH
suspension. The reaction mixture was stirred for 4 h at 233 K under CO
then filtered. The mother solution was collected and evaporated in vacuo.
2
at 233 K to afford benzylammonium carbamate, PhCH
2
NHCOO
3
1
P NMR shifts were referenced to the peak of H
3
PO
4
(85%, ext. ref). GC/
H
3
2
Ph. ClC(O)OMe (0.35 mL, 0.432 g, 4.57 mmol) was added to the
MS analyses were carried out with a gas chromatograph Shimadzu 17A
2
,
(
capillary column: 1000 (30 m  0.00025 m, 0.25 mm thickness)detector
linked to a Shimadzu GCMS-QP 5050 mass. HPLC analyses were
performed with a Perkin Elmer Series 4LC connected with a LC 290
UV/Vis spectrophotometer detector.
A white powder was obtained and identified as PhCH
2
NHC(O)O-
À1
C(O)OMe. IR (Nujol, KBr disks): nÄ ˆ 3360, 1805, 1740 cm (s, br, nCO);
4
elemental analysis calcd (%)for C 10H11NO : C 57.41, H 5.30, N 6.69; found:
C 58, H 5.87, N 7.01.
The synthesis of Group 1 carbamates by using MBPh
been described in ref. [23].
4 2
, CO and amines has
Synthesis of N-benzylmethylcarbamate: A solution of PhCH NH (1.0 mL,
2
2
Synthesis of the mixed anhydride Ph
2
P(O)OC(O)OMe: a)A solution of
0.981 g, 9.15 mmol)in DMC (10 mL)was prepared under N
2
and then
Ph P(O)Cl (0.39 mL, 2.05 mmol) in THF (10 mL) was added to NaO(O)-
2
2
saturated by bubbling CO . A
2 3 2 2
PhCH NH PhCH NHCO
white precipitated identified as
was obtained. The reaction mixture was
heated at 363 K for 24 h. After cooling to room temperature, a small
amount of a white solid was isolated by filtration, which analyzed as
PhCH NH PhCH NHCO . The solution was collected and fractionated
on a silica gel column with diethyl ether/hexane (2:1 v/v)mixture as eluent.
After evaporation of the solvent, the pure carbamate was isolated (1.07 g,
71%). IR (Nujol, KBr disks): nÄ ˆ 3374 (ms), 3350 (m, sh), 1715 (ms, sh),
‡
À
COMe (0.201 g, 2.05 mmol), dispersed in THF (20 mL). The reaction
solution was stirred at 253 K for 24 h, then concentrated to half volume and
filtered at 273 K. The solvent was evaporated in vacuo and the residue, a
‡
À
colorless oil, was identified as Ph
2
P(O)OC(O)OMe (396 mg, 70%). IR
2 3 2 2
À1
(
Nujol, KBr disks): nÄ ˆ 1770 (s, br, nCO), 1591 (m), 1440 (s), 1250 cm (s,
1
br); H NMR (CDCl
CH
3
, 200 MHz, 293 K): d ˆ 7.9 ± 7.3 (10H, Ar), 3.76 (s, 3H,
1
3
2
3
); C NMR (CDCl
3
, 50.3 MHz, 293 K): d ˆ 149.27 (brd, JCOP ˆ 5.6 Hz,
À1
1
OC(O)O), 132.99 (d, JCP ˆ 2.8 Hz, Cpara), 131.59 (JCP ˆ 10.8 Hz, Cortho),
1690 (vs), 1527 (vs), 1274 cm (vs); H NMR (CDCl
3
, 200 MHz, 293 K):
3
1
3
1
2
4
28.71 (JCP ˆ 14.2 Hz, Cmeta), 56.03 (CH
3
); P NMR (CDCl
3
, 50.3 MHz,
: C 60.86, H
d ˆ 7.27 (m, 5H, Haromatic), 5.44 (br, 1H, NH), 4.31 (d, 2H; JHCNH ˆ 5.32 Hz,
1
3
93 K): d ˆ 31.7; elemental analysis calcd (%)for C 14
H
13PO
4
CH
2
), 3.64 (s, 3H, CH
3
); C NMR (CDCl
3
, 200 MHz, 293 K): d ˆ 157.16
3
3
.74, P 11.22; found: C 60.76, H 4.66, P 11.15.
(sept, C(O)O;
J
COCH ˆ JCNCH ˆ 3.8 Hz); 127.43, 127.41, 128.61, 138.60
1
1
(
CAr); 52.20 (q;
J
CH ˆ 146.58 Hz, CH
3
); 45.07 (brt,
J
CH ˆ 137 Hz, CH
2
);
b)ClC(O )O Me (0.201 g, 2.05 mmol)was added to a solution of Ph
2
P(O)O-
elemental analysis calcd (%)for C
9
H
11NO
2
: C 65.45, H 6.67, N 8.48; found:
Na (0.39 mL, 2.05 mmol)in THF (10 mL ). The reaction solution was stirred
at 253 K for 24 h, then concentrated to half volume and filtered at 273 K.
The filtered solvent was evaporated in vacuo and the residue, a colorless
‡
C 65.70, H 6.87, N 8.37; GC/MS: m/e: 165 [M] , 150, 133, 121, 106, 91, 79, 77,
2
8.
1
13
31
Reaction of DMC with cyclohexylamine in the presence of 13CO : A
oil, was identified as Ph
NMR spectra were identical with those obtained for the sample isolated
according to procedure a). Elemental analysis calcd (%) for C14 : C
2
P(O)OC(O)OMe (396 mg, 70%). The H, C, P
2
solution of CyNH2 (2 mL, 1.734 g, 1.75 mmol)in DMC (20 mL)was
1
3
H
13PO
4
prepared under N2 and then saturated with CO2 to give CyN-
‡
13
À
6
0.86, H 4.74, P 11.22; found: C 60.81, H 4.72, P 11.20.
H3 CyNH CO . The reaction mixture was heated to 343 K. The pathway
2
of the reaction was monitored by GC/MS and IR spectroscopy. After 2 h
2 2
Deactivation of the mixed anhydride Ph P(O)OC(O)OMe: Ph P(O)O-
C(O)OMe was prepared as described above in the paragraph a). At 293 K,
both in the pure state and in THF solution, the mixed anhydride slowly
the main product was the cyclohexyl carbamate. IR (Nujol, KBr disks): nÄ ˆ
3
1
1
350 (s), 3320 (ms, sh), 1710 (s, sh), 1685 (vs), 1529 (vs), 1450 (vs), 1317 (v),
275 (s), 1250 (s), 1228 (s), 1052 cm (vs); GC/MS: m/e: 157 [M] , 142, 114,
01, 82, 76, 59, 28.
À1
‡
2 2
decarboxylates and converts into Ph P(O)OMe and CO . The GC/MS of
the reaction solution shows the presence of the diphenylphosphinic acid
methyl ester (m/z 232)in the reaction mixture. At 373 K the decarbox-
ylation reaction is much faster and completed within a few minutes. The
The related mass spectrum showed the I(M‡H)/I(M)isotope ratio which is
in agreement with the value expected for unlabelled carbamate. Moreover,
same behaviour has been observed when Ph
PhP(O)OMe and Ph P(O)OPh have been used as catalysts in the trans-
esterification reactions replacing the free parent acid (see the following
paragraphs)and shown to have a quite different reactivity. Ph P(O)OPh
still has good catalytic properties, while Ph P(O)OMe is totally inactive.
Reaction of Ph P(O)OC(O)OMe with aniline: The mixed anhydride
Ph P(O)OC(O)OMe (1.57 g, 5.7 mmol) was treated with aniline (0.5 mL,
.7 mmol)in THF at room temperature. The reaction immediately took
place and the phosphinic acid Ph P(O)OH and the carbamate
2
P(O)C(O)OPh is used. Both
13
the IR spectrum of the isolated carbamate showed that CO
incorporated into the product.
2
was not
2
[
24]
In a similar manner several other aliphatic amines and aminofunctional
silanes[ were converted into their respective carbamates using organic
carbonates.
2
20]
2
2
2
Kinetic studies to demonstrate the catalytic role of CO : The reaction flask
2
was a 30 mL tube sealed with a two-way valve which allowed withdrawing
of the solution with a chromatography syringe without no air contact. The
reaction was carried out using three different conditions.
5
2
PhHNCOOMe were formed. The aniline carbamate was isolated by
column chromatography, and shown identical with an authentic sample
synthesized by a different procedure.
‡
À
1
)PhCH
and CO
)PhCH NH
DMC (20 mL);
3)PhCH NH
2
NH
; pCO2 ˆ 0.1 MPa; DMC (20 mL);
(18.3 mmol); PhCH NH Cl (9.06 mmol); p 2
3
PhCH
2
NHCO
2
(9.15 mmol)obtained from PhCH
2
NH
2
2
2
2
2
2
3
N
ˆ 0.1 MPa;
Reaction of DPC with aniline in the presence of Ph
N-phenylcarbamate: Ph P(O)OH (0.118 mg, 0.54 mmol) was added to a
2
P(O)OH–Synthesis of
2
solution of aniline (1 mL, 11.4 mmol)and DPC (2.335 g, 10.9 mmol)in
THF (20 mL). The reaction mixture was stirred for 20 hours at 363 K, then
cooled to room temperature and concentrated under reduced pressure.
After addition of hexane (30 mL)the pure carbamate was isolated
2
2
(18.3 mmol); pN2 ˆ 0.1 MPa; DMC (20 mL).
In all cases the reaction vessel was heated to 393 K. At fixed times, the
reaction mixture was cooled to room temperature and a sample analyzed
by HPLC. Data are represented in Figure 3. The complete kinetic study
Chem. Eur. J. 2002, 8, No. 3
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0803-0689 $ 17.50+.50/0
689

M. Aresta and A. Dibenedetto
FULL PAPER
with evaluated DG= and isokinetic temperature estimation can be found in
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Received: July 24, 2001 [F3436]
690
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0803-0690 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 3