Reactions of dimethyl carbonate with aliphatic amines under high pressure

Article abstract of DOI:10.1080/00397911.2010.501644

A facile synthesis of methyl carbamates from primary amines and dimethyl carbonate has been achieved at room temperature using high pressure. High-pressure synthesis of methyl carbamates described herein provides access to the target molecules in an efficient and environmentally friendly way without solvent or catalyst. Better conversion and selectivity than previously published procedures were obtained. Copyright

Full text of DOI:10.1080/00397911.2010.501644

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Reactions of Dimethyl Carbonate with
Aliphatic Amines Under High Pressure
a
a
a
Davor Margetić , Irena Zrinski Antonac , Zoran Glasovac
,
a
b
Mirjana Eckert-Maksić & Ljiljana Maksimović
a
Laboratory for Physical-Organic Chemistry, Division of Organic
Chemistry and Biochemistry, Ruđer Bošković Institute , Zagreb ,
Croatia
b
PPG Industries, Inc. , Allison Park , Pennsylvania , USA
Published online: 25 May 2011.
To cite this article: Davor Margetić , Irena Zrinski Antonac , Zoran Glasovac , Mirjana Eckert-Maksić
&
Ljiljana Maksimović (2011) Reactions of Dimethyl Carbonate with Aliphatic Amines Under High
Pressure, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 41:15, 2283-2289, DOI: 10.1080/00397911.2010.501644
To link to this article: http://dx.doi.org/10.1080/00397911.2010.501644
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Synthetic Communications , 41: 2283–2289, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.501644
REACTIONS OF DIMETHYL CARBONATE WITH
ALIPHATIC AMINES UNDER HIGH PRESSURE
1
Davor Margeti c´ , Irena Zrinski Antonac, Zoran Glasovac,
1
1
1
Mirjana Eckert-Maksi c´ , and Ljiljana Maksimovi c´
2
1
Laboratory for Physical-Organic Chemistry, Division of Organic Chemistry
and Biochemistry, Ruder Bo ꢀs kovi c´ Institute, Zagreb, Croatia
2
PPG Industries, Inc., Allison Park, Pennsylvania, USA
GRAPHICAL ABSTRACT
Abstract A facile synthesis of methyl carbamates from primary amines and dimethyl
carbonate has been achieved at room temperature using high pressure. High-pressure
synthesis of methyl carbamates described herein provides access to the target molecules
in an efficient and environmentally friendly way without solvent or catalyst. Better conver-
sion and selectivity than previously published procedures were obtained.
Keywords Carbomethylation; dimethyl carbonate; green chemistry; high-pressure
reaction
INTRODUCTION
Environmental concerns have put great pressure on the chemical industry to
[
1]
develop green reagents for organic synthesis. Dimethylcarbonate (DMC) was
found to be a suitable substitute for toxic reagents such as phosgene, alkyl halides,
[
2–4]
and dimethyl sulfate.
Depending on the reaction conditions and hardness of
[
5]
nucleophile, DMC can act either as carbomethylating or methylating agent. For
instance, DMC reacts with alkyl amines at low temperatures to form carbamates.
The uncatalyzed reaction is generally slow and usually accompanied with methyla-
[6]
tion as the most important side reaction. On the other hand, reaction of amines
ꢀ
7,8]
with DMC conducted at elevated temperatures (over 130 C) results in
[
N-methylation as the dominant (or even exclusive) reaction.
[
reactions formation of ureas was also observed.
Besides that, in some
9]
Received March 18, 2010.
Address correspondence to Mirjana Eckert-Maksi c´ , Laboratory for Physical-Organic Chemistry,
Division of Organic Chemistry and Biochemistry, Ruder Bo ꢀs kovi c´ Institute, 10001 Zagreb, Croatia.
E-mail: mmaksic@emma.irb.hr
2
283

´
D. MARGETIC ET AL.
2284
To increase reaction rate and selectivity, various basic and acidic catalysts were
successfully employed: 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 1,5-diazabicyclo-
[
10]
[
triflate,
4.3.0]non-5-ene (DBN), 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU),
ytterbium
thiocyanic
However, design of environ-
[
11,12]
[13]
[14]
[6]
[15]
Lewis acids (Cu,
[7,17,18]
Mn,
and ion exchange resins.
Sc, Y and Yb compounds,
[
acid, ) alkoxides,
16]
[19]
mentally friendly chemical processes implies omission of all unnecessary chemicals
or catalysts, and the specific uncatalysed process is the ultimate goal in green
chemistry.
Our objective in this work was to investigate reaction of DMC with aliphatic
mono- and polyamines under high pressure, with the aim of increasing the rate
and the selectivity of carbomethylation reactions. The major premise for use of high
pressure is the known fact that high pressure is beneficial for number of conden-
[
20,21]
sation reactions.
of alkyl carbamates from primary aliphatic amines and DMC in supercritical carbon
For example, it has been shown that the uncatalyzed synthesis
ꢀ
[22]
dioxide at 130 C readily takes place. Success of the reaction was attributed to the
compressed CO , which favors formation of substituted ammonium carbamate, thus
2
inhibiting the undesirable N-methylation reaction.
RESULTS AND DISCUSSION
In this study, uncatalyzed carbomethylations of benzylamine 1, propylamine 2,
,3-diaminopropane 3, diethylenetriamine 4, bis-(3-aminopropyl)amine 5, and
1
triethylenetetramine 6 (Scheme 1) have been conducted, and results are collected
in Table 1.
The inspection of Table 1 reveals that use of high pressure (8 kbar) has a
beneficial effect on carbomethylation reaction. In spite of the absence of any catalyst,
Scheme 1. Reaction of DMC with the selected amines (1–6) tested under HP conditions.

REACTIONS OF DIMETHYL CARBONATE AND AMINES
2285
a
Table 1. Reactions of DMC with aliphatic amines under high pressure
Entry
Substrate
Product
Pressure (kbar)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
1
1
1
2
2
2
3
3
7
7
7
8
8
8
9
9
8
16
24
100
5
—
—
8
d
24
10
96
5
16
24
—
—
8
d
24
50
60
5
16
24
—
c
1
0
70
5
d
24
9
3
9
—
c
83
1
0
11
11
11
12
12
12
12
12
12
10
11
12
13
14
15
16
17
18
4
4
4
5
5
5
5
5
5
8
—
—
8
16
24
100
42
d
24
81
b
100
16
3
8
100
90
8
0.5
16
16
24
1
100
80
0.05
—
51
e
13
12
46
46
d
24
19
5
—
e
30
1
3
20
21
22
6
6
6
14
14
14
8
16
24
95
17
60
—
—
d
24
a
b
c
Room temperature, DMC=bis-amine ratio 10:1 (5:1 for each amino group).
1
Yields estimated by H NMR spectroscopy.
Monocarbonylated product 10.
ꢀ
d
Reaction was conducted at 50 C.
Monocarbonylated product 13.
e
in most reactions total conversion of amine to carbomethylated product occurred.
For instance, reaction of benzyl amine 1 and DMC at 8 kbar for 16 h resulted in
the total conversion of 1 to carbamate 7 (entry 1), as estimated by NMR analysis.
Under identical reaction conditions (rt, 8 kbar, 24 h), propyl amine 2, 1,3-diamino-
propane 3, diethylenetriamine 4, bis-(3-aminopropyl)amine 5, and triethylenetetra-
mine 6 produced carbamates 8, 9, 11, 12, and 14 in good yields (60–100%) (entries
4
, 7, 10, 13, and 20). Less reactive aromatic amines such as m-anisidine and aniline
gave no reaction.
A comparison of different reaction conditons on the efficiency of biscarbo-
methylation reaction is illustrated for substrate 2 (Fig. 1, Table 1, entries 4–6). When
the reaction time was shortened in the case of bis-(3-aminopropyl)amine 5 from 16 to
3
3
h, a similar result was obtained (entry 14). Further shortening of reaction time to
0 min gave somewhat smaller conversion to bis-carbamate (90%, entry 15). The
reduction of pressure to 1 kbar did not affect full conversion to product 12 (entry
6), while further decrease in reaction pressure to 50 bar diminishes reaction yield
1

´
D. MARGETIC ET AL.
2286
1
Figure 1. High field regions of H NMR spectra for the reaction of 2 with DMC: (a) rt, 24 h (entry 6), (b)
ꢀ
5
0 C, 24 h (entry 6), and (c) rt, 8 kbar, 16 h (entry 4).
to 80% (entry 17). It should be noted that in all experiments conducted under elev-
ated pressure, no presence of monocarbamate was detected. Comparison of these
results with experiments conducted under ambient pressure revealed that high press-
ure significantly enhances reaction rate even without catalysts employed. Reaction of
5
conducted at room temperature for 24 h afforded 51% of bis-carbamate 12 and
ꢀ
4
diminishes the reaction yield of both monocarbamate 13 and dicarbamate 12 (entry
6% of monocarbamate 13 (entry 18, Scheme 2). Increase in temperature to 50 C
1
9). Instead, formation of a side product, presumably cyclic urea, was evident.
It is interesting to note that the presence of a secondary amino group makes a
significant difference in terms of reactivity toward DMC, leading to the unidentified

REACTIONS OF DIMETHYL CARBONATE AND AMINES
2287
Scheme 2. Structure of monocarbamates 10 and 13 formed during the reaction of 3 (and 5) with DMC
under atmospheric pressure.
side reactions. These side reactions are evident only in the cases of triamines 4, 5, and
tetramine 6, when reactions are conducted at atmosperic pressure at room tempera-
ꢀ
ture or at 50 C (entries 11, 12, 21, and 22). No side reaction was detected in
any experiment with diamine 3 (entries 7–9). Evidently, high-pressure conditions
effectively suppressed all undesired side reactions.
CONCLUSIONS
In summary, the high-pressure synthesis of alkyl carbamate described herein
provides access to the target molecules in an efficient and environmentally friendly
way, even without catalyst added. It provides better conversion and selectivity than
previously published procedures. Easy workup procedure and the absence of toxic or
hardly removable side products are also highly advantageous. The reaction could be
applied to different polyamines, providing they have at least one nonaromatic pri-
mary amino group. Furthermore, the presence of secondary amino groups does
not affect reaction yield and composition of products.
EXPERIMENTAL
General Procedure
High-pressure reactions were performed using the high-pressure piston–
cylinder apparatus, and pentane as piezotransmitter liquid in a high pressure Teflon
vessels. Mixtures of DMC (900 mg, 10 mmol) and amine (2 mmol) were subjected to
high pressure at room temperature for the time period indicated in Table 1. Excess of
DMC was removed in vacuo to obtain products, which were analyzed by either gas
1
chromatography (GC) or H NMR spectroscopy. Products obtained in high-
pressure reactions (with the exception of 9) were of sufficient purity to be used
without purification for further chemical transformations. All new compounds gave
satisfactory spectroscopical data.
Selected Spectroscopic Data for Carbamates
1
Compound 7. H NMR (CDCl ): d ¼ 3.66 (3H, s), 4.33 (2H, s), 5.41 (1H, br
3
1
3
s), 7.27–7.28 (5H, m); C NMR (CDCl ): d ¼ 40.3, 47.4, 122.6, 122.7, 123.9, 133.9,
3
1
6
52.5. CHN: calc. for C H N O : C, 65.44; H, 6.71; N, 8.48. Found: C, 65.34; H,
9 11 1 2
.73; N, 8.39.
1
Compound 8. H NMR (CDCl ): d ¼ 0.66 (3H, t, J ¼ 7.2 Hz), 1.23–1.30 (2H,
3
m), 2.86–2.87 (2H, m), 3.38 (3H, s), 5.51 (1H, br s).

´
D. MARGETIC ET AL.
2288
1
Compound 9. H NMR (CDCl ): d ¼ 1.18–1.27 (2H, m), 2.78–2.79 (4H, m),
3
3
.22 (6H, s), 6.25 (2H, br s).
1
Compound 11. H NMR (CDCl ): d ¼ 1.50 (1H, br s), 2.71–2.73 (4H, m),
3
1
3
3
5
4
.18–3.18 (4H, m), 3.58 (6H, s), 5.29 (2H, s); C NMR (CDCl ): d ¼ 40.5, 48.5,
3
1.9, 157.2. CHN: calc. for C H N O : C, 43.83; H, 7.82; N, 19.17. Found: C,
1
0
21
3
4
3.77; H, 7.76; N, 19.09.
1
Compound 12. H NMR (CDCl ): d ¼ 1.43 (1H, br s), 1.64–1.65 (4H, m),
3
1
3
2
.64 (4H, t, J ¼ 6.5 Hz), 3.21–3.27 (4H, m), 3.63 (6H, s), 5.57 (2H, br s);
C
NMR (CDCl ): d ¼ 29.3, 38.9, 46.9, 51.5, 157.1. CHN: calc. for C H N O : C,
1
0
21
3
4
3
4
8.57; H, 8.56; N, 16.99. Found: C, 48.58; H, 8.36; N, 17.02.
1
Compound 14. H NMR (CDCl ): d ¼ 1.77 (2H, br s), 2.33–2.37 (4H, m),
3
2
.60–2.62 (4H, m), 3.11–3.13 (4H, m), 3.60 (6H, s), 5.27 (2H, br s).
ACKNOWLEDGMENT
The authors acknowledge the Croatian Ministry of Science, Education, and
Sport for financial support (Grants 098-0982933-2920 and 098-0982933-3218).
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