Stille reactions with tetraalkylstannanes and phenyltrialkylstannanes in low melting sugar-urea-salt mixtures

Article abstract of DOI:10.1002/adsc.200600248

The transfer of simple alkyl groups in Stille reactions usually requires special solvents (HMPA) or certain organotin reagents (stannatranes, monoorganotin halides) to be efficient. Using low-melting mixtures of sugar, urea and inorganic salt as solvent, a fast and efficient palladium-catalyzed alkyl transfer with tetraalkyltin reagents was observed. The high polarity and nucleophilic character of the solvent melt promotes the reaction. Stille biaryl synthesis using electron-poor and electron-rich aryl bromides proceeds with quantitative yields in the sugar-urea-salt melt. Catalyst loading may be reduced to 0.001 mol% and the catalyst melt mixture remains active in several reaction cycles. Showing the same or improved performance for Stille reactions than organic solvents and allowing a very simple work up, sugar-urea-salt melts are a non-toxic and cheap alternative reaction medium available in bulk quantities for the catalytic process.

Full text of DOI:10.1002/adsc.200600248

UPDATES
DOI: 10.1002/adsc.200600248
Stille Reactions with Tetraalkylstannanes and Phenyltrialkylstan-
nanes in Low Melting Sugar-Urea-Salt Mixtures
a
a
a,
Giovanni Imperato, Rudolf Vasold, and Burkhard Kçnig *
a
Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, 93040 Regensburg, Germany
Phone: (+49)-941-943-4576; fax: +49 941 943 1717; e-mail: burkhard.koenig@chemie.uni-regensburg.de
Received: May 28, 2006; Accepted: August 7, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The transfer of simple alkyl groups in
Stille reactions usually requires special solvents
ports have addressed the problem. Stille reported the
reaction to proceed well in HMPA, DMF and dioxane
[
5,6]
(
HMPA) or certain organotin reagents (stanna-
as solvent.
The addition of diethylamine to the
tranes, monoorganotin halides) to be efficient.
Using low-melting mixtures of sugar, urea and inor-
ganic salt as solvent, a fast and efficient palladium-
catalyzed alkyl transfer with tetraalkyltin reagents
was observed. The high polarity and nucleophilic
character of the solvent melt promotes the reaction.
Stille biaryl synthesis using electron-poor and elec-
tron-rich aryl bromides proceeds with quantitative
yields in the sugar-urea-salt melt. Catalyst loading
may be reduced to 0.001 mol% and the catalyst
melt mixture remains active in several reaction
cycles. Showing the same or improved performance
for Stille reactions than organic solvents and allow-
ing a very simple work up, sugar-urea-salt melts are
a non-toxic and cheap alternative reaction medium
available in bulk quantities for the catalytic process.
Stille alkylation reaction improves yields by reducing
[7]
competing b-hydride elimination and reduction.
Monoorganotin reagents, such as secondary alkyl hal-
[
8]
[9]
ides and stannatranes cross couple efficiently. The
effect of alkylimidazolium salt ionic liquids on the
transfer of alkyl groups from simple tetraorganotin re-
[10,11]
agents to iodobenzene was recently investigated,
but found to be difficult and accompanied by forma-
tion of biphenyl.
Likewise, the synthesis of biaryls by Stille coupling
has become an attractive process with a diverse spec-
trum of application, ranging from pharmaceuticals to
[
12]
material science.
Low-melting sugar-urea-salt mixtures as reaction
media represent a new type of solvent with interesting
[
13]
properties and benefits, such as low cost
and im-
proved safety in comparison to classical organic sol-
vents. The toxicity of the melt ingredients is generally
very low; e.g., NaCl LD50 orally in rats 3.8 gkg ; no
Keywords: carbohydrates; green chemistry; palladi-
um; Stille coupling; turnover number
À1
LD is reported for sorbitol, lactose, urea or dimethy-
5
0
[
14]
lurea. In addition, all components of the carbohy-
drate-based solvents are biodegradable. Furthermore,
a simplified work-up without the use of organic sol-
vents becomes possible. The use reported here of low-
melting sugar-urea-salt mixtures as solvents for effi-
Introduction
The Stille cross-coupling protocol is a powerful and cient Stille alkylation and biaryl synthesis may there-
widely used method for the construction of new fore contribute to a more sustainable chemistry.
[
1–4]
carbon-carbon bonds.
It is defined as the Pd-cata-
lyzed coupling of organic electrophiles, usually halides
or triflates, with organotin reagents. The reaction tol- Results and Discussion
erates a variety of functional groups and most organo-
tin reagents are not sensitive to either oxygen or Mixtures of sugars, urea and inorganic salts, which
moisture, which makes the process very versatile. melt at around 708C were recently introduced as sol-
[
15]
Aryl and alkenyl moieties are rapidly transferred, but vent for Diels–Alder reactions. The polarity of the
[
16]
the scope of the reaction is somewhat limited by the melts is very high,
although they do not contain
low efficiency of alkyl transfer from tetraalkyltin re- any water. The well-documented effect of the solvent
[
17]
agents; for this reason, they are used as non-transfera- polarity and nucleophilic assistance theory
on the
ble ligands in mixed organotin compounds. Several re- Stille alkylation with tetraalkyltin reagents, prompted
Adv. Synth. Catal. 2006, 348, 2243 – 2247
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2243

Giovanni Imperato et al.
UPDATES
us to investigate the reaction in this unusual medium if performed in the sugar-urea-salt melt. The butyl
Scheme 1). Iodobenzene was coupled at 908C with group is even more difficult to transfer from tetrabu-
(
tetravinyltin (entries 1–8, Table 1), tetramethyltin (en- tyltin. Three solvent melts were identified which al-
tries 9–16) and tetrabutyltin (entries 18–24) in differ- lowed a butyl group transfer with yields from 37% to
ent sugar-urea-salt melts using a tris(dibenzylidenea- 44% (entries 19, 20 and 24).
cetone)dipalladium(0) chloroform adduct as palladi-
The work-up of the reactions is very simple: at the
um(0) source and AsPh as ligand. As expected, the end of the reaction water and 1 mL of a hydrocarbon
3
transfer of the vinyl group to the arene is efficient are added. In our experiments pentane was used to
and complete in all experiments. GC analysis of the simplify GC analysis; for larger scale applications hy-
crude product shows that no iodobenzene starting ma- drocarbons with a higher flash point, for example, iso-
terial remains. Alkyl group transfer from tetraalkylor- octane should be used. After filtration, the separated
ganotin reagents typically requires special conditions pentane phase was analyzed by GC-MS. No addition-
(
toxic solvents such as HMPA, DMF or dioxane) or al extraction of the aqueous phase is necessary for
reagents to be effective as discussed above. Therefore, quantitative product isolation.
we were pleasantly surprised to observe product
The composition of the melt significantly affects
yields for the methyl group transfer from tetramethyl- the outcome of the reaction. The mixture of manni-
tin between 45% and 90% (entries 11, 13, 15 and 16) tol-dimethylurea-ammonium chloride (50:40:10) gave
best results for methyl group transfer, while maltose-
dimethylurea-ammonium chloride was good for butyl
group transfer. The presence of dimethylurea is not
crucial; replacing it by urea does not affect the reac-
[
18]
tion, as shown in entry 6. The molecular structure
of the melts is complex and currently we cannot de-
scribe the molecular origin of the differences of the
reaction course in different compositions. Stille alky-
lations in N-butyl-N-methylimidazolium salt ionic liq-
Scheme 1. Stille alkylation in sugar-urea-salt melts.
Table 1. Stille alkylations in sugar-urea-salt melts at a reaction temperature of 908C.
[a]
[b]
[c]
Entry
Composition of melt
R
Reaction time
Conversion [%]
Ph-R [%]
By-product
[
d]
1
2
3
4
5
6
7
8
9
Citric acid/DMU 40:60
C H
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
100
100
100
100
100
100
100
100
25
19
55
18
94
23
49
85
100
90
100
100
100
75
100
100
95
95
100
85
71
97
96
92
20
12
51
10
90
18
45
81
6
14
42
37
25
28
15
44
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
2
3
3
3
3
3
3
3
3
[d]
Sorbitol/DMU /NH Cl 70:20:10
Maltose/DMU /NH Cl 50:40:10
C H
4
2
[d]
C H
4
2
Fructose/Urea/NaCl 70:20:10
C H
2
[
d]
Mannitol/DMU /NH Cl 50:40:10
C H
4
2
Glucose/Urea/NaCl 60:30:10
C H
2
[
d]
Lactose/DMU /NH Cl 60:30:10
C H
4
2
[
d]
Mannose/DMU 30:70
C H
2
[d]
Citric acid/DMU 40:60
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
[
d]
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
Sorbitol/DMU /NH Cl 70:20:10
Maltose/DMU /NH Cl 50:40:10
4
[
d]
4
Fructose/Urea/NaCl 70:20:10
[
d]
Mannitol/DMU /NH Cl 50:40:10
4
Glucose/Urea/NaCl 60:30:10
[
d]
Lactose/DMU /NH Cl 60:30:10
4
[
d]
Mannose/DMU 30:70
[d]
Citric acid/DMU 40:60
C H
benzene
benzene
benzene
benzene
benzene
benzene
benzene
benzene
4
9
9
9
9
9
9
9
9
[
d]
Sorbitol/DMU /NH Cl 70:20:10
Maltose/DMU /NH Cl 50:40:10
C H
4
4
[
d]
C H
4
4
Fructose/Urea/NaCl 70:20:10
C H
4
[
d]
Mannitol/DMU /NH Cl 50:40:10
C H
4
4
Glucose/Urea/NaCl 60:30:10
C H
4
[
d]
Mannose/DMU 30:70
C H
4
[d]
Lactose/DMU /NH Cl 60:30:10
C H
4
4
[
[
[
[
a]
The ratio is given in weight%.
Determined using hexamethylbenzene as internal standard.
Determined by GC-MS analysis.
b]
c]
d]
DMU=dimethylurea.
2244
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2243 – 2247

Stille Reactions with Tetraalkylstannanes and Phenyltrialkylstannanes
UPDATES
[a]
Table 2. Stille coupling of arylbromides and tributylphenylstannane in sugar-urea-salt melts at 908C.
[
b]
[c]
[d]
Entry
1
Composition of melt
Aryl bromide
Product
Conversion /Yield [%]
[e]
Lactose/DMU /NH Cl 60:30:10
100/100
4
[
e]
2
3
4
5
6
7
8
9
Mannitol/DMU /NH Cl 50:40:10
100/100
100/100
90/80
4
[
e]
Maltose/DMU /NH Cl 50:40:10
4
[
e]
Sorbitol/DMU /NH Cl 70:20:10
4
[
e]
Lactose/DMU /NH Cl 60:30:10
100/100
100/100
100/100
100/85
95/90
4
[e]
Mannitol/DMU /NH Cl 50:40:10
4
[
e]
Maltose/DMU /NH Cl 50:40:10
4
[
e]
Sorbitol/DMU /NH Cl 70:20:10
4
[
e]
Lactose/DMU /NH Cl 60:30:10
4
[
e]
1
1
1
0
1
2
Mannitol/DMU /NH Cl 50:40:10
95/90
4
[
e]
Maltose/DMU /NH Cl 50:40:10
95/90
4
[
e]
Sorbitol/DMU /NH Cl 70:20:10
89/85
4
[
a]
To 3 mL of the sugar-urea-salt melt were added 1.5 mmol of aryl bromide, 1.6 mmol of phenyltributylstannane, 1 mol%
Pd (dba) and 4 mol% of AsPh as ligand. The reaction time was 6 h.
b]
ACHTREUNG
2
3
3
[
[
[
[
The composition ratio of the melt is given as weight%.
c]
d]
e]
1
Determined by H NMR of the crude product mixture.
Isolated yield of the analytically pure product after column chromatography (3:1 petrol ether:ethyl acetate).
DMU=dimethylurea.
[
10]
uids yield up to 30% biphenyl as a side product. In tolerate electronic variation of the aryl bromide com-
melted sugar-urea-salt mixtures no biphenyl, but ben- ponent and yield cleanly and in most cases quantita-
zene formation was observed, in the case of tetrabu- tively the biaryl coupling products. Next, the catalyst
tyltin coupling. A reductive process competes with loading was reduced to 0.001% and the coupling of 4-
the slow butyl group transfer.
We started our investigation of Stille biaryl synthe- gated using three different ligands. Table 3 summariz-
sis in sugar-urea-salt melts with the coupling of tribu- es the results. Using Pd (dba) and triphenylarsine as
bromoanisole and phenyltributylstannane was investi-
AHCTREUNG
2
3
tylphenylstannane with 4-bromoanisole and 1-bromo- ligand an 87% yield of isolated product was obtained
-methylbenzene, as electron-rich arenes, and 1- after 48 h, which corresponds to a catalyst turnover
4
bromo-4-nitrobenzene, as an electron-poor arene, number of 87,000. Using (2-biphenyl)dicyclohexyl-
using 1 mol% tris(dibenzylideneacetone)dipalladi- phosphine as ligand or ligandless conditions gives
um(0) as catalyst and AsPh as ligand. The melts con- lower conversion and yields. To benchmark the results
3
sisting of lactose/dimethylurea/NH Cl, maltose/dime- obtained in sugar-urea-salt melts the identical reac-
4
thylurea/NH Cl, mannitol/dimethyluera/NH Cl and tion was performed in 1,4-dioxane (entry 4) yielding
4
4
sorbitol/dimethylurea/NH Cl showed the best results comparable conversion and yield as entry 1.
4
for Stille alkylations and were selected for the biaryl
synthesis. Table 2 summarizes the results.
To test the robustness of the palladium catalyst
under the sugar-urea-salt melt conditions the coupling
Best results were obtained using a melt consisting of 4-bromoanisole with phenyltributylstannane was
of lactose, maltose or mannitol. Reactions in the melt performed at 908C in three subsequent batches using
Adv. Synth. Catal. 2006, 348, 2243 – 2247
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
2245

Giovanni Imperato et al.
UPDATES
Table 3. Stille coupling of 4-bromoanisole and phenyltributylstannane at 908C with different ligands and low catalyst load-
[a]
ing; reaction time 48 h.
[
b]
[c]
[d]
Entry
1
Solvent
Pd (mol%)
0.001%
Ligand
AsPh3
Conversion /yield [%]
[e]
Lactose/DMU /NH Cl 60:30:10
92/87
4
[e]
2
Lactose/DMU /NH Cl 60:30:10
0.001%
65/61
4
[e]
3
4
Lactose/DMU /NH Cl 60:30:10
Dioxane
0.001%
0.001%
No ligand
AsPh3
30/27
87/81
4
[
a]
To 3 mL of sugar-urea-salt melt was added 1.5 mmol of aryl bromide, 1.6 mmol of phenyltributylstannane, 0.001%mol of
Pd (dba) and AsPh as ligand.
ACHTREUNG
2
3
3
[
[
[
[
b]
c]
d]
e]
Composition of the melt given in weight%.
1
Determined by H NMR of the crude product mixture.
Isolated yield of the analytically pure product after column chromatography (3:1 petrol ether:ethyl acetate).
DMU=dimethylurea.
the same catalyst-melt mixture with 0.01 mol% Pd2
The synthesis of biaryls by Stille coupling proceeds
ACHTREUNG
(dba) and 0.04 mol% AsPh as ligand. The conver- in sugar-urea-salt melts with good yields for electron-
3
3
sion of the reaction was determined by removing the poor and electron-rich aryl bromides. The catalyst
organic phase under an argon atmosphere after 12, 24 loading may be reduced to 0.001 mol% still achieving
and 36 h and work-up of this phase. New starting ma- a turnover number of 87,000. Repeated use of the cat-
terial was added to the remaining melt. The catalyst alyst-melt mixture is possible and product isolation
remained active over the three cycles, although a de- does not require the use of organic solvents.
crease in conversion from 83% (first run) to 70%
Overall, the reported reaction conditions allow one
(
second run) and 66% (third run) indicates some loss to perform Stille coupling reactions of aryl iodides
of activity.
and aryl bromides as efficiently as in organic solvents.
Work-up and product isolation determines signifi- The use of polar additives, such as HMPA, is avoided
cantly the overall efficiency of a chemical transforma- and the work-up is simplified. In addition, the reac-
[
14]
tion. Here, the melt mixtures offer a very simple han- tion medium is non-toxic, has a low vapour pres-
[
15]
[19]
dling: after completion of the reaction, simply water sure and presumably high flash points, is rather
[
13]
is added. The components of the melt dissolve in cheap and readily available in bulk quantities. The
water and organic products precipitate amorphously, recycled use of a carbohydrate reaction melt was
the organic product was washed two times with water demonstrated in three cycles of a Stille coupling.
and analytically pure samples are obtained from the However, the economic or ecological benefit from
crude product after recrystallization. Solids with low melt recycling in batch reactions strongly depends on
melting points or liquids are isolated from the water the individual application. Being biodegradable, the
phase with minimal amounts of organic solvents. In disposal of carbohydrate melts may use typical organ-
any case, the work-up is simple and requires no or ic waste streams.
very small amounts of organic solvents for product
isolation.
Experimental Section
Conclusions
General Procedure for Stille Alkylation in Sugar-
Urea-Salt Melts
In summary, we have reported the use of sugar-urea-
salt melts as solvent for Stille alkylations and biaryl All reactions were carried out at 908C (oil bath tempera-
ture) in 10-mL sealed tubes under argon. The use of sealed
synthesis. The transfer of simple alkyl groups, such as
tubes avoids any loss of reagents or products under the reac-
methyl or butyl, which usually requires special re-
tion conditions and ensures a quantitative reaction monitor-
agents or conditions, proceeds smoothly with tetraal-
ing. Chemicals were used as purchased. In a typical experi-
kyltin in this unusual solvent. The high solvent polari-
ment 0.025 mmol of catalyst [tris(dibenzylideneacetone)di-
ty and the presence of nucleophilic groups may pro-
mote the alkyl transfer. The Stille alkylation reaction
in sugar-urea-salt melts is therefore a suitable alterna-
palladium(0)-chloroform adduct], 0.1 mmol of Ph As,
3
0
.4 mmol of iodobenzene and 0.6 mmol of the organostan-
nane were added to the sugar-urea-salt mixture (2.5 mL)
tive to the use of HMPA as solvent or the preparation under argon. The reaction mixture was stirred for 6 h at
of stannatranes for efficient alkyl group transfer. 908C. After cooling to room temperature water was added
2246
www.asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2243 – 2247

Stille Reactions with Tetraalkylstannanes and Phenyltrialkylstannanes
UPDATES
and the product was extracted with pentane (1”1 mL; the
first extraction collects all organic products) and analyzed
by GC-MS after the addition of hexamethylbenzene as an
internal standard.
Scott, G. T. Crisp, J. K. Stille, J. Am. Chem. Soc. 1984,
106, 4630–4632; d) Vinyl iodides: W. F. Goure, M. E.
Wright, P. D. Davis, S. S. Labadie, J. K. Stille, J. Am.
Chem. Soc 1984, 106, 6417–6422.
[
6] a) The addition of copper(I) generally improves the
yields of the Stille reaction: V. Farina, S. Kapadia, B.
Krishnan, C. Wang, L. S. Liebeskind, J. Org. Chem.
General Procedure for Stille Biaryl Synthesis in
Sugar-Urea-Salt Melts
1
994, 59, 5905–5911; b) use of nickel catalysts in car-
All reactions were carried out at 908C (oil bath tempera-
ture) in 10-mL sealed tubes under argon. The use of sealed
tubes avoids any loss of reagents or products under the reac-
tion conditions and ensures a quantitative reaction monitor-
ing. Chemicals were used as purchased. In a typical experi-
ment 1 mol% of catalyst [tris(dibenzylideneacetone)dipalla-
bonylative methylation: M. Tanaka, Synthesis 1981, 47.
7] M. T. Barros, C. D. Maycock, M. I. Madureira, M. R.
Ventura, Chem. Commun. 2001, 1662–1663.
[
[
[
8] D. A. Powell, T. Maki, G. C. Fu, J. Am. Chem. Soc.
2
005, 127, 510–511.
9] For a recent examples, see: a) M. S. Jensen, C. Yang, Y.
Hsiao, N. Rivera, K. M. Wells, J. Y. L. Chung, N.
Yasuda, D. L. Hughes, P. J. Reider, Org. Lett. 2000, 2,
dium(0)-chloroform adduct], 4 mol% of Ph As, 1.5 mmol of
3
aryl bromide and 1.6 mmol of the organostannane were
added to the sugar-urea-salt mixture (3 mL) under argon.
The reaction mixture was stirred for 6 h at 908C. After cool-
ing to room temperature, water was added to the mixture,
which precipitates the organic product. The crude organic
products were collected by filtration and washed with water
1
081–1084; b) A. I. Roshchin, N. A. Bumagin, I. P. Be-
letskaya, Tetrahedron Lett. 1995, 36, 125–128; c) E.
Fouquet, M. Pereyre, A. L. Rodriguez, J. Org. Chem.
1
997, 62, 5242–5243; d) “ligandless” conditions: A.
Herve, A. L. Rodriguez, E. Fouquet, E. J. Org. Chem.
005, 70, 1953–1956.
(
2”15 mL). The NMR analysis indicated that the crude
2
product was >95% pure. The slightly yellow crude product
was further purified by recrystallization or filtration over
silica gel (3:1 petrol ether:ethyl acetate) to give colorless
pure products with analytical data matching all literature re-
ported values.
[
[
[
10] C. Chiappe, G. Imperato, E. Napolitano, D. Pieraccini,
Green Chem. 2004, 6, 33–36.
11] C. Chiappe, D. Pieraccini, D. Zhao, Z. Fei, P. J. Dyson,
Adv. Synth. Catal. 2006, 348, 68–74.
12] K. C. Nicolaou, C. N. C. Boddy, S. Brase, N. Winssinger,
Angew. Chem. Int. Ed. 1999, 38, 2096; S. Kotha, K.
Lahiri, D. Kashinath, Tetrahedron 2002, 58, 9633; A. F.
Littke, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41, 4176.
13] Based on commercial prices for fine chemicals, which
do not fully reflect bulk material cost, the cost of the
sorbitol melt, entry 2 in Table 1, is estimated to be
approx. E 18.00/kg. Prices for DMSO, as a solvent with
comparable properties strongly depend on solvent
purity and are in the order of E 60.00/kg.
Supporting Information
Gas chromatographic analyses of Stille alkylations with tet-
ravinyltin, tetramethyltin and tetrabutyltin in different
sugar-urea-salt melts.
[
Acknowledgements
[
14] The Merck Index: An Encyclopedia of Chemicals,
G.I. thanks the Deutsche Bundesstiftung Umwelt for a gradu-
ate scholarship. We thank the Fonds der Chemischen Indus-
trie for support of the work. We thank Dr. V. Farina and Dr.
E. Napolitano for the helpful discussion.
th
Drugs, and Biologicals, 11 edn, Merck, 1989.
[
15] G. Imperato, E. Eibler, J. Niedermaier, B. Kçnig,
Chem. Commun. 2005, 1170–1172. The thermal stabili-
ty of the melts was determined by differential scanning
calorimetry; data are given in the supporting informa-
tion of the communication.
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[
[
16] The estimated polarity of the melts from solvatochro-
mic measurements is between DMSO and water: G.
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006, DOI: 10.1039/6603660k.
17] E. Napolitano, V. Farina, M. Persico, Organometallics
003, 22, 4030–4037. We underline that the concept of
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1
2
[
2] M. Kosugi, K. Fugami, in: Handbook of Organopalladi-
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2
nucleophilic assistance is only advanced on the basis of
simple kinetics and theoretical calculations and remains
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[
3] Metal-Catalyzed Cross-Coupling Reactions, (Eds.: F.
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[18] Melts containing dimethylurea are thermally more
stable than urea melts, which may produce ammonia at
elevated temperatures.
[19] No flash points are available for the components of the
melt. Only urea and dimethylurea have a significant
vapor pressure and sublime in vacuum.
2
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4
Kikukawa, K. Kono, F. Wada, T. Matsuda, J. Org.
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
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