Amino acid promoted ullmann type reaction with low catalyst loading via microwave technology

Article abstract of DOI:10.14233/ajchem.2014.16194

This work describes CuBr-catalyzed cross-coupling of sterically hindered phenols with substituted aryl halides and hetero aryl halides under microwave conditions using commercially available amino acids as the reaction promoters and K3PO4 as the base. Thi

Full text of DOI:10.14233/ajchem.2014.16194

Asian Journal of Chemistry; Vol. 26, No. 15 (2014), 4747-4751
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16194
Amino Acid Promoted Ullmann Type Reaction with
Low Catalyst Loading via Microwave Technology
*
K. UMA MAHESHWAR REDDY, K. SANTOSH KUMAR and A. PANASA REDDY
Department of Chemistry, University College of Engineering, Osmania University, Hyderabad-500 007, India
*Corresponding author: Tel: +91 40 27152892; Fax: +91 40 27095171; E-mail: reddypanasa@gmail.com
Received: 16 August 2013;
Accepted: 23 December 2013;
Published online: 16 July 2014;
AJC-15564
This work describes CuBr-catalyzed cross-coupling of sterically hindered phenols with substituted aryl halides and hetero aryl halides
under microwave conditions using commercially available amino acids as the reaction promoters and K3PO4 as the base. This protocol
shown to tolerate sensitive functional groups like CN, CHO etc., Especially, in case of 3-bromopyridine coupling with substituted phenols
supported this letter in track record of the reactivity.
Keywords: Aryl halide, Phenol, Ligand, Microwave.
INTRODUCTION
EXPERIMENTAL
Formation of C-O bond is a key step in synthetic chemistry
due to the importance of diaryl ether unit represents a very
important class of organic compounds1,2. The versatile strate-
gies to access diaryl ethers directly by the reaction of aryl
halide with phenols promoted by Cu-reagents3. Ullmann disco-
vered copper-catalyzed O-arylations of phenols with aryl
halides4. However, synthetic scope of this reaction conditions
are rather limited due to harsh reaction conditions, usually at
high temperatures (125-250 °C) in pyridine solvent, greater
quantities of the copper catalyst required and the low to
moderate yields. In recent modifications reported that the use
of catalyst-ligand combinations enhance the reaction rate and
allow the couplings to be carried out under milder reaction
conditions in the presence of catalytic amount of copper5-7.
Although several ligands such as 2,2,6,6,-tetramethyl-heptane-
3,5-dione (THMD)7b, N,N-dimethylglycine8 have been repor-
ted as reaction promoters, with different Cu source and ligand
combinations9,10 in the presence of different bases like K2CO3,
Cs2CO3 in polar, non polar solvents, these catalytic systems
still suffer from several common problems like stachiometric
quantity of ligand loading and high temperature.
General procedure: CuBr (2 mol %), L-proline (5 mol %),
aryl halide (1 eq), ArOH (1.05 eq) and K3PO4 (2.5 eq) were
suspended in DMF (3 mL) in a microwave vial. The tube was
then evacuated and backfilled with nitrogen. The vial was sealed
and placed in the Dicover-CEM microwave synthesizer;
(temperature was controlled using the in-built calibrated IR
sensor) and reaction mixture was irradiated at 70 °C in micro-
wave for 15-30 min (time variable for the different reactant).
In 2-3 min reaction temperature attained to 70 °C and 3 bar
pressure. The reaction mixture was cooled to room temperature
and further diluted with water (10 mL) and ethyl acetate (30 mL).
The organic layer was separated and back extracted twice with
ethyl acetate (20 mL). The combined organic layers were dried
over anhyd. Na2SO4 and concentrated via rota evaporator. The
residue was purified through silica gel (60-120 mesh) column
chromatography to afford diaryl ether product Scheme-I.
CuBr 2 mol%
O
CN
ligand 5 mol%
Cl
HO
CN
K3PO4 (2.5 eq); DMF
H3CO
H3CO
Reactant 1
MW; 15-30 min;
Product
Reactant 2
Yet, the development of this copper catalyzed Ullmann-
type reaction is required all the times most catalytic systems
still needed long reaction time (longer than 24 h), relatively
high temperature (≥ 120 °C) and high ratios of catalyst loading.
We focused on development of cost effective, efficient catalytic
system and the lowering the reaction time, temperature by
adopting microwave technology11.
Scheme 1:Copper-catalyzed coupling of 4-chloroanisole with 3-hydroxy
benzonitrile
3-(4-Methoxyphenoxy)benzonitrile (1c): Pale white
colour solid, m.p. 106-108 °C; 1H NMR (400 MHz, DMSOd6:
δ (ppm) 7.38 (t, J = 8.0 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H),
7.19-7.13 (m, 2H), 7.00-6.92 (m, 4H), 3.82 (s, 3H); 13C NMR

4748 Reddy et al.
Asian J. Chem.
(100 MHz, CDCl3): δ (ppm) 159.2, 156.8, 148.4, 130.5, 125.7,
121.7, 121.4, 119.9, 118.3, 115.2, 113.4, 55.6; MS (ESI) m/z
(M + H)+: 226.0; Anal. calcd. for C14H11NO2: C, 74.65; H,
4.92; N, 6.22; O, 14.21. Found: C, 74.75; H, 5.28.
4.0, 1H), 7.37-7.31 (m, 3H), 7.10 (dd, J = 3.4 Hz, 6.0 Hz, 1H),
3.09-3.02 (m, 1H), 1.16 (d, J = 6.8 Hz, 6H); 13C NMR (100
MHz, CDCl3): δ (ppm) 157.5, 150.8, 141.3, 140.7, 129.5,
127.8, 127.6, 126.5, 122.5, 120.6, 117.2, 27.1, 23.02; MS (ESI)
m/z (M + H)+: 239.02; Anal. calcd. for C15H14N2O: C, 75.61;
H, 5.92; N, 11.76; O, 6.71. Found: C, 75.74; H, 5.99.
3-(4-Methoxyphenoxy)benzaldehyde (2c): Colour less
syrup, 1H NMR (400 MHz, DMSOd6): δ (ppm) 9.95 (s, 1H),
7.63-7.59 (m, 2H), 7.32-7.30 (m, 2H), 7.08 (d, J = 6.8, 2H),
7.01 (d, J = 6.8, 2H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ (ppm) 191.7, 159.2, 156.5, 149.1, 130.3, 124.1, 123.5, 121.2,
119.5, 116.8, 115.1, 55.6; MS (ESI) m/z (M + H): 229.04;
Anal. calcd. for C14H12O3: C, 73.67; H, 5.30; O, 21.03. Found:
C, 73.73; H, 5.41;Anal. calcd. for C14H12O3: C, 73.67; H, 5.30;
O, 21.03. Found: C, 73.72; H, 5.40.
4-(2-Isopropylphenoxy)isoquinoline (9c): Pale brown
syrup, 1H NMR (400 MHz, DMSOd6): δ (ppm) 9.11 (s, 1H),
8.22 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.4, 1H), 7.90-7.77 (m,
3H), 7.48 (q, 1H), 7.24-7.22 (m, 2H) 6.92-6.90 (m, 1H), 3.28
(m, 1H), 1.25 (d, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3):
δ (ppm) 153.4, 149.5, 146.7, 139.7, 130.1, 129.5, 128.9, 127.8,
127.2, 127.2, 127.1, 127.7, 121.1, 119.3, 27.3, 23.0; MS (ESI)
m/z (M + H)+: 264.01; C18H17NO Anal. calcd. for C15H14N2O:
C, 82.10; H, 6.51; N, 5.32; O, 6.08. Found: C, 82.24; H, 6.45.
2-(Pyridin-3-yloxy)benzaldehyde (10c): Yellow
4-(4-Methoxyphenoxy)benzaldehyde (3c): Pale white
colour solid; m.p. 57-62 °C; 1H NMR (400 MHz, DMSOd6):
δ (ppm) 9.90 (s, 1H), 7.89 (d, J = 6.8 Hz, 2H), 7.11 (d, J = 6.8
Hz, 2H), 7.06-7.02 (m, 4H), 3.78 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ (ppm) 190.7, 164.1, 156.9, 148.2, 131.9, 130.9,
121.8, 116.7, 115.1, 55.6; MS (ESI) m/z (M + H)+ : 229.04;
Anal. calcd. for C14H12O3: C, 73.67; H, 5.30; O, 21.03. Found:
C, 73.73; H, 5.41.
1
crystalline solid; m.p. 75-79 °C; H NMR (400 MHz,
DMSOd6): δ (ppm) 10.41 (s, 1H), 8.50 (d, J = 2.8 Hz, 1H),
8.45 (dd, J = 1.2 Hz, 4.4 Hz, 1H), 7.89 (dd, J = 2.0 Hz, 8.0 Hz,
1H), 7.70 (d, J = 7.6 Hz, 1H), 7.60-7.57 (m, 1H), 7.50-7.47
(m, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ (ppm) 186.6, 158.8, 153.1, 145.3,
141.5, 135.9, 129.0, 127.1, 126.3, 124.4, 124.3, 118.4; MS
(ESI) m/z (M + H)+: 200.2;Anal. calcd. for C12H9NO2: C, 72.35;
H, 4.55; N, 7.03; O, 16.06. Found: C, 72.45; H, 4.64.
2-(4-Methoxyphenoxy)-5-(benzyloxy)benzaldehyde
(4c): Pale light colour solid, m.p. 121-125 °C; 1H NMR (400
MHz, DMSOd6): δ (ppm)10.33 (s, 1H), 7.47-7.31 (m, 7H),
7.05-6.89 (m, 5H), 5.15 (s, 2H), 3.75 (s, 3H); 13C NMR (100
MHz, CDCl3): δ (ppm) 189.2, 156.1, 155.0, 154.4, 150.6,
136.4, 128.6, 128.1, 127.6, 127.0, 124.3, 120.0, 119.9, 115.6,
111.0, 70.6, 55.7; MS (ESI) m/z (M + H)+: 335.1; Anal. calcd.
for C21H18O4: C, 75.43; H, 5.43; O, 19.14. Found: C, 75.52; H,
5.51.
4-Methoxy-3-(pyridin-3-yloxy)benzaldehyde (11c):
1
Pale yellow syrup, H NMR (400 MHz, DMSOd6): δ (ppm)
9.84 (s, 1 H), 8.35 (s, 2H), 7.72 (dd, J = 2.0, 8.4 Hz, 1H), 7.52
(d, J = 1.6 Hz, 1H), 7.25-7.32 (m, 2H), 7.12 (d, J = 8.4 Hz,
1H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm) 190.0,
156.3, 153.7, 144.9, 144.3, 140.1, 130.3, 129.0, 124.2, 120.5,
112.3, 56.2 ppm; MS (ESI) m/z (M + H)+: 230.1; Anal. calcd.
for C13H11NO3: C, 68.11; H, 4.84; N, 6.11; O, 20.94. Found:
C, 68.23; H, 4.95.
1-[4-(2-Methoxyphenoxy)phenyl]ethanone (5c): Colour
less syrup, 1H NMR (400 MHz, DMSOd6): δ (ppm) 7.93 (d, J
= 9.6 Hz 2H), 7.31-7.15 (m, 3H), 7.03 (t, J = 7.6 Hz 1H), 6.88
(d, J = 9.6 Hz, 2H), 3.73 (s, 3H), 2.51(s, 3H); 13C NMR (100
MHz, CDCl3): δ (ppm) 196.7, 162.4, 151.7, 143.2, 131.4,
130.4, 126.1, 122.4, 121.3, 115.7, 113.0, 55.8, 26 ppm. MS
(ESI) m/z (M + H)+: 243.05;Anal. calcd. for C15H14O3: C, 74.36;
H, 5.82; O, 19.81. Found: C, 74.45; H, 5.93.
1-(4-(Thiazol-2-yloxy)phenyl)ethanone (12c): Pale
1
brown semisolid; H NMR (400 MHz, DMSOd6): δ (ppm)
8.06 (d, J = 6.8 Hz, 2H), 7.46 (d, J = 6.8 Hz, 2H), 7.35 (d, J =
6.4 Hz, 2H), 2.60 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
(ppm) 196.6, 172.0, 158.9, 137.6, 134.2, 130.4, 119.4, 113.9,
26.5 ppm. MS (ESI) m/z (M + H)+: 220; Anal. calcd. for
C11H9NO2S: C, 60.26; H, 4.14; N, 6.39; O, 14.59; S, 14.62.
Found: C, 60.35; H,4.22.
3-(2-Formylphenoxy)benzonitrile (6c): Pale white
colour solid, m.p. 80- 84 °C; 1H NMR (400 MHz, DMSOd6):
δ (ppm) 10.32 (s, 1H), 7.91 (d, J = 1.2 Hz, 1H), 7.89-7.62 (m,
4H), 7.48 (t, J = 1.2 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.08 (d,
J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm) 189.4,
158.1, 157.2, 136.9, 132.1, 129.5, 128.4, 127.4, 125.2, 124.4,
122.8, 120.1, 118.4, 113.3; MS (ESI) m/z (M + H)+ : 224.03;
Anal. calcd. for C14H9NO2: C, 75.33; H, 4.06; N, 6.27; O, 14.33.
Found: C, 75.71; H, 4.12.
6-(Pyridin-3-yloxy)pyridine-3-carbonitrile (13c): Pale
yellow gummy solid; 1H NMR (400 MHz, DMSOd6): δ (ppm)
8.66 (d, J = 2.4 Hz, 1H), 8.53-8.50 (m, 2H), 8.38 (d, J = 8.8
Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.54-7.51 (m, 1H), 7.37 (d,
J = 8.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 164.7,
162.5, 151.7, 149.2, 146.7, 143.6, 142.5, 129.1, 127.1, 116.4,
112.3, 104.8. MS (ESI) m/z (M + H)+: 198.2; Anal. calcd. for
C11H7N3O:C, 67.00; H, 3.58; N, 21.31; O, 8.11. Found: C,
67.23; H, 3.95.
1
2-(O-tolyloxy)naphthalene (7c): Colourless syrup; H
NMR (400 MHz, DMSOd6): δ (ppm) 7.95 (d, J = 9.2 Hz, 1H),
7.90 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.48-7.37
(m, 3H) 7.29-7.25 (m, 2H), 7.19-7.14 (m, 2H), 7.00 (d, J =
8.0 Hz, 1H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
(ppm) 155.8, 154.3, 134.4, 131.5, 130.2, 129.8, 129.7, 127.7,
127.2, 126.4, 124.2, 120.1, 119.1, 111.6, 16.2; MS (ESI) m/z
(M + H)+ : 235.01; Anal. calcd. for C17H14O: C, C, 87.15; H,
6.02; O, 6.83. Found: C, 87.23; H, 6.12.
5-(Quinolin-3-yloxy)pyridine-3-carbaldehyde(14c):
1
pale yellow syrup, H NMR (400 MHz, DMSOd6): δ (ppm)
10.12 (s, 1H), 8.93 (d, J = 1.6 Hz, 1H), 8.89 (dd, J = 1.6 Hz,
4.0 Hz, 1H), 8.81(d, J = 2.8 Hz, 1H), 8.32 (dd, J = 1.2 Hz, J =
8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.88-7.87 (m, 1H), 7.67
(d, J = 2.8 Hz, 1H), 7.64 (s, 1H), 7.57-7.59 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ (ppm) 191.9, 153.5, 153.3, 149.8, 146.3,
146.1, 145.0, 135.4, 132.2, 131.5, 128.7, 124.3, 122.9, 122.0,
5-(2-Isopropylphenoxy)pyridine-2-carbonitrile (8c):
1
Pale yellow syrup, H NMR (400 MHz, DMSOd6): δ (ppm)
8.50 (d, J = 2.4 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.50 (d, J =

Vol. 26, No. 15 (2014)
Amino Acid Promoted Ullmann Type Reaction with Low Catalyst 4749
114.5; MS (ESI) m/z (M + H)+: 251.5; Anal. calcd. for
C15H10N2O2: C, 71.99; H, 4.03; N, 11.19; O, 12.79 Found: C,
72.08; H, 4.14.
We were curious about effect of substituent on the rate of
the coupling reaction. Generally, ortho-substituted phenol
coupling partners are often challenging due to steric hindrance.
By using the optimized conditions ortho-substituted halides
could be coupled with a variety of phenols (entriy 6). Electron-
donating groups on the phenol and electron-withdrawing
groups on the aryl halides make the reaction favourable.
Electron withdrawing group of ortho-substituted phenols
effectively formed ethers with hetero-aryl halides (entries
7-11) gave above 85 % yields. The steric hindrance of phenols
usually slightly disfavoured for the reaction. 4-Chloro-
acetophenone was used as the substrate and reacted with 2-
methoxyphenol resulted in 90 %, where considerably lower
yield in conventional heating. Spectacular electronic effects
were observed when 2-Isoproylphenol was submitted to
coupling with het hetero-aryl chlorides (entries 8, 9) more than
80 % yield. Only slight decrease in the reaction rate was noted
with electron rich and electron withdrawing substituted 2-
chloro-5-cyanopyridine (entry 9) here -CN group was well
tolerated on the aryl chloride. We please to note that we could
quantitatively couple 2-bromo napthalene with the sterically
hindered ortho-cresol under these conditions (entry 7) with
91 % yield.
RESULTS AND DISCUSSION
In preliminary studies, reaction of 4-chloroanisole with
3-hydroxy benzonitrile in DMF at 110 °C in the presence of
K3PO4 using 5 mol % of CuBr without using additives the
reaction was examined subsequent conventional heating and
microwave reaction. Conventional heating resulted 55 % of
product selectivity in 22 h at 110 °C, where 72 % product selec-
tivity was detected under microwave heating in 20 min. By
comparison, reaction completed in 15 min in the presence
of 10 mol % of L-proline under microwave heating (CEM
synthesizer) and product selectivity also increased to 95 %. It
has been suggested that such additives would increase the
solubility of copper salts by preventing their aggregation and
they could also enhance the reactivity. The reaction screened
with using commercially available amino acids such as L-proline,
N-methyl proline, pyrrole-2-carboxilic acid and 2-picolinic
acid, in DMF and K3PO4 as base and results are summarized
in Table-1.
After screening of above four ligands, L-proline was found
to be a superior ligand combination with CuBr to serve as
better ligand-catalytic system to make diaryl ethers at lower
temperature in very shorter reaction time under microwave
conditions.After optimizing the reaction conditions, we subse-
quently extended the scope of Ullmann-type coupling reaction
using 5 mol % of L-proline without affecting the product
selectivity.All the reactions performed efficiently using 2 mol
% of CuBr, 5 mol % of ligand under microwave conditions in
DMF and K3PO4 as base at 70 °C. To the best of our knowledge,
most of the diaryl ether formation reactions reported with
highly reactive aryl iodides with phenols, few reports have
been found with less reactive aryl chloride and moderate
reactive aryl bromides and very few reports on hetero aromatic
halides. We report here, CuBr and L-proline is the best combi-
nation for the C-O bond formation of less reactive aryl/hetero-
aryl chlorides and also moderate reactive aryl/hetero-aryl
bromides with sterically hindered phenols and hetero-aryl
alcohols with excellent yields using low catalyst-ligand loading
under microwave irradiation. During recent years, microwaves
have been extensively used for carrying out chemical reactions
and have become a useful non-conventional energy source for
performing organic synthesis12,13. This protocol mainly refer
the ligand loading, solvent ratio, time, temperature and yields.
And also observed stability in the presence of sensitive func-
tional groups. The isolated yields compared with conventional
heating and results are summarized in Table-2.
Next, the cross-coupling reaction between hetero-aryl
halides with substituted phenols (entries 8-12) and hetero-aryl
alcohols were examined (entries 13 and 14). The one, we
identified the substituted phenols coupling with 3-halopyridine
case is much differential. Where the much difference observed
in yield while comparing with the conventional and microwave
technologies. The earlier literature, failed to provide coupling
reaction of 3-halopyridines12 because less reactive than 2-
halopyridine. This letter strongly, supported here in getting
extreme reactivity observed in microwave condition (entries
10, 11, 14). The other substituted phenols possessing sensitive
functional groups are well tolerated during coupling under
microwave and also afforded reasonable yields (entries 1, 2,
8, 11, 13, 14). Hetero-aryl halides such as 3-chloro pyridine
(entries 10, 11), 3-Cyano-5-chloropyridines, 4-Chloroisoqui-
noline, 2-bromothiazole (entry 12), 5-bromonicotinaldehyde
(entry 14) could be coupled with electro-deficient, electron-
neutral and hindered phenols. However, 5-membered ring
hetero-aryl halides containing two hetero atoms such as
2-bromothiazole (entry 12) also gave product reaction with
3-hydroxypyridine in excellent yields under these reaction
conditions. The C-O bond formation of 3-hydroxyquinoline
(entry 14) with a substituted pyridine also proceeded smoothly
and also gave excellent yield 86 %. Common functional groups,
including cyano, aldehydes and ketones were tolerated under
the reaction conditions employed.
TABLE-1
COUPLING REACTION OF 4-CHLOROANISOL WITH PHENOL UNDER THE CATALYSIS OF CuBr AND AMINO ACIDS
Entry
Catalyst
CuBr
CuBr
CuBr
CuBr
CuI
Ligand
L-Proline
Conventional (Cal. Yield %)*
MW (Cal. Yield %)*
1
2
3
4
5
61
48
52
55
53
95
86
82
85
81
N-Methyl proline
2-Picolinic acid
Pyrrole-2-carboxilic acid
L-Proline
Reaction conditions: CuBr powder (2 mol %), ligand (5 mol %), 4-chloroanisole (1.0 eq), 3-hydroxy benzonitrile (1.05 eq), K3PO4 (2.5 eq), DMF
MW 15-30 min

4750 Reddy et al.
Asian J. Chem.
TABLE-2
CuBr-CATALYZED DIARYL ETHER FORMATION OF ARYL/HETERO-ARYL
HALIDES WITH SELECTED PHENOLS IN THE PRESENCE OF L-PROLINE
Entry
1
ArX (a)
ArOH (b)
Product (c)
Temp (oC)
Conventional yield (%)
MW yield (%)
95
HO
O
CN
H3CO
Cl
70
57
CN
H3CO
OHC
O
CHO
H3CO
H3CO
Cl
Cl
2
3
70
70
59
61
93
90
OH
H3CO
O
OH
OHC
O
CHO
CHO
CHO
O
OH
H3CO
Cl
4
5
70
75
48
67
86
90
H3CO
OBn
OCH3
BnO
OCH3
OH
O
Cl
O
O
OH
CHO
CHO
Cl
O
CN
6
7
8
70
70
80
46
59
55
87
91
87
CN
Br
OH
O
Cl
O
OH
OH
N
CN
NC
N
Cl
O
9
90
47
88
N
N
CHO
CHO
OH
Cl
O
10
11
12
90
90
80
63
49
51
90
86
91
N
N
N
OCH3
CHO
Cl
O
OHC
OCH3
N
OH
S
O
S
N
OH
N
Br
O
O
Cl
Br
OH
O
13
14
70
90
55
38
90
86
N
N
CN
CHO
NC
N
N
OH
OHC
O
N
N
N
N
Reaction conditions: Cu Br (2 mol %), L-proline (5 mol %), ArX (1 eq), ArOH (1.05 eq), K3PO4 (2.5 eq), DMF (3 V), 70-90oC, MW 15-25 min. b
Isolated yields after column chromatography
The best results were observed in microwave irradiation
rather thermal heating with remarkable reduction in reaction
time because of homogeneous heating throughout the reaction
media by microwave irradiation as compared to convection
currents in thermal heating. Evidently, the microwave irradia-
tion increased the reaction rate and selectivity rather than conven-
tional method taking much longer reaction time (requires 20-
30 h at 110-130 °C).
Conclusion
We have successfully demonstrated economical and
operationally simple CuBr-L-proline catalytic synthesis of
substituted di aryl, hetero-aryl ethers from the coupling of
substituted phenols towards halo pyridines, haloquinolines and
bromo benzothiazole in excellent yields with low loading
ligands in shorter time under microwave conditions. The best
results were observed in microwave irradiation rather than

Vol. 26, No. 15 (2014)
Amino Acid Promoted Ullmann Type Reaction with Low Catalyst 4751
3. (a) J. Lindley, Tetrahedron, 40, 1433 (1984); (b) F. Theil, Angew. Chem.
Int. Ed., 38, 2345 (1999); (c) F. Thomas, S. Schulz, H. Mansikkamäki
and M. Nieger, Angew. Chem. Int. Ed., 42, 5641 (2003).
4. (a) F. Ullmann, Ber. Dtsch. Chem. Ges, 36, 2382 (1903); (b) F. Ullmann,
Chem. Ber., 37, 853 (1904).
conventional heating with remarkable reduction in reaction
time.
ACKNOWLEDGEMENTS
5. H.J. Cristau, P. Cellier, S. Hamada, J.F. Spindler and M. Taillefer, Org.
Lett., 6, 913 (2004).
The authors acknowledged to Osmania University for
providing the research facility and the direct contributions for
the staff of Department of Chemistry and Analytical team.
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