Beckmann rearrangement of ketoximes induced by phenyl dichlorophosphate at ambient temperature

Article abstract of DOI:10.3390/molecules171113662

Upon treatment with phenyl dichlorophosphate (PhOP=OCl₂) in acetonitrile at ambient temperature, a variety of ketoximes underwent a Beckmann rearrangement in an effective manner to afford the corresponding amides in moderate to high yields.

Full text of DOI:10.3390/molecules171113662

Molecules 2012, 17, 13662-13672; doi:10.3390/molecules171113662
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Beckmann Rearrangement of Ketoximes Induced by Phenyl
Dichlorophosphate at Ambient Temperature
1
,2
3
2
1
2
Chun-Wei Kuo , Min-Tsang Hsieh , Shijay Gao , Yi-Ming Shao , Ching-Fa Yao and
1
,
Kak-Shan Shia *
1
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes,
Miaoli County 35053, Taiwan
2
Department of Chemistry, National Taiwan Normal University, Taipei 116, Taiwan
3
Chinese Medicinal Research and Development Center, China Medical University Hospital,
2
Yude Road, Taichung 40447, Taiwan
*
Author to whom correspondence should be addressed; E-Mail: ksshia@nhri.org.tw;
Tel.: +886-37-246-166 (ext. 35709); Fax: +886-37-586-456.
Received: 21 September 2012; in revised form: 12 November 2012 / Accepted: 14 November 2012 /
Published: 20 November 2012
2
Abstract: Upon treatment with phenyl dichlorophosphate (PhOP=OCl ) in acetonitrile at
ambient temperature, a variety of ketoximes underwent a Beckmann rearrangement in an
effective manner to afford the corresponding amides in moderate to high yields.
Keywords: Beckmann rearrangement; phenyl dichlorophosphate; ketoximes; ambient
temperature
1
. Introduction
The Beckmann rearrangement is a well-documented reaction for converting ketoximes into
N-substituted amides, and serves constantly as a topic of great interest in organic synthesis [1–4].
However, many conventional Beckmann rearrangement protocols involve drastic conditions and are
usually accompanied by environmentally harmful byproducts [5,6]. Thus, enormous efforts have been
devoted to the development of more effective and milder versions of this reaction. Along this line, a
wealth of useful reagents, including cyanuric chloride (TCT), TAPC, PTSA/ZnCl , BOP-Cl,
2
H
2
3 2 2 3 3 2 2
NSO H, (EtO) P=OCl, TISC, HgCl , Ru(PPh ) (CO)H /dppe/TsOH, BDMS/ZnCl , TsCl, PMSCl,
I
2
, and cyclopropenium ion, have been developed to effect the Beckmann rearrangement [7–21].

Molecules 2012, 17
13663
Though these protocols have proved effective, elevated temperatures, however, are usually required in
order to obtain satisfactory yields. Recently, supercritical water (scH O) [22,23] was reported to be
2
able to replace both common organic solvents and conventional acid catalysts to facilitate the
rearrangement; however, this approach was found synthetically useless in that high temperature and
pressure are essential for the reaction to occur. Herein, we wish to report that a convenient new
procedure, making use of phenyl dichlorophosphate (3) as a key activating agent, has been developed
in our laboratories to facilitate the title rearrangement at room temperature.
2
. Results and Discussion
Phosphorus chemicals are known as versatile activating/dehydrating agents in organic synthesis as
demonstrated by many historical cases [24–34]. Though silicaphosphine, prepared from silica gel and
trichlorophosphine [35], and trimethylsilyl polyphosphate, prepared from phosphorus pentoxide and
hexamethyldisiloxane [36], have been reported as effective promoters for the Beckmann rearrangement,
both need to be synthesized prior to the reaction; however, exploration of convention commercially
available phosphine-containing reagents, including phenyl dichlorophosphate (3), ethyl dichlorophosphate
(
4), diphenyl chlorophosphate (5), diethyl chlorophosphate (6) [13], and N,N-dimethylphosphoramidic
dichloride (7), to induce the same rearrangement at ambient temperature appears to be unknown.
Compiled in Table 1 are results of experiments wherein acetophenone oxime (1) was used as a model
substrate for the screening of various reaction conditions, containing reagents 3–7, respectively, to
afford the desired product N-phenylacetamide (2). Accordingly, when oxime 1 was treated with
phosphate 3 in low-polarity solvents, such as CH Cl , toluene, or CH CN, at room temperature,
2
2
3
3
product 2 was obtained in high yields (Entries 1, 3, and 4); among them, CH CN appeared to be the
solvent of choice in terms of reaction rate and isolated yield (Entry 4; 1 h, 86%). As well, it was
observed that the high-polarity solvents (i.e., THF) were extremely incompatible with 3 to promote the
desired 1,2-migration (Entry 2; 3 h, 40%). These significant solvent effects appear ascribable to the
hydrochloric acid formed in situ during the reaction, a potential migration-inducer whose oxophilicity
is much stronger in low-polar solvents, thus making the phenyl chlorophosphate moiety a better
leaving group. The intermediacy of hydrochloric acid was further evidenced by the fact that above
1
,2-migration process was completely stopped when bases, such as DBU or triethylamine, were added
to the initial reaction mixtures with the same equivalents of reagent 3. Reagent 4 was almost as
effective as 3 for the attempted Beckmann rearrangement under similar reaction conditions (Entries 5–7),
but in general, an extended reaction time was required as compared to reagent 3. Other structurally
related phosphorus reagents 5, 6 and 7 in low-polarity solvents were also investigated. In all cases
examined (Entries 8–16), they were found to be inferior to phosphate 3 in effecting the 1,2-migration,
presumably due to their less active phosphorous centers, potentially caused by a higher delocalization
of the electron density and/or more steric hindrance from ligands, as compared to reagent 3. Moreover,
inspired with the fact that Lewis acids could promote Beckmann rearrangement in a catalytic fashion as
reported in the literature [7], attempts to combine Lewis acid with reagent 3 to accelerate the reaction rate
were then made. Unfortunately, as shown in Table 1 (Entries 17–22), no significant synergistic effects on
reaction yield or rate were observed with the addition of Lewis acids as catalyst. However, it was noted
2 2
that when reagent 5 was combined with either ZnCl or ZnI as catalyst (Entries 23 and 24), reaction

Molecules 2012, 17
13664
rates are significantly enhanced along with a slight improvement in yields compared to the corresponding
reaction without any catalyst (Entry 8). The underlying cause of these phenomena is still not fully
understood and is worthy of further studies. Currently, the reaction system (PhOP=OCl /CH CN/rt)
2
3
exhibited in Entry 4 was tentatively considered optimum and adopted as a typical procedure. In fact, the
gram-scale synthesis of 2 has also been explored and was found to be equally simple and efficient. The
above synthetic procedures are detailed in the Experimental section.
Table 1. Beckmann rearrangement of acetophenone oxime promoted by phosphorous
reagents under various reaction conditions.
b
c
Entry Reagent Catalyst
Solvent Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
3
3
3
3
4
4
4
5
5
5
6
6
6
7
7
7
3
3
3
3
3
3
5
5
−
−
CH
3
CN
3
3
83
40
87
86
76
74
81
72
70
80
60
54
61
55
50
52
85
81
84
79
82
80
79
83
THF
−
Toluene
16
1
−
CH CN
3
−
CH Cl
6
2
2
−
Toluene
14
2
−
CH CN
3
−
CH Cl
20
20
5
2
2
−
Toluene
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
−
CH CN
3
1
1
1
1
1
1
1
1
1
2
2
2
2
2
−
CH Cl
24
26
7
2
2
−
Toluene
−
CH CN
3
−
CH Cl
30
30
8
2
2
−
Toluene
−
CH CN
3
ZnCl2
ZnCl2
ZnI2
ZnI2
BCl3
BCl3
ZnCl2
ZnI2
CH Cl
1
2
2
CH CN
3
1
CH Cl
2
2
0.6
0.8
0.8
0.8
5
CH CN
3
CH Cl
2
2
CH CN
3
CH Cl
2
2
CH Cl
2
2
3
a
All reactions were performed using oxime 1 (2 mmol) and phosphorous reagent (3 mmol) in 4 mL
b
c
of solvent as indicated above at room temperature; 10 mol% of catalyst was added; Yields are
for isolated, chromatographically pure products.

Molecules 2012, 17
13665
To examine the generality of the newly developed protocol, structurally diverse ketoximes were
then selected. As listed in Table 2, substrates bearing electron-donating groups in the para-position of
the phenyl ring (Entries 1–3; 0.5–1 h) were found to undergo 1,2-migration much faster than those with
electron-withdrawing functionalities (Entries 6–8; ~13 h), suggesting that when an electron-donating
group is present, the ring becomes more electrostatically negative, resulting in the enhancement of the
migration rate. Ketoximes, constrained with a six-membered ring such as Entries 5 and 10, required a
prolonged reaction time to complete the conversion with relatively lower yields (3367%), but it
appeared to not be problematic in the case of a large-ring system (Entry 11), suggesting that the
1
,2-migration process might be susceptible to the ring strain. More interestingly, when the migratory
groups are heterocyclic rings, a significant difference in reactivity was observed. A thiophene-containing
ketoxime (Entry 9) afforded the desired product within 1.5 h in a high yield of 84%; however, when
the corresponding pyridine-containing substrate (Entry 14) was employed, the starting material was
recovered intact even when the reaction time was prolonged under refluxing conditions for an
additional 6 h. The latter could apparently be attributed to the formation of a hydrochloride salt via
protonation of the pyridine nitrogen, rendering the adjacent C-2 migration center extremely positive
and thus the migration process was retarded. The aforementioned results also indicate that the
migratory aptitude of the alkyl linker appears to be poorer than that of the phenyl ring bearing either an
electron-donating or electron-withdrawing substituent (Entries 1–4 and Entries 6–8). Moreover, when
different alkyl linkers are present in the ketoxime, the longer ones seem to have a greater migratory
aptitude (Entry 12). Several aldoximes were also subjected to above standard conditions, and the
corresponding nitriles were isolated in satisfactory yields (70–86%). As well, it is noteworthy that the
present methodology can be carried out at ambient temperature with a commercially available reagent,
and thus its synthetic utility would be broader than many homogeneous and heterogeneous catalyst
systems, particularly the latter in which high temperatures are usually required [37–40].
Table 2. Conversion of ketoximes into amides under treatment with phenyl dichlorophosphate.
Entry
Substrate
Time (h)
Product
Yield (%)
1
1
86
2
3
0.5
0.5
88
90

Molecules 2012, 17
13666
Table 2. Cont.
Entry
Substrate
Time (h)
Product
Yield (%)
4
3.5
9
83
5
6
7
67
75
76
13
13
8
9
13
1.5
12
73
84
33
1
1
0
1
4.5
79
1
1
2
3
9
7
72
77
a
1
4
6
S.M.
NR
a
No reaction occurred at room temperature or under refluxing conditions.

Molecules 2012, 17
13667
The proposed mechanism of phenyl dichlorophosphate-induced Beckmann rearrangement is
depicted in Scheme 1 using acetophenone oxime (1) as a typical example. It is widely accepted that
product 2 should be formed following the conventional pathway a via intermediate 1A; however, a
shunt pathway b cannot be ruled out in that as the reaction was monitored by TLC, product 2 was seen
to grow at the expense of a potential intermediate 8 during the progress of reaction, the structure of
which was unambiguously identified by an X-ray analysis. A similar TLC behavior, however, was not
observed when the same reaction was carried out under refluxing conditions. An explanation for this
could be that an extremely rapid conversion of 8 into product 2 (ca. 5 min, 91% yield) might take place
at elevated temperatures and thus the intermediate was no longer detected by TLC. Dimer 8 thus
obtained could also demonstrate the existence of chloroimine and its delocalizing nitrilium ion as
proposed in the long-standing accepted pathway a.
Scheme 1. Proposed mechanism of the phenyl dichlorophosphate-induced Beckmann
rearrangement of ketoximes.
H
O
OH
O
P
N
N
OPh
Cl
Cl
N
H
N
Cl
a
N
PhOP=OCl
2
2
H O
O
Cl
1A
1
2
HCl
b
Cl
H
N
N
N
N
Cl
Cl
8
3. Experimental
3.1. General
Unless otherwise stated, all materials used were commercially available and used as supplied.
Reactions requiring anhydrous conditions were performed in flame-dried glassware, and cooled under
an argon or nitrogen atmosphere. Unless otherwise stated, reactions were carried out under argon or
nitrogen and monitored by analytical thin layer chromatography performed on glass-backed plates
(
5 × 10 cm) precoated with silica gel 60 F254 as supplied by Merck. Visualization of the resulting
chromatograms was done by looking under an ultraviolet lamp (λ = 254 nm) followed by dipping in an
ethanol solution of vanillin (5% w/v) containing sulfuric acid (3% v/v) or phosphomolybdic acid
(2.5% w/v), and charring by heat gun. Flash chromatography using silica gel 60 of 230−400 mesh size
as supplied by Merck was used routinely for purification and separation of product mixtures. Eluent
1
13
systems are given in volume/volume concentrations. H-NMR and C-NMR spectra were recorded at
00/600 and 100/150 MHz, respectively, on a Bruker Avance 400 FT-NMR or Bruker DMX-600
4

Molecules 2012, 17
13668
instrument. Chloroform-d or dimethyl sulfoxide-d was used as the solvent and TMS (δ 0.00 ppm) as
6
an internal standard. Chemical shift values are reported in ppm relative to the TMS in delta (δ) units.
Coupling constants (J) are expressed in Hz. High resolution electron impact mass spectra (HRMS (EI))
were recorded using a FINNIGAN MAT-95XL mass spectrometer. Spectral data were recorded as m/z
values. Combustion elemental analyses using Heraruc CHN-O Rapid Elemental Analyzer were performed
by the microanalytical laboratory at National Chung Hsing University, Taiwan. Crystallographic data can
be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or deposite@ccdc.cam.ac.uk
using CCDC No.: 690116.
3
.2. General Procedure for the Synthesis of Compounds in Table 2
Phenyl dichlorophosphate (3, 0.633 g, 3 mmol) was added dropwise at room temperature to a
solution of acetophenone oxime (1, 0.270 g, 2 mmol) in anhydrous acetonitrile (4 mL). The resulting
mixture was stirred at the same temperature for ca. 1 h, and then saturated sodium bicarbonate solution
(
5 mL) was added to quench the reaction. The aqueous layer was separated and extracted with ethyl
acetate (3 × 10 mL). The combined organic extracts were washed with brine, dried over MgSO4,
filtered and concentrated to give the crude product, which was purified by flash chromatography on
silical gel (30% EtOAc in n-hexane) to afford amide 2 (0.232 g, 86%) as a white solid.
1
N-Phenylacetamide (2). A white solid; m.p. 114–115 °C; H-NMR (CDCl
3
) δ 8.27 (brs, 1H, NH), 7.50
13
(
3
d, J = 7.9 Hz, 2H), 7.27 (d, J = 7.6 Hz, 2H), 7.07 (t, J = 7.4 Hz, 1H), 2.12(s, 3H); C-NMR (CDCl ) δ
1
69.2, 138.2, 129.0, 124.4, 120.3, 24.5; Anal. Calcd. for C
8
9
H NO: C 71.29, H 6.71, N 10.36; Found: C
71.09, H 6.71, N 10.26.
1
N-(4-Methylphenyl)acetamide (Table 2, Entry 1). A white solid; m.p. 149–150 °C; H-NMR (CDCl
3
) δ
7
.74 (brs, 1H, NH), 7.37 (d, J = 7.8 Hz, 2H), 7.08 (d, J = 7.8 Hz, 2H), 2.29 (s, 3H), 2.12 (s, 3H);
1
3
C-NMR (CDCl
3
) δ 168.8, 135.6, 134.0, 129.6, 120.4, 24.6, 21.0. Anal. Calcd. for C
9
H11NO: C 72.46,
H 7.43, N 9.39; Found: C 72.73, H 7.47, N, 9.08.
1
N-(4-Methoxyphenyl)acetamide (Table 2, Entry 2). A brown solid; m.p. 127–129 °C; H-NMR
(
3
CDCl ) δ 7.67 (brs, 1H, NH), 7.38 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 3.77 (s, 3H), 2.12
1
3
(
s, 3H); C-NMR (CDCl ) δ 168.7, 156.6, 131.3, 122.2, 114.3, 55.6, 24.4; Anal. Calcd. for C H NO :
3
9
11
2
C 65.44, H 6.71, N 8.48; Found: C 65.31, H 6.86, N 8.13.
1
N-(2,3-Dihydro-1,4-benzodioxin-6-yl)acetamide (Table 2, Entry 3). A colorless oil; H-NMR (CDCl
3
)
1
3
δ 7.08 (brs, 1H, NH), 7.09 (s, 1H), 6.85–6.76 (m, 2H), 4.20 (m, 4H), 2.11 (s, 3H); C-NMR (CDCl
3
) δ
1
68.2, 143.4, 140.5, 131.5, 117.1, 113.7, 109.9, 64.4, 64.2, 24.4; HRMS (FAB) calcd for C10
H12NO
3
+
(
M+H) : 194.0817; Found: 194.0829.
1
N-(2-Naphthyl)acetamide (Table 2, Entry 4). A colorless oil; H-NMR (400 MHz, CDCl
3
) δ 8.16
s, 1H), 7.94 (brs, 1H, NH), 7.75–7.70 (m, 3H), 7.46–7.24 (m, 3H), 2.19 (s, 3H); C-NMR (100 MHz,
CDCl ) δ 169.1, 135.6, 134.0, 130.8, 128.9, 127.7, 126.6, 125.1, 120.2, 117.0, 24.8; Anal. Calcd. for
11NO: C 77.81, H 5.99, N 7.56; Found: C 77.80, H 5.89, N 7.68.
1
3
(
3
12
C H

Molecules 2012, 17
13669
1
1
,2,3,4-Tetrahydro-7-methoxy-5H-benzazepin-2-one (Table 2, Entry 5). A colorless oil; H-NMR
CDCl ) δ 7.63 (m, 1H), 7.12 (brs, 1H, NH), 6.80 (m, 1H), 6.68 (s, 3H), 3.80 (s, 3H), 3.11–1.95
m, 6H); C-NMR (CDCl
(
(
3
1
3
3
) δ 174.1, 161.6, 140.6, 130.7, 127.4, 114.2, 111.8, 55.2, 39.7, 30.7, 30.4;
+
HRMS (FAB) calcd for C H NO (M+H) : 192.1025; Found: 192.1021.
1
1
14
2
1
N-(4-Chlorophenyl)acetamide (Table 2, Entry 6). A colorless oil; H-NMR (DMSO-d
6
) δ 10.1 (brs, 1H,
NH), 7.60 (d, J = 7.8 Hz, 2H), 7.32 (d, J = 7.8 Hz, 2H), 2.04 (s, 3H); C-NMR (DMSO-d ) δ 168.4,
38.3, 128.5, 126.5, 120.5, 24.0; Anal. Calcd. for C H ClNO: C 56.65, H 4.75, N 8.26; Found: C
13
6
1
5
8
8
6.70, H 4.92, N 8.12.
1
N-(4-Nitrophenyl)acetamide (Table 2, Entry 7). A colorless oil; H-NMR (DMSO-d
6
) δ 10.5 (brs, 1H,
13
NH), 8.20 (d, J = 9.2 Hz, 2H), 7.81 (d, J = 9.2 Hz, 2H), 2.11 (s, 3H); C-NMR (DMSO-d ) δ 169.3,
6
1
45.4, 142.0, 125.0, 118.5, 24.2; Anal. Calcd for C8H8N2O2: C 53.33, H 4.48, N 15.55; Found: C
3.08, H 4.55, N 15.24.
5
1
N-(2-Bromophenyl)acetamide (Table 2, Entry 8). A yellow solid: m.p. 98–99 °C; H-NMR (DMSO-d
6
) δ
1
3
9
1
4
6
.45 (brs, 1H, NH), 7.65–7.10 (m, 4H), 2.07 (s, 3H); C-NMR (DMSO-d ) δ 168.5, 136.5, 132.6,
27.9, 127.2, 126.8, 117.8, 23.3; Anal. Calcd for C
8
H
8
BrNO: C 44.89, H 3.77, N 6.54; Found: C
4.96, H 3.75, N 6.33.
1
N-(2-Thienyl)acetamide (Table 2, Entry 9). A colorless oil; H-NMR (DMSO-d
6
) δ 11.1 (brs, 1H, NH),
1
3
6
6
.90–6.61 (m, 3H), 2.05 (s, 3H); C-NMR (DMSO-d ) δ 166.2, 139.9, 123.5, 116.6, 110.3, 22.5; Anal.
Calcd for C
6
H
7
NOS: C, 51.04; H, 5.00; N, 9.92; S, 22.71; Found: C, 50.92; H, 5.29; N, 9.66; S, 22.50.
1

(
-Caprolactam (Table 2, Entry 10). A colorless oil; H-NMR (CDCl
3
) δ 7.11 (brs, 1H, NH), 3.14–3.11
1
3
m, 2H), 2.39–2.36 (m, 2H), 1.68–1.57 (m, 6H); C-NMR (CDCl
3
) δ 179.5, 42.8, 36.8, 30.7, 29.8,
2
3.3; Anal. Calcd for C
6
H11NO: C 63.68, H 9.80, N 12.38; Found: C 63.60, H 9.72, N 12.43.
1
Azacyclotridecan-2-one (Table 2, Entry 11). A colorless oil; H-NMR (DMSO-d
6
) δ 7.86 (brs, 1H,
1
3
NH), 3.07–3.03 (m, 2H), 2.06–2.03 (m, 2H), 1.55–1.24 (m, 18H); C-NMR (DMSO-d ) δ 172.7, 37.8,
6
+
3
1
5.4, 27.7, 26.3, 25.8, 25.7, 25.5, 24.8, 24.5, 24.2, 23.5; HRMS (FAB) calcd for C12
98.1858; Found: 198.1858.
H
24NO (M+H) :
1
N-Heptylacetamide (Table 2, Entry 12). A colorless oil; H-NMR (CDCl
3
) δ 6.20 (brs, 1H, NH), 3.20
13
(
s, 3H), 1.35–1.21 (m, 12H), 0.91–0.79 (m, 3H); C-NMR (CDCl
3
) δ 170.7, 39.9, 31.7, 29.7, 29.4,
+
2
8.9, 26.8, 22.5, 14.0; HRMS (EI) calcd for C
9
H
20NO (M+H) : 158.1545; Found: 158.1547.
1
N-Pentylhexanamide (Table 2, Entry 13). A colorless oil; H-NMR (DMSO-d
6
) δ 7.76 (brs, 1H, NH),
1
3
3
6
.03–2.98 (m, 2H), 2.04–2.01 (m, 2H), 1.50–1.20 (m, 12H), 0.86–0.82 (m, 6H); C-NMR (DMSO-d )
δ 170.0, 38.4, 35.4, 31.0, 28.9, 28.7, 25.1, 22.1, 22.0, 13.7; HRMS (FAB) calcd for C11
H24NO
+
(
M+H) : 186.1858; Found: 186.1857.
1
N-(1-Chlorovinyl)-N,N'-diphenylacetamidine (8). A white solid; m.p. 90–92 °C; H-NMR (CDCl ) δ
3
7.44–7.39 (m, 4H), 7.30–7.26 (m, 3H), 7.04–7.00 (m, 1H), 6.81–6.79 (m, 2H), 5.45 (d, J = 1.2 Hz, 1H),

Molecules 2012, 17
13670
1
3
5
1
.38 (d, J = 1.2 Hz, 1H), 1.93 (s, 3H); C-NMR (CDCl ) δ 155.4, 150.3, 142.3, 140.0, 129.3, 128.8,
3
+
16 2
26.9, 126.8, 122.6, 130.0, 114.6, 16.5; HRMS (FAB): calcd for C16H N Cl (M+H) : 271.1002;
Found: 271.1003.
3
.3. Gram-Scale Synthesis of Amide 2
A mixture of acetophenone oxime (1, 13.5 g, 100 mmol) and phenyl dichlorophosphate (3, 31.6 g,
1
50 mmol) was stirred in CH CN (200 mL) for 1 h, product 2 was obtained in 88% yield (11.9 g) as a
3
white solid after the usual work-up procedure and further recrystallization (ethyl acetate/n-hexane = 5:1).
4
. Conclusions
In summary, we have developed a mild and effective reaction system to induce the Beckmann
rearrangement of ketoximes at ambient temperature, leading to the corresponding amides in moderate
to high yields. It is believed that the title system will be a valuable addition to the synthetic organic
chemistry methodology in terms of its operational simplicity scale-up practicability and use of readily
accessible phosphorous reagents.
Acknowledgments
We are grateful to the National Health Research Institutes and National Science Council of the Republic
of China (NSC-100-2113-M-400-002 and NSC-101-2113-M-400-003-MY2) for financial support.
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Sample Availability: Samples of the compounds in Table 2 are available from the authors.
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