Iodobenzene diacetate (PIDA)/Zn(II)-mediated oxidation and cleavage of C-C bond: Formation of substituted N-aryl carbamoyl methyl diacetates and derivatives from 3-oxo-butanamides

Article abstract of DOI:10.3184/174751912X13445852334047

Various substituted N-aryl carbamoyl methyl diacetates have been synthesized from N-aryl-3-oxobutanamides via a diacetoxylation mediated by the combination of iodobenzene diacetate (PIDA)/Zn(OAc)2. This provides a new convenient method to form C-O bonds and cleave C-C bonds. Ten examples were obtained from easily available materials in good to excellent yields.

Full text of DOI:10.3184/174751912X13445852334047

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 571
OCTOBER, 571–572
Iodobenzene diacetate (PIDA)/Zn(II)-mediated oxidation and cleavage of
C–C bond: formation of substituted N-aryl carbamoyl methyl diacetates
and derivatives from 3-oxo-butanamides
Hu Wenjuna, Deng Zhaohuia, Cui Chenb and Wei-Bing Liub*
aInstitute for Drug and Instrument Control of Guangzhou Military Area, 79 Guangzhou Avenue North, Guangzhou 510500, P. R. China
bSchool of Chemistry and Life Science, Guangdong University of PetrochemicalTechnology, 2 Guangdu Road, Maoming 525000, P. R. China
Various substituted N-aryl carbamoyl methyl diacetates have been synthesized from N-aryl-3-oxobutanamides via a
diacetoxylation mediated by the combination of iodobenzene diacetate (PIDA)/Zn(OAc)2. This provides a new conven-
ient method to form C–O bonds and cleave C–C bonds. Ten examples were obtained from easily available materials
in good to excellent yields.
Keywords: cleave C–C bond, acetoxylation, oxidation of (N-aryl substituted-carbamoyl) methyl diacetates
Hypervalent iodine(III) reagents1,14 have received considerable
attention in the literature.15,17 We have developed novel reac-
tions by using hypervalent iodine(III) reagents, especially
iodobenzene diacetate (PIDA), and have applied them to
synthesise new compounds, such as polysubstituted pyrroles,
1,2-diheteroatom-substituted (E)-alkenes and tetrasubstituted
(E)-alkenes.18,19 Recently, we have reported an efficient oxida-
tive approach to the synthesis of 2,2-dihalo-N-phenylaceta-
mides by using PIDA (Scheme 1).20 In order to understand the
mechanism and the scope of this reaction, we replaced the
halogen anion of the zinc salt with acetate ion and surprisingly
found that (phenylcarbamoyl)methyl diacetate was produced
as the major product (Scheme 2).
This is followed by diacetoxylation of the activated methylene
of 3-oxo-N-phenylbutanamide in the presence of PIDA and
leads to the diacetylated product 4. Subsequent nucleophilic
attack of acetate ion on the carbon atom of the carbonyl
group affords intermediate 5. Then, the carbon–carbon bond
cleavage of the labile intermediate 5 by a retro-Claisen
condensation reaction22 generates intermediate 6. Finally, the
electrophilic attack of proton on carbon–carbon double bond
affords the final product (phenylcarbamoyl)methyl diacetate
(2a).
Table 1 Synthesis of (N-aryl substituted-carbamoyl)methyl
diacetate derivativesa
Subsequently, we used a range of 3-oxo-N-phenylbutan-
amides, under the same conditions (Table 1), to test this strat-
egy for the synthesis of (N-aryl substituted-carbamoyl)methyl
diacetate derivatives. From the results we can see that the yield
was decreased when the phenyl ring was substituted by elec-
tron-donating groups, such as halogen (Cl) (1c, ld), methyl
(1b), methoxyl group (1e, 1f). The positions of substituents on
the benzene ring had little effect on this transformation. A
para-substituent was more effective than an ortho-substitutent,
as shown by their corresponding yields. For example, N-(4-
chlorophenyl)-3-oxobutanamide (1c) and N-(4-methoxyphe-
nyl)-3-oxobutanamide (1e) were better substrates compared to
their ortho-substituted partners (1c, 1f) in this method and
gave the corresponding product in higher yield (Scheme 3,
2c, 2d, 2e and 2f). Additionally, 3-oxo-N-alkylbutanamides
were also suitable substrates for this protocol. For instance,
N-methyl-3-oxobutanamide (1j) reacted under the same con-
ditions to give (methylcarbamoyl)methyl acetate (2j) in 77%
isolated yield.
Entry
1
Product Yields/%b
1
2
R=H (1a)
R=o-methyl (1b)
2a
2b
2c
2d
2e
2f
80
72
76
79
71
69
67
63
61
77
3
R=o-chloro (1c)
4
R=p-chloro (1d)
5
R=p-methoxyl (1e)
6
R=o-methoxyl (1f)
7
R=p-oxethyl (1g)
2g
2h
2i
8
R=2,5-dimethoxyl (1h)
R=2,5-dimethoxyl-4chloro (1i)
N-methyl-3-oxobutanamide (1j)
9
10
2j
a All the reactions were carried out: 1 (1.0 mmol), dioxane (2 mL),
DIB (1.3 equiv.), Zn(OAc)2(1.0 equiv.).
b Isolated yields.
Based on our previous report,20 a mechanistic proposal for
this transformation, exemplified by the formation of 2a, is out-
lined in Scheme 3. In this process, the first step involves the
activation of 3-oxo-N-phenylbutanamide by Zn(II) to form 3.
Scheme 1 Synthesis of 2,2-dihalo-N-phenylacetamides.
Scheme 2 Synthesis of (phenylcarbamoyl)methyl diacetate.
Scheme 3 Possible reaction mechanism.
* Correspondent. E-mail: lwb409@yahoo.com.cn

572 JOURNAL OF CHEMICAL RESEARCH 2012
(2-Methoxyphenylcarbamoyl)methyl diacetate (2f): Pale yellow oil;
IR νmax (KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174, 968, 860,
810, 756 cm−1; 1H NMR (CDCl3, 400 Hz) δ 8.72 (s, 1H), 7.06–7.04 (d,
J = 8.0 Hz, 1H), 694–6.85 (m, 3H), 5.63 (s, 1H), 3.86 (s, 3H), 2.43 (s,
3H), 2.27 (s, 3H); 13C NMR (CDCl3, 100 Hz) δ 168.6, 160.8, 148.3,
126.2, 125.9, 124.8, 121.0, 119.9, 110.1, 79.4, 55.8, 27.6, 20.5; MS
(EI) m/z (%): 149.00 (100.00). Anal. Calcd for C13H15NO6: C, 55.51;
H, 5.38; N, 4.98. Found: C, 55.59; H, 5.21; N, 5.07%.
(4-Ethoxyphenylcarbamoyl)methyl diacetate (2g): Pale yellow oil;
IR νmax (KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174, 968, 860,
810, 756 cm−1; 1H NMR (CDCl3, 400 Hz) δ 8.05 (s, 1H), 7.37–7.35 (d,
J = 8.0 Hz, 2H), 6.83–6.81 (d, J = 8.0 Hz, 2H), 5.59 (s, 1H), 4.00–3.95
(q, J = 8.0 Hz, 2H), 2.42 (s, 3H), 2.24 (s, 3H), 1.38–1.34 (t, J = 8.0 Hz,
3H); 13C NMR (CDCl3, 100 Hz) δ 168.7, 160.9, 156.4, 129.3, 122.1,
114.9, 79.2, 63.7, 27.6, 20.5, 14.7; MS (EI) m/z (%): 163.08 (100.00).
Anal. Calcd for C14H17NO6: C, 56.94; H, 5.80; N, 4.74. Found: C,
56.77; H, 5.88; N, 4.83%.
In conclusion, we have developed an efficient method for
the synthesis of substituted N-aryl carbamoyl methyl diacetate
derivatives via an activated acetonylation process of a methy-
lene followed by a C–C bond cleavage using the combination
of PIDA/Zn(OAc)2. This protocol provides a new, useful route
to activate a methylene and construct C–O bonds. The two ace-
toxyl groups of the resultant products are ready to be converted
into other functional groups, such as, hydroxyl and carbonyl.
The current direction of our future research is aimed at extend-
ing the scope and potential synthetic applications of this
reaction.
Experimental
All the reactions were carried out at room temperature in a Schlenk
tube equipped with magnetic stirrer bar. Solvents and reagents were
used as received. 1H NMR spectra was recorded in CDCl3 at 400 MHz
and 13C NMR spectra was recorded in CDCl3 at 100 MHz. GC–MS
were obtained using electron ionisation (EI). IR spectra were obtained
as potassium bromide pellets or as liquid films between two potas-
sium bromide pellets with a Bruker Vector 22 spectrometer. TLC was
performed using commercially prepared 100–400 mesh silica gel
plates (GF254), and visualisation was effected at 254 nm. All the other
chemicals were purchased from Aldrich Chemicals.
(2,4-Dimethoxyphenylcarbamoyl)methyl diacetate (2h): Pale
yellow oil; IR νmax (KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174,
1
968, 860, 810, 756 cm−1; H NMR (CDCl3, 400 Hz) δ 8.47 (s, 1H),
6.48–6.40 (m, 3H), 5.61 (s, 1H), 3.82 (s, 3H), 3.74 (s, 3H), 2.42 (s,
3H), 2.25 (s, 3H); 13C NMR (CDCl3, 100 Hz) δ 168.6, 160.4, 157.2,
149.7, 120.9, 119.7, 103.8, 98.7, 79.3, 55.8, 55.5, 27.6, 20.5; MS (EI)
m/z (%): 123.00 (100.00). Anal. Calcd for C14H17NO7: C, 54.02; H,
5.50; N, 4.50. Found: C, 54.07; H, 5.66; N, 4.71%.
(2,5-Dimethoxy-4-chlorophenylcarbamoyl)methyl diacetate (2i):
Synthesis of 2, 2-dichloro-N-phenylacetamide (2a); typical procedure
Iodobenzene diacetate (PIDA) (419 mg, 1.3 mmol), dioxane (2 mL),
3-oxo-N-phenylbutanamide (1a) (177 mg, 1.0 mmol) and Zn(OAc)2
(183 mg, 1.0 mmol) were added to a 10 mL Schlenk tube. The mixture
was stirred at room temperature for 1 h. The solution was directly
subjected to separation by PTLC (GF254), and eluted with a 10:2
petroleum ether / ethyl acetate mixture, to furnished 2a (201 mg, 80%)
as a pale yellow oil.
Yellow oil; IR νmax (KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174,
1
968, 860, 810, 756 cm−1; H NMR (CDCl3, 400 Hz) δ 8.71 (s, 1H),
8.07 (s, 1H), 6.87 (s, 1H), 5.61 (s, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 2.43
(s, 3H), 2.27 (s, 3H); 13C NMR (CDCl3, 100 Hz) δ 168.5, 160.8, 149.0,
142.2, 125.5, 116.9, 112.4, 104.9, 79.0, 56.6, 56.5, 27.6, 20.4; MS
(EI) m/z (%): 153.00 (100.00). Anal. Calcd for C14H16ClNO7: C, 48.64;
H, 4.66; N, 4.05. Found: C, 48.66; H, 4.49; N, 4.11%.
(Methylcarbamoyl)methyl acetate (2j): Pale yellow oil; IR νmax
(KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174, 968, 860, 810, 756
cm−1; 1H NMR (CDCl3, 400 Hz) δ 6.49 (s, 1H), 5.46 (s, 1H), 2.37 (s,
3H), 2.18 (s, 3H), 2.02 (s, 3H); 13C NMR (CDCl3, 100 Hz) δ 168.6,
163.7, 79.1, 27.7, 26.1, 20.4; MS (EI) m/z (%): 193.05 (100.00). Anal.
Calcd for C7H11NO5: C, 44.45; H, 5.86; N, 7.40. Found: C, 44.31; H,
5.97; N, 7.45%.
(Phenylcarbamoyl)methyl diacetate (2a): Pale yellow oil; IR νmax
(KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174, 968, 860, 810,
1
756 cm−1; H NMR (CDCl3, 400 Hz) δ 8.17 (s, 1H), 8.07 (s, 1H),
7.50–7.48 (d, J = 8.0 Hz, 2H), 7.27–7.23 (t, J = 8.0 Hz, 2H), 7.15–7.11
(t, J = 8.0 Hz, 1H), 5.61 (s, 1H), 2.42 (s, 3H), 2.26 (s, 3H); 13C NMR
(CDCl3, 100 Hz) δ 168.7, 161.1, 136.4, 129.1, 125.3, 120.3, 79.3,
27.6, 20.5; MS (EI) m/z (%): 127.00 (100.00). Anal. Calcd for
C12H13NO5: C, 57.37; H, 5.22; N, 5.58. Found: C, 57.55; H, 5.19; N,
5.71%.
(o-Tolylcarbamoyl)methyl diacetate (2b): Pale yellow oil; IR νmax
(KBr): 3273, 1691, 1600, 1544, 1442, 1298, 1174, 968, 860, 810,
756 cm−1; 1H NMR (CDCl3, 400 Hz) δ 8.08 (s, 1H), 7.73–7.71 (d, J =
8.0 Hz, 1H), 7.20–7.18 (t, J = 8.0 Hz, 2H), 7.10–7.08 (d, J = 8.0 Hz,
1H), 5.64 (s, 1H), 2.43 (s, 3H), 2.26 (s, 3H) , 2.23 (s, 3H); 13C NMR
(CDCl3, 100 Hz) δ 168.7, 161.2, 134.2, 130.9, 129.5, 127.2, 126.0,
122.9, 79.2, 27.7, 20.4, 17.4; MS (EI) m/z (%): 108.00 (100.00). Anal.
Calcd for C13H15NO5: C, 58.86; H, 5.70; N, 5.28. Found: C, 58.77; H,
5.59; N, 5.45%.
The authors thank the Guangdong University of Petrochemical
Technology of China for financial support of this work.
Received 12 July 2012; accepted 24 July 2012
Paper 1201409 doi: 10.3184/174751912X13445852334047
Published online: 28 September 2012
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860, 810, 756 cm−1; 1H NMR (CDCl3, 400 Hz) δ 8.17 (s, 1H), 7.42–
7.40 (d, J = 8.0 Hz, 2H), 6.87–6.85 (d, J = 8.0 Hz, 2H), 5.63 (s, 1H),
3.79 (s, 3H), 2.45 (s, 3H), 2.27 (s, 3H); 13C NMR (CDCl3, 100 Hz) δ
168.7, 161.0, 157.0, 129.4, 122.1, 114.2, 79.2, 55.4, 27.6, 20.5; MS
(EI) m/z (%): 149.00 (100.00). Anal. Calcd for C13H15NO6: C, 55.51;
H, 5.38; N, 4.98. Found: C, 55.33; H, 5.29; N, 5.14%.
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