One-Pot Transformation of Aliphatic Carboxylic Acids into N-Alkylsuccin-imides with NIS and NCS/NaI

Article abstract of DOI:10.1002/ejoc.201501315

Primary aliphatic carboxylic acids were treated with N-iodosuccinimide (NIS) in 1,2-dichloroethane to form the corresponding alkyl iodides under warming conditions. Based on these results, those aliphatic carboxylic acids were treated with NIS, followed by the reaction with K₂CO₃to give the corresponding N-alkylsuccinimides in good yields in one pot. Moreover, those aliphatic carboxylic acids were treated with N-chlorosuccinimide (NCS) and NaI, followed by the reaction with K₂CO₃to provide the corresponding N-alkylsuccinimides in good to moderate yields in one pot. By using the present method, successive treatment of primary aliphatic carboxylic acids (10 mmol) with NIS, K₂CO₃, and then hydrazine provided the corresponding decarboxylated primary amines in good yield.

Full text of DOI:10.1002/ejoc.201501315

DOI: 10.1002/ejoc.201501315
Full Paper
Decarboxylative C–N Bond Formation
One-Pot Transformation of Aliphatic Carboxylic Acids into
N-Alkylsuccinimides with NIS and NCS/NaI
Yuhta Nakai,[a] Katsuhiko Moriyama,[a] and Hideo Togo*[a]
Abstract: Primary aliphatic carboxylic acids were treated with chlorosuccinimide (NCS) and NaI, followed by the reaction with
N-iodosuccinimide (NIS) in 1,2-dichloroethane to form the cor- K2CO3 to provide the corresponding N-alkylsuccinimides in
responding alkyl iodides under warming conditions. Based on good to moderate yields in one pot. By using the present
these results, those aliphatic carboxylic acids were treated with method, successive treatment of primary aliphatic carboxylic
NIS, followed by the reaction with K2CO3 to give the corre- acids (10 mmol) with NIS, K2CO3, and then hydrazine provided
sponding N-alkylsuccinimides in good yields in one pot. More- the corresponding decarboxylated primary amines in good
over, those aliphatic carboxylic acids were treated with N- yield.
Introduction
imides can be smoothly converted into the corresponding pri-
mary amines by treatment with hydrazine or aq. KOH solution.
The oxidative functionalization of carboxylic acids is an attract-
ive reaction, because various carboxylic acids, such as fatty
acids, are easily available. The decarboxylative halogenation of
carboxylic acids, in particular, is useful for organic synthesis.
Useful and well-known reactions include the Hunsdiecker–Boro-
din reaction with RCO2Ag and bromine, or the modified reac-
tion with carboxylic acids, HgO, and bromine,[1] and the decar-
boxylative iodination of carboxylic acids with Pb(OAc)4 and iod-
ine.[2] As transition-metal-free methods, the decarboxylative io-
dination of N-acyloxy-2-thiopyridone, prepared from aliphatic
carboxylic acids and N-hydroxy-2-thiopyridone, with CHI3 in
benzene under refluxing conditions or by tungsten-lamp irradi-
ation was reported.[3] Moreover, the decarboxylative iodination
of aliphatic carboxylic acids with (diacetoxyiodo)benzene and
iodine in carbon tetrachloride under refluxing and tungsten-
lamp irradiation conditions was also reported.[4] Both reactions
are useful for the preparation of alkyl iodides. However, some
disadvantages remain: the former reaction requires the prepara-
tion of moisture- and light-sensitive N-acyloxy-2-thiopyridone
with 2-pyridyl diiodomethyl sulfide being formed as the co-
product, and the latter reaction generates iodobenzene as the
co-product. Recently, the effective conversion of aliphatic carb-
oxylic acids into alkyl iodides with 1,3-diiodo-5,5-dimethylhy-
dantoin (DIH) in 1,2-dichloroethane under refluxing conditions
was reported.[5] N-Iodosuccinimide (NIS) was also studied, but
it was found that DIH was much more effective than NIS. Here,
as part of our synthetic study of iodine,[6] we would like to
report a one-pot conversion of primary aliphatic carboxylic
acids into N-alkylsuccinimides via alkyl iodides, as N-alkylsuccin-
Results and Discussion
Initially, the best conditions for the conversion of palmitic acid
into 1-iodopentadecane with NIS (1.2 equiv., 2.0 equiv.
3.0 equiv.) in 1,2-dichloroethane (DCE), carbon tetrachloride,
toluene, 1,4-dioxane, acetonitrile, and propionitrile at 80 °C or
100 °C in a 20 mL screw-capped flask were studied, as shown
in Table 1, and it was found that the treatment of palmitic acid
with NIS (3.0 equiv.) in the presence of iodine (1.0 equiv.) in
DCE at 100 °C for 12 h gave 1-iodopentadecane in 96 % yield
Table 1. Optimization for transformation of palmitic acid into 1-iodopentadec-
ane with NIS.
Entry
x
Solvent
T [°C]
t [h]
Yield [%]
1
2[b]
3[c]
4[d]
5
1.2
1.2
1.2
2.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
DCE (0.5
DCE (0.5
DCE (0.5
DCE (0.1
DCE (0.5
DCE (0.1
DCE (0.1
DCE (0.1
CCl4 (0.1
M
)
)
)
)
)
)
)
)
)
80
80
80
2
2
2
12
4
19 (78)[a]
11 (84)[a]
n.r.
M
M
M
M
M
M
M
M
100
100
100
100
100
80
100
100
100
110
82 (11)[a]
51 (43)[a]
89 (9)[a]
92
6
7
6
12
12
12
12
12
24
24
8[d]
9
96
76 (18)[a]
89 (5)[a]
24 (64)[a]
46 (48)[a]
44 (46)[a]
10
11
12
13
toluene (0.1
1,4-dioxane (0.1
MeCN (0.1
EtCN (0.1
M
)
M
)
[a] Graduate School of Science, Chiba University,
Yayoi-cho 1-33, Inage-ku, Chiba 263-8522 Japan
E-mail: togo@faculty.chiba-u.jp
M)
M
)
http://reaction-2.chem.chiba-u.jp/index.html
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501315.
[a] Values in parentheses: recovery of starting carboxylic acid; n.r.: no reaction.
[b] K2CO3 (10 mol-%) was added. [c] TsOH·H2O (10 mol-%) was added. [d] I2
(1.0 equiv.) was added.
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(Entry 8). Here, iodine works as an effective carbon radical scav- Table 3 (Entries 2, 5, 6). Based on the optimum reaction condi-
enger to form alkyl iodide smoothly.
tions, various primary aliphatic carboxylic acids, such as
nonanoic acid, decanoic acid, stearic acid, monomethyl suber-
ate, monomethyl sebacate, 3-cyclohexylpropanoic acid, 3-phen-
Based on those results, various primary aliphatic carboxylic
acids, such as nonanoic acid, decanoic acid, stearic acid, mono-
methyl suberate, monomethyl sebacate, 3-cyclohexylpropanoic
acid, 3-phenylpropanoic acid, 4-phenylbutanoic acid, 5-phenyl-
pentanoic acid, 2-(p-nitrophenyl)ethanoic acid, 3-(p-chloro-
phenyl)propanoic acid, and 4-(4′-benzoylphenoxy)butanoic
acid, were treated with NIS (3.0 equiv.) in DCE in a 20 mL screw-
capped flask at 100 °C to provide the corresponding alkyl
iodides in good yields, as shown in Table 2 (Entries 1, 2, 4–13).
Tri-O-acetylcholic acid was also converted into the correspond-
ing iodide in good yield under the same reaction conditions
(Entry 14). Then, a one-pot transformation of carboxylic acids
into N-alkylsuccinimides was carried out (Table 3). Treatment of
palmitic acid with NIS (3.0 equiv.) in DCE at 100 °C, followed by
the reaction with K2CO3 in the presence of tetra-
butylammonium bromide (TBAB) at 100 °C in a 20 mL screw-
capped flask gave the corresponding N-pentadecylsuccinimide.
However, the yield was dependent on the solvent. Thus, after
the first reaction with NIS in DCE, the solvent was removed by
evaporation, and acetonitrile, acetone, or 1,4-dioxane was
added to the residue, together with K2CO3 and TBAB, and the
mixture was warmed in the same 20 mL screw-capped flask to
give N-pentadecylsuccinimide in good yields, as shown in
Table 3. Optimization for the transformation of palmitic acid into N-pentadecyl-
succinimide with NIS.
Entry
Solvent
T [°C]
Yield [%]
1[b]
2
DCE
100
80
40
80
70
13
70
MeCN (2 mL)
MeCN (2 mL)
MeCN (2 mL)
acetone (2 mL)
1,4-dioxane (2 mL)
3
0 (80)[a]
17 (40)[a]
71
4[b]
5
6
100
70
[a] Values in parentheses: yield of alkyl iodide. [b] Without evaporation after
the 1st step.
Table 4. Transformation of carboxylic acids into N-alkylsuccinimides with NIS.
Table 2. Transformation of carboxylic acids into alkyl iodides with NIS.
[a] Reaction time was 12 h. [b] Reaction time was 4 h.
Eur. J. Org. Chem. 2016, 768–772 www.eurjoc.org
[a] Reaction time for 1st step was 12 h. [b] Reaction time for 1st step was 4 h.
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ylpropanoic acid, 4-phenylbutanoic acid, 5-phenylpentanoic
Finally, using the present method, 4-phenylbutanoic acid
acid, 2-(p-nitrophenyl)ethanoic acid, 3-(p-chlorophenyl)propan- was converted into 3-phenylpropan-1-amine through the for-
oic acid, and 4-(4′-benzoylphenoxy)butanoic acid, were treated mation of N-(3-phenylpropyl)succinimide by treatment with
with NIS (3.0 equiv.) in DCE at 100 °C in a 20 mL screw-capped hydrazine hydrate, as shown in Scheme 1. A semi-large-scale
flask, followed by the reaction with K2CO3 in the presence of conversion of 4-phenylbutanoic acid (10 mmol) into N-(3-phen-
TBAB in acetone at 70 °C to provide the corresponding N-alkyl- ylpropyl)succinimide and N-(3-phenylpropyl)succinimide into 3-
succinimides in good to moderate yields, as shown in Table 4 phenylpropan-1-amine was carried out in 80 % and 83 % yields,
(Entries 1, 2, 4–13). The same treatment with tri-O-acetylcholic respectively. Thus, the present method can be used for the
acid gave also the corresponding N-alkylsuccinimide in moder- semi-large-scale preparation of primary amines from aliphatic
ate yield (Entry 14).
carboxylic acids. This is similar to the Curtius reaction that uses
carboxylic acid chlorides and sodium azide to decarboxylatively
form primary amines. The important difference is that the
present method does not require toxic sodium azide.
NIS is expensive, whereas N-chlorosuccinimide (NCS) is
cheap. Therefore, the use of NCS instead of NIS was studied.
Treatment of aliphatic carboxylic acids, such as nonanoic acid,
decanoic acid, palmitic acid, stearic acid, monomethyl suberate,
monomethyl sebacate, 3-cyclohexylpropanoic acid, 3-phenyl-
propanoic acid, acid, 4-phenylbutanoic acid, 5-phenylpentanoic
acid, 3-(p-chlorophenyl)propanoic acid, 4-(4′-benzoylphen-
oxy)butanoic, and tri-O-acetyl cholic acid with NCS (5.0 equiv.)
and NaI (5.0 equiv.) in DCE in a 20 mL screw-capped flask at
100 °C, followed by the reaction with K2CO3 in the presence of
TBAB at 70 °C in acetone gave the corresponding N-alkylsuccin-
imides in good to moderate yields, as shown in Table 5 (En-
tries 1–13).
Scheme 1. Preparation of primary amine from 4-phenylbutanoic acid.
Table 5. Transformation of carboxylic acids into N-alkylsuccinimides with NCS
and NaI.
The same treatment of aromatic carboxylic acids, such as p-
toluic acid and p-chlorobenzoic acid, with NIS under the same
conditions gave p-iodotoluene and p-chloroiodobenzene in
13 % and 10 % yields, respectively, together with much recov-
ered starting aromatic carboxylic acids. Thus, the present
method cannot be used for aromatic carboxylic acids.
A plausible reaction pathway for the present reaction is
shown in Scheme 2. Aliphatic carboxylic acid 1 (RCOOH) reacts
with NIS to form acyl hypoiodite A (RCOOI) and succinimide.
Acyl hypoiodite A is reactive under thermal conditions to form
carboxyl radical B (RCOO·) and an iodine atom. Once carboxyl
radical B is formed, it rapidly decarboxylates to produce an alkyl
radical (R·) and carbon dioxide. The alkyl radical reacts with
RCOOI (A) (major process) and iodine (minor process) to form
alkyl iodide 2. Treatment of alkyl iodide 2 with K2CO3 in the
presence of TBAB in acetone induces the N-alkylation of succin-
[a] Reaction time for 1st step was 12 h. [b] 3rd step conditions: Cs2CO3
(5.0 equiv.), acetone (2.0 mL), 70 °C, 24 h. [c] Reaction time for 1st step was
4 h.
Scheme 2. Plausible reaction mechanism.
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CDCl3): δ = 0.87 (t, J = 6.9 Hz, 3 H), 1.26–1.29 (m, 10 H), 1.55 (quint,
J = 7.2 Hz, 2 H), 2.70 (s, 4 H), 3.49 (t, J = 7.5 Hz, 2 H) ppm. 13C NMR
(125 Hz, CDCl3): δ = 14.03, 22.56, 26.81, 27.66, 28.10, 29.06, 31.69,
38.86, 177.26 ppm. HRMS (APCI): calcd. for C12H22O2N [M + H]+
212.1645; found 212.1649.
imide formed in situ at the second reaction step, generating N-
alkylsuccinimide 3 by an SN2 pathway.
Conclusions
1-Nonylpyrrolidine-2,5-dione (3b): Yield: 143.7 mg (68 %); color-
less oil. IR (neat): ν = 1696, 2855, 2925 cm–1 1H NMR (400 MHz,
.
Various primary aliphatic carboxylic acids were treated with NIS
in 1,2-dichloroethane, followed by the reaction with K2CO3 in
acetone to give N-alkylsuccinimides in one pot. Moreover, those
carboxylic acids were also treated with NCS and NaI in 1,2-di-
chloroethane, followed by the reaction with K2CO3 in acetone
to provide N-alkylsuccinimides. A semi-large-scale transforma-
˜
CDCl3): δ = 0.88 (t, J = 6.9 Hz, 3 H), 1.25–1.29 (m, 12 H), 1.55 (quint,
J = 7.2 Hz, 2 H), 2.74 (s, 4 H), 3.49 (t, J = 7.5 Hz, 2 H) ppm. 13C NMR
(125 Hz, CDCl3): δ = 14.08, 22.62, 26.83, 27.69, 28.13, 29.13, 29.18,
29.40, 31.79, 38.89, 177.29 ppm. HRMS (APCI): calcd. for C13H24O2N
[M + H]+ 226.1802; found 226.1806.
tion of aliphatic carboxylic acid into N-alkylsuccinimide and 1-Pentadecylpyrrolidine-2,5-dione (3c): Yield: 219.7 mg (71 %);
1
white solid; m.p. 61–64 °C. IR (neat): ν = 1698, 2849, 2916 cm–1. H
conversion into primary alkylamine were also carried out suc-
cessfully. We believe the present method should be useful for
the transformation of primary aliphatic carboxylic acids into de-
carboxylated N-alkylsuccinimides in one pot.
˜
NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.9 Hz, 3 H), 1.25–1.32 (m,
24 H), 1.55 (quint, J = 7.2 Hz, 2 H), 2.70 (s, 4 H), 3.49 (t, J = 7.6 Hz,
2 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 14.11, 22.68, 26.86, 27.71,
28.13, 29.15, 29.34, 29.46, 29.54, 29.64 (3 C), 29.66 (2 C), 31.91, 38.90,
177.28 ppm. HRMS (APCI): calcd. for C19H36O2N [M + H]+ 310.2741;
found 310.2748.
Experimental Section
1-Heptadecylpyrrolidine-2,5-dione (3d): Yield: 236.3 mg (70 %);
General: 1H and 13C NMR spectra were obtained with JEOL-JNM-
ECX400, JEOL-JNM-ECS400, and JEOL-JNM-ECA500 spectrometers.
Chemical shifts are expressed in ppm downfield from TMS in δ
units. Mass spectra were recorded with a Thermo Fisher Exactive
spectrometer. IR spectra were measured with a JASCO FT/IR-4100
spectrometer. Melting points were determined with a Yamato Melt-
ing Point Apparatus Model MP-21. Silica gel 60F254 (Merck) was
used for TLC, and Silica gel 60 (Kanto Kagaku Co.) was used for
short column chromatography.
1
white solid; m.p. 65–68 °C. IR (neat): ν = 1699, 2849, 2916 cm–1. H
˜
NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3 H), 1.25–1.32 (m,
28 H), 1.55 (quint, J = 7.2 Hz, 2 H), 2.70 (s, 4 H), 3.49 (t, J = 7.7 Hz,
2 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 14.09, 22.66, 26.83, 27.68,
28.11, 29.13, 29.33, 29.45, 29.52, 29.59, 29.63 (2 C), 29.66 (4 C), 31.89,
38.88, 177.28 ppm. HRMS (APCI): calcd. for C21H40O2N [M + H]+
338.3054; found 338.3056.
Methyl 7-(2′,5′-Dioxopyrrolidin-1′-yl)heptanoate (3e): Yield:
193.0 mg (80 %); colorless oil. IR (neat): ν = 1694, 2941 cm–1 1H
.
˜
General Experimental Procedure with NIS: To a solution of
RCOOH (1) (1.0 mmol) of 1,2-dichloroethane (DCE) (10 mL) in a
20 mL screw-capped flask were added N-iodosuccinimide
(3.0 mmol, 675.0 mg) and molecular iodine (1.0 mmol, 253.8 mg).
The mixture was stirred at 100 °C for 4–12 h. After cooling to room
temperature, the solvent was removed by evaporation, and acetone
(2 mL) was added to the residue, together with K2CO3 (10 mmol,
1382.0 mg) and TBAB (0.2 mmol, 64.5 mg). Then, the mixture was
stirred in the same 20 mL screw-capped flask at 70–100 °C for 4–
12 h. After cooling to room temperature, the reaction mixture was
filtered, and the vessel was washed with EtOAc (3 × 5 mL). The
filtrate obtained was concentrated under reduced pressure, and
then the residue was purified by short column chromatography on
silica gel (AcOEt/hexane, 1:2) to afford the desired product 3.
NMR (400 MHz, CDCl3): δ = 1.28–1.36 (m, 4 H), 1.55–1.63 (m, 4 H),
2.30 (t, J = 7.6 Hz, 2 H), 2.71 (s, 4 H), 3.49 (t, J = 7.4 Hz, 2 H), 3.66
(s, 3 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 24.63, 26.39, 27.42, 28.06,
28.51, 33.81, 38.62, 51.39, 174.01, 177.21 ppm. HRMS (APPI): calcd.
for C12H20O4N [M + H]+ 242.1387; found 242.1387.
Methyl 9-(2′,5′-Dioxopyrrolidin-1′-yl)nonanoate (3f): Yield:
202.0 mg (75 %); colorless oil. IR (neat): ν = 1695, 2857, 2932 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 1.22–1.26 (m, 8 H), 1.53–1.63 (m, 4
H), 2.30 (t, J = 7.6 Hz, 2 H), 2.70 (s, 4 H), 3.49 (t, J = 7.4 Hz, 2 H),
3.67 (s, 3 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 24.83, 26.72, 27.63,
28.12, 28.88, 28.95, 29.01, 34.01, 38.81, 51.43, 174.26, 177.28 ppm.
HRMS (APPI): calcd. for C14H24O4N [M + H]+ 270.1700; found
270.1695.
1-(2′-Cyclohexylethyl)pyrrolidine-2,5-dione (3g): Yield: 175.8 mg
General Experimental Procedure with NCS and NaI: A mixture
of N-chlorosuccinimide (5.0 mmol, 667.7 mg) and NaI (5.0 mmol,
749.5 mg) in DCE (10 mL) was stirred at 0 °C for 2 h. Then, RCOOH
(1) (1.0 mmol) and molecular iodine (1.0 mmol, 253.8 mg) were
added. The obtained mixture was stirred at 100 °C for 4–12 h. After
cooling to room temperature, the solvent was removed by evapora-
tion, and acetone (2 mL) was added to the residue, together with
K2CO3 (10 mmol, 1382 mg) and TBAB (0.2 mmol, 64.5 mg). Then,
the mixture was stirred in the same 20 mL screw-capped flask at
(84 %); colorless oil. IR (neat): ν = 1695, 2851, 2922 cm–1 1H NMR
.
˜
(400 MHz, CDCl3): δ = 0.88–0.98 (m, 2 H), 1.08–1.30 (m, 4 H), 1.41–
1.47 (m, 2 H), 1.62–1.77 (m, 5 H), 2.69 (s, 4 H), 3.52 (t, J = 7.9 Hz, 2
H) ppm. 13C NMR (125 Hz, CDCl3): δ = 26.11, 26.44, 28.16, 32.94,
35.00, 35.48, 36.93, 177.24 ppm. HRMS (APCI): calcd. for C12H20O2N
[M + H]+ 210.1489; found 210.1493.
1-(2′-Phenylethyl)pyrrolidine-2,5-dione (3h): Yield: 130.0 mg
(64 %); white solid; m.p. 133–135 °C. IR (neat): ν = 1693, 2940 cm–1.
˜
70–100 °C for 4–12 h. After cooling to room temperature, the reac- H NMR (400 MHz, CDCl3): δ = 2.65 (s, 4 H), 2.88 (t, J = 7.9 Hz, 2 H),
tion mixture was filtered, and the vessel was washed with EtOAc
(3 × 5 mL). The filtrate obtained was concentrated under reduced
pressure, and then the residue was purified by short column chro-
matography on silica gel (AcOEt/hexane, 1:2) to afford the desired
product 3.
3.75 (t, J = 7.9 Hz, 2 H), 7.21–7.31 (m, 5 H) ppm. 13C NMR (125 Hz,
CDCl3): δ = 28.04, 33.50, 39.89, 126.65, 128.49, 128.79, 137.70,
176.96 ppm. HRMS (APCI): calcd. for C12H14O2N [M + H]+ 204.1019;
found 204.1024.
1-(3′-Phenylpropyl)pyrrolidine-2,5-dione (3i): Yield: 176.0 mg
1-Octylpyrrolidine-2,5-dione (3a): Yield: 150.0 mg (71 %); color-
(81 %); colorless oil. IR (neat): ν = 1692, 2940 cm–1. 1H NMR (400 MHz,
˜
less oil. IR (neat): ν = 1695, 2856, 2926 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.94 (quint, J = 7.6 Hz, 2 H), 2.56 (s, 4 H), 2.64 (t, J =
˜
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7.9 Hz, 2 H), 3.56 (t, J = 7.3 Hz, 2 H), 7.15–7.19 (m, 3 H), 7.25–7.29 (m
2 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 27.99, 28.32, 33.08, 38.58,
125.89, 128.11, 128.26, 140.84, 177.19 ppm. HRMS (APCI): calcd. for
C13H16O2N [M + H]+ 218.1176; found 218.1178.
tions for 48 h. After cooling to room temperature, the reaction mix-
ture was filtered, and the vessel was washed with CHCl3 (3 × 5 mL).
The filtrate obtained was concentrated under reduced pressure, and
then the residue was purified by short column chromatography on
silica gel (CH2Cl2/MeOH/NH4OH, 80:20:1) to afford the desired prod-
1-(4′-Phenylbutyl)pyrrolidine-2,5-dione (3j): Yield: 138.8 mg
uct 4i. Yield: 112.2 mg (83 %); colorless oil. IR (neat): ν = 3362,
˜
(60 %); white solid; m.p. 85–88 °C. IR (neat): ν = 1687, 2946 cm–1. 1H
˜
1
3287 cm–1. H NMR (400 MHz, CDCl3): δ = 1.77 (quint, J = 7.5 Hz, 2
NMR (400 MHz, CDCl3): δ = 1.61 (m, 4 H), 2.63 (t, J = 7.1 Hz, 2 H),
2.68 (s, 4 H), 3.53 (t, J = 7.1 Hz, 2 H), 7.15–7.19 (m, 3 H), 7.25–7.29 (m
2 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 27.25, 28.11, 28.59, 35.30,
38.58, 125.80, 128.30, 128.38, 141.88, 177.23 ppm. HRMS (APCI): calcd.
for C14H18O2N [M + H]+ 232.1332; found 232.1333.
H), 2.65 (t, J = 7.9 Hz, 2 H), 2.71 (t, J = 7.2 Hz, 2 H), 7.18–7.19 (m, 3
H), 7.26–7.29 (m, 2 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 32.64,
33.16, 35.08, 41.48, 125.70, 128.26, 141.96 ppm.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra of all N-alkylsuccinimides.
1-(4′-Nitrobenzyl)pyrrolidine-2,5-dione (3k): Yield: 138.2 mg
(59 %); white solid; m.p. 146–147 °C. IR (neat): ν = 1692, 2952 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 2.77 (s, 4 H), 4.75 (s, 2 H), 7.56 (d, J =
8.8 Hz, 2 H), 8.17 (d, J = 9.2 Hz, 2 H) ppm. 13C NMR (125 Hz, CDCl3):
δ = 28.19, 41.63, 123.91, 129.76, 142.54, 147.62, 176.59 ppm. HRMS
(APCI): calcd. for C11H11O4N2 [M + H]+ 235.0713; found 235.0716.
Acknowledgments
Financial support from the Ministry of Education, Culture, Sports,
Science, and Technology in Japan in the form of a Grant-in-Aid
for Scientific Research (no. 25105710) the and Iodine Research
Project in Chiba University is gratefully acknowledged.
1-(4′-Chlorophenylethyl)pyrrolidine-2,5-dione
(3l):
Yield:
130.7 mg (55 %); yellow solid; m.p. 149–151 °C. IR (neat): ν = 1687,
˜
1
2934 cm–1. H NMR (400 MHz, CDCl3): δ = 2.66 (s, 4 H), 2.86 (t, J =
Keywords: Carboxylic acids · Iodine · N-Alkylsuccinimide · N-
Iodosuccinimide · Decarboxylation · Halogenation
7.8 Hz, 2 H), 3.73 (t, J = 7.8 Hz, 2 H), 7.15 (d, J = 8.5 Hz, 2 H), 7.26 (d,
J = 8.5 Hz, 2 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 28.05, 32.82,
39.63, 128.67, 130.15, 132.55, 136.13, 176.93 ppm. HRMS (APPI): calcd.
for C12H13O2NCl [M + H]+ 238.0629; found 238.0626.
[1] a) H. Hunsdiecker, C. Hunsdiecker, Ber. Dtsch. Chem. Ges. 1942, 75, 291–
297; b) R. A. Sheldon, J. K. Kochi, Org. React. 1972, 19, 279–421; c) S. J.
Cristol, W. C. Firth, Jr., J. Org. Chem. 1961, 26, 280–280.
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4979–4982.
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Suarez, J. Org. Chem. 1986, 51, 402–404.
1-[3′-(4′′-Benzoylphenoxy)propyl]pyrrolidine-2,5-dione (3m ):
1
Yield: 219.2 mg (65 %); yellow oil. IR (neat): ν = 1693, 2942 cm–1. H
˜
NMR (400 MHz, CDCl3): δ = 2.13 (quint, J = 6.6 Hz, 2 H), 2.72 (s, 4 H),
3.76 (t, J = 7.0 Hz, 2 H), 4.08 (t, J = 6.1 Hz, 2 H), 6.93 (d, J = 8.8 Hz, 2
H), 7.48 (t, J = 7.9 Hz, 2 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.75 (d, J = 7.3 Hz,
2 H), 7.82 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR (125 Hz, CDCl3): δ =
27.36, 28.14, 36.26, 65.96, 113.90, 128.16, 129.70, 130.26, 131.89,
132.56, 138.18, 162.26, 177.18, 195.54 ppm. HRMS (APCI): calcd. for
C20H20O4N [M + H]+ 338.1387; found 338.1393.
[5] K. Kulbitski, G. Nisnevich, M. Gandelman, Adv. Synth. Catal. 2011, 353,
1438–1442.
[6] Reviews: a) H. Togo, S. Iida, Synlett 2006, 2159–2175; b) H. Togo, J. Synth.
Org. Chem. Jpn. 2008, 66, 652–663; recent papers: c) G. Ishii, R. Harigae,
K. Moriyama, H. Togo, Tetrahedron 2013, 69, 1462–1469; d) H. Shimojo, K.
Moriyama, H. Togo, Synthesis 2013, 45, 2155–2164; e) K. Miyagi, K. Mori-
yama, H. Togo, Eur. J. Org. Chem. 2013, 5886–5892; f) D. Tsuchiya, Y.
Kawagoe, K. Moriyama, H. Togo, Org. Lett. 2013, 15, 4194–4197; g) S. Dohi,
K. Moriyama, H. Togo, Eur. J. Org. Chem. 2013, 7815–7822; h) Y. Kawagoe,
K. Moriyama, H. Togo, Eur. J. Org. Chem. 2014, 4115–4122; i) R. Harigae, K.
Moriyama, H. Togo, J. Org. Chem. 2014, 79, 2049–2058; j) Y. Nakai, K. Mori-
yama, H. Togo, Eur. J. Org. Chem. 2014, 6077–6083; k) T. Tamura, K. Mori-
yama, H. Togo, Eur. J. Org. Chem. 2015, 2023–2029.
3n: Yield: 317.4 mg (54 %); white solid; m.p. 65–68 °C. IR (neat): ν =
˜
1
1698, 2968 cm–1. H NMR (400 MHz, CDCl3): δ = 0.72 (s, 3 H), 0.90–
0.92 (m, 6 H), 1.03–2.03 (m, 22 H), 2.05 (s, 3 H), 2.10 (s, 3 H), 2.14 (s,
3 H), 2.70 (s, 4 H), 3.40–3.57 (m, 2 H), 4.57 (m, 1 H), 4.90 (s 1 H), 5.08
(s, 1 H) ppm. 13C NMR (125 Hz, CDCl3): δ = 12.09, 17.74, 21.35, 21.41,
21.59, 22.47, 22.67, 25.46, 26.79, 27.04, 28.08, 28.78, 29.50, 31.13,
33.18, 33.29, 34.23, 34.50, 34.59, 36.27, 37.62, 40.82, 43.23, 44.98,
47.02, 70.58, 73.98, 75.22, 170.33, 170.41, 170.48, 177.14 ppm. HRMS
(ESI): calcd. for C33H49O8NNa [M + Na]+ 610.3350; found 610.3345.
3-Phenylpropan-1-amine (4i, commercially available): To a solution
of 3i (1 mmol, 217.3 mg) in dry 1,4-dioxane (4.0 mL) was added
NH2NH2·H2O (0.5 mL). The mixture was stirred under reflux condi-
Received: October 14, 2015
Published Online: December 15, 2015
Eur. J. Org. Chem. 2016, 768–772
www.eurjoc.org
772
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim