Efficient synthesis of α-(N-Boc)aminoamides by addition of a carbamoylsilane to N-Boc-imines

Article abstract of DOI:10.1016/j.tet.2016.10.066

N,N-Dimethylcarbamoyl(trimethyl)silane reacted with N-Boc-imines in anhydrous benzene under catalysts-free conditions to afford N-Boc-protected α-amino amides in good yields (72-89%). The electronic property and the steric hindrance of substituent on the N-Boc-imines affected the reaction.

Full text of DOI:10.1016/j.tet.2016.10.066

Accepted Manuscript
Efficient synthesis of α-(N-Boc)aminoamides by addition of a carbamoylsilane to N-
Boc-imines
Qilin Guo, Xueping Wen, Jianxin Chen
PII:
S0040-4020(16)31125-5
10.1016/j.tet.2016.10.066
TET 28207
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 September 2016
Revised Date: 22 October 2016
Accepted Date: 25 October 2016
Please cite this article as: Guo Q, Wen X, Chen J, Efficient synthesis of α-(N-Boc)aminoamides by
addition of a carbamoylsilane to N-Boc-imines, Tetrahedron (2016), doi: 10.1016/j.tet.2016.10.066.
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Efficient synthesis of α-(N-Boc)aminoamides
by addition of a carbamoylsilane to N-Boc-
imines
Leave this area blank for abstract info.
Qilin Guo, Xueping Wen and Jianxin Chen
College of Chemistry and Materials Science, Shanxi Normal University, Linfen 041004, PR China

1
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Tetrahedron
journal homepage: www.elsevier.com
Efficient synthesis of α-(N-Boc)aminoamides by addition of a carbamoylsilane to
N-Boc-imines
Qilin Guo, Xueping Wen and Jianxin Chen
College of Chemistry and Materials Science, Shanxi Normal University, Linfen 041004, PR China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
N,N-Dimethylcarbamoyl(trimethyl)silane reacted with N-Boc-imines in anhydrous benzene
under catalysts-free conditions to afford N-Boc-protected α-amino amides in good yields (72–
89%). The electronic property and the steric hindrance of substituent on the N-Boc-imines
affected the reaction.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
N-Boc-imines
Carbamoylsilanes
Amides
Addition
Synthetic methods
1. Introduction
for the synthesis of Boc-protected α-amino amides, we report
here on the successful attempt in this regard.
α-Amino amides have been investigated extensively, as they
are a common structural feature in a wide range of natural
products and pharmaceutical agents, and are the basic subunit of
peptides and proteins.1 They have also been used as building
blocks for the synthesis of different heterocycles, and ligands for
the metal-catalysts.2 Commonly, the Ugi reaction has been used
to provide α-amino amides,3 whose various limitations are under
continual improvement.4 Recently, Mita et al. have shown that
the copper-catalyzed silylation of N-benzenesulfonyl imines, then
carboxylation under a CO2 atmosphere can afford α-amino acids.5
Reeves et al. reported that the addition of the carbamoyl anion to
N-sulfinylimines can also afford α-amino amides.6 However,
these methods limited by the restricted availability of
isocyanides, the difficulty of deacylating the protected amino
function, the unstable of lithium reagents, the high pressure of
carbon dioxide, low reaction temperature and harsh reaction
conditions. We have recently found that carbamoylsilanes add to
the C=N bond of sulfonylimines to afford α-(N-sulfonyl)amino
amides.7 However, the desulfonation of α-(N-sulfonyl)amino
amides require metal Na or Li,8 which influence other groups in
pharmaceutical synthesis. So the search for a simple and practical
method remains a challenge. We now found that the addition of
N,N-dimethylcarbamoyl(trimethyl)silane to many types of easily
obtainable N-Boc-imines could offer good yields of Boc-
protected α-amino amides derivatives, which can be deprotected
under mildly acidic conditions to form α-amino amides. To the
2. Results and discussion
Scheme 1 The preparation of N-Boc-imines 2
N-Boc-imines 2 were easily prepared by the reaction of
aldehydes, tert-butyl carbamate and sodium benzene sulfinic acid
in a mixture solution of methanol, formic acid and water,
followed by removing benzene sulfinic acid in basic solution
(Scheme 1),9, 10 which were allowed to react with 1.1 equiv of N,
N-dimethylcarbamoyl(trimethyl)silane 111 under anhydrous con-
ditions, good yields of N-Boc-protected α-amino amides 3 were
obtained, generally within a matter of hours at 60 (Table 2).
Table 1 Solvent effect on the addition of N,N-dimethylcarbamoyl(tri-
methyl)silane to benzaldehyde N-Boc imine
Entry
Solvent
Temp (ꢀ)
Timea (h) Yieldb,c (％)
1
2
3
4
5
dichloromethane
acetonitrile
THF
toluene
benzene
35
75
60
60
60
46
33
28
26
22
0
58
64
67
74
aTo complete consumption of carbamoylsilane. bIsolated yield based on
benzaldehyde N-Boc imine. c1:1.2 mol ratio of benzaldehyde N-Boc imine
best of our knowledge, carbamoylsilane has never been reported
———
Corresponding author. E-mail address: jjxxcc2002@yahoo.com

2
Tetrahedron
ACCEPTED MANUSCRIPT
and carbamoylsilane.
all tested solvents except dichloromethane (no product). When
the reaction was conducted in benzene, the product was obtained
in high yield and the reaction time was short. Several other
solvents, including toluene, acetonitrile and THF, gave inferior
results compared to benzene (Table 1).
Initial examination was focused on the investigation of the
solvent effect in the reaction. The addition of N,N-dimethyl-
carbamoyl(trimethyl)silane to benzaldehyde N-Boc imine was
chosen as a model reaction. The reaction proceeded smoothly in
Table 2 α-(N-Boc)aminoamides from N-Boc-imines 2 and carbamoylsilane 1
Entry
N-Boc-imines
Product
Timea (h)
Yield b,c (%)
2a
1
2
17
23
89
86
3a
3b
2b
3
4
20
20
76
77
2c
3c
2d
3d
3e
3f
2e
2f
5
6
7
24
22
19
72
74
89
2g
3g
8
17
84
2h
2i
3h
3i
9
19
21
18
76
73
82
2j
10
11
3j
2k
3k

3
ACCEPTED MANUSCRIPT
2l
12
16
78
3l
a To complete consumption of carbamoylsilane 1 in benzene at 60 ꢀ
b Isolated yield based on N-Boc-imines.
c 1:1.1 mol ratio of N-Boc-imines and carbamoylsilane.
Next, to explore the scope of the reaction between different N-
Boc-imines and carbamoylsilane 1 under optimal conditions to
furnish the N-Boc-protected α-amino amides, we tested the
representative N-Boc-imines bearing aliphatic group, aryl or
heteroaryl on the C=N bond. Experimental results were
summarized in Table 2. For the N-Boc-imines derived from
different aldehydes, all of the reactions gave good yields. A
comparison of the results obtained from 2a, 2b indicates that the
steric environment is an important factor in the addition reaction
since longer reaction time was needed and lower yield of product
was achieved in case of 2b than in case of 2a. The data of Table
2 (entries 3-11) indicates that the addition reaction is sensitive to
electronic factors. Aromatic aldehyde N-Boc imines possessing
an electron-donating group on the aromatic ring, such as the
dimethylamino, methoxy or methyl group, gave slightly lower
yields (entries 3-5). In contrast, substitution of an electron-
withdrawing group on the aromatic ring, such as a nitro or chloro,
led to higher yields (entries 7 and 8). Benzaldehyde N-Boc imine
2f afforded the addition product in moderate yield (entry 6). N-
Boc-imines 2i and 2j containing an electron-rich heteroaryl group,
the furyl and thienyl, reacted with carbamoylsilane 1 to afford
good yields of desired addition products 3i and 3j (entries 9 and
10). Reaction rate was faster compared to benzaldehyde N-Boc
imine 2f. N-Boc-imine 2k possessing an electron-deficient
heteroaryl (pyridyl) gave the addition product in high yield (entry
11). We conclude that, in general, aromatic aldehyde N-Boc
imines possessing an electron-withdrawing group (or electron-
deficient heteroaryl aldehyde N-Boc imines) gave a better yield
than those having an electron-donating group (or electron-rich
heteroaryl aldehyde N-Boc imines). An electron-withdrawing
substituent on the N-Boc-imines accelerates the reaction and
leads to an improved yield. In addition, the cinnamic aldehyde N-
Boc imine 2l has proved more reactive toward reaction of 1 than
all of aromatic aldehyde N-Boc imines, since the reaction
proceeded with faster rate in case of 2l than in case of 2c-h, and
compound 3l corresponding to 1,2-addition product was
exclusively obtained in good yield. This result further confirms
steric hindrance play an important role in addition reaction.
form A,12 which attacked the N-Boc-imines to produce an
unstable intermediate B, followed by silyl group 1,4-migration to
give the adducts C. The latter can be hydrolyzed in the separation
process to form α-(N-Boc)amino amides 3.
3. Conclusions
In conclusion, a novel and highly efficient procedure has been
developed for the preparation of a series of N-Boc-protected α-
amino amides by the addition of N,N-dimethylcarbamoyl-
(trimethyl)silane to N-Boc-imines. In all cases, good yields of the
products were obtained under mild reaction conditions. This
approach is simple and mild procedure, no catalysts
conditions, less byproducts and good yields for the preparation
of various α-amino amides. We anticipate that our study may
draw significant attention of chemists working on the develop-
ment of synthetic methodologies and will find applications in
organic and medicinal chemistry. Further investigations to
develop an asymmetric version of this reaction are now in
progress.
4. Experimental section
4.1 General
All reactions were carried out using standard Schlenk
techniques unless specified other otherwise. Dry benzene was
freshly distilled from sodium and benzophenone as a moisture
indicator under Ar atmosphere before use. All liquid aldehydes
1
were freshly distilled under reduced pressure. H (600 MHz) and
13C (150.8 MHz) NMR spectra were recorded on Bruker (AV600)
NMR spectrometer. All spectra were recorded at room tempera-
ture in deuterated chloroform (CDCl3) δ=7.28 ppm for proton
NMR, δ=77.00 ppm for carbon NMR) unless otherwise stated
using tetramethylsilane (TMS) as an internal standard. Chemical
shifts are expressed in parts per million (ppm) and coupling
constants in Hertz (Hz). Infrared spectra were recorded as
potassium bromide (KBr) discs for solids or thin films on sodium
chloride plates for oils on an IMPACT-410 spectrophotometer.
Elemental analysis was performed on an EA-1108 analyzer.
Melting points were measured with a STUART SMP 10 melting
point apparatus and uncorrected. The monitoring of reaction and
checking of purity of the product were done using pre-coated
silica gel plates (Merck 60 PF254). Column chromatography was
performed using Merck silica gel 200. Visualization was
achieved by UV (254 nm) light detection and iodine staining.
4.2 General procedure for Boc-sulfonyl carbamates 9,10
To a 50 mL round bottom flask charged with a stir bar was
added tert-butyl carbamate (1 g, 8.55 mmol), sodium benzenesul-
finic acid (2.8 g, 17.09 mmol), methanol (8.5 mL), water (17 mL),
aldehyde (8.55mmol) and formic acid (98%, 8.55 mmol)
sequentially. The reaction mixture was stirred at 23 ℃for 48 h.
The reaction mixture was filtered and the precipitate was washed
with water and diethyl ether to yield clean Boc-sulfonyl
carbamates.
Scheme 2 Proposed reaction mechanism
A possible route to addition products 3 is presented in Scheme
2. Carbamoylsilane 1 can rearrange to its nucleophilic carbene

4
Tetrahedron
4.3 General procedure for the preparation of N-Boc-imines
C1 H20N2O2: C, 67.71; H, 8.12; N, 11.28. Found: C, 67.91; H,
ACCEPTED MANUSCRIPT
4
2f, 2h, 2k and 2l9,10
8.36; N, 11.08.
4.4.4. (4-Methoxy)benzaldehyde N-Boc imine (2d).10a, 13 1H NMR
(600MHz, CDCl3) δH: 8.91 (s, 1H, CH=N), 7.91 (d, 2H, J = 7.8
Hz, Ar–H), 6.99 (d, 2H, J = 7.8 Hz, Ar–H), 3.90 (s, 3H, CH3),
1.60 (s, 9H, (CH3)3C); H NMR (600MHz, CDCl3) δH: 168.3,
163.3, 160.1, 132.2, 128.5, 114.4, 80.7, 54.7, 28.0.
4.4.5. (4-Methyl)benzaldehyde N-Boc imine (2e).10a, 13 Colourless
oil; 1H NMR (600MHz, CDCl3) δH: 8.85 (s, 1H, CH=N), 7.67 (d,
2H, J = 7.8 Hz, Ar–H), 6.85 (d, 2H, J = 7.8 Hz, Ar–H), 2.42 (s,
3H, CH3), 1.59 (s, 9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC:
168.4, 163.3, 143.7, 132.5, 130.2, 129.7, 81.0, 28.0, 21.4.
4.4.6. (4-Chloro)benzaldehyde N-Boc imine (2g).10a, 16 1H NMR
(600MHz, CDCl3) δH: 8.86 (s, 1H, CH=N), 7.88 (d, 2H, J = 8.4
Hz, Ar–H), 7.47 (d, 2H, J = 8.4 Hz, Ar–H), 1.61 (s, 9H, (CH3)3C);
13C NMR (151MHz, CDCl3) δC: 168.2, 162.3, 139.8, 132.5,
131.3, 129.3, 82.5, 27.9.
To a 25 mL round bottom flask containing a stirring solution
of Boc-sulfonyl carbamate (1.0 mmol) in dichloromethane (16
mL) was added aqueous K2CO3 (16 mL, 1.4 mol·L–1), the
resulting biphasic mixture was vigorously stirred at 23℃for 5 h.
The organic layer was separated and the aquoaus layer was
extracted with dichloromethane (2×20 mL). The combined
organics were dried over MgSO4 and concentrated in vacuo at
room temperature to yield the desired N-Boc-imines.
1
13
1
4.3.1. Benzaldehyde N-Boc imine (2f).10a, Colourless oil; H
NMR (600MHz, CDCl3) δH: 8.90 (s, 1H, CH=N), 7.95–7.93 (m,
2H, Ar–H), 7.60–7.28 (m, 3H, Ar–H), 1.61 (s, 9H, (CH3)3C); 13
C
NMR (151MHz, CDCl3) δC: 168.2, 163.1, 134.9, 132.9, 130.0,
128.8, 81.2, 27.9.
16
4.3.2. (4-Nitro)benzaldehyde N-Boc imine (2h).10c,
White
1
solid, mp=101.0–103.0 ℃; H NMR (600MHz, CDCl3) δH: 8.89
(s, 1H, CH=N), 8.34 (d, 2H, J = 8.4 Hz, Ar–H), 8.10 (d, 2H, J =
8.4 Hz, Ar–H), 1.62 (s, 9H, (CH3)3C); 13C NMR (151MHz,
CDCl3) δC: 166.2, 161.7, 150.5, 139.3, 130.6, 124.0, 83.2, 27.9.
1
4.4.7. 2-Furaldehyde N-Boc imine (2i).10b, 14 Pale yellow oil; H
NMR (600MHz, CDCl3) δH: 8.79 (s, 1H, CH=N), 7.70 (s, 1H,
Furyl-5-H), 7.25 (d, 1H, J = 3.0 Hz, Furyl-3-H), 6.62–6.59 (dd,
1H, J = 3.0, 1.7 Hz, Furyl-4-H), 1.58 (s, 9H, (CH3)3C); 13C NMR
(151MHz, CDCl3) δC: 162.3, 157.6, 150.9, 148.2, 121.5, 113.2,
82.6, 28.0.
4.4.8. 2-Thenylaldehyde N-Boc imine (2j).10b, 15 Pale yellow oil;
1H NMR (600 MHz, CDCl3) δH: 9.10 (s, 1H, CH=N), 7.69 (d, 1H,
J = 3.6 Hz, Thienyl-3-H), 7.68 (d, 1H, J = 1.8 Hz, Thienyl-5-H),
7.20–7.19 (m, 1H, Thienyl-4-H), 1.59 (s, 9H, (CH3)3C); 13C
NMR (151MHz, CDCl3) δC: 163.6, 162.2, 140.2, 137.1, 134.2,
128.4, 82.2, 27.9.
4.3.3. 2-Pyridinecarboxaldimine (2k). Yellow solid, mp=145.0–
147.0 ℃; IR (KBr) νmax: 3424, 2980, 1715, 1494, 1244, 1149,
1
1011, 774 cm–1; H NMR (600MHz, CDCl3) δH: 9.97 (1H, s,
CH=N), 8.61 (d, 1H, J = 4.2 Hz, pyridyl-6-H), 7.74 (t, 1H, J =
7.8 Hz, pyridyl-4-H), 7.57 (d, 1H, J = 8.4 Hz, pyridyl-3-H),
7.22–7.20 (m, 1H, pyridyl-5-H), 1.27 (s, 9H, (CH3)3C); 13C NMR
(151MHz, CDCl3) δC: 156.1, 153.9, 147.6, 136.3, 123.2, 121.8,
80.0, 28.0. Anal. Calcd for C11H14N2O2: C ,64.06; H, 6.84; N,
13.58. Found: C, 64.23; H, 6.62; N, 13.76.
4.3.4. Cinnamicaldehyde N-Boc imine (2l). 9,17 Pale yellow oil; 1H
NMR (600MHz, CDCl3) δH: 8.70 (d, 1H, J = 9.2 Hz, CH=N),
7.54 (d, 2H, J = 3.7 Hz, Ar–H), 7.42-7.38 (m, 3H, Ar–H), 7.36 (d,
1H, J = 15.9 Hz, =CH), 6.99 (dd, 1H, J = 9.2, 15.9 Hz, =CH=),
1.57 (s, 9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC: 171.6,
162.3, 150.5, 134.7, 130.8, 129.0, 128.1, 126.8, 81.9, 27.9.
4.5 General procedure for the synthesis of α-(N-Boc) amino-
N’,N’-dimethyl amides 3
A Schlenk tube fitted with a Teflon vacuum stopcock and
micro stirbar was flame heated under vacuum and refilled with
Ar. N-Boc-imines 2 (0.50 mmol) and anhydrous benzene (2 mL)
were added at ice bath temperature. After 20 min, carbamoyl-
silane 1 (0.55 mmol) was added. The sealed reaction mixture was
stirred at 60 ℃until no carbamoylsilane 1 could be detected by
TLC. Volatiles were removed in vacuo to afford the crude
product which was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate combination) to give N-Boc-
protected α-amino amides 3.
4.4 General procedure for the preparation of N-Boc-imines
2a-e, 2g, 2i and 2j9,10
To a 25 mL round bottom flask containing a stirring solution
of Boc-sulfonyl carbamate (1.0 mmol) in dichloromethane (13.3
mL) was added dry Cs2CO3 (3.26 g, 7.5 mmol). The mixture was
vigorously stirred at 23 ℃for 1 h. The slurry was filtered and the
organic phase was concentrated in vacuo at 23 ℃ to yield the
desired N-Boc-imines.
4.4.1. Butylaldehyde N-Boc imine (2a).18 Colourless oil; 1H NMR
(600MHz, CDCl3) δH: 8.27 (s, 1H, CH=N), 1.64 (t, 2H, J = 7.2
Hz, CH2C=), 1.52 (s, 9H, (CH3)3C), 1.46–1.43 (m, 2H, CH2),
0.98 (t, 3H, J = 7.2 Hz, CH3); 13C NMR (151MHz, CDCl3) δC:
175.4, 162.1, 82.0, 38.1, 27.8, 18.3, 13.7.
4.5.1. α-(N-Boc)amino-N’,N’-dimethyl pentanamide (3a). Yield=
89%; mp=63.5–65.0 ℃; IR (KBr) νmax: 3254, 1711, 1638, 1550,
1
1279, 1175, 1118 cm–1; H NMR (600MHz, CDCl3) δH: 5.38 (d,
1H, J = 8.4 Hz, NH), 4.62 (q, 1H, J = 8.4, 5.4 Hz, CHN), 3.09,
3.08 (ss, 3H, CH3N), 2.98, 2.97 (ss, 3H, CH3N), 1.43–1.64 (m,
13H, (CH3)3C, CH2CH2), 0.95 (t, 3H, J = 7.2, CH3); 13C NMR
(151MHz, CDCl3) δC: 172.5, 155.6, 79.4, 49.9, 37.1, 35.7, 35.6,
28.4, 18.6, 13.9; Anal. Calcd for C12H24N2O3: C, 58.99; H, 9.90;
N, 11.47. Found: C, 58.76; H, 10.15; N, 11.23.
1
4.4.2. iso-Butylaldehyde N-Boc imine (2b).18 Colourless oil; H
NMR (600MHz, CDCl3) δH: 8.14 (s, 1H, CH=N), 2.55–2.51 (m,
1H, CH), 1.50 (s, 9H, (CH3)3C), 1.09, 1.02 (dd, 6H, J = 5.4 Hz,
(CH3)2CH); 13C NMR (151MHz, CDCl3) δC: 178.8, 162.4, 82.0,
34.4, 27.8, 18.1.
4.5.2. α-(N-Boc)amino-N’,N’-dimethyl-iso-pentanamide (3b).
Yield=86%; mp=81.5–83.0 ℃; IR (KBr) νmax: 3318, 1711, 1638,
1
1539, 1397, 1252, 1175 cm–1; H NMR (600MHz, CDCl3) δH:
5.32 (d, 1H, J = 9.0, NH), 4.49 (q, 1H, J = 9.0, 6.0 Hz, CHN),
3.11 (s, 3H, CH3N), 2.98, (s, 3H, CH3N), 1.93–1.97 (m, 1H,
CH(CH3)2), 1.45 (s, 9H, (CH3)3C), 0.98 (d, 3H, J = 7.2, CH3CH),
0.91 (d, 3H, J = 7.2, CH3CH); 13C NMR (151MHz, CDCl3) δC:
172.2, 155.9, 79.4, 54.9, 37.4, 35.6, 31.6, 28.4, 19.5, 17.3; Anal.
Calcd for C12H24N2O3: C, 58.99; H, 9.90; N, 11.47. Found: C,
58.79; H, 9.67; N, 11.68.
4.4.3. (4-Dimethylamino)benzaldehyde N-Boc imine (2c). Yellow
solid, mp=99.0–101.0 ℃; IR (KBr) νmax: 3340, 2980, 1683, 1583,
1
1535, 1366, 1240, 1144, 990, 826 cm–1; H NMR (600MHz,
CDCl3) δH: 8.94 (s, 1H, CH=N), 7.84 (d, 2H, J = 8.4 Hz, Ar–H),
6.70 (d, 2H, J = 8.4 Hz, Ar–H), 3.10 (s, 6H, (CH3)2N), 1.60 (s,
9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC: 171.1, 163.4,
154.2, 133.0, 121.6, 111.3, 81.1, 40.0, 28.0; Anal. calcd for

5
4.5.3.
α-(N-Boc)amino-N’,N’-dimethyl-(4-dimethylamino)phe-
107.9, 80.0, 49.2, 36.9, 36.9, 28.4; Anal. Calcd for C13H20N2O4:
C, 58.19; H, 7.51; N, 10.44. Found: C, 58.45; H, 7.73; N, 10.21.
ACCEPTED MANUSCRIPT
nylacetamide (3c). Yield=76%; mp=148.5–150.0 ; IR (KBr)
1
ν
max: 3291, 1706, 1654, 1524, 1366, 1248, 1165 cm–1; H NMR
4.5.10. α-(N-Boc)amino-N’,N’-dimethyl-(2)-thienylacetamide (3j).
Yield=73%; mp=73.5–74.5 ; IR (KBr) νmax: 3409, 3314, 1703,
(600MHz, CDCl3) δH: 6.67–7.24 (m, 4H, Ar–H), 5.94 (d, 1H, J =
7.8 Hz, NH), 5.47 (d, 1H, J = 7.8 Hz, CHN), 2.90–2.97 (m, 12H,
(CH3)2NPh, (CH3)2N), 1.41 (s, 9H, (CH3)3C); 13C NMR (151MHz,
CDCl3) δC: 170.6, 155.1, 150.2, 128.6, 125.5, 112.6, 79.3, 54.6,
40.4, 36.9, 35.9, 28.4; Anal. Calcd for C17H27N3O3: C, 63.53; H,
8.47; N, 13.07. Found: C, 63.81; H, 8.69; N, 12.89.
1645, 1523, 1482, 1167 cm–1; H NMR (600MHz, CDCl3) δH:
1
7.26 (d, 1H, J = 4.8 Hz, Thienyl-5-H), 6.94–7.01 (m, 2H,
Thienyl-3-H, Thienyl-4-H), 5.99 (d, 1H, J = 7.8 Hz, NH), 5.83 (d,
1H, J = 7.8 Hz, CHN), 3.01 (s, 3H, CH3N), 2.99 (s, 3H, CH3N),
1.43 (s, 9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC: 169.3,
154.9, 140.5, 126.8, 126.0, 125.9, 79.9, 50.2, 37.1, 36.0, 28.4;
Anal. Calcd for C13H20N2O3S: C, 54.91; H, 7.09; N, 9.85. Found:
C, 54.68; H, 7.31; N, 9.62.
4.5.4. α-(N-Boc)amino-N’,N’-dimethyl-(4-methoxy)phenylacet-
amide (3d). Yield=77%; mp=138.0–139.5 ; IR (KBr) νmax
:
3302, 1703, 1641, 1510, 1263, 1162 cm–1; H NMR (600MHz,
CDCl3) δH: 6.87–7.32 (m, 4H, Ar–H), 6.01(d, 1H, J = 7.2 Hz,
NH), 5.51 (d, 1H, J = 7.2 Hz, CHN), 3.81 (s, 3H, CH3O), 2.99 (s,
3H, CH3N), 2.09 (s, 3H, CH3N), 1.42 (s, 9H, (CH3)3C); 13C NMR
(151MHz, CDCl3) δC: 170.3, 159.4, 155.1, 130.1, 129.0, 114.3,
79.6, 55.3, 54.6, 36.9, 36.0, 28.4; Anal. Calcd for C16H24N2O4: C,
62.32; H, 7.84; N, 9.08. Found: C, 62.56; H, 7.56; N, 9.29.
1
4.5.11.
α-(N-Boc)amino-N’,N’-dimethyl-(2)-pyridylacetamide
(3k). Yield=82%; yellow liquid; IR (KBr) νmax: 3414, 3387, 1710,
1653, 1485, 1390, 1247, 1164 cm–1; H NMR (600MHz, CDCl3)
1
δH: 8.55 (d, 1H, J = 4.2 Hz, pyridyl-6-H), 7.68-7.71 (m, 1H,
pyridyl-4-H), 7.46 (d, 1H, J = 7.8 Hz, pyridyl-3-H), 7.20–7.22
(m, 1H, pyridyl-5-H), 6.25 (d, 1H, J = 7.2 Hz, NH), 5.80 (d, 1H,
J = 7.2 Hz, CHN), 3.11 (s, 3H, CH3N), 3.01 (s, 3H, CH3N),
1.44 (s, 9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC: 169.5,
158.0, 155.2, 149.4, 137.1, 122.8, 121.8, 79.8, 56.6, 37.4, 36.1,
28.4; Anal. Calcd for C14H21N3O3: C, 60.20; H, 7.58; N, 15.04.
Found: C, 60.46; H, 7.79; N, 15.33.
4.5.5. α-(N-Boc)amino-N’,N’-dimethyl-(4-methyl)phenylacetam-
ide (3e). Yield=72%; mp=133.0–134.5 ; IR (KBr) νmax: 3296,
1703, 1641, 1523, 1392, 1263, 1162 cm–1; H NMR (600MHz,
1
CDCl3) δH: 7.16–7.28 (m, 4H, Ar–H), 6.20 (d, 1H, J = 7.2 Hz,
NH), 5.30 (d, 1H, J = 7.2 Hz, CHN), 3.00 (s, 3H, CH3N), 2.90 (s,
3H, CH3N), 2.35 (d, 3H, J = 2.4 Hz, CH3), 1.42 (s, 9H, (CH3)3C);
13C NMR (151MHz, CDCl3) δC: 170.2, 155.1, 137.9, 135.0,
130.0, 127.6, 79.6, 54.9, 36.9, 36.0, 28.4, 21.2; Anal. Calcd for
C16H24N2O3: C, 65.73; H, 8.27; N, 9.58. Found: C, 65.90; H,
8.56; N, 9.79.
4.5.12. α-(N-Boc)amino-N’,N’-dimethyl-4-phenyl-2-butenylam-
ide (3l). Yield=78%; yellow liquid; IR (KBr) νmax: 3417, 3387,
1710, 1649, 1489, 1396, 1256, 1168 cm–1; H NMR (600MHz,
1
CDCl3) δH: 7.27–7.40 (m, 5H, Ar–H), 6.65 (d, 1H, J = 16.2 Hz,
Ar-CH=), 6.15 (q, 1H, J = 16.2, 7.2 Hz, =CH-CHN), 5.82 (d,
1H, J = 7.8 Hz, NH), 5.23 (t, 1H, J = 7.8, 7.2 Hz, CHN), 3.11
(s, 3H, CH3N), 3.03 (s, 3H, CH3N), 1.46 (s, 9H, (CH3)3C); 13C
NMR (151MHz, CDCl3) δC: 169.9, 155.0, 136.1, 133.3, 128.6,
128.1, 126.7, 124.5, 79.7, 53.5, 53.0, 37.0, 36.0, 28.4; Anal.
Calcd for C17H24N2O3: C, 67.08; H, 7.95; N, 9.20. Found: C,
67.26; H, 7.74; N, 9.30.
4.5.6. α-(N-Boc)amino-N’,N’-dimethylphenylacetamide (3f).
Yield=74%; mp=121.5–123.0 ; IR (KBr) νmax: 3410, 1706,
1638, 1485, 1397, 1164 cm–1; H NMR (600MHz, CDCl3) δH:
1
7.30–7.40 (m, 5H, Ar–H), 6.05 (d, 1H, J = 7.8 Hz, NH), 5.57 (d,
1H, J = 7.8 Hz, CHN), 2.99 (s, 3H, CH3N), 2.91 (s, 3H, CH3N),
1.42 (s, 9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC: 170.1,
155.1, 138.0, 129.0, 128.2, 127.9, 127.7, 79.7, 55.2, 36.9, 36.0,
28.4; Anal. Calcd for C15H22N2O3: C, 64.73; H, 7.97; N, 10.06.
Found: C, 64.51; H, 7.74; N, 10.16.
Acknowledgments
This research was supported by Shanxi Province Foundation
for Returness (No. 0713), the Natural Science Foundation of
Shanxi Province (No. 2012011046-9) and Foundation of Shanxi
Normal University (No. WL2015CXCY-YJ-21), China.
4.5.7. α-(N-Boc)amino-N’,N’-dimethyl-(4-chloro)phenylacetam-
ide (3g). Yield=89%; mp=137.5–139.0 ; IR (KBr) νmax: 3287,
1
1695, 1638, 1535, 1396, 1164 cm–1; H NMR (600MHz, CDCl3)
δH: 7.33–7.36 (m, 4H, Ar–H), 6.09 (d, 1H, J = 7.2 Hz, NH), 5.53
(d, 1H, J = 7.2 Hz, CHN), 3.00 (s, 3H, CH3N), 2.91 (s, 3H,
CH3N), 1.42 (s, 9H, (CH3)3C); 13C NMR (151MHz, CDCl3) δC:
169.2, 155.0, 136.6, 134.1, 129.2, 79.9, 54.5, 36.9, 36.0, 28.4;
Anal. Calcd for C15H21ClN2O3: C, 57.60; H, 6.77; N, 8.96.
Found: C, 57.80; H, 6.68; N, 8.73.
References and notes
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1
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6.21 (d, 1H, J = 7.2 Hz, NH), 5.65 (d, 1H, J = 7.2 Hz, CHN),
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1
1489, 1405, 1169 cm–1; H NMR (600MHz, CDCl3) δH: 7.37, (d,
1H, J = 10.2 Hz, Furyl-5-H), 6.30–6.34 (m, 2H, Furyl-3-H,
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C
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