Electronic Supporting Information A Fully Recyclable ... · PDF fileElectronic Supporting...
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Electronic Supporting Information
A Fully Recyclable Heterogenized Cu Catalyst for the General Carbene Transfer Reaction in Batch and Flow
Lourdes Maestre, a Erhan Ozkal,b Carles Ayats,b Álvaro Beltrán,a M. Mar Díaz-Requejo,a,*
Pedro J. Péreza,* and Miquel A. Pericàsb,*
aLaboratorio de Catálisis Homogénea, Unidad Asociada al CSIC, CIQSO-Centro de Investigación en Química
Sostenible and Departamento de Química y Ciencia de Materiales, Universidad de Huelva , 21007 Huelva,
Spain bInstitute of Chemical Research of Catalonia (ICIQ), Avda. Països Catalans 16, 43007, Tarragona, Catalonia,
Spain. cDepartament de Química Orgànica, Universitat de Barcelona, 08028 Barcelona, Spain.
Table of contents
1. General Information S2
2. Synthesis of the polymer-supported copper complex PS-TTMCu(NCMe)PF6. S2
3. Catalytic experiments under batch conditions S3
4. Description of the experimental setup for the continuous-flow process S5
5. Continuous-flow experiment with ethyl diazoacetate and ethanol S6
6. Continuous flow production of a family of compounds resulting from carbene transfer reactions S7
7. 1H NMR and 13C NMR data for products 1-6 S8
8. 1H NMR and 13C NMR spectra for products 1-6 S11
9. GC chromatograms for products 1-6 S17
Electronic Supplementary Material (ESI) for Chemical Science.This journal is © The Royal Society of Chemistry 2014
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1. General Information
Unless otherwise stated all the reactions were done under inert conditions (exclusion of air and moisture);
under positive pressure of nitrogen (catalyst preparation and batch catalytic experiments) or argon
(continuous flow experiments). Reactions were monitored by GC analyses performed on Agilent Technologies
model 6890N gas chromatography instrument with a FID detector using 30 m x 0.25 mm HP-5 capillary
column [He as carrier gas: 1.2 mL/min; initial temperature: 50 ºC (1.5 min); then heating at a rate of 10 ºC/min
till 250 ºC (25 min)]. NMR spectra were recorded on a Bruker Advance 300 or 400 Ultrashield NMR
spectrometers for 1H NMR at 300 or 400 MHz and 13C at 75 or 101 MHz. All samples were recorded in CDCl3.
Chemical shifts (δ) for protons are quoted in parts per million (ppm) downfield from tetramethylsilane and were
referenced to residual proton resonances of the NMR solvent. Flash chromatography was carried out using 60
mesh silica gel and dry-packed columns. Commercial materials were used as received with following
exceptions: all the solvents were used from a MBRAUN Solvent Purification System, and absolute ethanol
was dried over Mg and further kept over activated 4 Å molecular sieves. Tetrakis(acetonitrile)copper(I)
hexafluorophosphate, [(CH3CN)4Cu]PF6, was purchased from Aldrich and was stored and used inside a glove
box. Ethyl diazoacetate (EDA) was purchased from Aldrich and used as received. Tris(triazolyl)methane
ligand1 and polymer-supported ligand2 were synthesized according to the previously published methods
without any modifications. Elemental analyses and analysis of copper content (ICP-OES) were performed by
Medac Ltd, Surrey (UK). The products of carbene transfer reactions were identified by comparison of their
NMR spectra with those previously reported.3
2. Synthesis of the polymer-supported copper complex PS-TTMCu(NCMe)PF6.
A mixture of PS-supported tris(triazolyl)methoxy ligand (300 mg, 1 equiv., f = 0.495 mmol·g-1) and
[(CH3CN)4Cu]PF6 (65 mg, 0.176 mmol, 1.20 equiv.) was stirred in 20 mL of dry dichloromethane for 16 h
under nitrogen. After filtration, the solid was washed with dry dichloromethane (2 x 20 mL) and petroleum
ether (2 x 20 mL) and dried under vacuum. No changes in color were observed in the isolated solid from that
of the starting material. In the event that some greenish color was observed, this would be indicative of partial
oxidation to Cu(II). This problem can be avoided by working under inert atmosphere.
In the case of the catalyst for continuous flow, the procedure for the formation of the Cu(I) complex was
carried out inside a glovebox, with the resin sample loaded in the flow column. The column was then taken
outside from the glovebox, and was shaken at room temperature under positive pressure of argon for 16 h.
The column was then connected to the flow instrument and was washed with dry dichloromethane (20 mL)
with a flow rate of 500 µL/min prior to use.
1 a) S. Özçubukçu, E. Ozkal, C. Jimeno, M.A. Pericàs, Org. Lett. 2009, 11, 4680–4683. b) E. Ozkal, P. Llanes, F. Bravo, A. Ferrali, M.A. Pericàs Adv. Synth. Cat. 2014, 356, 857-869. 2 E. Ozkal, S. Özçubukçu, C. Jimeno, M.A. Pericàs Catal. Sci. Technol. 2012, 2, 195-200. 3 a) M. J. Joung, J. H. Ahn, D. W. Lee, N. M. Yoon J. Org. Chem. 1998, 63, 2755-2757. b) P. Müller, C. Gränicher Helv. Chim. Acta 1993, 76, 521-534. c) M. E. Morilla, J. Molina, M. M. Díaz-Requejo, T. R. Belderraín, M. C. Nicasio, S. Trofimenko, P. J. Pérez Organometallics 2003, 22, 2914-2918. d) J. A. Flores, V. Badarinarayana, S. Singh, C. J. Lovely, H. V. R. Dias Dalton. Trans. 2009, 7648-7652. e) L. K. Baumann, H. M. Mbuvi, G. Du, L. K. Woo Organometallics 2007, 26, 3995-4002. f) M. E. Morilla, M. M. Díaz-Requejo, T. R. Belderraín, M. C. Nicasio, S. Trofimenko, P. J. Pérez Organometallics 2004, 23, 293-295.
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Elemental analysis of the resin PS-TTMCu(NCMe)PF6:
N, 5.40%; C, 73.35%; H, 6.10%; Cu, 2.74%
The functionalization of the resin PS-TTMCu(NCMe)PF6 (f = 0.39 mmol·g-1) was calculated from the results of
elemental analysis of nitrogen.4 These results are consistent with those resulting from the analysis of Cu by
ICP-OES.
3. Catalytic experiments under batch conditions
Carbene insertion into the O-H bond of ethanol
a) Small scale experiments: Dry and deoxygenated ethanol (5 mL) was added to a Schlenk flask containing
PS-TTMCu(NCMe)PF6 (100 mg, 0.039 mmol) under nitrogen atmosphere. EDA (0.75 mmol, 79 µL) was
added in one portion and the mixture was stirred for 3 h at room temperature. The mixture was then filtered,
the solid washed with CH2Cl2 (2 x 5mL), dried under vacuum and loaded again with solvent and reactants.
The filtrate from the reaction mixture was analyzed by GC, identifying exclusively the product derived from
ethanol functionalization3 and some diethyl fumarate and maleate from the formal dimerization of the
CHCO2Et units from EDA. The filtrate was taken to dryness, at 0º C to avoid evaporation of the product, and
the residue was dissolved in CDCl3. and analyzed by NMR.
Average productivity in batch after 5 cycles : 6.3 mmolproduct ·mmolCu-1·h-1
b) Preparative, large scale experiment: Dry and deoxygenated ethanol (30 mL) was added to a Schlenk flask
containing freshly prepared PS-TTMCu(NCMe)PF6 (600 mg, 0.234 mmol, recovered from the preparative
experiment with aniline described below) under nitrogen atmosphere. EDA (4.5 mmol, 0.47 mL) was added in
one portion and the mixture was stirred for 3 h at room temperature. The catalyst was separated by filtration,
washed with CH2Cl2 (2 x 30 mL), dried and stored for further use. The filtrate from the reaction mixture was
analyzed by GC, showing exclusively the peak corresponding to 3 (>99% conversion and >99% selectivity).
Solvents were removed under reduced pressure (P = 150 mbar, 30 ºC) to a weight of 1.15 g. At this point,
CH2Cl2 (7 mL) was added, and the solvents (dichloromethane and residual ethanol) were removed under
reduced pressure (P = 400 mbar, 30 ºC) to give pure 3 (0.58 g, 4.41 mmol, 98% isolated yield).
4 The degree of functionalization of a resin can be calculated from the results of elemental analysis with the formulas: fN = (0.714/nN)%N, where nN is the number of nitrogen atoms in the functional unit and %N is the percent of nitrogen provided by the elemental analysis. See: A. Bastero, D. Font and M. A. Pericàs J. Org. Chem. 2007, 72, 2460-2468. The corresponding formula from the results of Cu analysis is: fCu = (0.157/nCu)%Cu.
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Carbene insertion into N-H bonds of aniline
a) Small scale experiments: Dry deoxygenated dichloromethane (3 mL) was added to a Schlenk flask
containing PS-TTMCu(NCMe)PF6 (100 mg, 0.039 mmol) under nitrogen atmosphere, followed by 3.75 mmol
(0.34 mL) of freshly distilled aniline. A solution of 0.75 mmol (79 µL) of EDA in 10 mL of CH2Cl2 was slowly
added over 6 h with the aid of a syringe pump. Workup was similar to that described above, removal of
volatiles being performed at room temperature.
Average productivity in batch after 5 cycles : 3.0 mmolproduct ·mmolCu-1·h-1
b) Preparative, large scale experiment: Dry deoxygenated dichloromethane (15 mL) was added to a Schlenk
flask containing freshly prepared PS-TTMCu(NCMe)PF6 (600 mg, 0.234 mmol) under nitrogen atmosphere,
followed by 22.5 mmol (2.0 mL) of freshly distilled aniline. A solution of 4.5 mmol (0.47 mL) of EDA in 30 mL
of CH2Cl2 was slowly added over 6 h with the aid of a syringe pump. The catalyst was separated by filtration,
washed with CH2Cl2 (2 x 30 mL), dried and used for the preparative experiment with ethanol (see above). The
filtrate from the reaction mixture was analyzed by GC, showing exclusively the peak corresponding to 4 (>99%
conversion and >99% selectivity). Dichloromethane was removed under reduced pressure (P = 400 mbar, 30
ºC), and excess aniline was evaporatively distilled using a rotary microdistillation equipment at 60-70 ºC/0.3
mbar. The residue in the flask was pure 4 (0.801 g, 4.47 mmol, 99% isolated yield).
Carbene insertion into C-H bonds of cyclohexane and tetrahydrofuran
Following the above procedure, cyclohexane (3 mL) was reacted with EDA (0.75 mmol, 79 µL) in the
presence of the solid catalyst (100 mg, 0.039 mmol) under nitrogen atmosphere. EDA was slowly added for
18 h (dissolved in cyclohexane). Identical protocol and amounts of reactants were employed in the case of
tetrahydrofuran. Workup was similar to that described above, removal of volatiles being performed at room
temperature.
Average productivity for cyclohexane in batch after 5 cycles : 0.81 mmolproduct ·mmolCu-1·h-1
Average productivity for tetrahydrofuran in batch after 5 cycles : 0.95 mmolproduct ·mmolCu-1·h-1
Cyclopropenation of 1-phenyl-1-propyne .
3 mL of dry deoxygenated dichloromethane was added to a Schlenk containing the catalyst (100 mg,
0.039 mmol) under nitrogen atmosphere, followed by 3.75 mmol (0.42 mL) of 1-phenyl-1-propyne. A solution
of 0.75 mmol (79 µL) of EDA in 10 mL of dichloromethane was slowly added over 6 hours. Workup was
similar to that described above, removal of volatiles being performed at room temperature.
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Average productivity in batch after 5 cycles : 2.9 mmolproduct ·mmolCu-1·h-1
Büchner ring expansion of benzene
3 mL of dry deoxygenated benzene was added to a Schlenk containing the catalyst (100 mg, 0.039 mmol)
under nitrogen atmosphere. A solution of 0.75 mmol (79 µL) of EDA in 10 mL of benzene was slowly added
for 6 h, before workup, that was similar to that described above, removal of volatiles being performed at room
temperature.
Average productivity in batch after 5 cycles : 2.6 mmolproduct ·mmolCu-1·h-1
Consecutive experiments with different substrates
The above conditions were employed in a consecutive manner with the same initial loading of catalyst for an
overall number of 12 experiments, two with each substrate (see Table 2 in the manuscript).
4. Description of the experimental setup for the continuous flow process
For the continuous flow experiments, the instrumental set-up shown in Figure S1 was used. The packed bed
reactor consisted of a vertical mounted and fritted low-pressure Omnifit glass chromatography column (10 mm
bore size and up to maximal 70 mm of adjustable bed height) loaded with 300 mg of PS-TTMCu(NCMe)PF6 (ƒ
= 0.39 mmol·g-1). The reactor inlet was connected to a three-way connector that allows switching between two
channels, connected to an Asia120® flow chemistry system developed by Syrris. One channel was connected
to a solution of ethyl diazoacetate (EDA) and distilled ethanol in deoxygenated dichloromethane under argon
(no reaction occurs in the absence of catalyst) through Pump 1, and the other channel was connected to a
flask containing deoxygenated dichloromethane to rinse the system through Pump 2. The reactor outlet was
connected to a receiving flask, where the product was collected. Conversions of the product at any moment
were determined by gas chromatography of periodically collected samples. At the end of the experiment the
solvent was removed under reduced pressure to give the final product. During operation, all the system was
kept under argon using either balloons (picture) or connections to an argon manifold.
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Figure S1. The experimental set-up for the continuous-flow experiment, e.g. with ethyl diazoacetate and ethanol.
5. Continuous flow experiment with ethyl diazoacetate and ethanol
The column was assembled to the Asia120® flow chemistry system developed by Syrris as shown in Figure
S1. Deoxygenated dichloromethane was flushed by an Asian pump through the column at 500 µL·min-1 flow
rate to swell the resin. After 30 min, the solvent channel was switched to the reagents and a solution of ethyl
diazoacetate (11.2 mL, 106 mmol) and distilled ethanol (31 mL, 531 mmol) in deoxygenated dichloromethane
(1400 mL) was pumped with a flow rate of 500 µL·min-1 through the system and the system was run for 48 h.
Periodically collected samples were analysed by gas chromatography to determine conversion of the final
product. Samples were collected and solvent was removed under reduced pressure to give pure product 3
(12.6 g, 95.83 mmol, 89 % yield) as a brownish liquid.
Productivity: 17.1 mmolproduct ·mmolCu-1·h-1; TON: 819 (referred to the product formed).
Figure S2. Conversion over time for continuous-flow reaction of ethanol and EDA.
CH2Cl2%
O
OEtOEt
O
OEt +N2
EtOH
CH2Cl2
Pump%1:%solu.on%
Pump%2:%CH2Cl2%reservoir%
Column%with%%catalyst%
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6. Continuous flow production of a family of compounds resulting from carbene transfer reactions.
a) The column was filled with the catalyst as described above and assembled to an Asia120® flow chemistry
system developed by Syrris (Figure S1). Deoxygenated dichloromethane was first flushed through the column
at 500 µL·min-1 flow rate to ensure that no unligated Cu(I) is available. After 30 min, the solvent was changed
to dry tetrahydrofuran, which was pumped through the column at 500 µL·min-1 flow rate. After 1 h, the solvent
channel was switched to the reagents and a solution of EDA (0.56 mL, 5.3 mmol) in dry THF (70 mL) under
argon was pumped with a flow rate of 500 µL·min-1. After a 10 min stabilization period, collection of the efluent
was started and the process was kept running for 2 h. The collected samples were evaporated and analyzed
by GC to determine conversion of the final product. The system was flushed with deoxygenated
dichloromethane for 10 min at 500 µL·min-1 flow rate to clean the resin and the same procedure was repeated
with the next substrate.
The solvent from the collected efluent was removed under reduced pressure (P = 200 mbar, 30 ºC) to give a
yellow liquid which was submitted to flash column chromatography on silicagel (cyclohexane/ethyl acetate
95:5). The solvent was distilled off through a Vigreux column under reduced pressure (P = 200 mbar, 40 ºC)
to give pure product 2 (0.40 g, 2.53 mmol, 56% yield).
Productivity: 10.8 mmolproduct ·mmolCu-1·h-1
b) Continuous flow reaction of EDA (0.28 mL, 2.65 mmol) and distilled and deoxygenated cyclohexane (35
mL, 0.32 mol) in deoxygenated DCM (35 mL).
The procedure described under a) was followed. Most of the solvent from the collected efluent was removed
under reduced pressure (P = 400 mbar, 30 ºC) and residual solvent was distilled off through a Vigreux column
under reduced pressure (P = 200 mbar, 40 ºC). The residue, a yellow liquid, was submitted to flash column
chromatography on silicagel (cyclohexane 100%). The solvent of the collected fractions was distilled off
through a Vigreux column under reduced pressure (P = 200 mbar, 40 ºC) to give pure product 1 (0.16 g, 0.94
mmol, 41% yield).
Productivity: 4.0 mmolproduct ·mmolCu-1·h-1
c) Continuous flow reaction of EDA (0.12 mL, 1.15 mmol) and 1-phenyl-1-propyne (1.3 mL, 10.4 mmol) in
deoxygenated DCM (30 mL).5
The procedure described under a) was followed. The solvent from the collected efluent was removed under
reduced pressure (P = 400 mbar, 30 ºC) to give a brown liquid, which was submitted to flash column
chromatography on silicagel (cyclohexane/ethyl acetate 9:1). The solvent of the collected fractions was
distilled off through a Vigreux column under reduced pressure (P = 200 mbar, 40 ºC) to give pure product 6
(0.11 g, 0.54 mmol, 70 % yield).
Productivity: 2.3 mmolproduct ·mmolCu-1·h-1
5 In this experiment the flow rate was 175 µL/min.
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d) Continuous flow reaction of EDA (0.56 mL, 5.3 mmol) and aniline (2.38 mL, 26.25 mmol) in deoxygenated
DCM (70 mL).
The procedure described under a) was followed. The solvent from the collected efluent was removed under
reduced pressure (P = 400 mbar, 30 ºC) to give a brown liquid which was submitted to bulb-to-bulb distillation
at 60-70 ºC/0.3 mbar to remove traces of aniline. The material remaining in the flask was product 4 in pure
form (0.70 g, 3.91 mmol, 89% yield).
Productivity: 16.7 mmolproduct ·mmolCu-1·h-1
e) Continuous flow reaction of EDA (0.56 mL, 5.3 mmol) and ethanol (1.54 mL, 26.4 mmol) in deoxygenated
DCM (70 mL).
The procedure described under a) was followed. The solvent from the collected efluent was removed under
reduced pressure (P = 400 mbar, 30 ºC) to give pure product 3 (0.54 g, 4.10 mmol, 93% yield).
Productivity: 17.5 mmolproduct ·mmolCu-1·h-1
7. 1H NMR and 13C NMR data for products 1-6.
Ethyl 2-cyclohexanylacetate, 13a
1
1H-NMR (300 MHz, CDCl3): δ = 0.93-1.02 (m, 2 H), 1.16-1.30 (m, 4 H), 1.25 (t, J = 6.9 Hz, 3 H), 1.63-1.75 (m,
5 H), 2.17 (d, J = 6.9 Hz, 2 H), 4.12 (q, J = 6.9 Hz, 2 H) ppm. 13C-NMR (75 MHz, CDCl3): δ = 14.3, 26.0, 26.2,
33.0, 34.9, 42.2, 60.1, 173.2 ppm.
Ethyl (tetrahydrofuran-2-yl)acetate, 23d
2
O OEt
O
O OEt
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1H-NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.2 Hz, 3 H), 1.49-1.59 (m, 1 H), 1.85-1.96 (m, 2 H), 2.03-2.14 (m,
1 H), 2.45 (dd, J = 15.0 and 6.3 Hz, 1 H), 2.59 (dd, J = 15.0 and 7.2 Hz, 1 H), 3.71-3.79 (m, 1 H), 3.84-3.92
(m, 1 H), 4.15 (q, J = 7.2 Hz, 2 H), 4.20-4.29 (m, 1H) ppm. 13C-NMR (75 MHz, CDCl3): δ = 14.2, 25.6, 31.2,
40.7, 60.5, 68.0, 75.3, 171.3 ppm.
Ethyl 2-ethoxyacetate, 33c
3
1H-NMR (300 MHz, CDCl3): δ = 1.24 (t, J = 6.9 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 3.58 (q, J = 6.9 Hz, 2 H),
4.05 (s, 2 H), 4.21 (q, J = 7.2 Hz, 2 H) ppm. 13C-NMR (75 MHz, CDCl3): δ = 14.1, 14.9, 60.7, 67.1, 68.0,
170.5 ppm.
Ethyl 2-(phenylamino)acetate, 43e
4
1H-NMR (300 MHz, CDCl3): δ = 1.30 (t, J = 6.9 Hz, 3 H), 3.9 (s, 2 H), 4.25 (q, J = 6.9 Hz, 2 H), 4.29 (br s, 1
H), 6.60-6.63 (m, 2 H), 6.73-6.78 (m, 1 H), 7.17-7.23 (m, 2 H) ppm. 13C-NMR (75 MHz, CDCl3): δ = 14.1,
45.8, 61.3, 112.9, 118.1, 129.3, 147.0, 171.1 ppm.
Ethyl cyclohepta-2,4,6-trienecarboxylate, 53f
5
EtO
OOEt
HN
OOEt
EtO2C
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1H-NMR (400 MHz, CDCl3): δ = 1.31 (t, J = 7.2 Hz, 3 H), 2.53 (tt, J = 5.6 and 1.2 Hz, 1 H), 4.26 (q, J = 7.2 Hz,
2 H), 5.44 (dd, J = 9.6 and 5.6 Hz, 2 H), 6.24-6.28 (m, 2 H), 6.65-6.66 (m, 2 H) ppm. 13C-NMR (101 MHz,
CDCl3): δ = 14.2, 44.1, 61.0, 117.3, 125.5, 130.9, 173.0 ppm.
Ethyl 2-methyl-3-phenylcycloprop-2-enecarboxylate, 63b
6
1H-NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.2 Hz, 3 H), 2.33 (s, 3 H), 2.43 (s, 1 H), 4.15 (qd, J = 7.2 and 2.1
Hz, 2 H), 7.28-7.48 (m, 5 H) ppm. 13C-NMR (75 MHz, CDCl3): δ = 10.7, 14.4, 22.5, 60.1, 105.2, 106.3, 127.1,
128.5, 128.6, 129.2, 175.7 ppm.
Ph
O OEt
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0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
300 MHz, 1H NMR, CDCl3
2.02
7.36
5.52
1.99
2.00
0.939
0.975
0.984
1.228
1.252
1.276
1.663
1.716
1.719
1.735
2.156
2.179
4.084
4.108
4.132
4.156
102030405060708090100110120130140150160170180190200f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
18000
19000
75 MHz, 13C NMR, CDCl3
14.291
26.030
26.157
33.019
34.910
42.248
60.056
173.186
8. 1H NMR and 13C NMR spectra for products 1-6.
Ethyl 2-cyclohexanylacetate, 1
1H NMR (300 MHz, CDCl3)
13C NMR (75 MHz, CDCl3)
O OEt
O OEt
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0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
300 MHz, 1H NMR, CDCl3
3.19
1.16
1.99
1.00
1.00
0.96
1.00
1.01
2.01
1.04
1.238
1.262
1.286
1.518
1.557
1.586
1.884
1.927
2.422
2.443
2.473
2.493
2.555
2.579
2.605
2.629
3.712
3.739
3.763
3.786
3.843
3.871
3.888
3.893
3.916
4.119
4.143
4.228
4.250
4.273
4.295
0102030405060708090100110120130140150160170180190200f1 (ppm)
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
1200075 MHz, 13C NMR, CDCl3
14.195
25.580
31.245
40.727
60.458
67.981
75.311
171.328
Ethyl (tetrahydrofuran-2-yl)acetate, 2
1H NMR (300 MHz, CDCl3)
13C NMR (75 MHz, CDCl3)
O
O OEt
O
O OEt
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102030405060708090100110120130140150160170180190200f1 (ppm)
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
2800075 MHz, 13C NMR, CDCl3
14.110
14.889
60.712
67.078
68.032
170.462
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
300 MHz, 1H NMR, CDCl3
6.82
2.04
2.00
2.54
1.220
1.243
1.252
1.267
1.276
1.300
3.551
3.574
3.598
3.621
4.055
4.176
4.200
4.224
4.247
Ethyl 2-ethoxyacetate, 3
1H NMR (300 MHz, CDCl3)
13C NMR (75 MHz, CDCl3)
EtO
OOEt
EtO
OOEt
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102030405060708090100110120130140150160170180190200f1 (ppm)
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
75 MHz, 13C NMR, CDCl3
14.153
45.817
61.263
112.950
118.127
129.257
146.989
171.083
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
700
750
800300 MHz, H NMR, CDCl3
3.05
1.99
2.97
2.00
1.04
1.90
1.279
1.303
1.326
3.904
4.216
4.240
4.263
4.287
6.602
6.605
6.609
6.628
6.631
6.634
6.733
6.753
6.757
6.761
6.778
6.782
6.785
7.174
7.198
7.202
7.227
Ethyl 2-(phenylamino)acetate, 4
1H NMR (300 MHz, CDCl3)
13C NMR (75 MHz, CDCl3)
HN
OOEt
HN
OOEt
S15
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
50
100
150
200
250
300
400 MHz, 1H NMR, CDCl3
3.29
1.00
2.16
2.02
2.07
2.03
1.292
1.310
1.328
2.518
2.521
2.525
2.532
2.535
2.538
2.546
2.549
2.552
4.232
4.249
4.267
4.285
5.426
5.438
5.440
5.446
5.448
5.462
6.242
6.245
6.248
6.251
6.255
6.258
6.261
6.264
6.267
6.271
6.274
6.277
6.280
6.283
6.649
6.656
6.658
6.665
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
101 MHz, 13C NMR, CDCl314.226
44.059
61.054
117.279
125.540
130.903
173.053
Ethyl cyclohepta-2,4,6-trienecarboxylate, 5
1H NMR (400 MHz, CDCl3)
13C NMR (101 MHz, CDCl3)
EtO2C
S16
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
700
750
800
300 MHz, 1H NMR, CDCl3
3.13
3.00
0.98
1.99
5.02
1.227
1.251
1.274
2.333
2.429
4.117
4.124
4.141
4.148
4.165
4.172
4.188
4.196
7.286
7.291
7.301
7.311
7.319
7.329
7.334
7.340
7.357
7.362
7.364
7.368
7.383
7.388
7.391
7.395
7.405
7.412
7.417
7.444
7.450
7.455
7.460
7.470
7.477
7.483
102030405060708090100110120130140150160170180190200f1 (ppm)
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
2800075 MHz, 13C NMR, CDCl3
10.686
14.396
22.539
60.124
105.228
106.324
127.106
128.536
128.576
129.237
175.752
Ethyl 2-methyl-3-phenylcycloprop-2-enecarboxylate, 6
1H NMR (300 MHz, CDCl3)
13C NMR (75 MHz, CDCl3)
Ph
O OEt
Ph
O OEt
S17
9. GC chromatograms for products 1-6.
O
O OEt
O OEt
S18
EtO
OOEt
HN
OOEt
S19
Ph
O OEt
EtO2C