Synthesis of N-(Hetero)aryl Carbamates via CuI/MNAO Catalyzed Cross-Coupling of (Hetero)aryl Halides with Potassium Cyanate in Alcohols

Article abstract of DOI:10.1021/acs.joc.7b03175

An efficient route to N-(hetero)aryl carbamates was developed through CuI/MNAO [2-((2-methylnaphthalen-1-yl)amino)-2-oxoacetic acid] catalyzed cross-coupling of (hetero)aryl chlorides with potassium cyanate in alcohols at 120-130 °C. This method utilizes

Full text of DOI:10.1021/acs.joc.7b03175

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Article
Synthesis of N-(Hetero)Aryl Carbamates via CuI/MNAO Catalyzed Cross-
Coupling of (Hetero)Aryl Halides with Potassium Cyanate in Alcohols
S. Vijay Kumar, and Dawei Ma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03175 • Publication Date (Web): 06 Feb 2018
Downloaded from http://pubs.acs.org on February 7, 2018
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Synthesis of N-(Hetero)Aryl Carbamates via CuI/MNAO
Catalyzed Cross-Coupling of (Hetero)Aryl Halides with
Potassium Cyanate in Alcohols
9
S. Vijay Kumar and Dawei Ma*
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu,
Shanghai 200032, China
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E-mail: madw@sioc.ac.cn
Abstract
An efficient route to N-(hetero)aryl carbamates has been developed through
CuI/MNAO [2-((2-methylnaphthalen-1-yl)amino)-2-oxoacetic acid] catalyzed cross-
°
coupling of (hetero)aryl chlorides with potassium cyanate in alcohols at 120-130 C.
This method utilizes broadly available substrates to afford various N-(hetero)aryl
carbamates in good to excellent yields. Moreover, (hetero)aryl bromides and
(hetero)aryl iodides were also reacted at low catalyst loadings and relatively low
temperatures to provide N-(hetero)aryl carbamates.
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Introduction
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Carbamate-containing molecules play an important role in medicinal
chemistry and the pharmaceutical industry, where they exhibit important biological
activities such as anticancer,1 antitubercolosis,2 and HIV-1 protease.3 Carbamate
derivatives are widely represented in agrochemicals4 such as pesticides, herbicides,
insecticides and fungicides. They are often used in the chemical and paint industry as
starting materials, intermediates, and solvents.5 Carbamates serve as protecting groups
in organic synthesis, especially in peptide chemistry due to their chemical stability
toward acids, bases, and hydrogenation6 and also as linkers in combinatorial
chemistry.7 As a result, there is continuing interest in the development of efficient
methods for the synthesis of carbamates. The most important classical approaches to
carbamates are based on condensation of anilines with phosgene and its derivatives8
or reaction of alcohols with isocyanates generated in situ via Hofmann,9 Curtius,10
Lossen,11 and Schmidt12 rearrangement reactions. These reactions are limited by the
availability of starting materials, as well as the highly reactive nature of the
compounds. The other well known methods to synthesize carbamates are the reaction
of amide with lead tetra-acetate,13 from isonitriles,14 and reductive carbonylation of
aromatic nitro compounds.15
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Transition metal catalyzed C-N bond formation reactions have recently
enabled the development of alternative methodologies for carbamate synthesis. In this
context, palladium-catalyzed reductive carbonylation of nitroarenes16 as well as Pd-
catalyzed cross-coupling of aryl chlorides or aryl triflates with sodium cyanate18 have
been reported for the synthesis of carbamates. Due to the less toxic and lower cost of
copper catalysts, several new efficient routes to carbamate synthesis have also been
developed via copper-catalyzed reactions. This includes CuBr2-catalyzed coupling of
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arylboronic acids with potassium cyanates17 and CuCl-catalyzed Chan-Lam coupling
of azidoformates with boronic acids at room temperature.19 We have recently reported
CuI/DMPAO-catalyzed cross-coupling reaction for the synthesis of aryl carbamates
from aryl halides (Br, I) and potassium cyanate in alcohols.20 The problem for this
reaction is the requirement of 20 mol % CuI and DMPAO for complete conversion.
Additionally, (hetero)aryl chlorides are difficult substrates under these conditions.
Encouraged by our success in coupling of (hetero)aryl chlorides with nucleophiles
using copper salt/oxalic diamide catalyst systems,21 we reinvestigated the Cu-
catalyzed coupling reaction of (hetero)aryl halides with potassium cyanate in alcohols
using newly developed ligands, and identified that 2-[(2-methylnaphthalen-1-
yl)amino]-2-oxoacetic acid (MNAO) is a more powerful ligand for this reaction.
Under the assistance of this ligand, Cu-catalyzed coupling between (hetero)aryl
chlorides and potassium cyanate in alcohols proceeded smoothly at 120-130 °C, while
only 3-5 mol % CuI and MNAO are needed for complete conversion in case of
(hetero)aryl bromides and iodides as the coupling partners. Herein, we wish to
disclose these results.
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Results and Discussion
The copper catalyzed coupling of 4-chloroanisole 1a with potassium cyanate
in n-butanol was first examined using 10 mol % CuI and various ligands to optimize
the reaction conditions for the synthesis of N-aryl carbamate 2a. Initially, several
bis(N-aryl/alkyl)-substituted oxalamides (L1-L4) that led to excellent yields in the
amination/amidation of (hetero)aryl halides were examined.21 However, none of them
o
led to the formation of 2a at 120 C after 48 h (Table 1, entries 1-4). Interestingly,
when two naphthalene-containing ligands (L5 and L6) were used, the desired product
could be isolated in 62-68% yields under the same conditions. These results clearly
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indicate that the naphthalene group might have a dramatic influence on this coupling
reaction. This speculation was further corroborated by the observation that 2-[(2-
methylnaphthalen-1-yl)amino]-2-oxoacetic acid (L8, MNAO) gave the best yield,
while L9 (DMPAO) gave a poor conversion. Noteworthy is that when L8 was
replaced with 2-[(naphthalen-1-yl)amino]-2-oxoacetic acid (L7, NAO), only a slight
decrease in yield was observed. Considering that (naphthalen-1-yl)amine is much
cheaper than (2-methylnaphthalen-1-yl)amine, L7 should be also considered as an
alternative practical ligand in large-scale synthesis.
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Table 1. Cu-Catalyzed Coupling of 4-Chloroanisole with Potassium Cyanate in n-
Butanol in the Presence of Various Ligandsa
entry catalyst ligand
base
yield (%)b
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6
CuI
CuI
CuI
CuI
CuI
CuI
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
0
0
L1
L2
L3
L4
L5
L6
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0
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CuI
CuI
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Cs2CO3
K2CO3
Na2CO3
KOH
78
85
16
76
57
20
15
8
L7
L8
L9
L8
L8
L8
L8
L8
L8
L8
L8
9
CuI
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12
13
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16
17c
CuBr
CuCl
Cu2O
CuI
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CuI
CuI
5
CuI
82
42
CuI
K3PO4
aReaction conditions: 1a (2.0 mmol), KOCN (4.0 mmol), CuI (0.2 mmol), ligand (0.2 mmol),
base (0.2 mmol), n-BuOH (3 mL), 120 oC, 48 h. bYield was determined by 1H NMR of crude
reaction mixture using CH2Br2 as the internal standard. c5 mol % CuI and L8 were used, 72 h.
After identifying L8 as the best ligand, we examined other copper catalysts
and bases. When CuBr and CuCl were used, reaction yields were decreased (entries
10-11). However, a much lower yield was observed in case of Cu2O as the catalyst
(entry 12). Further screening revealed that although Cs2CO3, K2CO3, and Na2CO3
gave very poor yields, a comparable yield was observed in case of KOH as the base
(entries 13-16). Attempt to reduce the catalyst loadings failed to give complete
conversion even after prolonging reaction time (entry 17). Therefore, we concluded
that optimal conditions are using 10 mol % CuI and L8 as the catalytic system and
K3PO4 (0.1 equiv) as the base.
We next explored the scope of the present protocol using the established
optimized conditions, and the results are summarized in Table 2. As expected, a
number of aryl chlorides bearing a functional group at the para-position worked well,
providing carbamates 2a-2j in 65-88% yields. Some meta-substituted aryl chlorides
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were also applicable, leading to the formation of 2l-2o in good yields. However, no
conversion was observed in case of ortho-substituted substrates as the coupling
partners. Additionally, coupling reaction with some heteroaryl chlorides proceeded
smoothly to deliver quinolone-, quinoxaline-, isoquinoline-, thiophene- and pyridine-
containing carbamates 2p-2u. Changing the solvent to other alcohols such as
methanol, ethanol, isopropanol and 2-methylpentanol could afford the corresponding
carbamates 2v-2z.
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Table 2. CuI/MNAO-Catalyzed Coupling of (Hetero)Aryl Chlorides with Potassium
Cyanate in Alcoholsa,b
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aReaction conditions: 1 (2.0 mmol), KOCN (4.0 mmol), CuI (0.2 mmol), MNAO (0.2
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o
b
mmol), K3PO4 (0.2 mmol), ROH (3 mL), 120 C, 48 h. Isolated yield. cThe reaction
was carried out at 130 oC.
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In our previous report, more than 20 mol % CuI and DMPAO were required
for catalysing the coupling reaction of (hetero)aryl bromides with KOCN. This
problem prompted us to check if MNAO can give a better result. After a quick
optimization, we found that using 3 mol % of CuI and MNAO catalytic system was
sufficient for the coupling of 4-bromoanisole with KOCN in n-butanol to give n-butyl
(4-methoxyphenyl)carbamate 2a in 88% yield (Table 3, entry 1), and the reaction was
applicable to a broad range of substituted aryl bromides (2d, 2g, 2l and 2aa-2af).
Notably, highly electron-rich 3,4,5-trimethoxybromobenzene also reacted smoothly
with KOCN in n-butanol to afford 2ad in 94% yield. Additionally, the (hetero)aryl
bromides such as substituted pyridines (2ag and 2ah), thiophene (2s), quinolines (2p,
2ai and 2aj), benzo[b]thiophenes (2ak and 2al) and indole (2am) worked under these
conditions, giving the corresponding N-(hetero)aryl carbamates in good yields. In case
of coupling with 4-bromo-2-methoxyaniline, 3-bromothiophene, and 3-
bromobenzo[b]thiophene, the reactions were relatively sluggish, and an increase in
catalyst loading to 5 mol % was required to get a complete conversion (2ae, 2s and
2al). In addition, by using other alcohols as the solvents, carbamates 2an-2aq were
obtained in 75-85% yields. It is notable that 2aq, known as URB602, is a selective
monoacylglycerol lipase (MGL) inhibitor that can selectively block 2-
arachidonoylglycerol degradation.22 Considering that L7 was derived from a relatively
cheap aniline, we tried to replace L8 with L7 in the formation of 2a, 2ad, 2ah and 2p,
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and were pleased that the complete conversion was still observed, although the yields
were slightly decreased.
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Table 3. CuI/MNAO-Catalyzed Coupling of (Hetero)Aryl Bromides with Potassium
Cyanate in Alcoholsa,b
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3-5 mol % CuI
3-5 mol % MNAO
H
N
OR
Ar(Hetero)
Me
(Hetero)ArBr + KOCN
K3PO4, ROH
110 oC, 36 h
O
3
2
H
H
N
On-Bu
H
N
On-Bu
N
On-Bu
O
O
O
R
O
O
Me
2ac (82%)
2l (90%)
2a: R = 4-OMe
(88%, 82%d)
H
N
MeO
MeO
On-Bu
2d: R = 4-Me (82%)
2g: R = 4-CF3 (92%)
2aa: R = 4-SiMe3 (91%)
2ab: R = 3-OMe (83%)
H
H
MeO
N
On-Bu
O
O
OMe
2ad (94%, 90%d)
H2N
Me
2ae (58%, 76%c)
H2N
N
On-Bu
H
N
On-Bu
O
O
O
N
N
On-Bu
MeO
N
CF3
H
2ah (87%, 80%d)
2af (72%)
2ag (90%)
H
N
H
O
On-Bu
On-Bu
N
N
N
On-Bu
O
O
S
N
H
2s (82%)c
2p (82%, 75%d)
2ai (85%)
H
H
N
On-Bu
H
On-Bu
N
N
On-Bu
O
O
Me
N
O
S
S
2aj (88%)
2al (80%)c
2ak (80%)
H
N
H
N
H
N
On-Bu Me
Ot-Bu Ph
OMe
O
O
O
N
H
2am (82%)
2an (78%)
On-Pr Ph
2ao (85%)
H
H
N
N
O
O
O
F
2ap (80%)
2aq (75%)
aReaction conditions: 3 (4 mmol), KOCN (8 mmol), CuI (0.12 mmol), MNAO (0.12
mmol), K3PO4 (0.12 mmol), ROH (5 mL), 110 oC, 36 h. bIsolated yield. c5 mol % CuI,
MNAO and K3PO4 were used. dUsing L7 as the ligand.
When more reactive (hetero)aryl iodides were employed as the coupling
partners, both the reaction temperature and time could be further reduced (Table 4).
The reaction proceeded smoothly with the catalysis of 3 mol % CuI and MNAO at
o
100 C to give the corresponding carbamates in good to excellent yields. Using
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inexpensive L7 also gave satisfactory results (2d, 2ab, 2as and 2au). When 6-
iodoquinoline and 4-iodobiphenyl were coupled with KOCN in t-butanol, the
corresponding carbamates 2av and 2aw were obtained in 78-90% yields. By changing
solvent to i-PrOH, we could synthesize two herbicides, propham (2w), an effective
pre-and postemergent herbicide used for the control of annual grasses,23 and
chlorpropham (2ay), a plant growth regulator and herbicide used as sprouting
inhibitor for stored potatoes.24
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Table 4. CuI/MNAO-Catalyzed Coupling of (Hetero)Aryl Iodides with Potassium
Cyanate in Alcoholsa,b
aReaction conditions: (Hetero)ArI (4 mmol), KOCN (8 mmol), CuI (0.12 mmol), L8
o
(0.12 mmol), K3PO4 (0.12 mmol), ROH (5 mL), 100 C, 24 h. bIsolated yield. cUsing
L7 as the ligand.
A plausible reaction mechanism for this transformation is illustrated in Scheme 1.
The Cu(I) complex 5 formed from CuI and ligand, undergoes oxidative addition with
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(hetero)aryl halides to give Cu(III) complex 6, followed by ligand exchange with
KOCN gives Cu(III) complex 7, which would undergo reductive elimination to
produce (hetero)aryl isocyanide 8 and regenerates the Cu(I) complex 5. Subsequent
condensation of 8 with alcohol gives the (hetero)aryl carbamate 2.
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CuI + L8
H
N
OR
(Het)Ar
O
2
(Het)ArX
Me
O
ROH
O
NH
O
Cu
N
C
(Het)Ar
O
8
5
Me
Me
O
O
NH
O
NH
O
(Het)Ar
OCN
(Het)Ar
X
Cu
Cu
O
O
7
6
KX
KOCN
Scheme 1. Proposed reaction mechanism for the synthesis of (hetero)aryl carbamates
Conclusion
In summary, we have developed an efficient and practical route for preparing
N-(hetero)aryl carbamates by CuI/MNAO-catalyzed coupling of (hetero)aryl halides
and potassium cyanate in alcohols. The new methodology allows direct access to a
broad range of N-(hetero)aryl carbamates from less reactive and less expensive
(hetero)aryl chlorides. In addition, (hetero)aryl bromides and (hetero)aryl iodides
were reactive at relatively low catalyst loadings and reaction temperatures. The usage
of the methodology was further illustrated with the synthesis of URB602 (2aq, a
selective MGL inhibitor) and few herbicides such as propham (2w) and chlorpropham
(2ay) in good yields. The easy availability of starting materials along with the
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efficiency of the present protocol should make it useful complement to the existing
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methods for the synthesis of N-(hetero)aryl carbamates.
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Experimental Section
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General Information. All the Cu-catalyzed coupling reactions were set up on
the benchtop in the open air and carried out in re-sealable test tubes with Teflon septa
under an argon atmosphere. Unless otherwise noted, the solvents and the solutions of
reagents/reactants were transferred via micro syringe or plastic syringe (fitted with
metal needle) into the reaction test tubes under a positive argon pressure.
Commercially available dry solvents such as tetrahydrofuran (THF), n-butanol (n-
BuOH), ethanol (EtOH), isopropanol (i-PrOH), tert-butanol (t-BuOH) and n-propanol
(n-PrOH) were used for reaction. Other solvents such as ethyl acetate (EtOAc) and n-
hexane were used as received. The reagents such as various amines, oxalyl chloride,
KOCN, (hetero)aryl halides (Cl, Br, I) and potassium phosphate (Sigma-Aldrich) etc.
were used as received, unless otherwise noted. Thin layer chromatography was
performed using silicagel 60 F-254 precoated glass plates (0.25 mm) and visualized
by UV irradiation. Flash chromatography was performed using 230-400 mesh
SiliaFlash® P60. Melting points were recorded on a digital melting point apparatus
1
13
19
and are uncorrected. H, C and F NMR spectra were recorded on 400 MHz, 500
1
MHz, 125 MHz, 101 MHz, 376 MHz spectrometer (400 or 500 MHz for H-NMR ;
101 or 125 MHz for 13C-NMR; 376 MHz for 19F-NMR). Chemical shifts were
reported in δ ppm (parts per million) with residual solvent protons as internal standard
(δ 7.26 for CDCl3, δ 2.50 for DMSO-d6, in 1H NMR; δ 77.16 for CDCl3, δ 39.52 for
DMSO-d6 in 13C NMR). Coupling constant (J) values are given in Hertz (Hz).
Splitting patterns are designated as s (singlet), d (doublet), t (triplet), q (quartet), dd
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(double doublet), m (multiplet), and br (broad). High resolution mass experiments
were operated on a Bruker Daltonics, Inc. APEXIII 7.0 TESLA FTMS instrument and
a Thermo Fisher Scientific LTQ FT Ultra instrument (Ion Trap based Fourier
Transform ICR Mass Spectrometer).
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The commercially available copper(I) iodide was purified according to a
slightly modified literature procedure.25 In a round-bottom flask, saturated aqueous
solution of NaI (50 mL) was taken and approximately 25 g of copper iodide (from
Acros Organics) was added to it and then heated at 100 °C for 30 min until the dark
brown cleared solution formed. After that the clear solution was cooled and diluted
with water. The white solid precipitate was then filtered and washed sequentially with
H2O, EtOH, EtOAc, ether, and n-hexane and dried in vacuo for 24 h. All the ligands
(L1-L9) were prepared according to the earlier reported procedures from our group.21
The known ligands were characterized by comparison of their spectral and analytical
data with the reported data,20-21 whereas the spectral and analytical data for the
unknown ligands L7 and L8 are given below.
2ꢀ(Naphthalenꢀ1ꢀylamino)ꢀ2ꢀoxoacetic acid (L7). White solid (4.20 g, 95%); mp
o
1
195-197 C; H NMR (400 MHz, DMSO-d6) δ 14.24 (br s, 1H), 10.85 (s, 1H), 8.05-
7.90 (m, 2H), 7.88 (d, J = 8.0 Hz, 1H), 7.67-7.48 (m, 4H); 13C NMR (101 MHz,
DMSO) δ 162.5, 158.3, 133.8, 132.4, 128.5, 128.2, 126.9, 126.4, 126.3, 125.6, 123.3,
123.0; HRMS (DART): m/z calculated for C12H10NO3 [M + H]+ 216.0654, found
216.0655.
2ꢀ((2ꢀMethylnaphthalenꢀ1ꢀyl)amino)ꢀ2ꢀoxoacetic acid (L8). Off-white solid (4.01 g,
o
1
92%); mp 210-212 C; H NMR (400 MHz, DMSO-d6) δ 14.21 (br s, 1H), 10.69 (s,
1H), 7.93 (d, J = 7.7 Hz, 1H), 7.85-7.81 (m, 2H), 7.55-7.45 (m, 3H), 2.33 (s, 3H); 13C
NMR (101 MHz, DMSO) δ 162.3, 158.0, 132.7, 132.3, 130.10, 130.09, 128.7, 127.9,
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127.2, 126.5, 125.4, 122.9, 18.1; HRMS (DART): m/z calculated for C13H11NNaO3
[M + Na]+ 252.0637, found 252.0632.
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General Procedure for the Synthesis of N-(Hetero)Aryl Carbamates from
(Hetero)Aryl Chlorides. The (hetero)aryl chloride (2.0 mmol), KOCN (4.0 mmol),
CuI (0.2 mmol, 38 mg), L8 (0.2 mmol, 46 mg) and K3PO4 (0.2 mmol, 42.4 mg) were
placed into a Schlenk flask (10 mL) with a magnetic stir bar. The reaction vessel was
evacuated and backfilled with argon three times, and alcohol (3 mL) was added
afterwards (Note: for liquid substrates, they were added after the tube was backfilled
with argon). The mixture was sealed and stirred vigorously at 120 °C for 48 h before
being diluted with 20 mL of ethyl acetate and filtered through celite pad and washed it
two times with ethyl acetate. The filtrate was concentrated and residue was purified
by flash chromatography (EtOAc:n-hexane = 1:33 to 1:1.5) on silica gel to afford the
corresponding Nꢀ(hetero)aryl carbamates.
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General Procedure for the Synthesis of N-(Hetero)Aryl Carbamates from
(Hetero)Aryl Bromides. The (hetero)aryl bromide (4.0 mmol), KOCN (8.0 mmol),
CuI (0.12 mmol, 22.8 mg), L8 (0.12 mmol, 27.5 mg) or L7 (0.12 mmol, 25.8 mg) and
K3PO4 (0.12 mmol, 25.5 mg) were placed into a Schlenk flask (20 mL) with a
magnetic stir bar. The reaction vessel was evacuated and backfilled with argon three
times, and alcohol (5 mL) was added afterwards (Note: for liquid substrates, they
were added after the tube was backfilled with argon). The mixture was sealed and
stirred vigorously at 110 °C for 36 h before being diluted with 40 mL of ethyl acetate
and filtered through celite pad and washed it two times with ethyl acetate. The filtrate
was concentrated and residue was purified by flash chromatography (EtOAc:n-hexane
= 1:33 to 1:2.3) on silica gel to afford the corresponding Nꢀ(hetero)aryl carbamates.
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General Procedure for the Synthesis of N-(Hetero)Aryl Carbamates from
(Hetero)Aryl Iodides. The (hetero)aryl iodide (4.0 mmol), KOCN (8.0 mmol), CuI
(0.12 mmol, 22.8 mg), L8 (0.12 mmol, 27.5 mg) or L7 (0.12 mmol, 25.8 mg) and
K3PO4 (0.12 mmol, 25.5 mg) were placed into a Schlenk flask (20 mL) with a
magnetic stir bar. The reaction vessel was evacuated and backfilled with argon three
times, and alcohol (5 mL) was added afterwards (Note: for liquid substrates, they
were added after the tube was backfilled with argon). The mixture was sealed and
stirred vigorously at 100 °C for 24 h before being diluted with 40 mL of ethyl acetate
and filtered through celite pad and washed it two times with ethyl acetate. The filtrate
was concentrated and residue was purified by flash chromatography (EtOAc:n-hexane
= 1:33 to 1:4) on silica gel to afford the corresponding Nꢀ(hetero)aryl carbamates.
Butyl (4ꢀmethoxyphenyl)carbamate (2a).20 Off-white solid (370 mg, 83% from 4-
chloroanisole; 785 mg, 88% from 4-bromoanisole; 758 mg, 85% from 4-iodoanisole);
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o
mp 63-65 C; 1H NMR (400 MHz, DMSO-d6) δ 9.38 (br s, 1H), 7.35 (d, J = 8.0 Hz,
1H), 6.84 (d, J = 9.0 Hz, 1H), 4.04 (t, J = 8.0 Hz, 1H), 3.69 (s, 3H), 1.62-1.55 (m, 2H),
1.41–1.32 (m, 1H), 0.91 (t, J = 8.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 154.7,
153.8, 132.3, 119.7, 113.9, 63.7, 55.1, 30.7, 18.6, 13.6.
1
Butyl (4ꢀ(tꢀbutoxy)phenyl)carbamate (2b). Brown liquid (424 mg, 80%); H NMR
(400 MHz, DMSO-d6) δ 9.49 (br s, 1H), 7.35 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 9.0 Hz,
2H), 4.05 (t, J = 6.6 Hz, 2H), 1.62–1.55 (m, 2H), 1.41–1.32 (m, 2H), 1.23 (s, 9H),
0.90 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.8, 149.8, 134.8, 124.2,
118.9, 77.6, 63.8, 30.7, 28.5, 18.7, 13.6; HRMS (DART): m/z calculated for
C15H24NO3 [M + H]+ 266.1751, found 266.1750.
Butyl (4ꢀ(methylthio)phenyl)carbamate (2c). Off-white solid (372 mg, 78%); mp
o
1
73–75 C; H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.42 (d, J = 8.3 Hz, 2H),
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7.20 (d, J = 8.5 Hz, 2H), 4.06 (t, J = 6.6 Hz, 2H), 2.42 (s, 3H), 1.69–1.47 (m, 2H),
1.45–1.25 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.7,
136.9, 130.6, 127.6, 118.9, 63.9, 30.6, 18.7, 15.8, 13.6; HRMS (DART): m/z
calculated for C12H18NO2S [M + H]+ 240.1053, found 240.1052.
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Butyl pꢀtolylcarbamate (2d). Off-white solid (352 mg, 85% from 4-chlorotoluene;
o
679 mg, 82% from 4-bromotoluene; 662 mg, 80% from 4-iodotoluene); mp 63-65 C;
1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.0 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.54
(br s, 1H), 4.16 (t, J = 6.0 Hz, 2H), 2.30 (s, 1H), 1.69–1.62 (m, 2H), 1.47-1.37 (m,
2H), 0.96 (t, J = 6.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 154.0, 135.5, 132.9,
129.6, 118.9, 65.1, 31.1, 20.8, 19.2, 13.8; HRMS (DART): m/z calculated for
C12H18NO2 [M + H]+ 208.1332, found 208.1331.
Butyl [4ꢀ(tertꢀbutyl)phenyl]carbamate (2e). Pale yellow liquid (398 mg, 80% from
1
1-tert-butyl-4-chlorobenzene; 896 mg, 90% from 1-tert-butyl-4-iodobenzene); H
NMR (400 MHz, CDCl3) δ 7.32 (s, 4H), 6.60 (br s, 1H), 4.17 (t, J = 6.0 Hz, 2H),
1.67–1.64 (m, 2H), 1.45–1.39 (m, 2H), 1.30 (s, 9H), 0.95 (t, J = 6.0 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ 154.0, 146.4, 135.5, 126.0, 118.6, 65.2, 34.4, 31.5, 31.1,
19.2, 13.9; HRMS (DART): m/z calculated for C15H24NO2 [M + H]+ 250.1802, found
250.1801.
Butyl [1,1'ꢀbiphenyl]ꢀ4ꢀylcarbamate (2f).20 White solid (452 mg, 84%); mp 110-
1
112 oC; H NMR (400 MHz, DMSO-d6) δ 9.73 (br s, 1H), 7.63–7.58 (m, 6H), 7.42 (t,
J = 8.0 Hz, 2H), 7.30 (t, J = 8.0 Hz, 1H), 4.09 (t, J = 6.0 Hz, 2H), 1.64–1.57 (m, 2H),
1.43–1.34 (m, 2H), 0.92 (t, J = 6.0 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 153.7,
139.8, 138.8, 134.1, 128.9, 127.0, 126.9, 126.2, 118.5, 64.0, 30.6, 18.7, 13.6; HRMS
(DART): m/z calculated for C17H20NO2 [M + H]+ 270.1494, found 270.1488.
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Butyl (4ꢀ(trifluoromethyl)phenyl)carbamate (2g). White solid (391 mg, 75% from
1-chloro-4-(trifluoromethyl)benzene; 960 mg, 92% from 1-bromo-4-(trifluoromethyl)
benzene); mp 88–90 oC; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (br s, 1H), 7.68-7.61
(m, 4H), 4.10 (t, J = 8.0 Hz, 2H), 1.64–1.57 (m, 2H), 1.42–1.33 (m, 2H), 0.90 (t, J =
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6.0 Hz, 3H); C NMR (101 MHz, DMSO-d6) δ 153.5, 143.0, 126.0 (q, J = 3.0 Hz),
124.5 (q, J = 272.0 Hz), 122.4 (q, J = 32.3 Hz), 117.8, 64.2, 30.5, 18.6, 13.5; 19F
NMR (376 MHz, DMSO-d6) δ –64.5; HRMS (DART): m/z calculated for
C12H13F3NO2 [M – H]+ 260.0898, found 260.0898.
Butyl (4ꢀaminophenyl)carbamate (2h).20 Brown semisolid (270 mg, 65%); 1H NMR
(400 MHz, DMSO-d6) δ 9.06 (s, 0H), 7.08 (d, J = 4.0 Hz, 2H), 6.48 (d, J = 8.0 Hz,
2H), 4.77 (br s, 2H), 4.01 (t, J = 8.0 Hz, 2H), 1.60–1.53 (m, 2H), 1.40–1.31 (m, 2H),
0.90 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 154.0, 144.2, 128.3, 120.3,
114.1, 63.5, 30.8, 18.7, 13.7; HRMS (DART): m/z calculated for C11H17N2O2 [M +
H]+ 209.1290, found 209.1285.
Butyl (4ꢀ(dimethylamino)phenyl)carbamate (2i). Off-white solid (386 mg, 82%);
mp 68–69 C; 1H NMR (400 MHz, DMSO-d6) δ 9.20 (br s, 1H), 7.26 (d, J = 8.0 Hz,
o
2H), 6.66 (d, J = 12.0 Hz, 2H), 4.03 (t, J = 6.0 Hz, 2H), 2.81 (s, 6H), 1.61–1.54 (m,
2H), 1.41–1.32 (m, 2H), 0.91 (t, J = 8.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ
153.8, 146.6, 129.1, 119.7, 113.0, 63.5, 40.6, 30.7, 18.7, 13.6; HRMS (DART): m/z
calculated for C13H21N2O2 [M + H]+ 237.1598, found 237.1597.
Butyl (4ꢀmorpholinophenyl)carbamate (2j). Off-white solid (489 mg, 88%); mp
o
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122-124 C; H NMR (400 MHz, DMSO-d6) δ 9.34 (br s, 1H), 7.31 (d, J = 8.0 Hz,
1H), 6.86 (d, J = 8.0 Hz, 1H), 4.04 (t, J = 6.0 Hz, 2H), 3.71 (t, J = 6.0 Hz, 4H), 3.0 (m,
J = 4.0 Hz, 4H), 1.61–1.54 (m, 2H), 1.41–1.32 (m, 2H), 0.90 (t, J = 6.0 Hz, 3H); 13C
NMR (101 MHz, DMSO-d6) δ 153.8, 146.7, 131.6, 119.3, 115.8, 66.2, 63.7, 49.2,
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30.7, 18.7, 13.7; HRMS (DART): m/z calculated for C15H23N2O3 [M + H]+ 279.1709,
found 279.1703.
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Butyl naphthalenꢀ2ꢀylcarbamate (2k). Off-white solid (379 mg, 78%); mp 68-69 oC;
1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.78-7.76 (m, 3H), 7.47–7.37 (m, 3H),
6.93 (s, 1H), 4.23 (t, J = 8.0 Hz, 2H), 1.73–1.66 (m, 2H), 1.50–1.41 (m, 2H), 0.98 (t, J
= 8.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 154.0, 135.6, 134.0, 130.2, 128.9,
127.6, 127.5, 126.6, 124.7, 119.3, 114.9, 65.3, 31.1, 19.2, 13.9; HRMS (DART): m/z
calculated for C15H18NO2 [M + H]+ 244.1332, found 244.1332.
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Butyl benzo[d][1,3]dioxolꢀ5ꢀylcarbamate (2l). Off-white solid (388 mg, 82% from
5-chlorobenzo[d][1,3]dioxole; 853 mg, 90% from 5-bromobenzo[d][1,3]dioxole); mp
o
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58-59 C; H NMR (400 MHz, CDCl3) δ 7.09 (br s, 1H), 6.72–6.61 (m, 3H), 5.92 (s,
2H), 4.14 (t, J = 6.0 Hz, 2H), 1.67–1.62 (m, 2H), 1.42–1.37 (m, 2H), 0.94 (t, J = 8.0
Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 154.1, 148.0, 143.8, 132.4, 111.9, 108.2,
101.9, 101.3, 65.2, 31.1, 19.2, 13.8; HRMS (DART): m/z calculated for C12H16NO4
[M + H]+ 238.1074, found 238.1073.
Butyl (3,5ꢀdimethoxyphenyl)carbamate (2m). Pale yellow liquid (394 mg, 78%); 1H
NMR (400 MHz, DMSO-d6) δ 9.55 (s, 1H), 6.72 (d, J = 4.0 Hz, 2H), 6.15 (t, J = 4.0
Hz, 1H), 4.06 (t, J = 8.0 Hz, 2H), 3.69 (s, 6H), 1.62–1.55 (m, 2H), 1.41–1.32 (m, 2H),
0.91 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 160.6, 153.5, 141.0, 96.6,
94.2, 63.9, 55.0, 30.6, 18.6, 13.6; HRMS (DART): m/z calculated for C13H20NO4 [M
+ H]+ 254.1387, found 254.1386.
Butyl (3-fluoro-5-methoxyphenyl)carbamate (2n). Colourless liquid (366 mg, 76%);
1H NMR (400 MHz, DMSO-d6) δ 9.80 (br s, 1H), 6.96–6.91 (m, 2H), 6.43 (d, J =
12.0 Hz, 0H), 4.07 (t, J = 8.0 Hz, 2H), 3.71 (s, 3H), 1.562–1.55 (m, 2H), 1.41–1.32
13
(m, 2H), 0.90 (t, J = 8.0 Hz, 3H); C NMR (101 MHz, DMSO-d6) δ 164.3, 162.0,
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95.2 (d, J = 26.3 Hz), 64.1, 55.4, 30.5, 18.6, 13.6; F NMR (376 MHz, CDCl3) δ –
116.0; HRMS (DART): m/z calculated for C12H17FNO3 [M + H]+ 242.1192, found
242.1187.
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Butyl (3ꢀ(trifluoromethyl)phenyl)carbamate (2o). Pale yellow liquid (376 mg, 72%);
1H NMR (500 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.94 (s, 1H), 7.69 (d, J = 8.5 Hz, 1H),
7.47 (t, J = 8.0 Hz, 1H), 7.28 (d, J = 7.0 Hz, 1H), 4.09 (t, J = 7.0 Hz, 2H), 1.62–1.56
(m, 2H), 1.39–1.32 (m, 2H), 0.89 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, DMSO-d6)
δ 153.6, 140.2, 129.8, 129.7 (q, J = 31.3 Hz), 124.2 (q, J = 271.3 Hz), 121.6, 118.4 (q,
19
J = 3.8 Hz), 114.1, 64.2, 30.6, 18.6, 13.4; F NMR (376 MHz, DMSO-d6) δ –66.1;
HRMS (DART): m/z calculated for C12H15F3NO2 [M + H]+ 262.1055, found 262.1048.
Butyl quinolinꢀ3ꢀylcarbamate (2p). Off-white solid (366 mg, 75% from 3-
o
chloroquinoline; 800 mg, 82% from 3-bromoquinoline); mp 115-117 C; 1H NMR
(400 MHz, DMSO-d6) δ 10.13 (s, 0H), 8.87 (s, 1H), 8.46 (s, 0H), 7.91 (dd, J = 19.3,
8.0 Hz, 1H), 7.57 (dd, J = 17.0, 7.6 Hz, 1H), 4.15 (t, J = 6.4 Hz, 2H), 1.63 (dd, J =
13.9, 6.7 Hz, 2H), 1.40 (dd, J = 14.6, 7.3 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR
(101 MHz, DMSO-d6) δ 153.9, 144.0, 143.8, 133.1, 128. 6, 127.9, 127.5, 127.4, 127.0,
120.4, 64.4, 30.5, 18.6, 13.6; HRMS (DART): m/z calculated for C14H17N2O2 [M +
H]+ 245.1285, found 245.1284.
Butyl quinoxalinꢀ6ꢀylcarbamate (2q). Off-white solid (416 mg, 85%); mp 91-93 oC;
1H NMR (400 MHz, DMSO-d6) δ 10.21 (s, 1H), 8.80 (d, J = 28.0 Hz, 1H), 8.28 (s,
1H), 8.00 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 4.14 (t, J = 6.0 Hz, 2H), 1.64–
13
1.61 (m, 2H), 1.42–1.36 (m, 2H), 0.91 (t, J = 8.0Hz, 3H); C NMR (101 MHz,
DMSO-d6) δ 153.6, 145.9, 143.6, 143.2, 140.7, 138.8, 129.6, 123.1, 113.8, 64.4, 30.5,
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246.1236.
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Butyl isoquinolinꢀ6ꢀylcarbamate (2r). Off-white solid (366 mg, 75%); mp 130-132
oC; 1H NMR (400 MHz, CDCl3) δ 9.14 (br s, 1H), 8.47 (s, 1H), 8.05 (s, 1H), 7.90 (d,
J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 0H), 7.48 (dd, J = 8.0, 4.0 Hz, 1H), 7.21 (s, 1H),
4.23 (t, J = 6.0 Hz, 2H), 1.73–1.65 (m, 2H), 1.48–1.39 (m, 2H), 0.96 (t, J = 6.0 Hz,
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3H); C NMR (101 MHz, CDCl3) δ 153.7, 151.9, 143.6, 139.9, 137.1, 129.0, 120.3,
112.5, 65.6, 31.1, 19.2, 13.8; HRMS (DART): m/z calculated for C14H17N2O2 [M +
H]+ 245.1285, found 245.1284.
Butyl thiophenꢀ2ꢀylcarbamate (2s). Yellow liquid (246 mg, 62% from 3-
1
chlorothiophene; 652 mg, 82% from 3-bromothiophene); H NMR (400 MHz,
DMSO-d6) δ 9.88 (br s, 1H), 7.40 (dd, J = 8.0, 4.0 Hz, 1H), 7.19 (s, 1H), 7.01 (d, J =
8.0 Hz, 1H), 4.07 (t, J = 6.0 Hz, 2H), 1.62–1.55 (m, 2H), 1.41–1.32 (m, 2H), 0.91 (t, J
= 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.7, 137.1, 124.8, 121.0, 106.1,
63.9, 30.6, 18.6, 13.6; HRMS (DART): m/z calculated for C9H14NO2S [M + H]+
200.0740, found 200.0739.
1
Butyl (6ꢀmethylpyridinꢀ2ꢀyl)carbamate (2t). Colourless liquid (316 mg, 76%); H
NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 7.62–7.61 (m, 2H), 6.88 (m, 1H), 4.06 (t,
J = 6.0 Hz, 2H), 2.36 (s, 3H), 1.60–1.53 (m, 2H), 1.39–1.30 (m, 2H), 0.89 (t, J = 6.0
13
Hz, 3H); C NMR (101 MHz, DMSO-d6) δ 156.43, 153.77, 151.68, 138.39, 117.75,
109.20, 64.04, 30.60, 23.64, 18.58, 13.64; HRMS (DART): m/z calculated for
C11H17N2O2 [M + H]+ 209.1285, found 209.1284.
Butyl pyridinꢀ2ꢀylcarbamate (2u).20 White solid (272 mg, 70% from 2-
o
1
chloropyridine; 605 mg, 78% from 2-iodopyridine); mp 60-62 C; H NMR (400
MHz, CDCl3) δ 9.96 (s, 1H), 8.35 (s, 1H), 8.05 (d, J = 12.0 Hz, 1H), 7.69 (t, J = 8.0
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Hz, 1H), 6.97 (s, 1H), 4.21 (t, J = 6.0 Hz, 2H), 1.72–1.69 (m, 2H), 1.46-1.40 (m, 2H),
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5
6
13
0.96 (t, J = 6.0 Hz, 3H); C NMR (101 MHz, CDCl3) δ 154.0, 152.7, 147.7, 138.6,
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8
9
118.5, 112.7, 65.3, 31.1, 19.2, 13.9; HRMS (DART): m/z calculated for C10H15N2O2
[M + H]+ 195.1128, found 195.1127.
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Methyl (4ꢀmethoxyphenyl)carbamate (2v). Off-white solid (260 mg, 72%); mp 90-
°
92 C; 1H NMR (500 MHz, CDCl3) δ 7.28 (d, J = 5.0 Hz, 2H), 6.84 (d, J = 10.0 Hz,
2H), 6.62 (br s, 1H), 3.78 (s, 3H), 3.75 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 156.0,
154.6, 131.1, 120.8, 114.2, 55.5, 52.3; HRMS (DART): m/z calculated for C9H12NO3
[M + H]+ 182.0813, found 182.0817.
Ethyl 4ꢀ((ethoxycarbonyl)amino)benzoate (2w). White solid (308 mg, 65%); mp
o
137-139 C; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.0
Hz, 1H), 6.88 (s, 1H), 4.35 (q, J = 8.0 Hz, 2H), 4.24 (q, J = 8.0 Hz, 2H), 1.38 (t, J =
13
8.0 Hz, 3H), 1.31 (t, J = 8.0 Hz, 3H); C NMR (101 MHz, CDCl3) δ 166.4, 153.3,
142.3, 131.0, 125.2, 117.6, 61.7, 60.9, 14.6, 14.5; HRMS (DART): m/z calculated for
C12H16NO4 [M + H]+ 238.1074, found 238.1073.
Isopropyl phenylcarbamate (2x). White solid (250 mg, 70% from chlorobenzene;
o
587 mg, 82% from iodobenzene); mp 86-88 C; 1H NMR (400 MHz, CDCl3) δ 7.32-
7.19 (m, 4H), 6.98 (t, J = 8.0 Hz, 1H), 6.50 (br s, 1H), 4.98-4.91 (m, 1H), 1.23 (d, J =
13
8.0 Hz, 6H); C NMR (101 MHz, CDCl3) δ 153.3, 138.2, 129.2, 123.4, 118.7, 68.9,
22.2; HRMS (DART): m/z calculated for C10H14NO2 [M + H]+ 180.1025, found
180.1019.
Isopropyl (4ꢀcyanophenyl)carbamate (2y). White solid (306 mg, 75%); mp 140-142
oC; 1H NMR (400 MHz, DMSO-d6) δ 10.09 (br s, 1H), 7.72 (d, J = 8.0 Hz, 0H), 7.63
(d, J = 8.0 Hz, 0H), 4.94-4.88 (m, 1H), 1.25 (d, J = 4.0 Hz, 6H); 13C NMR (101 MHz,
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DMSO-d6) δ 152.9, 143.8, 133.3, 119.2, 118.0, 103.9, 68.2, 21.9; HRMS (DART):
m/z calculated for C11H13N2O2 [M + H]+ 205.0977, found 205.0972.
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2ꢀmethylpentyl (4ꢀmethoxyphenyl)carbamate (2z). Off-white solid (346 mg, 69%);
mp 60-62 oC; 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0
Hz, 2H), 6.50 (br s, 1H), 4.06–3.91 (m, 2H), 3.78 (s, 3H), 1.86–1.78 (m, 1H), 1.39–
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1.25 (m, 3H), 1.17-1.12 (m, 1H), 0.95-0.89 (m, 6H); C NMR (101 MHz, CDCl3) δ
156.1, 154.3, 131.2, 120.7, 114.4, 70.3, 55.6, 35.7, 32.7, 20.1, 17.0, 14.4; HRMS
(DART): m/z calculated for C14H22NO3 [M + H]+ 252.1600, found 252.1594.
Butyl (4ꢀ(trimethylsilyl)phenyl)carbamate (2aa). Colourless liquid (241 mg, 91%),
1H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 7.26 (d, J = 8.0 Hz, 2H), 7.19 (d, J =
8.0 Hz, 2H), 3.87 (t, J = 8.0 Hz, 2H), 1.40–1.36 (m, 2H), 1.22–1.13 (m, 2H), 0.71 (t, J
= 8.0 Hz, 3H), 0.00 (s, 9H); 13C NMR (101 MHz, DMSO-d6) δ 153.6, 140.0, 133.7,
132.5, 117.5, 63.8, 30.6, 18.6, 13.59, -1.0; HRMS (DART): m/z calculated for
C14H24NO2Si [M + H]+ 266.1571, found 266.1569.
Butyl (3ꢀmethoxyphenyl)carbamate (2ab). Pale yellow liquid (740 mg, 83% from 1-
1
bromo-3-methoxybenzene; 749 mg, 84% from 1-iodo-3-methoxybenzene); H NMR
(400 MHz, DMSO-d6) δ 9.59 (s, 1H), 7.18–7.14 (m, 2H), 7.01 (d, J = 8.0 Hz, 1H),
6.56 (dd, J = 8.0 Hz, 4.0 Hz, 1H), 4.06 (t, J = 6.0 Hz, 2H), 3.70 (s, 3H), 1.63–1.56 (m,
13
2H), 1.42–1.33 (m, 2H), 0.91 (t, J = 8.0 Hz, 3H); C NMR (101 MHz, DMSO-d6) δ
159.6, 153.6, 140.5, 129.5, 110.5, 107.6, 104.0, 63.8, 54.9, 30.6, 18.6, 13.6; HRMS
(DART): m/z calculated for C12H18NO3 [M + H]+ 224.1281, found 224.1281.
Butyl (3,5ꢀdimethylphenyl)carbamate (2ac). Pale yellow solid (724 mg, 82% from
1-bromo-3,5-dimethylbenzene; 751 mg, 85% from 1-iodo-3,5-dimethylbenzene); mp
o
61-63 C; 1H NMR (400 MHz, DMSO-d6) δ 9.44 (s, 1H), 7.09 (s, 2H), 6.61 (s, 1H),
4.05 (t, J = 6.0 Hz, 2H), 2.20 (s, 3H), 1.62–1.55 (m, 1H), 1.41-1.32 (m, 2H), 0.91 (t, J
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= 8.0 Hz, 3H); C NMR (101 MHz, DMSO-d6) δ 153.6, 139.1, 137.6, 123.9, 116.0,
63.7, 30.7, 21.1, 18.7, 13.6; HRMS (DART): m/z calculated for C13H20NO2 [M + H]+
222.1489, found 222.1487.
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Butyl (3,4,5ꢀtrimethoxyphenyl)carbamate (2ad). White solid (1.06 g, 94%); mp 95-
96 oC; 1H NMR (400 MHz, DMSO-d6) δ 9.48 (s, 1H), 6.85 (s, 2H), 4.06 (t, J = 6.5 Hz,
2H), 3.72 (s, 6H), 3.60 (s, 3H), 1.65–1.53 (m, 2H), 1.37 (dq, J = 14.8, 7.4 Hz, 2H),
0.91 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.6, 152.9, 135.4, 132.8,
96.0, 63.8, 60.1, 55.6, 30.6, 18.7, 13.6; HRMS (DART): m/z calculated for
C14H22NO5 [M + H]+ 284.1498, found 284.1492.
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Butyl (4ꢀaminoꢀ3ꢀmethoxyphenyl)carbamate (2ae). Brown solid (723 mg, 76%);
o
mp 91-93 C; 1H NMR (400 MHz, DMSO-d6) δ 9.13 (s, 1H), 7.02 (s, 1H), 6.71 (s,
1H), 6.52 (d, J = 8.0 Hz, 1H), 4.41 (br s, 2H), 4.02 (t, J = 6.0 Hz, 2H), 3.71 (s, 3H),
1.59-1.56 (m, 2H), 1.39–1.35 (m, 2H), 0.91 (t, J = 6.0 Hz, 1H). 13C NMR (101 MHz,
DMSO-d6) δ 153.8, 146.2, 132.9, 129.0, 113.6, 111.4, 103.0, 63.5, 55.1, 30.7, 18.7,
13.6. HRMS (DART): m/z calculated for C12H19N2O3 [M + H]+ 239.1396, found
239.1390.
Butyl (3ꢀaminoꢀ5ꢀ(trifluoromethyl)phenyl)carbamate (2af). Brown liquid (792 mg,
72%); 1H NMR (400 MHz, DMSO-d6) δ 9.64 (s, 1H), 6.96 (d, J = 12.0 Hz, 2H), 6.49
(s, 1H), 5.57 (s, 2H), 4.06 (t, J = 8.0 Hz, 2H), 1.62–1.55 (m, 2H), 1.41–1.32 (m, 2H),
0.90 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.6, 150.0, 140.7, 130.0
(q, J = 31.3 Hz), 124.5 (q, J = 272.7 Hz), 106.1, 104.1 (q, J = 4.3 Hz), 101.8 (q, J =
4.0 Hz), 63.9, 30.6, 18.6, 13.6; 19F NMR (376 MHz, DMSO-d6) δ –66.2; HRMS
(DART): m/z calculated for C12H16F3N2O2 [M + H]+ 277.1158, found 277.1157.
Butyl (6ꢀmethoxypyridinꢀ3ꢀyl)carbamate (2ag). Pale yellow oily liquid (804 mg,
90%); 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.63 (t, J = 8.0 Hz, 1H), 7.37 (d,
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J = 8.0 Hz, 1H), 6.43 (d, J = 8.0 Hz, 1H), 4.08 (t, J = 8.0 Hz, 2H), 3.80 (s, 3H), 1.62–
1.55 (m, 2H), 1.42–1.32 (m, 2H), 0.90 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz,
DMSO-d6) δ 162.4, 153.5, 150.3, 140.8, 104.0, 103.8, 64.0, 53.0, 30.5, 18.6, 13.6;
HRMS (DART): m/z calculated for C11H17N2O3 [M + H]+ 225.1234, found 225.1233.
butyl (5ꢀmethylpyridinꢀ2ꢀyl)carbamate (2ah). Off-white solid (724 mg, 87%); mp
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o
114-116 C; 1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.08 (s, 1H), 7.71 (d, J =
4.0 Hz, 1H), 7.56 (dd, J = 8.0, 1.9 Hz, 1H), 4.07 (t, J = 6.0 Hz, 2H), 2.22 (s, 3H),
1.61–1056 (m, 2H), 1.40–1.33 (m, 2H), 0.90 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz,
DMSO-d6) δ 153.7, 150.1, 147.5, 138.5, 127.3, 111.9, 64.0, 30.6, 18.6, 17.2, 13.6;
HRMS (DART): m/z calculated for C11H17N2O2 [M + H]+ 209.1285, found 209.1284.
o
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Butyl quinolinꢀ2ꢀylcarbamate (2ai). White solid (829 mg, 85%); mp 78–80 C; H
NMR (400 MHz, DMSO-d6) δ 10.45 (s, 1H), 8.31 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.0
Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H),
7.44 (t, J = 8.0 Hz, 1H), 4.12 (t, J = 6.0 Hz, 2H), 1.63–1.56 (m, 2H), 1.39–1.32 (m,
2H), 0.89 (t, J = 6.0 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 154.0, 151.8, 146.4,
138.2, 129.9, 127.7, 126.8, 125.2, 124.6, 113.3, 64.3, 30.5, 18.6, 13.6; HRMS
(DART): m/z calculated for C14H17N2O2 [M + H]+ 245.1290, found 245.1284.
Butyl (2ꢀmethylquinolinꢀ6ꢀyl)carbamate (2aj). White solid (908 mg, 88%); mp 183-
o
185 C; 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 8.11-8.09 (m, 2H), 7.83 (d, J
= 12.0 Hz, 1H), 7.70 (dd, J = 8.0 Hz, 4.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 4.12 (t, J
= 6.0 Hz, 2H), 2.59 (s, 3H), 1.65–1.58 (m, 2H), 1.41–1.33 (m, 2H), 0.91 (t, J = 6.0 Hz,
3H); 13C NMR (101 MHz, DMSO-d6) δ 156.7, 153.8, 143.9, 136.5, 135.4, 128.7,
126.6, 122.5, 122.4, 113.3, 64.0, 30.6, 24.6, 18.6, 13.6; HRMS (DART): m/z
calculated for C15H19N2O2 [M + H]+ 259.1447, found 259.1440.
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Butyl benzo[b]thiophenꢀ5ꢀylcarbamate (2ak). Off-white solid (796 mg, 80%); mp
4
5
6
o
65-66 C; 1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.08 (s, 1H), 7.87 (d, J =
7
8
9
12.0 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.43–7.38 (m, 2H), 4.10 (t, J = 8.0 Hz, 2H),
1.65-1.58 (m, 2H), 1.43–1.34 (m, 2H), 0.91 (t, J = 8.0 Hz, 3H); 13C NMR (101 MHz,
DMSO-d6) δ 153.8, 140.0, 136.3, 133.1, 128.1, 124.0, 122.6, 116.7, 112.2, 63.9, 30.7,
18.7, 13.6; HRMS (DART): m/z calculated for C13H16NO2S [M + H]+ 250.0896,
found 250.0896.
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Butyl benzo[b]thiophenꢀ3ꢀylcarbamate (2al). Pale yellow solid (796 mg, 80%); mp
o
70–72 C; 1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.13 (d, J = 4.0 Hz, 1H),
7.93–7.92 (m, 1H), 7.63 (s, 1H), 7.41–7.36 (m, 2H), 4.15 (t, J = 4.0 Hz, 2H), 1.67–
1.62 (m, 2H), 1.44–1.37 (m, 2H), 0.93 (t, J = 6.0 Hz, 3H); 13C NMR (101 MHz,
DMSO-d6) δ 154.5, 137.3, 132.9, 130.3, 124.7, 123.8, 122.9, 121.2, 109.4, 64.3, 30.6,
18.6, 13.6; HRMS (DART): m/z calculated for C13H16NO2S [M + H]+ 250.0902,
found 250.0896.
o
Butyl 1Hꢀindolꢀ5ꢀylcarbamate (2am).20 White solid (760 mg, 82%); mp 78–79 C;
1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1H), 9.32 (s, 1H), 7.70 (s, 1H), 7.31–7.29
(m, 2H), 7.17 (d, J = 12.0 Hz, 1H), 6.36 (s, 1H), 4.08 (t, J = 8.0 Hz, 2H), 1.64–1.57
(m, 2H), 1.44–1.35 (m, 2H), 0.93 (t, J = 6.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6)
δ 154.1, 132.4, 131.1, 127.6, 125.8, 114.4, 111.2, 109.7, 100.9, 63.6, 30.8, 18.7, 13.7;
HRMS (DART): m/z calculated for C13H17N2O2 [M + H]+ 233.1285, found 233.1284.
o
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Tertꢀbutyl mꢀtolylcarbamate (2an). White solid (645 mg, 78%); mp 60–62 C; H
NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 7.34 (s, 1H), 7.23 (t, J = 8.0 Hz, 1H);
7.11 (t, J = 8.0 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 2.24 (s, 3H), 1.47 (s, 9H); 13C NMR
(101 MHz, DMSO-d6) δ 152.8, 139.5, 137.7, 128.4, 122.7, 118.6, 115.4, 78.8, 28.1,
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21.3; HRMS (DART): m/z calculated for C12H18NO2 [M + H]+ 208.1332, found
208.1334.
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Methyl [1,1'ꢀbiphenyl]ꢀ3ꢀylcarbamate (2ao). White solid (772 mg, 85%); mp 106-
o
1
9
108 C; H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 7.78 (s, 1H), 7.60-7.58 (m,
2H), 7.48-7.44 (m, 3H), 7.39-7.35 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 3.69 (s, 3H); 13C
NMR (101 MHz, DMSO-d6) δ 154.1, 140.9, 140.3, 139.8, 129.4, 129.0, 127.6, 126.7,
120.9, 117.3, 116.5, 51.7; HRMS (DART): m/z calculated for C14H14NO2 [M + H]+
228.1019, found 228.1021.
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Propyl (4ꢀfluorophenyl)carbamate (2ap). Off-white solid (632 mg, 80%); mp 50-52
oC; 1H NMR (400 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.47 (dd, J = 8.0 Hz, 4.0 Hz, 2H),
7.10 (t, J = 8.0 Hz, 2H), 4.02 (t, J = 8.0 Hz, 2H), 1.67–1.58 (m, 2H), 0.92 (t, J = 8.0
Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 157.6 (d, J = 239.4 Hz), 153.8, 135.6 (d,
J = 2.0 Hz), 119.8, 115.2 (d, J = 22.2 Hz), 65.7, 21.9, 10.2; 19F NMR (376 MHz,
DMSO-d6) δ –125.4; HRMS (DART): m/z calculated for C10H13FNO2 [M + H]+
198.0930, found 198.0925.
Cyclohexyl [1,1'ꢀbiphenyl]ꢀ3ꢀylcarbamate (2aq). White solid (885 mg, 75%); mp
o
1
129–131 C; H NMR (400 MHz, DMSO-d6) δ 9.67 (br s, 1H), 7.80 (s, 1H), 7.60–
7.57 (m, 2H), 7.48–7.44 (m, 3H), 7.38–7.33 (m, 2H), 7.26 (d, J = 8.0 Hz, 1H), 4.67–
4.61 (m, 1H), 1.92–1.89 (2H), 1.73–1.70 (m, 2H), 1.54–1.51 (m, 1H), 1.43–1.22 (m,
5H); 13C NMR (101 MHz, DMSO-d6) δ 153.1, 140.8, 140.3, 139.9, 129.3, 129.0,
127.5, 126.6, 120.7, 117.2, 116.4, 72.4, 31.7, 24.9, 23.5; HRMS (DART): m/z
calculated for C19H22NO2 [M + H]+ 296.1651, found 296.1645.
o
Butyl (4ꢀcyanophenyl)carbamate (2ar). White solid (697 mg, 80%); mp 80-82 C;
1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.63 (d, J =
8.0 Hz, 2H), 4.09 (t, J = 6.0 Hz, 2H), 1.63-1.56 (m, 2H), 1.41-1.31 (m, 2H), 0.89 (t, J
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= 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.3, 143.7, 133.2, 119.2, 118.0,
104.0, 64.4, 30.5, 18.6, 13.5; HRMS (DART): m/z calculated for C12H15N2O2 [M +
H]+ 219.1134, found 219.1128.
o
Butyl pyridinꢀ3ꢀylcarbamate (2as).20 White solid (636 mg, 82%); mp 78–80 C; 1H
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NMR (400 MHz, DMSO-d6) δ 9.84 (s, 1H), 8.64 (s, 1H), 8.20 (s, 1H), 7.89 (d, J = 8.0
Hz, 1H), 7.31 (dd, J = 8.0, 4.0 Hz, 1H), 4.09 (t, J = 6.0 Hz, 2H), 1.64–1.57 (m, 2H),
1.4–1.33 (m, 2H), 0.91 (t, J = 6.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.7,
143.3, 140.0, 136.0, 124.9, 123.6, 64.2, 30.5, 18.6, 13.6; HRMS (DART): m/z
calculated for C10H15N2O2 [M + H]+ 195.1134, found 195.1128.
Butyl 9Hꢀcarbazolꢀ3ꢀylcarbamate (2at). Off-white solid (820 mg, 73%); mp 158-
o
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160 C; H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 9.49 (s, 1H), 8.22 (s, 1H),
8.00 (d, J = 8.0 Hz, 1H), 7.46–7.34 (m, 4H), 7.12 (t, J = 8.0 Hz, 1H), 4.10 (t, J = 6.0
Hz, 2H), 1.64–1.61 (m, 2H), 1.43–1.38 (m, 2H), 0.93 (t, J = 8.0 Hz, 2H); 13C NMR
(101 MHz, DMSO-d6) δ 154.2, 140.3, 136.0, 130.9, 125.5, 122.3, 122.3, 120.0, 118.5,
118.3, 111.0, 110.8, 110.2, 63.7, 30.8, 18.7, 13.7; HRMS (DART): m/z calculated for
C17H19N2O2 [M + H]+ 283.1441, found 283.1439.
o
Butyl quinolinꢀ6ꢀylcarbamate (2au). White solid (888 mg, 91%); mp 122-124 C;
1H NMR (400 MHz, DMSO-d6) δ 9.99 (s, 1H), 8.74 (d, J = 4 Hz, 1H), 8.23 (d, J = 8.0
Hz, 1H), 8.15 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.78–7.76 (m, 1H), 7.43 (dd, J = 8.0,
4.0 Hz, 1H), 4.12 (t, J = 6.0 Hz, 2H), 1.65–1.58 (m, 2H), 1.43–1.33 (m, 2H), 0.90 (t, J
= 8.0 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 153.8, 148.6, 144.36, 137.3, 135.2,
129.5, 128.4, 122.7, 121.7, 113.2, 64.1, 30.6, 18.6, 13.6; HRMS (DART): m/z
calculated for C14H17N2O2 [M + H]+ 245.1285, found 245.1284.
Tertꢀbutyl quinolinꢀ6ꢀylcarbamate (2av). Off-white solid (760 mg, 78%); mp 140-
142 oC; 1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.73 (d, J = 4.0 Hz, 1H), 8.22
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(d, J = 4.0 Hz, 1H), 8.18 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.74 (dd, J = 8.0 Hz, 4.0 Hz,
0H), 7.43 (dd, J = 8.0 Hz, 4.0 Hz, 1H), 1.50 (s, 9H); 13C NMR (125 MHz, DMSO-d6)
δ 152.8, 148.4, 144.2, 137.5, 135.1, 129.4, 128.4, 122.8, 121.6, 113.0, 79.4, 28.1;
HRMS (DART): m/z calculated for C14H17N2O2 [M + H]+ 245.1285, found 245.1284.
Tertꢀbutyl [1,1'ꢀbiphenyl]ꢀ4ꢀylcarbamate (2aw). White solid (968 mg, 90%); mp
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152-154 C; 1H NMR (400 MHz, CDCl3) δ 7.60-7.54 (m, 4H), 7.46-7.42 (m, 4H),
7.36-7.32 (m, 1H), 6.65 (br s, 1H), 1.56 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 152.9,
140.7, 137.8, 136.0, 128.8, 127.7, 127.0, 126.9, 118.9, 80.7, 28.5; HRMS (DART):
m/z calculated for C17H20NO2 [M + H]+ 270.1489, found 270.1491
Methyl benzo[d][1,3]dioxolꢀ5ꢀylcarbamate (2ax). Off-white solid (663 mg, 85%);
o
mp 83-85 C; 1H NMR (500 MHz, DMSO-d6) δ 7.06 (br s, 1H), 6.76 (s, 1H), 6.71-
13
6.66 (m, 2H), 5.92 (s, 2H), 3.74 (s, 3H); C NMR (125 MHz, DMSO-d6) δ 154.5,
148.0, 143.9, 132.2, 112.1, 108.1, 102.0, 101.3, 52.4; HRMS (DART): m/z calculated
for C9H10NO4 [M + H]+ 196.0604, found 196.0605.
Isopropyl (3ꢀchlorophenyl)carbamate (2ay).20 Colourless liquid (568 mg, 67%); 1H
NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H), 7.62 (s, 1H), 7.39–7.37 (m, 1H), 7.27 (t, J
= 8.0 Hz, 1H), 7.01 (dd, J = 8.0, 1.2 Hz, 1H), 4.89 (hept, J = 6.6 Hz, 1H), 1.25 (d, J =
4.0 Hz, 6H); 13C NMR (101 MHz, DMSO-d6) δ 153.0, 140.9, 133.2, 130.3, 121.9,
117.4, 116.5, 67.8, 21.9; HRMS (DART): m/z calculated for C10H13ClNO2 [M + H]+
214.0635, found 214.0629.
Supporting Information. Copies of 1H and 13C NMR spectra of the products. This
material is available free of charge via the Internet at http://pubs.acs.org.
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