Copper-catalyzed N- tert -butylation of aromatic amines under mild conditions using tert -butyl 2,2,2-trichloroacetimidate

Article abstract of DOI:10.1055/s-0033-1339107

A variety of aromatic amines have been found to expediently undergo copper-catalyzed N-tert-butylation in the presence of tert-butyl 2,2,2-trichloroactimidate at room temperature. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1339107

LETTER
▌A
lCettoerpper-Catalyzed N-tert-Butylation of Aromatic Amines under Mild Condi-
tions Using tert-Butyl 2,2,2-Trichloroacetimidate
Copper-Catalyzed N-tert-Butylation
John W. Cran,* Dinesh V. Vidhani, Marie E. Krafft
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA
Fax +1(850)6447409; E-mail: jcran@chem.fsu.edu
Received: 10.03.2014; Accepted after revision: 10.04.2014
mised that this offered an opportunity to develop a more
Abstract: A variety of aromatic amines have been found to expedi-
effective catalytic process by identifying conditions more
ently undergo copper-catalyzed N-tert-butylation in the presence of
compatible with aromatic amines. Therefore, a study was
undertaken to screen a number of readily available Lewis
acids under different conditions in the presence of tert-
tert-butyl 2,2,2-trichloroactimidate at room temperature.
Key words: anilines, tert-butylation, copper, catalysis, alkylation
butyl trichloroacetimidate (1) and with aniline as the test
substrate (Table 1). Our initial studies showed coinage
The tert-butylation of anilines is a reaction that has tradi-
tionally been difficult to accomplish, requiring the use of
metals to be the most effective catalyst systems.5 While
unactivated AuCl and AuCl3 were found to be ineffective
harsh reaction conditions and long reaction times and of-
6
catalysts, AuCl activated with AgClO4 in the presence of
ten delivering only poor to moderate yields.1 To date, an
2.5 equivalents of 1 gave moderate yields after two hours
efficient and mild general protocol has not been devel-
at room temperature (Table 1, entries 1–3) with dry
oped. As such, the only efficient method remains the
MeNO2 proving to be an effective solvent.7 While silver
Buchwald–Hartwig amination reaction,2 which still re-
perchlorate was also found to be an active catalyst the re-
quires high temperatures and long reaction times and is
action did not progress beyond 52% (Table 1, entry 4),
not always tactically desirable. Furthermore, anilines con-
even after an extended period of time. The presence of a
stitute a fundamental building block in organic chemistry
triphenylphosphine ligand on gold was found to be detri-
and there is a continuing need for general procedures for
their functionalization, including alkylation.
mental to catalytic activity, presumably blocking a coor-
dination site at the metal center (Table 1, entry 5).
Herein, we describe such a protocol using tert-butyl 2,2,2-
trichloroacetimidate in the presence of readily available
copper catalysts under mild conditions.
From further catalyst screening, PtCl2/AgClO4 was also
found to be an active catalytic system (Table 1, entry 6),
however, less expensive copper(I) and (II) catalysts were
The Jackson group has previously reported that tert-butyl
2,2,2-trichloroacetimidate is an effective tert-butylating
agent for alcohols and carboxylic acids in the presence of
BF3·OEt2 (Scheme 1).3
identified as being the most effective, giving yields of up
to 85% (Table 1, entries 7–12). Copper(I) salts required a
silver-activating agent as did CuCl2. While Cu(OAc)2 was
inert (Table 1, entry 11), commercially available
Cu(OTf)2 proved to be an excellent catalyst and did not re-
quire activation (Table 1, entry 12). The reaction was ob-
served to be clean with no significant byproducts formed.
Significantly, no C-alkylation products were seen. Other
transition-metal salts were found to promote the reaction
to some extent, but not as effectively, in general giving
yields below 50%, even after extended reaction times (Ta-
ble 1, entries 13–16). Tosic acid also catalyzed the reac-
tion but did not give full conversion to the product (Table
1, entry 17), and employing stronger or weaker protic ac-
ids did not result in effective conversions (Table 1, entries
18 and 19). Finally, in the absence of a catalyst no product
formation was observed at all after two hours (Table 1, en-
try 20).
NH
t-BuO
CCl3
ROt-Bu
ROH
BF3⋅OEt2, cyclohexane
Scheme 1 Jackson’s protocol for the tert-butylation of alcohols and
carboxylic acids3
Previous attempts to tert-butylate aromatic amines utiliz-
ing Jackson’s conditions have resulted in long reaction
times and modest yields, probably due to the reactivity of
BF3·OEt2 in the presence of such amines.4 Due to their ba-
sic nature, amines are not generally compatible with
strong Lewis acids. However, the reduced basicity of aro-
matic amines originating from conjugation of the nitrogen
lone pair with the adjacent aromatic system prevents irre-
versible coordination to the Lewis acid catalyst. We sur-
A diverse range of anilines underwent tert-butylation
when subjected to our optimized conditions (Figure 1). In
the presence of electron-withdrawing substituents
(EWG), yields were generally quantitative (3–11) and
while most reactions were generally complete in under
two hours, where an EWG was present, the reaction was
observed to be complete in as little as ten minutes. Where
a nitrile group was present, a large excess of 1 was re-
SYNLETT 2014, 25, 000A–000E
Advanced online publication: 23.05.2014
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9
3
6
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5
2
1
4
1
4
3
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2
0
9
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DOI: 10.1055/s-0033-1339107; Art ID: st-2014-r0212-l
© Georg Thieme Verlag Stuttgart · New York

B
J. W. Cran et al.
LETTER
observed at all where three methoxy groups were present.
This is possibly due to strong coordination of the substrate
to the catalyst either through heteroatom coordination or
π-complexation.8,9 The weaker π-donating phenyl group
did not have a deleterious effect on the reaction with tert-
butylated product 19, formed in a high yield.
Table 1 Optimization of Reaction Conditions
HN
Cl3C
Ot-Bu
t-Bu
1
NH2
NH
(2.5 equiv)
[M], r.t., conditions
NHt-Bu
NHt-Bu
NHt-Bu
Entry [M] (5mol%)
Solvent
Time (h) Yield (%)b
a
a
a
MeO2C
MeOC
1
2
AuCl/AgClO4
AuCl/AgClO4
AuCl/AgClO4
AgClO4
cyclohexane
CH2Cl2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
4
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
50
63
72
52c
<5
70
81
80
38
67
<5
85
25c
51c
48c
36c
60c
45c
<5
0
2, 84%
3, 99%a
6, 99%
4, 85%a
7, 97%
NHt-Bu
NHt-Bu
NHt-Bu
NHt-Bu
NHt-Bu
3
NC
O2N
F3C
NO2
4
5, 95%b
a
5
PPh3AuCl/AgClO4
NHt-Bu
6
PtCl2/AgClO4 (1:2)
Cl
F3C
Cl
a
7
CuCl/AgClO4
CF3
8, 99%
Br
9, 99%
10, 99%
a
8
CuI/AgClO4
t-Bu
Br
9
CuCl2
NHt-Bu
NH
NHt-Bu
10
11
12
13
14
15
16
17
18
19
20
CuCl2/AgClO4 (1:2)
Cu(OAc)2
Cu(OTf)2
Sc(OTf)3
Fe(OTf)3
Pd(OTf)2
Zn(OTf)2
TsOH
Me
12, 88%a
Me
11, 99%
14, 83%
13, 60%
Me
NHt-Bu
Me
NHt-Bu
NHt-Bu
NHt-Bu
Me
Me
16, 19%c
15, 81%
NHt-Bu
MeO
MeO
NHt-Bu
MeO
OMe
HClO4
17, 72%a
18, 0%
19, 87%
TfOH
Figure 1 Isolated yields: in most cases the mass balance was ac-
counted for by unreacted starting material. Reaction conditions: 1 (2.5
equiv), Cu(OTf)2 (5 mol%), MeNO2, r.t., 2 h. a 3.5 equiv of 1 used. b
4.5 equiv of 1 used. c Yield estimated from 1H NMR.
–
a 1 equiv of AgClO4 added with respect to the precatalyst.
b Mass balance was predominantly starting material.
c No significant increase in yield observed after 24 h.
When naphthylamines were subjected to the reaction con-
ditions (Figure 2) it was found that with Cu(OTf)2 low
yields and complex product mixtures were observed.
However, using CuI/AgClO4, it was possible to isolate
compounds 20 and 22 (Figure 2) in good to moderate
yields. Compounds 21 and 23 were still not cleanly isol-
able, with complex mixtures of alkylation products ob-
served in these cases. Overall a trend mirroring that shown
for anilines was apparent with the electron-withdrawing
nitro group giving the highest yield. The lower yields and
substrate scope are probably due to the less aromatic na-
ture of naphthylamines (cf. anilines) leading to side reac-
tions and decomposition as a result of higher reactivity.10
quired to drive the reaction to completion (5). We rea-
soned that this was most likely due to unproductive
coordination of the nitrile lone pair to the catalyst. Indeed,
in support of this assertion, when a control reaction was
run in MeCN, with aniline as the substrate, no reaction
was observed. The presence of the mildly σ-donating
methyl substituent was well tolerated by the reaction (see
examples 12–16), although here steric hindrance had a no-
table effect, cf. 13–16, inhibiting product formation. The
effect appeared to be cancelled out by the presence of a σ-
accepting bromide group (12). The presence of a methoxy
substituent, a strong π-donor group, lowered the yield of
tert-butylated product 17, and the formation of 18 was not
Synlett 2014, 25, A–E
© Georg Thieme Verlag Stuttgart · New York

LETTER
Copper-Catalyzed N-tert-Butylation
C
NH
NHt-Bu
NHt-Bu
O
CCl3
[Cu]
H
N
21, mixture
+
[Cu]
NO2
O
CCl3
20, 83%
NHt-Bu
NHt-Bu
NH2
H
O
H
N
NH
+
22, 62%
CCl3
OMe
23, mixture
Figure 2 Reaction conditions: 1 (2.5 equiv), CuI (5 mol%), AgClO4
(5 mol%), MeNO2, r.t., 2 h.
Scheme 2 Proposed mechanism
To shed further light on the mechanism, particularly our
hypothesis that an unproductive interaction between elec-
tron-rich aromatic amines and the catalyst hindered the re-
action, a preliminary computation study, performed at the
M05-2X/LANL2DZ level,11 was carried out. p-Methoxy-
aniline and p-nitroaniline were compared to determine the
substituent effects on catalyst-substrate affinity. The re-
sults suggested an unproductive reactant stabilization of
the electron-rich p-methoxy aniline, upon coordination
with the copper(II) catalyst (–59.2 kcal/mol), much stron-
ger than with the imidate and in agreement with our hy-
pothesis.9 This could account for the lower yield as the
active catalyst concentration is reduced. In contrast, p-ni-
tro aniline forms a weaker complex (12.9 kcal/mmol) with
copper(II) than the imidate, leaving the catalyst available
for promoting the desired tert-butylation reaction.
A reasonable mechanism is given in Scheme 2, whereby
the copper species initially coordinates to tert-butyl 2,2,2-
trichloroacetimidate, catalyzing its decomposition and re-
leasing the tert-butyl cation to be captured by the aniline,
which is possibly already catalyst-bound. The notion that
the aromatic amine is already coordinated in the catalyst
complex is supported by the observation that its presence
is required to effectively solubilize the catalyst and that in
its absence, decomposition of 1 takes almost two hours
compared with less than ten minutes for the tert-butyl-
ation of 4-nitroaniline to give 4. At least two equivalents
of the tert-butylating agent are usually needed, presum-
ably due to the tert-butyl cation undergoing competitive
proton elimination to give isobutene. The strongly polar
aprotic nature of nitromethane most likely stabilizes the
tert-butyl cation, increasing its half-life and accounting
for its suitability as a reaction medium. Increasing the
amount of the tert-butylating agent 1 to four equivalents
or more had little observable effect on the reaction rate or
yield in most cases, suggesting that the rate-determining
step is interception of the tert-butyl cation by the sub-
strate. Intriguingly, given the presumed SN1 characteris-
tics of the proposed mechanism, the copper(II)-catalyzed
tert-butylation showed a significant dependence on the
nature of nucleophile. This was unexpected given that SN1
reactions generally display the first-order and the zero-
order dependence on the electrophile and the nucleophile,
respectively.
Interestingly, the methoxy group formed a stronger com-
plex with copper(II) than the amino group (11.6
kcal/mol). The observed anomaly is due to the stereoelec-
tronic effect of the electron pair on the amino group which
deconjugates the electrons on the methoxy group from the
aromatic ring, thereby making those electrons more nu-
cleophilic than the amino group electrons (Figure 3). This
is a result of the lone pair on the oxygen of the methoxy
group being more tightly held than the lone pair on the ni-
trogen, hence, deconjugation of the electrons of the amino
group, by the methoxy group, would require higher ener-
gy and is therefore energetically unfavorable.
Figure 3 The M05-2X/LANL2DZ optimized geometries of the Cu(II)–substrate complex. Structure A represents the Cu(II)–methoxy com-
plex. Structure B represents the Cu(II)–amine complex. Values in parenthesis correspond to relative energy difference between structure A and
B.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, A–E

D
J. W. Cran et al.
LETTER
(8) Quenching of the catalyst by electron-rich substrates is also
supported by the observation that 1 did not decompose in the
presence of 3,4,5-trimethoxy aniline and the catalyst.
(9) (a) Vidhani, D. V.; Cran, J. W.; Krafft, M. E.; Manoharan,
M.; Alabugin, I. V. J. Org. Chem. 2013, 78, 2059.
(b) Vidhani, D. V.; Cran, J. W.; Krafft, M. E.; Alabugin, I.
V. Org. Biomol. Chem. 2013, 11, 1624. (c) Vidhani, D. V.;
Krafft, M. E.; Alabugin, I. V. Org. Lett. 2013, 15, 4462.
(d) Vidhani, D. V.; Krafft, M. E.; Alabugin, I. V. J. Org.
Chem. 2014, 79, 352. (e) Krafft, M. E.; Hallal, K. M.;
Vidhani, D. V.; Cran, J. W. Org. Biomol. Chem. 2011, 9,
7535.
In conclusion, a new expedient, mild, and general method
for the synthesis of tert-butyl aromatic amines at room
temperature has been developed, catalyzed by Cu(OTf)2,
utilizing
tert-butyl
2,2,2-trichloroacetimidate
in
MeNO2.12,13 Additionally, a preliminary computational
study supports the experimentally observed difference in
rates and yields between electron-rich and electron-poor
aromatic amines, suggesting the presence of unproductive
catalyst–substrate interactions with electron-rich aromatic
amines. Our current studies are concentrated on further
applications of the methodology and determination of the
mechanistic details.
(10) Albright, T. A.; Burdett, J. K.; Whangbo, M. H. Orbital
Interactions in Chemistry; John Wiley and Sons: Hoboken,
NJ, 1984.
(11) (a) Zhao, Y.; González-García, N.; Truhlar, D. G. J. Phys.
Chem. A 2005, 109, 2012. (b) Tsipis, A. C.; Orpen, A. G.;
Harvey, J. N. Dalton Trans. 2005, 2849. (c) Zhao, Y.;
Truhlar, D. G. Org. Lett. 2007, 9, 1967. (d) Reiher, M.;
Salomon, O.; Hess, B. A. Theor. Chem. Acc. 2001, 107, 48.
(e) Schultz, N.; Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A
2005, 109, 4388. (f) Schultz, N.; Zhao, Y.; Truhlar, D. G.
J. Phys. Chem. A 2005, 109, 11127. (g) Harvey, J. N. Annu.
Rep. Prog. Chem. Sect. C 2006, 102, 203.
Acknowledgment
This work was supported by the MDS Research Foundation. We
would like to thank the Mass Spectrometry Facility at the Universi-
ty of Florida for data obtained from the Agilent 6220 TOF-MS
(NSF CRIF Grant 0541761).
References and Notes
(12) General Experimental Methods
(1) (a) Gage, J. R.; Wagner, J. M. J. Org. Chem. 1995, 60, 2613.
(b) Masaharu, I.; Takumi, K.; Ikuo, T. JP 9357082
19930317, 1994. (c) Dixon, D. D.; Burgoyne, W. F. Appl.
Catal. 1990, 62, 161. (d) Hickinbottom, W. J. J. Chem. Soc.
1933, 946. (e) Yamamoto, H.; Maruoka, K. J. Org. Chem.
1980, 45, 2739.
(2) For some examples of the employment of the Buchwald–
Hartwig amination for the synthesis of tert-butyl amines,
see: (a) Seo, H.; Roberts, B. P.; Abboud, K. A.; Merz, K. M.
Jr.; Hong, S. Org. Lett. 2010, 12, 4860. (b) Lundgren, R. J.;
Sappong-Kumankumah, A.; Stradiotto, M. Chem. Eur. J.
2010, 16, 1983. (c) Tewari, A.; Hein, M.; Zapf, A.; Beller,
M. Tetrahedron 2005, 61, 9705. For an overview of the field,
see: (d) Hartwig, J. F. Nature (London) 2008, 455, 314; and
references cited therein.
All commercially available chemicals were used as received.
MeNO2 and CH2Cl2 were distilled from CaH2. Reagent-
grade solvents were used for solvent extraction, and organic
extracts were dried over anhydrous Na2SO4 or MgSO4.
Alumina gel (80–200 mesh) was used for flash
chromatography with dry hexane–EtOAc eluent system.1H
NMR spectra were recorded on a 500 MHz Bruker or a 300
MHz Varian spectrometer. 13C NMR spectra were recorded
on a 125 MHz Bruker or a 75 MHz Varian spectrometer. The
proton chemical shifts (δ) are reported as parts per million
relative to 7.26 ppm for CDCl3. The carbon chemical shifts
(δ) were reported as parts per million relative to the
centerline of the triplet for CDCl3 at 77.1 ppm. Mass spectra
were recorded using a Jeol JMS-600 instrument or an
Agilent 6220 TOF-MS (NSF CRIF Grant 0541761).
Typical Procedure for tert-Butylation Reaction
(3) Armstrong, A.; Brackenridge, I.; Jackson, R. F. W.; Kirk, J.
M. Tetrahedron. Lett. 1988, 29, 2483.
To a dry round-bottom flask, equipped with a stirrer bar,
under argon was added freshly distilled MeNO2 (2.5 mL),
tert-butyl 2,2,2-trichloroacetimidate (0.45 mL, 2.5 mmol),
amine (1.0 mmol), and CuOTf (18 mg, 0.05 mmol). The
reaction was stirred at r.t. for 2 h, or until the reaction was
observed to have gone to completion by TLC or 1H NMR
spectroscopy of small aliquots of the reaction mixture. The
reaction mixture was then diluted with EtOAc (25 mL) and
washed with aq sat. NaHCO3 solution (20 mL). The aqueous
phase was extracted with an additional portion of EtOAc (20
mL). The combined organic extracts were dried with Na2SO4
and filtered through a plug of alumina before being reduced
in vacuo. The crude product was purified by flash column
chromatography (typically 20:1, hexane–EtOAc).
(4) (a) Bourgeois, M.-J.; Montaudon, E.; Maillard, B.
Tetrahedron 1993, 49, 2477. (b) Anderson, J. C.; Cran, J.
W.; King, N. P. Tetrahedron Lett. 2002, 43, 3849.
(c) Watanabe, T.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett.
2008, 10, 1759.
(5) Fürstner, A.; Davies, P. W. Angew. Chem. Int. Ed. 2007, 46,
3410.
(6) Ligand exchange gives AgCl and MClO4. For a detailed
discussion of the use of noncoordinating ligands in catalysis,
see: (a) Ruiz-Martínez, A.; Casanova, D.; Alvarez, S. Chem.
Eur. J. 2010, 16, 6567. (b) Wulfsberg, G.; Parks, K. D.;
Rutherford, R.; Jackson, D. J.; Jones, F. E.; Derrick, D.;
Ilsley, W.; Strauss, S. H.; Miller, S. M.; Anderson, O. P.;
Babushkina, T. A.; Gushchin, S. I.; Kravchenko, E. A.;
Morgunov, V. G. Inorg. Chem. 2002, 41, 2032. (c) Krossing,
I.; Raabe, I. Angew. Chem. Int. Ed. 2004, 43, 2066.
(d) Yakelis, N. A.; Bergman, R. G. Organometallics 2005,
24, 3579. (e) Geiger, W. E.; Barrière, F. Acc. Chem. Res.
2010, 43, 1030.
(7) Undistilled MeNO2 proved to be a less effective medium
giving 74% conversion after 24 h with Cu(OTf)2 as the
catalyst. Our previous studies have shown that hydrated
MeNO2 suppressed the catalytic activity of transition metals.
See: Cran, J. W.; Krafft, M. E. Angew. Chem. Int. Ed. 2012,
51, 9398.
(13) tert-Butylphenylamine (2)
Clear oil (125 mg, 0.84 mmol, 84% yield). 1H NMR (300
MHz, CDCl3): δ = 7.16 (dd, J = 8.1, 8.1 Hz, 2 H), 6.79–6.73
(m, 3 H), 3.30–2.30 (br s, 1 H), 1.34 (s, 9 H). Compound
identified by 1H NMR spectroscopy by comparison with
data previously published in the literature.1a
4-tert-Butylaminobenzoic Acid Methyl Ester (3)
Light yellow oil (208 mg, 1.00 mmol, 99% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.81 (d, J = 9.0 Hz, 2 H), 6.63 (d,
J = 9.0 Hz, 2 H), 4.25–4.00 (br s, 1 H), 3.84 (s, 3 H), 1.40 (s,
9 H). 13C NMR (125 MHz, CDCl3): δ = 167.4, 151.0, 131.3
(2 C), 117,7, 113.7 (2 C), 51.3, 29.7 (3 C). ESI-HRMS: m/z
Synlett 2014, 25, A–E
© Georg Thieme Verlag Stuttgart · New York

LETTER
calcd for C12H18NO2 [MH]+: 208.1338; found: 208.1349.
Copper-Catalyzed N-tert-Butylation
E
Hz, 1 H), 6.82 (dd, J = 7.8, 7.8 Hz, 1 H), 3.37–3.29 (br s, 1
H), 2.42 (s, 3 H), 1.26 (s, 9 H). 13C NMR (125 MHz, CDCl3):
δ = 143.9, 137.2, 130.5, 130.2, 124.3, 124.2, 56.1, 31.1 (3 C),
21.6. HRMS (EI): m/z calcd for C11H16BrN [M]+: 241.0466;
found: 241.0476.
1-(4-tert-Butylaminophenyl)-ethanone (4)
Yellow oil (189 mg, 0.99 mmol, 99% yield). 1H NMR (300
MHz, CDCl3): δ = 7.78 (d, J = 8.4 Hz, 2 H), 6.63 (d, J = 8.4
Hz, 2 H), 4.32 (br s, 1 H), 2.49 (s, 3 H), 1.41 (s, 9 H). 13
C
NMR (125 MHz, CDCl3): δ = 196.4, 151.2, 130.6 (2 C),
126.0, 113.5 (2 C), 51.3, 29.7 (3 C), 26.0. ESI-HRMS: m/z
calcd for C12H18NO [MH]+: 192.1383; found: 192.1374.
4-tert-Butylaminobenzonitrile (5)
tert-Butyl-o-tolylamine (13)
Light brown oil (98 mg, 0.60 mmol, 60% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.13–7.04 (m, 2 H), 6.92 (d, J = 8.4
Hz, 1 H), 6.66 (dd, J = 7.2, 7.2 Hz, 1 H), 3.60–3.25 (br s, 1
H), 2.13 (s, 3 H), 1.40 (s, 9 H). Compound identified by 1H
NMR spectroscopy by comparison with data previously
published in the literature.1a
Light brown oil (165 mg, 0.95 mmol, 95% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.37 (d, J = 9.0 Hz, 2 H), 6.62 (d,
J = 9.0 Hz, 2 H), 4.30-4.10 (br s, 1 H), 1.40 (s, 9 H).
Compound identified by 1H NMR spectroscopy by
comparison with data previously published in the
literature.14
tert-Butyl-m-tolylamine (14)
Light brown oil (135 mg, 0.83 mmol, 83% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.06 (dd, J = 9.0, 9.0 Hz, 1 H), 6.62–
6.55 (m, 3 H), 3.20–2.65 (br s, 1 H), 2.28 (s, 3 H), 1.34 (s, 9
H). Compound identified by 1H NMR spectroscopy by
comparison with data previously published in the
literature.1c
tert-Butyl-(4-nitrophenyl)-amine (6)
Yellow oil (192 mg, 0.99 mmol, 99% yield). 1H NMR (300
MHz, CDCl3): δ = 8.03 (d, J = 9.0 Hz, 2 H), 6.59 (d, J = 9.0
Hz, 2 H), 4.70–4.50 (br s, 1 H), 1.43 (s, 9 H). Compound
identified by 1H NMR spectroscopy by comparison with
data previously published in the literature.1a
tert-Butyl-p-tolylamine (15)
Light brown oil (132 mg, 0.81 mmol, 81% yield). 1H NMR
(300 MHz, CDCl3): δ = 6.99 (d, J = 8.4 Hz, 2 H), 6.71 (d,
J = 8.4 Hz, 2 H), 3.30–2.40 (br s, 1 H), 2.26 (s, 3 H), 1.30 (s,
9 H). Compound identified by 1H NMR spectroscopy by
comparison with data previously published in the
literature.1a
tert-Butyl-(2-nitro-4-trifluoromethyl-phenyl)-amine (7)
Yellow oil (262 mg, 1.00 mmol, 99% yield). 1H NMR (300
MHz, CDCl3): δ = 8.68–8.56 (br s, 1 H), 8.45 (d, J = 2.4 Hz,
1 H), 7.56 (dd, J = 9.0, 2.4 Hz, 1 H), 7.18 (d, J = 15.0 Hz, 1
H), 1.53 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 146.3,
133.4, 133.3 (q, J = 3.8 Hz), 125.5 (q, J = 43.8 Hz), 123.7,
(q, J = 268.8 Hz), 116.7 (q, J = 30.0 Hz), 116.3, 52.3, 29.6
(3 C). ESI-HRMS: m/z calcd for C11H14N2O2F3 [MH]+:
263.1002; found: 263.1002.
tert-Butyl-(4-trifluoromethyl-phenyl)-amine (8)
Light brown oil (210 mg, 0.97 mmol, 97% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.37 (d, J = 9.0 Hz, 2 H), 6.69 (d,
J = 9.0 Hz, 2 H), 3.97 (s, 1 H), 1.39 (s, 9 H). 13C NMR (75
MHz, CDCl3): δ = 149.7, 126.4 (q, J = 3.4 Hz, 2 C), 125.1
(q, J = 268.7 Hz), 118.5 (q, J = 32.4 Hz), 114.4 (2 C), 51.3,
29.8. ESI-HRMS: m/z calcd for C11H15NF3 [MH]+:
218.1151; found: 218.1153.
tert-Butyl-(4-chloro-3-trifluoromethyl-phenyl)-amine (9)
Light yellow oil (251 mg, 1.00 mmol, 99% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.22 (d, J = 9.0 Hz, 1 H), 6.97 (d,
J = 3.0 Hz, 1 H), 6.77 (dd, J = 9.0, 3.0 Hz, 1 H), 4.02–3.02
(br s, 1 H), 1.35 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ =
145.6, 131.8, 128.4 (q, J = 31.3 Hz), 123.1 (q, J = 271.3 Hz),
119.3, 119.2 (q, J = 1.3 Hz), 114.7 (q, J = 6.3 Hz), 51.6, 29.8
(3 C). HRMS (EI): m/z calcd for C11H13F3NCl [M]+:
251.0689; found: 251.0690.
tert-Butyl-(4-methoxyphenyl)-amine (17)
Red oil (127 mg, 0.72 mmol, 72% yield). 1H NMR (300
MHz, CDCl3): δ = 6.84–6.73 (m, 4 H), 3.76 (s, 3 H), 1.23 (s,
9 H). Compound identified by 1H NMR spectroscopy by
comparison with data previously published in the
literature.1a
Biphenyl-4-yl-tert-butylamine (19)
Light yellow oil (196 mg, 0.87 mmol, 87% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.55 (d, J = 7.2 Hz, 2 H), 793 (d, J =
8.4 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.26 (t, J = 7.5 Hz, 1
H), 6.82 (d, J = 9.0 Hz, 2 H), 4.00–3.20 (br s, 1 H), 1.39 (s,
9 H). Compound identified by 1H NMR spectroscopy by
comparison with data previously published in the
literature.15
tert-Butyl-(4-nitro-naphthalen-1-yl)-amine (20)
Yellow oil (203 mg, 0.83 mmol, 83% yield). 1H NMR (300
MHz, CDCl3): δ = 9.05 (d, J = 9.0 Hz, 1 H), 8.46 (d, J = 9.0
Hz, 1 H), 7.76 (d, J = 9.0 Hz, 1 H), 7.67 (dd, J = 7.8, 7.8 Hz,
1 H), 7.51 (dd, J = 7.8, 7.8 Hz, 1 H), 6.78 (d, J = 9.0 Hz, 1
H), 5.38–5.31 (br s, 1 H), 1.58 (s, 9 H). 13C NMR (75 MHz,
CDCl3): δ = 148.5, 134.1, 129.5, 129.1, 128.1, 125.7, 125.0,
122.5, 120.1, 103.5, 52.2, 29.4 (3 C). HRMS (EI): m/z calcd
for C14H16O2N2 [M]+: 244.1212; found: 244.1212.
tert-Butyl-naphthalen-2-yl-amine (22)
tert-Butyl-(4-chlorophenyl)-amine (10)
Light orange oil (0.181 g, 0.99 mmol, 99% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.10 (d, J = 9.0 Hz, 2 H), 6.65 (d,
J = 9.0 Hz, 2 H), 1.32 (s, 9 H). Compound identified by 1H
NMR spectroscopy by comparison with data previously
published in the literature.1a
Red oil (123 mg, 0.62 mmol, 62% yield). 1H NMR (300
MHz, CDCl3): δ = 7.66 (d, J = 8.4 Hz, 1 H), 7.61 (d, J = 8.4
Hz, 2 H), 7.36 (dd, J = 7.5, 7.5 Hz, 1 H), 7.20 (dd, J = 7.5,
7.5 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.90 (dd, J = 9.0, 2.4
Hz, 1 H), 4.00–3.20 (br s, 1 H), 1.43 (s, 9 H). Compound
identified by 1H NMR spectroscopy by comparison with
data previously published in the literature.16
(2-Bromo-phenyl)-tert-butylamine (11)
Pink oil (228 mg, 1.00 mmol, 99% yield). 1H NMR (300
MHz, CDCl3): δ = 7.43 (dd, J = 7.8, 1.8 Hz, 1 H), 7.14 (ddd,
J = 7.8, 7.8, 1.8 Hz, 1 H), 6.97 (dd, J = 7.8, 1.8 Hz, 1 H), 6.55
(ddd, J = 7.8, 7.8, 1.8 Hz, 1 H), 4.40–4.25 (br s, 1 H), 1.41
(s, 9 H). Compound identified by 1H NMR spectroscopy by
comparison with data previously published in the
literature.4c
(14) Zachariasse, K. A.; Druzhinin, S. I.; Bosch, W.; Machinek,
R. J. Am. Chem. Soc. 2004, 126, 1705.
(15) Gassman, P. G.; Campbell, G. A.; Fredrick, R. C. J. Am.
Chem. Soc. 1972, 94, 3884.
(2-Bromo-6-methylphenyl)-tert-butylamine (12)
Light pink oil (213 mg, 0.88 mmol, 88% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.39 (d, J = 7.8, 1 H), 7.11 (d, J = 7.8
(16) Cortright, S. B.; Huffman, J. C.; Yoder, R. A.; Coalter, J. N.
III; Johnston, J. N. Organometallics 2004, 23, 2238.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, A–E