Development of a Triazine-Based tert-Butylating Reagent, TriAT-tBu

Article abstract of DOI:10.1002/ejoc.201600663

A new tert-butylating reagent, 2,4,6-tris(tert-butoxy)-1,3,5-triazine (TriAT-tBu) has been developed for the acid-catalyzed tert-butylation of alcohols and carboxylic acids. The reaction of various alcohols and carboxylic acids with TriAT-tBu in the presence of a catalytic amount of an acid provided the corresponding tert-butyl ethers and esters in good to high yields. TriAT-tBu is an air-stable solid synthesized in good yield from inexpensive starting materials, namely, cyanuric chloride, tBuOH, and sodium hydride.

Full text of DOI:10.1002/ejoc.201600663

DOI: 10.1002/ejoc.201600663
Full Paper
tert-Butylating Reagent
Development of a Triazine-Based tert-Butylating Reagent,
TriAT-tBu
[a]
[a]
[a]
[a]
Kohei Yamada, Naoko Hayakawa, Hikaru Fujita, Masanori Kitamura, and
Munetaka Kunishima*[
a]
Abstract: A new tert-butylating reagent, 2,4,6-tris(tert-butoxy)- corresponding tert-butyl ethers and esters in good to high
1,3,5-triazine (TriAT-tBu) has been developed for the acid-cata- yields. TriAT-tBu is an air-stable solid synthesized in good yield
lyzed tert-butylation of alcohols and carboxylic acids. The reac- from inexpensive starting materials, namely, cyanuric chloride,
tion of various alcohols and carboxylic acids with TriAT-tBu in tBuOH, and sodium hydride.
the presence of a catalytic amount of an acid provided the
Introduction
deprotection can be readily achieved under acidic conditions
with the liberation of isobutene, while tert-butyl ethers are tol-
We have recently reported the development of a triazine-based
[
3]
erated under various reaction conditions. The traditional
methods for preparing tert-butyl ethers and esters involve the
reaction of a large excess of isobutene or tert-butyl 2,2,2-trichlo-
O-benzylating reagent, 2,4,6-tris(benzyloxy)-1,3,5-triazine (Tri-
[
1]
[2]
BOT) and a para-methoxybenzylating reagent (TriBOT-PM),
which can be considered as the formal trimer of the smallest
unit of benzyl imidate (Figure 1). These reagents have several
characteristic features: (1) they can be easily synthesized from
the corresponding inexpensive alcohols and cyanuric chloride
in one step; (2) they are non-hygroscopic solids, non-irritants,
and non-allergens and can be stored and handled in air at room
temperature; (3) the co-product isocyanuric acid can be easily
removed by filtration under standard workup conditions. Our
next goal is to demonstrate the possibility of using this concept
for designing an alkylating reagent, 2,4,6-tris(alkyloxy)-1,3,5-tri-
azine (TriAT).
[
3,4]
roacetimidate (tert-BTCAI) in the presence of an acid catalyst.
However, handling and storage of the flammable gaseous iso-
butene is inconvenient and potentially hazardous, and tert-
[
5]
BTCAI is sensitive to moisture and heat. By analogy with Tri-
BOT and TriBOT-PM, a triazine-based tert-butylating reagent is
expected to solve these problems.
Herein, we report the development of a tert-butylating rea-
[
6]
gent, 2,4,6-tris(tert-butoxy)-1,3,5-triazine (TriAT-tBu).
Results and Discussion
According to the procedure for the synthesis of TriBOT-PM,[2]
TriAT-tBu was synthesized from cyanuric chloride and 3.5 equiv.
of tBuONa prepared from tBuOH and sodium hydride, in 81 %
yield (Scheme 1). As expected, TriAT-tBu is a non-hygroscopic
crystalline solid and stable in air at room temperature for over
one year. Irritating or allergenic properties were not observed
[
7]
in our laboratory.
Figure 1. Concept for the design of TriAT-tBu.
The tert-butyl group has been widely employed as a protect-
ing group for hydroxy and carboxy functional groups, because
[
a] Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical,
and Health Sciences, Kanazawa University
Scheme 1. Synthesis of TriAT-tBu.
Kakuma-machi, Kanazawa 920-1192, Japan
E-mail: kunisima@p.kanazawa-u.ac.jp
http://www.p.kanazawa-u.ac.jp/e/lab/seibutsu.html
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201600663.
Our investigations began with the tert-butylation of hexa-
decanol (1a) with TriAT-tBu using TfOH as an acid catalyst
(Table 1). The reaction of 1a proceeded to give tert-butyl ether
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2
a in 95 % yield (Entry 1). The reaction using Bi(OTf)3 as a tolerated in the reaction, affording the expected product in
strong Lewis acid afforded the product in an excellent yield 95 % yield (Entry 7). Amino protecting groups such as benzyl-
[
8]
(
Entry 2), while the use of Sc(OTf) as a mild Lewis acid neces- oxycarbonyl (Cbz) and tert-butoxycarbonyl (Boc) groups are
3
sitated a longer reaction time of 12 h (Entry 3). On the other compatible with the reaction conditions (Entries 8, 10). When
hand, dropwise addition of TriAT-tBu solution (CH Cl ) in the the reaction of an alcohol bearing a Cbz group (1i) was con-
2
2
presence of Sc(OTf) considerably shortened the reaction time ducted by adding TriAT-tBu in one portion in the presence of
3
(
initial concentration of 1a: 0.14
M
; final concentration: 0.1
M
;
TfOH as a catalyst, the reaction was complete in only 2.5 h
dropwise addition time: 4 h; total reaction time: 5.5 h, vide infra; (Entry 9). However, the reaction of an alcohol having a Boc
Entry 4). Reduction of the amount of TriAT-tBu to 1.0 equiv. group (1j) under the same conditions resulted in 61 % yield of
decreased the yield to 85 % (Entry 5). Compared with the reac- tert-butyl ether, perhaps due to the deprotection of the Boc
[
4a,4b]
tion using isobutene (approximately 10 equiv.),
it can be group and the inevitable neutralization of TfOH by the resulting
said that the reaction using 1.6 equiv. of TriAT-tBu is efficient. amine (Entry 11). Addition of TriAT-tBu in one portion in the
Unlike benzylation using TriBOT and TriBOT-PM, ethereal sol- presence of a strong acid catalyst such as TfOH is effective for
vents (1,4-dioxane, DME, Et O) were not effective for the reac- the tert-butylation of acid-stable alcohols. No racemization oc-
2
tion (Entries 6–8). Since the tert-butyl cation was reported to curred during the reaction of 1k (Entry 12). The reaction of
[
9]
be more stable than the benzyl cation, we expected that the para-chlorophenol gave the corresponding tert-butyl ether in
reaction could be conducted under milder conditions. However, 59 % yield (Entry 13). Aliphatic and aromatic carboxylic acids
even 20 mol-% of other acids such as H SO , 10-camphor- 3a and 3b were also converted into the corresponding tert-
2
4
sulfonic acid (CSA), and LiClO afforded poor to moderate yields butyl esters 4a and 4b in moderate yields (Entries 14, 17) by
4
(
Entries 9–11). We used Sc(OTf) as a standard catalyst for fur- TriAT-tBu under the same conditions. In the case of carboxylic
3
[
8]
ther investigations, because it is a milder and easy-to-handle acids, the yields of the esters were increased when TriAT-tBu
reagent.
was added in one portion rather than dropwise, in the presence
of 40 mol-% of sulfuric acid (Entries 15, 18) or 5 mol-% of
Bi(OTf) (Entry 16).
3
Table 1. Screening of solvents and acid catalysts for the tert-butylation of
alcohol 1a.
Time-course analysis was performed to clarify the reaction
profile of the tert-butylation of 1a. The reaction was initiated
by the addition of Sc(OTf) to a CH Cl solution of 1a (0.1
M)
3
2
2
and TriAT-tBu (0.16 M) in an air-tight tube. Aliquots of the reac-
tion mixture were withdrawn at appropriate intervals and ana-
1
Yield [%][a]
lyzed by H NMR spectroscopy using p-nitrotoluene as an inter-
Entry
Solvent
Acid catalyst (mol-%)
TfOH (5)
Time [h]
[
10]
nal standard (Figure 2).
the amount of TriAT-tBu (triangles) decreased rapidly and com-
pletely disappeared within 30 min (Figure 2b, Table 3).
this time, the yield of 2a (squares) was 47 % based on 1a, and
.8 % based on the total number (4.8 equiv.) of tert-butyl
After the initiation of the reaction,
1
2
3
4
5
6
7
8
9
CH
2
CH
2
CH
2
CH
2
CH
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
3
3
12
5.5
4
24
24
24
36
36
63
95
93[
92
93
85
32
26
51
51
b]
Bi(OTf)
Sc(OTf)
Sc(OTf)
Sc(OTf)
3
(5)
(5)
[
11,12]
At
3
[
c]
3
(5)
[
d]
3
(5)
9
1,4-dioxane
DME
Sc(OTf)
Sc(OTf)
Sc(OTf)
3
3
3
(5)
(5)
(5)
groups. Other products formed were isobutene (dots) (54 %),
N-tert-butylisocyanuric acid (5) (29 %), which was probably gen-
erated by N-tert-butylation of TriAT-tBu (the yields in parenthe-
ses were calculated based on the number of tert-butyl
Et
2
O
Cl
Cl
Cl
CH
2
CH
2
CH
2
2
2
2
H
2
SO
CSA (20)
LiClO (20)
4
(20)
[
e]
[b]
1
1
0
1
12
59[
b]
4
[2]
groups). Almost all of the tert-butyl groups generated from
[
a] Isolated yields. [b] NMR yields using an internal standard. [c] Solution
of TriAT-tBu was added dropwise over 4 h (additional reaction time: 1.5 h).
d] Solution of TriAT-tBu (1.0 equiv.) was added dropwise over 3 h (additional
reaction time: 1 h). [e] TriAT-tBu (1.0 equiv.) was used.
TriAT-tBu (93 % based on 4.8 equiv. of tert-butyl groups) were
successfully monitored, despite the formation of the volatile iso-
butene. After complete decomposition of TriAT-tBu, the rate of
formation of 2a decreased sharply, and it took 10 h to reach
[
9
0 % yield of 2a (based on 1a) (Figure 2c). During this time, the
We explored the scope of this newly designed protocol for a isobutene concentration also gradually decreased. Other experi-
variety of alcohols and carboxylic acids to establish the general ments revealed that the tert-butylation of 1a using isobutene
synthetic applicability of this method (Table 2). The reaction of under similar conditions requires a longer time [Equation (1)],
3
-phenylpropanol (1b) gave the corresponding ether 2b in an while the reaction using 5 does not proceed at all [Equation (2)].
excellent yield (Entry 1). Secondary alcohols 1c and 1d afforded Thus, these results may indicate the reaction mechanism
the tert-butyl ethers 2c and 2d in 74 % and 67 % yields, respec- changed after TriAT-tBu had disappeared; during the first
tively (Entries 2, 3), although an excess amount of TriAT-tBu 30 min, the highly reactive tert-butyl cation species, which is
(
4 equiv.) was required. A tertiary alcohol was found to be inert rapidly liberated from TriAT-tBu, reacts with alcohol 1a to give
to tert-butylation (Entry 4). High yields were maintained when 2a in competition with elimination to form the stable iso-
base-labile functionalities such as bromoalkyl and acetoxy butene; however, once has TriAT-tBu disappeared, the cationic
groups are present in the alcohols (Entries 5, 6). The tert-butyldi- species needs to be regenerated from isobutene. Thus, it is rea-
phenylsilyl group (TBDPS) as a hydroxy protecting group was sonable to assume that suppression of the competing genera-
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Table 2. Scope and limitations of alcohols and carboxylic acids for tert-butylation.
[
a] Isolated yield. [b] Sc(OTf)
3 2 4
(10 mol-%) was used. [c] TfOH (5 mol-%) was used. [d] TriAT-tBu was added in one portion. [e] H SO (40 mol-%) was used as
an acid catalyst. [f] Bi(OTf)
3
(5 mol-%) was used.
tion of isobutene from TriAT-tBu would be effective for reducing
the reaction time. Recently, we showed that the nitrogen atom
of TriBOT exhibits basic character under strongly acidic condi-
[
13]
tions. Thus, in the present system, TriAT-tBu can act as a pro-
ton acceptor to promote the generation of isobutene from the
tert-butyl cation species (Figure 2a). Therefore, maintaining a
low concentration of TriAT-tBu using the dilution method would
be effective for shortening the reaction time. This consideration
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agrees with the fact (Table 1, Entries 3 and 4) that dropwise Conclusions
addition of TriAT-tBu solution shortened the reaction time as
We have developed a new tert-butylating reagent based on tri-
azine chemistry. The reactions of several alcohols and carboxylic
acids with TriAT-tBu in the presence of an acid catalyst pro-
ceeded to give the corresponding tert-butyl ethers and esters
in good yields. Time-course analysis of the reaction revealed
that the tert-butyl cation generated in situ from activated TriAT-
tBu is responsible for the rapid formation of the product.
compared with a one-portion addition.
Experimental Section
1
General: H NMR spectra were recorded with 400 MHz spectrome-
1
ters. Chemical shifts for H NMR are reported in parts per million
(δ) relative to tetramethylsilane as the internal standard. Coupling
constant (J) are reported in Hertz [Hz]. The following abbreviations
are used for spin multiplicities: s = singlet, d = doublet, t = triplet,
m = multiplet, br. = broad. 1 C NMR spectra were recorded with
3
1
00 MHz spectrometers. Chemical shifts for 13C NMR are reported
in parts per million (δ) relative to the solvent (CDCl : δ = 77.16;
3
[
(
D ]DMSO: δ = 39.52 ppm). Analytical thin layer chromatography
TLC) was performed using glass plates precoated with 0.25 mm
6
silica gel impregnated with a fluorescent indicator (254 nm). Flash
chromatography was performed using silica gel (spherical, neutral,
40–100 mesh). Chiral HPLC was performed using Daicel CHIRALPAK
IA-3. Reagents were of commercial grade and used without any
purification unless otherwise noted. High-purity, solvent-grade di-
chloromethane, THF and diethyl ether were purchased from com-
mercial sources. 1,4-Dioxane and 1,2-dimethoxyethane were pur-
chased from commercial sources and distilled from calcium hydride
before use.
General Procedure for the tert-Butylation of Alcohol 1 by Using
TriAT-tBu: To a solution of alcohol 1 (0.500 mmol) and Sc(OTf)3
(
0.025 mmol) in CH Cl (3.5 mL), a solution of TriAT-tBu (237.9 mg,
2 2
0
.800 mmol) in CH Cl (1.36 mL) was added dropwise at room tem-
2 2
perature over 4 h. After the dropwise addition was complete, the
residual TriAT-tBu in the test tube was rinsed with CH Cl (0.14 mL)
2
2
into the mixture over 1 min. The mixture was stirred for a total of
.5 h and washed with satd. aqueous NaHCO3 (60 mL), H O
5
2
(100 mL), and brine (40 mL). The organic layer was dried with
MgSO , filtered, and concentrated under reduced pressure. The resi-
due was purified by column chromatography (hexane/EtOAc) to af-
4
Figure 2. Reaction profile of the tert-butylation using TriAT-tBu.
ford 2.
2,4,6-Tris(tert-butoxy)-1,3,5-triazine (TriAT-tBu): To a suspension
of NaH (60 %, 11.20 g, 280 mmol) in THF (100 mL), tert-butyl alcohol
(26.6 mL, 280 mmol) in THF (50 mL) was added dropwise at 0 °C
over 30 min. Cyanuric chloride (14.75 g, 80.0 mmol) in THF (50 mL)
was added dropwise over 15 min. After stirring at 0 °C for an addi-
tional 10 min and at room temperature for 2 h, the mixture was
Table 3. Amount of tert-butyl derivatives at 30 min after initiation of the
reaction.
poured into H O and ice. The precipitate was filtered, and washed
2
with hexane (100 mL). The precipitate was recrystallized from
CH Cl to give 2,4,6-tris(tert-butoxy)-1,3,5-triazine (TriAT-tBu, 16.2 g,
2
2
68 %) as colorless crystals. The residue and hexane filtrate were
combined and recrystallized to give TriAT-tBu (3.1 g, 13 %). M.p.
1
13
1
70 °C (decomp.). H NMR (CDCl ): δ = 1.61 (s, 27 H) ppm. C NMR
3
(
CDCl ): δ = 172.0, 82.0, 28.5 ppm. C H N O (297.40): calcd. C
3 15 27 3 3
6
0.58, H 9.15, N 14.13; found C 60.42, H 9.34, N 14.03. HRMS
+
+
(DART ): calcd. for C H N O [M + H] 298.2131; found 298.2129.
15 28 3 3
IR (KBr): ν˜ = 3006, 2985, 2933, 1562, 1392, 1163, 1132, 850, 820,
–
1
4
99, 471 cm .
1
tert-Butyl Hexadecyl Ether (2a): H NMR (CDCl ): δ = 3.32 (t, J =
3
[
a] Yield based on 1a.
6.8 Hz, 2 H), 1.51 (m, 2 H), 1.37–1.25 (m, 26 H), 1.18 (s, 9 H), 0.88 (t,
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J = 7.3 Hz, 3 H) ppm. 13C NMR (CDCl ): δ = 72.5, 61.8, 32.1, 30.9,
tert-Butyl N-(6-tert-Butoxyhexyl)carbamate (2j): H NMR (CDCl ):
1
3
3
2
9.84, 29.83, 29.81, 29.80, 29.7, 29.5, 27.7, 26.4, 22.8, 14.3 ppm.
δ = 4.53 (br. s, 1 H), 3.32 (t, J = 6.4 Hz, 2 H), 3.16–3.01 (m, 2 H),
C H O (298.55): calcd. C 80.46, H 14.18; found C 80.06, H 14.54.
1.57–1.44 (m, 4 H), 1.44 (s, 9 H), 1.38–1.29 (m, 4 H), 1.18 (s, 9 H)
20 42
+
+
13
HRMS (DART ): calcd. for C H O [M + H] 299.3314; found
ppm. C NMR (CDCl ): δ = 156.1, 79.1, 72.5, 61.6, 40.7, 30.7, 30.1,
2
0
43
3
–
1
2
99.3299. IR (CHCl ): ν˜ = 2927, 2854, 1466, 1363, 1182, 1072 cm .
28.5, 27.7, 26.8, 26.1 ppm. C H NO (273.41): calcd. C 65.89, H
3
15 31
3
+
tert-Butyl 3-Phenylpropyl Ether (2b):[
14]
1
11.43, N 5.12; found C 65.55, H 11.58, N 5.10. HRMS (DART ): calcd.
H NMR (CDCl ): δ =
3
+
for C H NO [M + H] 274.2382; found 274.2396. IR (CHCl ): ν˜ =
15
32
3
3
7
(
.30–7.24 (m, 2 H), 7.23–7.14 (m, 3 H), 3.36 (t, J = 6.4 Hz, 2 H), 2.68
t, J = 7.9 Hz, 2 H), 1.90–1.80 (m, 2 H), 1.19 (s, 9 H) ppm. 1 C NMR
3
3456, 2981, 2937, 2860, 1707, 1508, 1365, 1255, 1171, 1074, 908,
–
1
7
91, 725, 669, 436 cm .
(
2
CDCl ): δ = 142.4, 128.6, 128.4, 125.8, 72.7, 60.9, 32.6, 32.3,
3
+
+
1
7.8 ppm. HRMS (DART ): calcd. for C H O [M + H] 193.1592;
Boc- -Ser(OtBu)OMe (2k): M.p. 41.0–41.6 °C. H NMR (CDCl ): δ =
L
1
3
21
3
found 193.1573. IR (CHCl ): ν˜ = 3041, 2981, 2935, 2871, 1603, 1363, 5.36 (br. d, 1 H), 4.39 (ddd, J = 3.0, 3.0, 9.2 Hz, 1 H), 3.80 (dd, J =
3
–1
1
074 cm .
tert-Butyl 1-Methyl-3-phenylpropyl Ether (2c):[15] 1H NMR
CDCl ): δ = 7.31–7.14 (m, 5 H), 3.68–3.58 (m, 1 H), 2.74–2.54 (m, 2
3.0, 9.2 Hz, 1 H), 3.74 (s, 3 H), 3.56 (dd, J = 3.0, 9.2 Hz, 1 H), 1.46 (s,
9 H), 1.13 (s, 9 H) ppm. 13C NMR (CDCl
): δ = 171.6, 155.8, 79.9, 73.4,
2.2, 54.4, 52.3, 28.4, 27.4 ppm. C H NO (275.34): calcd. C 56.71,
3
6
13
25
5
(
3
+
H 9.15, N 5.09; found C 56.73, H 9.32, N 5.05, HRMS (DART ): calcd.
H), 1.85–1.64 (m, 2 H), 1.19 (s, 9 H), 1.16 (d, J = 6.4 Hz, 3 H) ppm.
+
13
for C13
3
H26NO
5
[M + H] 276.1811; found 276.1808. IR (CHCl
3
): ν˜ =
C NMR (CDCl ): δ = 142.7, 128.45, 128.43, 125.8, 73.4, 67.1, 40.7,
3
444, 3041, 2981, 1749, 1709, 1506, 1367, 1350, 1298, 1165, 1101,
1070, 1045, 804, 727, 665, 457 cm .
3
2.6, 28.8, 23.2 ppm. C H O (206.33): calcd. C 81.50, H 10.75; found
14 22
–
1
+
+
C 81.14, H 11.03. HRMS (DART ): calcd. for C H O [M + H]
1
4 23
2
2
07.1749; found 207.1745. IR (CHCl ): ν˜ = 3037, 2987, 2966, 2933, tert-Butyl p-Chlorophenyl Ether (2l):[16] 1H NMR (CDCl ): δ = 7.25–
3
3
–
1
13
866, 1603, 1496, 1456, 1365, 1254, 1182, 1126, 815, 467 cm .
7.19 (m, 2 H), 6.95–6.88 (m, 2 H), 1.33 (s, 9 H) ppm. C NMR (CDCl ):
3
+
tert-Butyl Cyclododecyl Ether (2d):[5j] 1H NMR (CDCl ): δ = 3.66–
3
ppm. C NMR (CDCl ): δ = 73.2, 68.7, 32.1, 28.9, 24.7, 24.2, 23.41,
δ = 154.1, 129.0, 128.7, 125.6, 79.0, 28.9 ppm. HRMS (DART ): calcd.
3
+
for C H ClNO [M + NH ] 202.0999,; found 202.0990. IR (CHCl3):
10
17
4
.55 (m, 1 H), 1.65–1.51 (m, 2 H), 1.47–1.24 (m, 20 H), 1.19 (s, 9 H)
13
ν˜ = 2985, 1487, 1367, 1157, 1093, 1011, 926, 893, 850, 810, 787,
3
–1
+
+
733, 681, 538 cm .
2
2
1
3.39, 21.2 ppm. HRMS (DART ): calcd. for C H O [M + H]
16 33
41.2531; found 241.2539. IR (CHCl ): ν˜ = 3035, 2939, 2864, 1471, tert-Butyl 3-Phenylpropionate (4a):[14] 1H NMR (CDCl ): δ = 7.31–
3
3
–
1
363, 1255, 1184, 1012, 737, 702, 455 cm .
7.23 (m, 2 H), 7.23–7.15 (m, 3 H), 2.91 (t, J = 7.8 Hz, 2 H), 2.54 (t, J =
7.8 Hz, 2 H), 1.42 (s, 9 H) ppm. 13C NMR (CDCl
): δ = 172.4, 140.9,
1
3
1
2-Bromododecyl tert-Butyl Ether (2f): H NMR (CDCl ): δ = 3.41
3
+
1
28.51, 128.46, 126.2, 80.4, 37.2, 31.3, 28.2 ppm. HRMS (DART ):
(t, J = 6.9 Hz, 2 H), 3.32 (t, J = 6.9 Hz, 2 H), 1.90–1.80 (m, 2 H), 1.58–
+
.37 (m, 4 H), 1.37–1.22 (m, 14 H), 1.18 (s, 9 H) ppm. 1 C NMR
3
calcd. for C13
H22NO
2
[M + NH
4
]
224.1651; found 224.1632. IR
1
(
1
CHCl ): ν˜ = 3066, 2987, 2933, 2868, 1722, 1496, 1454, 1369, 1300,
3
(CDCl ): δ = 72.5, 61.8, 34.2, 33.0, 30.9, 29.74, 29.70, 29.67, 29.6, 28.9,
3
–
1
147, 953, 847, 739, 478 cm .
2
8.3, 27.7, 26.4 ppm. C H BrO (321.34): calcd. C 59.80, H 10.35;
16 33
+
tert-Butyl Benzoate (4b):[17] 1H NMR (CDCl ): δ = 8.02–7.97 (m, 2
found C 59.71, H 10.63. HRMS (DART ): calcd. for C H BrO [M +
1
6
34
3
+
13
H] 321.1793; found 321.1778. IR (CHCl ): ν˜ = 2985, 2929, 2856, H), 7.54–7.49 (m, 1 H), 7.44–7.39 (m, 2 H), 1.60 (s, 9 H) ppm.
C
3
1
4
466, 1392, 1363, 1234, 1186, 1074, 1018, 908, 870, 746, 561,
NMR (CDCl ): δ = 165.9, 132.5, 132.1, 129.5, 128.3, 81.1, 28.3 ppm.
3
–
1
+
+
53 cm .
HRMS (DART ): calcd. for C H O [M + H] 179.1072; found
11 15 2
0-Acetoxy-1-tert-butoxydecane (2g): 1H NMR (CDCl ): δ = 4.05
179.1069. IR (CHCl
3
): ν˜ = 2983, 1707, 1450, 1369, 1315, 1296, 1254,
–1
1
(
(
3
1167, 1120, 908, 849, 741, 463 cm .
t, J = 6.9 Hz, 2 H), 3.32 (t, J = 6.9 Hz, 2 H), 2.05 (s, 3 H), 1.67–1.45
1
3
1
m, 4 H), 1.38–1.24 (m, 12 H), 1.18 (s, 9 H) ppm. C NMR (CDCl3):
N-(tert-Butyl)isocyanuric Acid (5): M.p. 188 °C (decomp.). H NMR
δ = 171.4, 72.5, 64.8, 61.8, 30.8, 29.64, 29.58, 29.4, 28.7, 27.7, 26.4, (DMSO): δ = 11.10 (br. s, 2 H), 1.58 (s, 9 H) ppm. 13C NMR (DMSO):
2
7
2
1
6.0, 21.2 ppm. C H O (272.43): calcd. C 70.54, H 11.84; found C δ = 150.2, 148.4, 60.6, 29.5 ppm. C H N O (185.18): calcd. C 45.40,
16 32 3
7 11 3 3
+
+
+
0.33, H 11.94. HRMS (DART ): calcd. for C H O [M + H]
H 5.99, N 22.69; found C 45.36, H 5.85, N 22.55. HRMS (DART ):
1
6 33 3
+
73.2430; found 273.2447. IR (CHCl ): ν = 2931, 2856, 1728, 1465,
calcd. for C H N O [M + H] 186.0879; found 186.0855. IR (CHCl ):
3
˜
7
12
3
3
3
–
1
392, 1365, 1072, 800, 742, 679, 430 cm .
ν = 3219, 3093, 2987, 2945, 2854, 1755, 1714, 1684, 1460, 1396,
˜
–
1
1
1236, 1022, 812, 764, 719, 450 cm .
tert-Butyl 6-(tert-Butyldiphenylsilyloxy)hexyl Ether (2h): H NMR
CDCl ): δ = 7.70–7.64 (m, 4 H), 7.45–7.33 (m, 6 H), 3.65 (t, J = 6.4 Hz,
(
3
2
1
1
1
H), 3.31 (t, J = 6.9 Hz, 2 H), 1.62–1.45 (m, 4 H), 1.42–1.24 (m, 4 H),
1
3
.18 (s, 9 H), 1.04 (s, 9 H) ppm. C NMR (CDCl ): δ = 135.7, 134.3,
3
Acknowledgments
29.6, 127.7, 72.5, 64.1, 61.7, 32.7, 30.8, 27.7, 27.0, 26.2, 25.9,
9.4 ppm. C H O Si (412.69): calcd. C 75.67, H 9.77; found C 75.39, This work was partially supported by the Japan Society for the
26 40 2
+
+
H 9.99. HRMS (DART ): calcd. for C H O Si [M + H] 413.2876; Promotion of Science (JSPS KAKENHI) (grant number 25460012)
2
6 41 2
found 413.2899. IR (CHCl ): ν˜ = 3072, 2989, 2935, 2810, 1473, 1427,
3
and by the Adaptable and Seamless Technology Transfer Pro-
gram through Target-driven R&D (A-STEP AS242Z03610M) from
–
1
1
363, 1109, 1005, 823, 615, 505 cm .
Benzyl N-(6-tert-Butoxyhexyl)carbamate (2i): 1H NMR (CDCl3): the Japan Science and Technology Agency.
δ = 7.38–7.28 (m, 5 H), 5.09 (s, 2 H), 4.73 (br. s, 1 H), 3.31 (t, J =
6
.6 Hz, 2 H), 3.24–3.11 (m, 2 H), 1.58–1.43 (m, 4 H), 1.40–1.28 (m, 4
Keywords: Alkylation · tert-Butylation · Carbocations ·
Triazines
1
3
H), 1.18 (s, 9 H) ppm. C NMR (CDCl ): δ = 156.5, 136.8, 128.6,
1
3
28.3, 128.2, 72.6, 66.7, 61.6, 41.2, 30.7, 30.1, 27.7, 26.8, 26.1 ppm.
C H NO (307.43): calcd. C 70.32, H 9.51, N 4.56; found C 70.27, H
1
8
29
3
+
+
9
.80, N 4.52. HRMS (DART ): calcd. for C H NO [M + H] 308.2226;
18 30 3
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K. Yamada, S. Yoshida, H. Fujita, M. Kitamura, M. Kunishima, Eur. J. Org.
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found 308.2248. IR (CHCl ): ν˜ = 3452, 3006, 2937, 2862, 1716, 1516,
3
–
1
1
363, 1257, 1186, 1136, 1076, 924, 800, 661, 445 cm .
Eur. J. Org. Chem. 0000, 0–0
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
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Published Online: ■
Eur. J. Org. Chem. 0000, 0–0
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Full Paper
tert-Butylating Reagent
K. Yamada, N. Hayakawa, H. Fujita,
M. Kitamura, M. Kunishima* .......... 1–7
Development of a Triazine-Based
tert-Butylating Reagent, TriAT-tBu
A new tert-butylating reagent, 2,4,6- various alcohols and carboxylic acid
tris(tert-butoxy)-1,3,5-triazine
(TriAT- with TriAT-tBu in the presence of a cat-
tBu) has been developed for the acid- alytic amount of an acid provided the
catalyzed tert-butylation of alcohols corresponding tert-butyl ethers and
and carboxylic acids. The reaction of esters in good yields.
DOI: 10.1002/ejoc.201600663
Eur. J. Org. Chem. 0000, 0–0
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim