Detritylation of N-tritylamines via a naphthalene-catalyzed lithiation process

Article abstract of DOI:10.1055/s-2004-822358

The reaction of aliphatic and aromatic secondary and tertiary N-tritylamines 1 with lithium powder and a catalytic amount of naphthalene led to reductive detritylation, affording the corresponding amines 2 in good to excellent yields. The trityl group could selectively be removed in the presence of an allyl or a benzyl group. The detritylation process could successfully be extended to several hydroxy, alkoxy and amino functionalized N-tritylamines. The chemoselectivity between the trityl-nitrogen and the trityl-oxygen bond cleavages was also studied. This methodology represents an efficient deprotection of N-tritylamines under nonacidic reaction conditions.

Full text of DOI:10.1055/s-2004-822358

1274
PAPER
Detritylation of N-Tritylamines via a Naphthalene-Catalyzed Lithiation
Process
Detritylation of
N
h
-Tritylamine
e
s
rif Behloul, David Guijarro, Miguel Yus*
Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo. 99,
03080 Alicante, Spain
Fax +34(96)5903549; E-mail: yus@ua.es
Received 23 February 2004
Dedicated to the memory of Prof. Roberto Fernández de Calella
lithium exchange or by ring opening of heterocycles.13
Abstract: The reaction of aliphatic and aromatic secondary and ter-
Using this lithiation methodology, we have been able to
tiary N-tritylamines 1 with lithium powder and a catalytic amount
achieve the reductive cleavage of carbon–nitrogen bonds
of naphthalene led to reductive detritylation, affording the corre-
sponding amines 2 in good to excellent yields. The trityl group
in different substrates.14 We have recently described the
could selectively be removed in the presence of an allyl or a benzyl reductive detritylation of trityl ethers by a naphthalene
catalyzed lithiation process.15 In this paper, we report the
group. The detritylation process could successfully be extended to
several hydroxy, alkoxy and amino functionalized N-tritylamines.
The chemoselectivity between the trityl–nitrogen and the trityl–ox-
of the trityl group in several N-tritylamines, which leads
ygen bond cleavages was also studied. This methodology represents
an efficient deprotection of N-tritylamines under nonacidic reaction
conditions.
application of this lithiation methodology to the removal
to the corresponding deprotected amines under mild reac-
tion conditions.
According to our previous experience in the reductive
cleavage of trityl ethers,15 we first tried to perform the
detrytilation of dioctyl(trityl)amine (1a) (Table 1, entry 1)
at –78 °C. When a solution of 1a in THF was added to a
green suspension of an excess of lithium powder and a
catalytic amount of naphthalene (1:0.2 molar ratio) in the
same solvent at –78 °C, the reaction mixture took a red
color, which could be indicative of the formation of the
trityl radical16 and/or the trityl anion.17 When the reaction
was complete (TLC monitoring), the hydrolysis with wa-
ter at the same temperature gave a mixture of dioctyl-
amine and triphenylmethane (Equation 1, Table 1, entry
1). The formation of the latter could be explained by pro-
tonation of the generated triphenylmethyllithium in the fi-
nal hydrolysis step. The yield of dioctylamine was 61%,
according to a quantitative GC analysis. In order to find
the optimum reaction conditions, we performed the reac-
tion at different temperatures (–78, –30 and 0 °C, Table 1,
entries 1–3). The highest yield (90%) of dioctylamine was
obtained at 0 °C (Table 1, entry 3). 4,4¢-Di-tert-butylbi-
phenyl (DTBB) was also tried as an electron carrier, but
the yield of dioctylamine was lower than in the naphtha-
lene catalyzed detritylation reaction under the same con-
ditions (compare entries 3 and 4 in Table 1).
Key words: tritylamine, lithium, lithiation, detritylation, reductive
cleavage
The trityl (triphenylmethyl) group has been used to pro-
tect a variety of amines,1 especially amino acids in the
synthesis of peptides2 and cephalosporins.3 The role of the
trityl group is to create steric hindrance around the nitro-
gen atom, which reduces the nucleophilicity of the latter.
Due to this steric hindrance, the tritylation of the amino
functionality of a-amino esters prevents epimerization at
the adjacent asymmetric carbon atom and protects the es-
ter from hydrolysis.1 This protecting group can easily be
removed by acid hydrolysis,1c but the undesired elimina-
tion of tritylamine has been observed in some cases.4 Al-
ternative detritylation procedures are palladium catalyzed
hydrogenolysis,1c reduction with sodium in liquid ammo-
nia,1c treatment with mercury salts and sodium boro-
hydride5 and reductive cleavage using triethylsilane6 or
low-valent titanium reagents.7 Recently, a one-pot reduc-
tive transformation of N-trityl amines into the correspond-
ing tert-butylcarbamates using polymethylhydrosiloxane
under palladium catalysis has been reported.8
In the last few years, we have been using an arene-cata-
lyzed lithiation9,10 to prepare organolithium compounds
under very mild reaction conditions. The use of an excess
of lithium powder and a catalytic amount of an arene
[mainly naphthalene or 4,4¢-di-tert-butylbiphenyl (DT-
BB)] allowed us to generate simple organolithium com-
pounds starting from nonhalogenated materials,11 and
functionalized organolithium compounds12 by chlorine–
Equation 1
Several other tertiary N-tritylamines 1b–e were subjected
to the above-mentioned detritylation process under the
optimum reaction conditions (naphthalene-catalyzed
lithiation at 0 °C) and the results are indicated in Table 1
SYNTHESIS 2004, No. 8, pp 1274–1280
Advanced online publication: 04.05.2004
DOI: 10.1055/s-2004-822358; Art ID: Z03504SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
4

PAPER
Detritylation of N-Tritylamines
1275
(entries 5–8). Cyclic amine 1b gave the expected detrity- by reaction with lithium.14 The naphthalene-catalyzed
lation product in 91% yield (Table 1, entry 5). The aro- lithiation of substrates 1d and 1e afforded the correspond-
matic amine 1c gave a 94% yield of N-methylaniline ing detritylated amines 2d and 2e in 62 and 84% yield, re-
(Table 1, entry 6). The trityl group could be chemoselec- spectively (Table 1, entries 7 and 8).
tively removed in the presence of an allyl or a benzyl
group, which are also prone to undergo reductive cleavage
Table 1 Reductive Detrytilation of N-Tritylamines 1 by a Naphthalene-Catalyzed Lithiation Process
Entry
1
Substrate
Temp (°C)
–78
Time (h)
4.0
Product
Yield (%)a
61
H
N
7
7
2a
1a
1a
2
3
4
5
–30
0
2.0
3.5
2.0
1.0
2a
2a
2a
84
1a
1a
90 (86%)b
0
79c
91
0
Tr
NH
N
Ph
Ph
2b
1b
6
7
0
0
1.0
6.0
94
62
Tr
Tr
NH
N
2c
1c
N
NH
1d
2d
2e
8
0
1.0
84
N
N
H
Tr
1e
1f
9d
0
0
2.0
1.0
78 (37%)e
NH2
H
N
7
Tr
7
2f
10d
87
H
NH2
N
Tr
2g
1g
11f
12
0
0
4.5
2.0
41
90
OH
OH
N
N
H
Tr
2h
1h
MeO
MeO
Tr
NH
N
MeO
MeO
2i
1i
13f
0
4.0
80
H
N
H
N
Tr
OH
Tr
OTr
5
5
2j
1j
Synthesis 2004, No. 8, 1274–1280 © Thieme Stuttgart · New York

1276
C. Behloul et al.
PAPER
Table 1 Reductive Detrytilation of N-Tritylamines 1 by a Naphthalene-Catalyzed Lithiation Process (continued)
Entry
14
Substrate
Temp (°C)
–78
Time (h)
2.5
Product
Yield (%)a
92g
N
N
Tr
OTr
Tr
OH
5
5
1k
2k
15f
0
4.5
87g
Tr
H
N
N
NH
Tr
NH
Tr
2l
1l
a Yield determined by quantitative GC, using commercially available amine 2 and n-dodecane (internal standard) in the determination of re-
sponse factors.
b Isolated yield after column chromatography (basic aluminum oxide, hexane–EtOAc) based on the starting material 1a is given in parentheses.
c DTBB was used as electron carrier instead of naphthalene.
d Compounds 1f and 1g were deprotonated with n-BuLi and treated with TMSCl before performing the naphthalene-catalyzed lithiation step.
e Isolated yield after acid-base extraction is given in parentheses.
f Compounds 1h, 1j and 1l were deprotonated with n-BuLi before performing the naphthalene-catalyzed lithiation step.
g Isolated yield after column chromatography (basic aluminum oxide, hexane–EtOAc) based on the starting material 1.
Interestingly, our methodology could also be applied to On the other hand, deprotonation with n-butyllithium ef-
the deprotection of N-tritylated primary amines by a slight fectively protected the nitrogen atom from detritylation.
modification of the general procedure. These substrates The lithiation of the lithium amide derived from 1j at 0 °C
possess a proton acidic enough to decompose the naphtha- selectively gave the N-tritylated amino alcohol 2j in 80%
lene radical-anion and/or dianion involved in our lithia- yield (Table 1, entry 13 and footnote f).
tion reaction. As expected, the lithium amides derived
The selectivity of the reductive cleavage of a ditritylated
from amines 1f and 1g (Table 1, entries 9 and 10; gener-
diamine, 1l (Table 1, entry 15), was also studied. Com-
ated by reaction of the amines with n-butyllithium) did not
pound 1l holds two different amino groups, one of them
react in the lithiation step, the starting tritylated amines
being secondary and the other one tertiary. According to
the result obtained in the lithiation of amino alcohol 1j, we
thought that deprotonation of 1l with n-butyllithium
being recovered unchanged after hydrolysis. However,
when amines 1f and 1g were deprotonated with n-butyl-
lithium and treated with trimethylsilyl chloride before
would prevent removal or the trityl group from the sec-
submitting them to the naphthalene-catalyzed lithiation
ondary amino moiety. As expected, the lithiation of the
step, the expected primary amines 2f and 2g were ob-
lithium amide derived from 1l led, after hydrolysis, to
monodetritylated diamine 2l as the only reaction product
in 87% yield (Table 1, entry 15 and footnote f).
tained after hydrolysis in 78 and 87% yields, respectively
(Table 1, entries 9 and 10 and footnote d). The silyl group
on nitrogen was also removed during the workup.
In all cases, triphenylmethane was obtained (>90%) as a
The detritylation procedure could successfully be extend-
by-product, resulting from hydrolysis of the triphenylme-
ed to several hydroxy, alkoxy and amino functionalized
thyllithium generated during the process, but it could eas-
N-tritylamines (Table 1, entries 11–15). N-Tritylated ami-
ily be separated from the desired detritylation products by
column chromatography.
no alcohol 1h was previously treated with n-butyllithium
in order to remove the acidic proton of the hydroxy group.
The lithiation of the generated lithium alkoxide gave the
expected deprotected amino alcohol 2h in moderate yield
(Table 1, entry 11 and footnote f). Complete detritylation
of amino alkoxide 1i was achieved after 2 h, affording
The starting N-tritylamines 1 were prepared by reaction of
the corresponding amines with trityl chloride in the pres-
ence of triethylamine and a catalytic amount of 4-(dime-
thylamino)pyridine.
secondary amine 2i in 90% yield (Table 1, entry 12).
In summary, in this paper we have presented a very effi-
cient method for the removal of the trityl group in N-trityl-
amines via a naphthalene-catalyzed lithiation process.
The methodology has proved to be useful for the depro-
tection of N-tritylated primary and secondary amines, in-
cluding allylic, benzylic and functionalized substrates.
Chemoselectivity of O-trityl versus N-trityl bond cleav-
age has been observed. Removal of the trityl group from
a tertiary amine was selectively achieved in the presence
of a N-trityl secondary amino moiety. This method repre-
sents a good alternative to the commonly used detrityla-
Since we have recently achieved the naphthalene-cata-
lyzed reductive cleavage of trityl ethers,15 we decided to
investigate the chemoselectivity of the detritylation pro-
cess in molecules having both a N-trityl and an O-trityl
group. Thus, compound 1k was submitted to the naphtha-
lene-catalyzed lithiation reaction at –78 °C (Table 1, entry
14). As expected, product 2k, resulting from the reductive
cleavage of the trityl ether, was selectively obtained in
92% yield. The product of monodetritylation of the nitro-
gen atom was not detected in the crude reaction mixture.
Synthesis 2004, No. 8, 1274–1280 © Thieme Stuttgart · New York

PAPER
Detritylation of N-Tritylamines
1277
13C NMR: d = 14.1 (2 C, 2 CH3), 22.65 (2 C), 27.9 (2 C), 29.25 (2
C), 29.55 (2 C), 30.5 (2 C), 31.8 (2 C) [2 Me(CH2)6], 53.45 (2 C, 2
CH2N), 79.1 (CN), 125.7 (3 C), 127.3 (6 C), 129.4 (6 C), 144.45 (3
C, ArC).
MS (DIP): m/z (%) = 483 (M+, <1), 294 (14), 288 (11), 254 (12),
244 (86), 243 (100), 228 (12), 211 (17), 166 (12), 165 (85), 105
(20).
tion procedures for amines, which use acidic reaction
conditions.
FT-IR spectra were obtained on a Nicolet Impact 400D spectropho-
tometer using NaCl plates (for oils) or KBr pellets (for solid com-
pounds). NMR spectra were recorded on a Bruker AC-300 (300
MHz for 1H and 75 MHz for 13C) using CDCl3 as solvent and TMS
1
(0.00 ppm, H) and CDCl3 (77.0 ppm, 13C) as internal standards;
HRMS: m/z calcd for C35H49N, 483.3865; found, 483.3867.
chemical shifts are given in d (ppm) and coupling constants (J) in
Hz. 13C NMR assignments were made on the basis of DEPT exper-
iments. Mass spectra (EI) were obtained at 70 eV on a Shimadzu
QP-5000 spectrometer, giving fragment ions in m/z with relative in-
tensities (%) in parentheses. High-resolution mass spectra and ele-
mental analysis were performed by the Technical Services at the
University of Alicante. TLC was carried out on Schleicher &
Schuell F1400/LS 254 plates coated with a 0.2 mm layer of silica
gel; detection was done by UV254 light and staining with phospho-
molybdic acid (5 g of phosphomolybdic acid in 120 mL of absolute
EtOH); Rf values are given under these conditions. Column chro-
matography was performed using silica gel 60 (35–70 mesh) or ba-
sic aluminum oxide (50–160 mm particle size). When mentioned,
deactivated silica gel means that it was treated with 5% Et3N in hex-
ane and the column was eluted with the same solvent mixture until
the coming eluent was basic according to pH paper. All reagents
used for the synthesis of N-tritylamines 1, naphthalene and trimeth-
ylsilyl chloride were commercially available (Acros, Aldrich) and
were used without further purification. Li powder was prepared ac-
cording to the procedure described in Ref.18 Commercially avail-
able n-BuLi was titrated with a 1 M solution of sec-butyl alcohol in
xylene using 1,10-phenanthroline as indicator.19 Commercially
available anhyd THF (99.9%, H2O content £ 0.006%, Acros) was
used as solvent in all the lithiation reactions.
4-Benzyl-N-tritylpiperidine (1b)20
White solid; yield: 86%; mp 194 °C; Rf 0.20 (hexane).
IR (KBr): 3080, 3057, 3023, 1595, 1491 (HC=C), 1216 cm–1 (CN).
1H NMR: d = 1.15–1.83 (m, 7 H, 2 CHHN, 2 CH2CN and CHCH2),
2.55 (d, 2 H, CH2Ph), 2.91–3.16 (m, 2 H, 2 CHHN), 6.96–7.58 (m,
20 H, ArH).
13C NMR: d = 33.0 (2 C, 2 CH2CN), 38.5 (CHCH2), 43.5 (CH2Ph),
48.55 (2 C, 2 CH2N), 77.35 (CN), 125.35, 125.75 (3 C), 127.3 (6 C),
128.05 (2 C), 129.0 (6 C), 129.25 (2 C), 140.4, 140.85 (3 C, ArC).
MS (DIP): m/z (%) = 419 (M+ + 2, <1), 418 (M+ + 1, 1), 417 (M+,
4), 340 (11), 244 (50), 243 (100), 165 (59), 91 (11).
N-Methyl-N-tritylaniline (1c)
White solid; yield: 77%; mp 95 °C; Rf 0.47 (hexane–EtOAc, 9:1).
IR (KBr): 3085, 3051, 3031, 1594, 1498 (HC=C), 1194 cm–1 (CN).
1H NMR: d = 3.05 (s, 3 H, CH3), 6.55–6.77, 6.88–7.01, 7.08–7.33,
7.36–7.51 (4 m, 3 H, 2 H, 9 H and 6 H, respectively, ArH).
13C NMR: d = 40.95 (CH3), 77.35 (CN), 117.95, 120.2 (2 C), 126.4
(3 C), 127.7 (8 C), 130.5 (6 C), 144.05 (3 C), 149.9 (ArC).
MS (DIP): m/z (%) = 349 (M+, <1), 244 (43), 243 (100), 228 (13),
166 (12), 165 (85).
N-Tritylamines 1a–j, 1l, 2j and 2l; General Procedure
HRMS: m/z calcd for C26H23N, 349.1830; found, 349.1826.
A solution of the corresponding amine 2 (10.0 mmol) in CH2Cl2 (5
mL) was added to a solution of trityl chloride (3.1 g, 11.0 mmol),
Et3N (2.5 mL, 17.6 mmol) and 4-(dimethylamino)pyridine (92 mg,
0.4 mmol) in CH2Cl2 (10 mL) at r.t. and the mixture was stirred
overnight. The reaction was then quenched with H2O (5 mL) and
extracted with EtOAc (3 × 15 mL) and the combined organic phases
were washed with brine (5 mL) and dried (Na2SO4). After evapora-
tion of the solvents (15 Torr), the resulting residue was purified by
column chromatography (deactivated silica gel, hexane–EtOAc) af-
fording the expected tritylamines 1. For the preparation of the dou-
ble tritylated compound 1j, the amounts of all the reagents and
solvent used were doubled, except for the starting amino alcohol
6-aminohexanol, from which 10.0 mmol was utilized. The synthesis
of compound 1l was performed in a two-step sequence: after stirring
overnight the mixture of reagents in the proportions indicated
above, the same amounts of trityl chloride, Et3N and 4-(dimethyl-
amino)pyridine were added and the reaction was stirred overnight
again. Monotritylated amino alcohol 2j and diamine 2l were ob-
tained as by-products in the reactions performed to synthesize ditri-
tylated compounds 1j and 1l, respectively, and they could be
separated from the latter by column chromatography [deactivated
silica gel, hexane–EtOAc (for 2j) and basic aluminum oxide, hex-
ane–EtOAc (for 2l)]. The corresponding physical, spectroscopic
and analytical data for tritylamines 1a–1j, 1l, 2j and 2l follow.
N,N-Diallyltritylamine (1d)
White solid; yield: 86%; mp 93° C; Rf 0.28 (hexane).
IR (KBr): 3079, 3055, 3029, 3017, 1635, 1603, 1594, 1487
(HC=C), 1212 cm–1 (CN).
1H NMR: d = 3.05 (d, 4 H, J = 6.1 Hz, 2 CH2N), 4.87–5.05 (m, 4 H,
2 CH2=C), 5.78–5.99 (m, 2 H, 2 CH=CH2), 7.07–7.34, 7.45–7.63 (2
m, 9 H and 6 H, respectively, ArH).
13C NMR: d = 56.2 (2 C, 2 CH2N], 78.55 (CN), 115.25 (2 C, 2
CH2=C), 125.95 (3 C), 127.5 (6 C), 129.3 (6 C), 143.85 (3 C, ArC),
138.65 (2 C, 2 CH=CH2).
MS (DIP): m/z (%) = 340 (M+ + 1, <1), 339 (M+, 1), 244 (45), 243
(100), 228 (10), 166 (10), 165 (71).
HRMS: m/z calcd for C25H25N, 339.1987; found, 339.1973.
Anal. Calcd for C25H25N: C, 88.45; H, 7.42; N, 4.13. Found: C,
88.16; H, 7.42; N, 4.45.
N-Benzyl-N-methyltritylamine (1e)
White solid; yield: 90%; mp 106–107 °C; Rf 0.14 (hexane).
IR (KBr): 3082, 3052, 1594, 1487 (HC = C), 1199 cm–1 (CN).
1H NMR: d = 1.96 (s, 3 H, CH3), 3.40 (s, 2 H, CH2), 7.07–7.42,
7.47–7.68 (2 m, 12 H and 8 H, respectively, ArH).
13C NMR: d = 37.15 (CH3), 56.45 (CH2), 77.6 (CN), 126.0 (3 C),
126.55, 127.5 (6 C), 128.0 (2 C), 128.35 (2 C), 129.4 (6 C), 140.15
(3 C), 142.9 (ArC).
N,N-Dioctyltritylamine (1a)
Colorless oil; yield: 85%; Rf 0.24 (hexane).
IR (neat): 3084, 3057, 3031, 1595, 1488 (HC=C), 1211 cm–1 (CN).
1H NMR: d = 0.87 (t, 6 H, J = 6.8 Hz, 2 CH3), 1.04–1.38, 1.39–1.58
[2 m, 20 H and 4 H, respectively, 2 Me(CH2)6], 2.27 (t, 4 H, J = 7.8
Hz, 2 CH2N), 7.07–7.35, 7.38–7.56 (2 m, 9 H and 6 H, respectively,
ArH).
MS (DIP): m/z (%) = 363 (M+, 1), 244 (59), 243 (100), 166 (12),
165 (87), 91 (30).
HRMS: m/z calcd for C27H25N, 363.1987; found, 363.1972.
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1278
C. Behloul et al.
PAPER
N-Octyltritylamine (1f)21
White solid; yield: 86%; mp 93 °C; Rf 0.88 (hexane).
1H NMR: d = 1.07–1.71 [m, 9 H, (CH2)4CO and NH], 1.97–2.17 (m,
2 H, CH2N), 3.00 (t, 2 H, J = 6.5 Hz, CH2O), 7.10–7.33, 7.36–7.56
(2 m, 18 H and 12 H, respectively, ArH).
13C NMR: d = 26.2, 27.15, 29.95, 30.95 [(CH2)4CO], 43.45 (CH2N),
63.45 (CH2O), 70.8 (CN), 86.2 (CO), 126.1 (3 C), 126.75 (3 C),
127.65 (6 C), 127.7 (6 C), 128.65 (12 C), 144.45 (3 C), 146.3 (3 C,
ArC).
IR (KBr): 3332 (NH), 3082, 3057, 3029, 1596, 1489 (HC=C), 1209
cm–1 (CN).
1H NMR: d = 0.87 (t, 3 H, J = 6.7 Hz, CH3), 1.11–1.36, 1.39–1.66
[2 m, 10 H and 3 H, respectively, Me(CH2)6 and NH], 2.11 (t,
J = 6.8 Hz, CH2N), 7.11–7.36, 7.40–7.57 (2 m, 9 H and 6 H, respec-
tively, ArH).
MS (DIP): m/z (%) = 601 (M+, <1), 358 (10), 258 (34), 244 (50),
243 (100), 165 (46).
13C NMR: d = 14.1 (CH3), 22.65, 27.35, 29.25, 29.6, 30.85, 31.85
[Me(CH2)6], 43.55 (CH2N), 70.85 (CN), 126.1 (3 C), 127.7 (6 C),
128.65 (6 C), 146.35 (3 C, ArC).
HRMS: m/z calcd for C44H43NO, 601.3345; found, 601.3317.
Anal. Calcd for C44H43NO: C, 87.81; H, 7.20; N, 2.33. Found: C,
87.64; H, 7.39; N, 2.84.
MS: m/z (%) = 371 (M+, <1), 294 (18), 244 (19), 243 (69), 242 (22),
241 (25), 239 (16), 166 (18), 165 (100).
N-Propyl-N,N¢-ditritylethane-1,2-diamine (1l)
White solid; yield: 63%; mp 125 °C; Rf 0.30 (hexane–EtOAc, 9:1).
N-Cyclooctyltritylamine (1g)20
White solid; yield: 97%; mp 55 °C; Rf 0.23 (hexane).
IR (KBr): 3333 (NH), 3082, 3052, 3017, 1594, 1489 (HC=C), 1207
cm–1 (CN).
1H NMR: d = 0.44 (t, 3 H, J = 7.2 Hz, CH3), 0.96–1.13 (m, 2 H,
CH2Me), 1.78 (br s, 1 H, NH), 1.95–2.10 (m, 2 H, CH2CH2Me),
2.30 (t, 2 H, J = 7.0 Hz, CH2CH2NH), 2.42–2.58 (m, 2 H, CH2NH),
7.08–7.36, 7.39–7.61 (2 m, 18 H and 12 H, respectively, ArH).
IR (KBr): 3319 (NH), 3087, 3052, 3016, 1594, 1488 (HC=C), 1210
cm–1 (CN).
1H NMR: d = 1.05–1.65 [m, 15 H, (CH2)7 and NH], 2.46–2.62 (m,
1 H, CHN), 7.05–7.35, 7.49–7.65 (2 m, 9 H and 6 H, respectively,
ArH).
13C NMR: d = 24.2 (2 C), 26.05, 27.05 (2 C), 34.65 (2 C) [(CH2)7],
52.2 (CHN), 71.6 (CN), 126.0 (3 C), 127.6 (6 C), 128.85 (6 C),
147.35 (3 C, ArC).
13C NMR: d = 11.9 (CH3), 23.4 (CH2Me), 43.65, 53.95, 55.65 (3
CH2N), 70.85 (CNH), 78.85 (CN), 125.8 (3 C), 126.15 (3 C),
127.35 (6 C), 127.75 (6 C), 128.6 (6 C), 129.4 (6 C), 144.1 (3 C),
146.15 (3 C, ArC).
MS (DIP): m/z (%) = 343 (M+ – 243, <1), 292 (18), 244 (24), 243
(100), 183 (20), 182 (51), 167 (26), 165 (43), 127 (14), 105 (12),
104 (13), 97 (13), 88 (23), 85 (18), 83 (14), 77 (11), 71 (24), 70 (12),
69 (16), 57 (40), 55 (20), 43 (25), 41 (14).
MS: m/z (%) = 369 (M+, <1), 244 (21), 243 (100), 165 (52).
2-(N-Ethyltritylamino)ethanol (1h)
White solid; yield: 60%; mp 82 °C; Rf 0.08 (hexane–EtOAc, 9:1).
IR (KBr): 3477 (OH), 3083, 3058, 3028, 1594, 1487 (HC=C), 1209
(CN), 1064 cm–1 (CO).
HRMS: m/z calcd for C43H42N2, 586.3348; found, 586.3367.
1H NMR: d = 1.09 (t, 3 H, J = 7.2 Hz, CH3), 2.41 (q, 2 H, J = 7.2
Hz, MeCH2N), 2.56 (t, 2 H, J = 6.6 Hz, CH2CH2N), 2.90 (br s, 1 H,
OH), 3.78 (t, 2 H, J = 6.6 Hz, CH2O), 7.09–7.37, 7.45–7.58 (2 m, 9
H and 6 H, respectively, ArH).
13C NMR: d = 15.8 (CH3), 47.5 (CH2Me), 54.6 (CH2CO), 61.9
(CO), 78.85 (CN), 126.0 (3 C), 127.5 (6 C), 129.3 (6 C), 143.75 (3
C, ArC).
6-Tritylamino-1-hexanol (2j)22
White solid; yield: 70%; mp 85 °C; Rf 0.45 (hexane–EtOAc, 9:1).
IR (KBr): 3292 (OH and NH), 3081, 3058, 3029, 1594, 1489
(HC=C), 1213 (CN), 1080 cm–1 (CO).
1H NMR: d = 1.18–1.63 [m, 9 H, (CH2)4CO and OH], 1.99–2.21 (m,
2 H, CH2N), 3.54–3.69 (m, 2 H, CH2O), 7.13–7.37, 7.40–7.58 (2
m, 9 H and 6 H, respectively, ArH).
13C NMR: d = 25.7, 27.1, 30.8, 32.65 [(CH2)4CO], 43.45 (CH2N),
62.9 (CH2O), 70.8 (CN), 126.1 (3 C), 127.7 (6 C), 128.6 (6 C),
146.25 (3 C, ArC).
MS (DIP): m/z (%) = 331 (M+, <1), 244 (32), 243 (100), 165 (51).
HRMS: m/z calcd for C23H25NO, 331.1936; found, 331.1897.
N,N-Bis(2-methoxyethyl)tritylamine (1i)
White solid; yield: 37%; mp 100 °C; Rf 0.30 (hexane–EtOAc, 4:1).
MS (DIP): m/z (%) = 360 (M+ + 1, <1), 359 (M+, 2), 283 (19), 282
(89), 258 (28), 244 (23), 243 (100), 165 (35).
IR (KBr): 3085, 3051, 3032, 1594, 1498 (HC=C), 1195 (CN), 1035
cm–1 (CO).
1H NMR: d = 2.53 (t, 4 H, J = 7.2 Hz, 2 CH2N), 3.29 (s, 6 H, 2
CH3), 3.53 (t, 4 H, J = 7.2 Hz, 2 CH2O), 7.07–7.35, 7.42–7.59 (2 m,
9 H and 6 H, respectively, ArH).
13C NMR: d = 52.9 (2 C, 2 CH2N), 58.75 (2 C, 2 CH3), 72.65 (2 C,
2 CH2O), 78.65 (CN), 126.0 (3 C), 127.5 (6 C), 129.3 (6 C), 143.65
(3 C, ArC).
N-Propyl-N¢-tritylethane-1,2-diamine (2l)
Colorless oil; yield: 25%; Rf = 0.45 (hexane–EtOAc, 4:1).
IR (KBr): 3311 (NH), 3083, 3057, 3029, 1596, 1489 (HC=C), 1209
cm–1 (CN).
1H NMR: d = 0.90 (t, 3 H, J = 7.8 Hz, CH3), 1.39–1.58 (m, 2 H,
CH2Me), 1.78 (br s, 2 H, 2 NH), 2.28, 2.72 (2 t, 2 H each, J = 6.0
Hz each, NCH2CH2N), 2.49 (t, 2 H, J = 7.3 Hz, CH2CH2Me), 7.10–
7.35, 7.42–7.60 (2 m, 9 H and 6 H, respectively, ArH).
13C NMR: d = 11.75 (CH3), 23.15 (CH2Me), 43.05, 50.1, 51.6 (3
CH2N), 70.7 (CN), 126.2 (3 C), 127.75 (6 C), 128.65 (6 C), 146.1
(3 C, ArC).
MS (DIP): m/z (%) = 375 (M+, <1), 244 (63), 243 (100), 228 (12),
166 (12), 165 (85).
HRMS: m/z calcd for C25H29NO2, 375.2198; found, 375.2219.
N-(6-Trityloxyhexyl)tritylamine (1j)
White solid; yield: 70%; mp 138 °C; Rf 0.11 (hexane).
MS (DIP): m/z (%) = 344 (M+, <1), 258 (34), 244 (50), 243 (100),
165 (46).
IR (KBr): 3440 (NH), 3084, 3057, 3018, 1596, 1488 (HC=C), 1210
(CN), 1065 cm–1 (CO).
HRMS: m/z calcd for C24H28N2, 344.2252; found, 344.2282.
Synthesis 2004, No. 8, 1274–1280 © Thieme Stuttgart · New York

PAPER
Detritylation of N-Tritylamines
1279
N-Methyl-N-(6-trityloxyhexyl)tritylamine (1k)
13C NMR: d = 25.85, 27.2, 28.25, 32.7 [(CH2)4CO], 37.1 (CH3),
52.5 (CH2N), 63.0 (CO), 77.95 (CN), 125.75 (3 C), 127.3 (6 C),
127.9 (6 C), 144.45 (3 C, ArC).
MS (DIP): m/z (%) = 373 (M+, <1), 258 (13), 257 (59), 244 (21),
243 (100), 165 (31).
n-BuLi (1.6 mL of a 1.6 M solution of n-BuLi in hexane, 2.5 mmol)
was added dropwise to a solution of tritylamine 1j (898 mg, 2.5
mmol) in THF (10 mL) at 0 °C. After 10 min, MeI (0.16 mL, 2.5
mmol) was added at 0 °C and the reaction mixture was stirred for 12
h at r.t. The reaction was then quenched with H2O (5 mL) and ex-
tracted with EtOAc (3 × 15 mL). The combined organic phases were
washed with brine (5 mL) and dried (Na2SO4). After evaporation of
the solvents (15 Torr), the resulting residue was purified by column
chromatography (basic aluminum oxide, hexane–EtOAc) to afford
the expected compound 1k in 58% yield; colorless oil; yield: 58%;
Rf 0.61 (hexane–EtOAc, 9:1).
HRMS: m/z calcd for C26H31NO, 373.2406; found, 373.2408.
Reductive Cleavage of Tritylated Primary Amines 1f and 1g by
a Naphthalene-Catalyzed Lithiation; Octylamine (2f); Typical
Procedure
To a solution of 1f (186 mg, 0.5 mmol) in THF (2 mL), under Ar at
0 ºC, was added dropwise n-BuLi until a red color developed in the
reaction mixture (0.45 mL of a 1.6 M solution of n-BuLi in hexane,
0.7 mmol). After stirring for 10 min, Me3SiCl was added until the
red color vanished (0.15 mL, 1.2 mmol). The mixture was stirred for
10 min and then transferred dropwise via syringe to a green suspen-
sion of Li powder (50 mg, 7.2 mmol) and naphthalene (26 mg, 0.2
mmol) in THF (5 mL), under Ar at 0 ºC. The mixture turned to a
dark red color. After stirring at the same temperature for the time in-
dicated in Table 1, H2O (5 mL) was carefully added, the cooling
bath was removed and the mixture was stirred until it reached r.t.
The mixture was acidified with 2 M HCl (5 mL) and extracted with
CH2Cl2 (3 × 15 mL). The combined organic phases were discarded.
The aqueous phase was basified with 2 M NaOH (5 mL) and ex-
tracted with CH2Cl2 (3 × 15 mL). The combined organic phases
were dried (Na2SO4). Evaporation of the solvents afforded a 37%
yield of pure octylamine 2f. Cyclooctylamine was prepared from
the trityl derivative 2g in the same way.
IR (neat): 3084, 3057, 3031, 1596, 1489 (HC = C), 1216 (CN),
1079 cm–1 (CO).
1H NMR: d = 1.05–1.67 [m, 8 H, (CH2)4CO], 1.88–2.13 (m, 5 H,
CH2N and CH3), 3.01 (t, 2 H, J = 6.4 Hz, CH2O), 7.05–7.34, 7.36–
7.55 (2 m, 18 H and 12 H, respectively, ArH).
13C NMR: d = 26.3, 27.3, 28.2, 30.0 [(CH2)4CO], 37.1 (Me), 52.5
(CH2N), 63.5 (CH2O), 76.15 (CN), 86.2 (CO), 125.7 (3 C), 126.75
(3 C), 127.65 (6 C), 127.85 (6 C), 127.9 (6 C), 128.65 (6 C), 144.45
(3 C), 146.8 (3 C, ArC).
MS (DIP): m/z (%) = 615 (M+, <1), 258 (14), 257 (66), 244 (20),
243 (100), 165 (26), 44 (13).
HRMS: m/z calcd for C45H45NO, 615.3501; found, 615.3497.
Reductive Cleavage of Tritylamines 1a–e and 1h–l via Naphtha-
lene-Catalyzed Lithiation; Dioctylamine (2a); Typical Proce-
dure
For the reactions whose yields were determined by quantitative GC
(see Table 1, entries 9 and 10), they were hydrolyzed with MeOH
(5 mL) instead of H2O. Commercially available amines 2f and 2g,
and n-dodecane (internal standard) were used in the determination
of response factors. Compounds 2f and 2g (commercially available)
were characterized by comparison of their physical and spectro-
scopic data with authentic samples.
A solution of tritylamine 1a (1.0 mmol) in THF (2 mL) was added
dropwise to a green suspension of Li powder (70 mg, 10.0 mmol)
and naphthalene (26 mg, 0.2 mmol) in THF (5 mL), under Ar at 0
ºC. The reaction mixture turned to a dark red color after the addition
of a few drops of the solution of 1a. After stirring at the same tem-
perature for the time indicated in Table 1, H2O (5 mL) was carefully
added, the cooling bath was removed and the reaction mixture was
stirred till it reached r.t. The mixture was extracted with EtOAc (3
× 15 mL) and the combined organic phases were washed with brine
(5 mL), and then dried (Na2SO4). After evaporation of the solvents
(15 Torr), the resulting residue was purified by column chromatog-
raphy (basic aluminum oxide, hexane–EtOAc) to give dioctylamine
(2a) in 86% yield.
Acknowledgment
This work was financially supported by the DGES from the Spanish
Ministerio de Educación, Cultura y Deporte (MECD) (project no.
BQU2001-0538). C. B. thanks the Department of Organic Chemi-
stry of the University of Alicante for a fellowship.
Compounds 1h, 1j and 1l were deprotonated with n-BuLi (0.69 mL
of a 1.6 M solution in hexane, 1.1 mmol) at 0 °C before submitting
them to the reductive cleavage step.
References
All reactions whose yields were determined by quantitative GC (see
Table 1) were hydrolyzed with MeOH (5 mL) instead of H2O. Com-
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us, see above), and n-dodecane (internal standard) were used in the
determination of response factors. Compounds 2a–e, 2h and 2i
(commercially available) and 2j and 2l (prepared by us, see above)
were characterized by comparison of their physical and spectro-
scopic data with authentic samples. The corresponding physical,
spectroscopic and analytical data for compound 2k follow.
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C. Behloul et al.
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Synthesis 2004, No. 8, 1274–1280 © Thieme Stuttgart · New York