TiCl4-activated selective nucleophilic substitutions of tert-butyl alcohol and benzyl alcohols with π-donating substituents

Article abstract of DOI:10.1016/j.tet.2010.06.046

TiCl₄-activated selective nucleophilic substitution reactions of tert-butyl alcohol and benzyl alcohols with π-donating substituents in the presence of primary and secondary alcohols can be carried out with various oxygen, nitrogen and carbon nucleophiles in good yields.

Full text of DOI:10.1016/j.tet.2010.06.046

Tetrahedron 66 (2010) 6869e6872
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
TiCl4-activated selective nucleophilic substitutions of tert-butyl alcohol
and benzyl alcohols with
p-donating substituents
,
Chen-Yu Tsai a, Robert Sung b, Bo-Ren Zhuang a, Kuangsen Sung a
*
a Department of Chemistry, National Cheng Kung University, No. 1, University Rd., Tainan, Taiwan, ROC
b Faculty of Science, University of British Columbia, 1505-6270 University Boulevard, Vancouver, Canada BC V6T 1Z4
a r t i c l e i n f o
a b s t r a c t
Article history:
TiCl4-activated selective nucleophilic substitution reactions of tert-butyl alcohol and benzyl alcohols with
Received 2 February 2010
Received in revised form 6 June 2010
Accepted 21 June 2010
p
-donating substituents in the presence of primary and secondary alcohols can be carried out with
various oxygen, nitrogen and carbon nucleophiles in good yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 25 June 2010
Keywords:
Ti(IV)
Lewis acid
Alcohol
1. Introduction
resonance by the lone pair of electrons of oxygen at the other ether
linkage.3 This activation results in more electrophilic acetal carbon,
which is susceptible to various nucleophiles.
Ti(IV) as a Lewis acid facilitates a variety of reactions by acti-
vating various functional groups, such as aldehydes,1 carboxylates,2
acetals,3 sulfonates,4 epoxides,5 and so on. Ti(IV) in the activation of
aldehydes, carboxylates, or sulfonates significantly polarizes car-
There was some research that reported Lewis-acid-activated
nucleophilic substitutions of alcohols.6 However, to our knowledge,
it was rare that Ti(IV) was used as a Lewis acid in activation of
alcohols for their nucleophilic substitutions. It was reported that
benzylic, allylic, or tertiary alcohols react smoothly with an excess
of HN3 in the presence of 0.5 equiv of TiCl4, while primary alcohols
appear to be inert in the same condition.7 To our knowledge, so far,
no other literature has applied this method involving Ti(IV)-
activated nucleophilic substitution of alcohols to organic synthesis.
It implies that some more information is needed about this method.
For example, whether or not other nucleophiles like oxygen, carbon
and nitrogen nucleophiles work well with this method? Also, what
type of alcohol structures may facilitate their Ti(IV)-activated
nucleophilic substitutions? It is likely that these data will enhance
usage rate of this method.
A hydroxyl group of alcohol is not a good-leaving group, so in
order for an alcohol to carry out nucleophilic substitution, one
needs to convert a hydroxyl group to a good-leaving group. There
are several ways to do that. Some of them do that in situ, followed
by nucleophilic substitution in the same pot. For example, alcohols
are treated with HBr, HI, SOCl2, PBr3, PCl5, CCl4/PPh3, or H2SO4 to get
the corresponding alkyl halides or ethers.8a This way involves
a one-pot reaction, but products from this way are usually limited
to alkyl halides and ethers. Some other ways involve isolable
intermediates that have their hydroxyl groups converted to good-
leaving groups, and subsequent nucleophilic substitution of the
bonyl or sulfonyl
p bond, resulting in more electrophilic carbonyl
carbon or sulfonyl sulfur, which is susceptible to various nucleo-
philes.1,2,4 The activation of an epoxide by Ti(IV) releases its angle
strain by partially breaking epoxide CeO bond, forming a partially
positive charge on the more substituted carbon of the epoxide.5 As
shown in Scheme 1, Ti(IV) in the activation of an acetal facilitates
the partial breakage of acetal CeO bond, developing a partially
positive charge on acetal carbon, which is stabilized through
R'
R'
R
R
H
H
(VI)Ti
(VI)Ti
O
O
O
O
OH
O
R
SiMe
Scheme 1.
* Corresponding author. Tel.: þ886 6 2757575x65338; e-mail address: kssung@
mail.ncku.edu.tw (K. Sung).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.046

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C.-Y. Tsai et al. / Tetrahedron 66 (2010) 6869e6872
intermediates is usually carried out in another pot.8a For example,
alcohols are converted to isolable sulfonates, followed by reacting
with various kinds of nucleophiles. The advantage of this way is
that isolable sulfonates may react with a variety of nucleophiles to
generate various types of products, but this way usually involves
two pots. In this paper, we tried to explore (1) if TiCl4 can activate
alcohols in situ for further nucleophilic substitution with various
kinds of nucleophiles, (2) what types of alcohols may facilitate this
TiCl4-activated nucleophilic substitution reaction, and (3) if TiCl4
can selectively activate some types of alcohols for their nucleophilic
substitution reactions in the presence of other types of alcohols.
substitution product 6b was obtained in 82% yield. The yield was
significantly improved by -donating p-methoxy substituent.
p
When reacting with 2 equiv of CH3OH in the presence of 0.3 equiv
of TiCl4 in CDCl3 under a reflux condition for 2 days, benzyl alcohol
5g with o-methoxy substituent also generated the substitution
product 6g in a good yield. Different types of amines, including
a primary amine, secondary amine and aniline, were used as nu-
cleophiles for nucleophilic substitution reactions of benzyl alcohol
5b with p-methoxy substituent in the presence of 0.1 equiv of TiCl4
in CDCl3 under a reflux condition for 1 or 1.5 days. The nucleophilic
substitutions worked very well and the products 6cee were
obtained in good yields.
2. Results and discussion
X
OH
+ HX
R
R
TiCl4
We first explored if TiCl4 is able to activate primary, secondary,
or tertiary alcohols in situ for their nucleophilic substitution
reactions with a primary alcohol as a nucleophile. As shown in
Table 1, the primary alcohol 1 was treated with 0.2 equiv of TiCl4 in
CDCl3 under a reflux condition for 4 days, but no reaction occurred.
This is consistent with the literature7 that has HN3 as a nucleophile.
We also found that no reaction occurred when the secondary
alcohol 2 was treated with 2 equiv of the primary alcohol 1 in the
presence of 0.2 equiv of TiCl4 in CDCl3 under a reflux condition for 4
days. However, reaction of the tertiary alcohol 3 with 2 equiv of the
primary alcohol 1 in the presence of 0.2 equiv of TiCl4 in CDCl3
under a reflux condition for 2 days generated the nucleophilic
substitution product 4 in a good yield. This is consistent with the
literature7 in which HN3 serves as a nucleophile. It indicates that
TiCl4 activates a tertiary alcohol for nucleophilic substitution pos-
sibly through a tertiary carbon cation. It is likely that TiCl4 may
activate other alcohols, forming less unstable carbon cations, for
nucleophilic substitution. Hence, we tested how well TiCl4 activates
substituted benzyl alcohols for nucleophilic substitution with
oxygen, nitrogen or carbon nucleophiles.
6a~n
5a, 5b, 5g, 5h
5a, 6a : R = H, X = CH3O;
5b, 6b : R = p-CH3O, X = CH3O;
5b, 6d : R = p-CH3O, X = Et2N;
5b, 6c : R = p-CH3O, X = n-BuNH;
5b, 6e : R = p-CH3O, X = PhNH;
5g, 6g : R = o-CH3O, X = CH3O;
5h, 6i : R = p-Me2N, X = n-BuNH;
5h, 6k: R = p-Me2N, X = PhNH;
5b, 6f : R = p-CH3O, X = [CH3C(O)]2CH
5h, 6h : R = p-Me2N, X = CH3O;
5h, 6j : R = p-Me2N, X = Et2N;
5h, 6l: R = p-Me2N, X = [CH3C(O)]2CH;
5b, 6m: R = p-CH3O, X = p-HOC6H4; 5h, 6n: R = p-Me2N, X = p-HOC6H4;
Scheme 2.
We were thinking to make a new CeC bond by this method with
a carbon nucleophile. The carbon nucleophile we tried for the nu-
cleophilic substitution was a
b
-diketone. When benzyl alcohol 5b
-diketone in
with p-methoxy substituent reacted with 2 equiv of a
b
the presence of 0.1 equiv of TiCl4 in CDCl3 under a reflux condition
for 2 days, the nucleophilic substitution product 6f was obtained in
a good yield. The pKa of
qualified base in the reaction system, so its conjugate base may not
b
-diketone is ca. 98a but we did not add any
Table 1
TiCl4-activated nucleophilic substitutions of alcohols produceda via Scheme 2
Substrate
Nucleophile (HX)
TiCl4
Rxn time
Product
Yield (%)
Ph(CH2)3OH (1)
(CH3)2CHOH (2)
t-BuOH (3)
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
CH3OH
CH3OH
n-BuNH2
Et2NH
PhNH2
[CH3C(O)]2CH2
CH3OH
CH3OH
n-BuNH2
Et2NH
0.2 equiv
0.2 equiv
0.2 equiv
0.3 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.3 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
0.1 equiv
4 days
4 days
2 days
3 days
9 h
1.5 days
1.5 days
1 days
2 days
2 days
1.5 days
1.5 days
1.5 days
1 days
2 days
1 days
1 days
No rxn
No rxn
t-BuO(CH2)3Ph (4)
d
d
73
20
82
69
71
75
58
50
72
61
63
62
48
65
60
5a
5b
5b
5b
5b
5b
5g
5h
5h
5h
5h
5h
5b
5h
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
PhNH2
[CH3C(O)]2CH2
PhOH
PhOH
a
The reaction was conducted at a reflux condition in CDCl3.
As shown in Scheme 2 and Table 1, the reaction of benzyl alcohol
5a with 2 equiv of CH3OH in the presence of 0.3 equiv of TiCl4 in
CDCl3 under a reflux condition for 3 days generated the nucleo-
philic substitution product 6a with 20% conversion, and what left
was the unreacted benzyl alcohol. The same reaction condition was
applied toTiCl4-activated nucleophilic substitution of p-nitrobenzyl
alcohol with 2 equiv of CH3OH, but no reaction occurred. Con-
versely, when benzyl alcohol 5b with p-methoxy substituent
reacted with 2 equiv of CH3OH in the presence of 0.1 equiv of TiCl4
in CDCl3 under a reflux condition for 9 h, the nucleophilic
be the nucleophile that makes the reaction work. The
b
-diketone
follows tautomerization equilibrium and 80% of the equilibrium
mixture is thermodynamically more stable enol tautomer. It is
likely that the enol tautomer serves as a nucleophile for the
nucleophilic substitution reaction.
The p-N,N-dimethylamino substituent is a stronger p-donating
group than p-methoxy substituent.8a Like TiCl4-activated nucleo-
philic substitution of benzyl alcohol 5b with p-methoxy sub-
stituent, benzyl alcohol 5h with p-N,N-dimethylamino substituent
was able to be activated by TiCl4 for the next nucleophilic

C.-Y. Tsai et al. / Tetrahedron 66 (2010) 6869e6872
6871
ꢀ
substitution reactions with oxygen nucleophile (methanol), nitro-
gen nucleophiles (primary amine, secondary amine, and aniline),
4 A molecular sieves is proposed in Scheme 3. At first, TiCl4 would
do ligand-exchange reaction with 5b, making hydroxyl group of 5b
be activated by TiCl4. According to the literature,8b only some but
not all chloro ligands would be exchanged with alcohols in the
absence of a base. In addition, because TiCl4 activated a tertiary
alcohol 3 for the nucleophilic substitution and generated 4, it
suggests that the reaction went through a carbon cation. Hence, the
TiCl4-activated 5b might be dissociated into a transient of benzyl
cation, which would be stabilized by p-methoxy group. The
nucleophile that had the most concentration in the reaction system
would be methanol, and it would react with benzyl cation to form
the product 6b.
and carbon nucleophile (b-diketone). The nucleophilic substitution
products 6hel were obtained in good yields with newly formed
CeO, CeN, and CeC bonds.
When benzyl alcohol 5b with p-methoxy substituent or benzyl
alcohol 5h with p-N,N-dimethylamino substituent reacted with
2 equiv of phenol in the presence of 0.1 equiv of TiCl4 in CDCl3
under a reflux condition for 1 day, the substitution product 6m or
6n was obtained in a good yield. Actually, we planed to use phenol
as an oxygen nucleophile in the Ti(IV)-activated nucleophilic sub-
stitution, but a new CeC bond was formed between benzyl carbon
and C-4 of phenol. It indicates that electrophilic substitution occurs
at the para-position of phenol with TiCl4-activated benzyl alcohols
as electrophiles. We tried to use toluene to replace phenol for the
electrophilic substitution reaction with 5b in the presence of
0.1 equiv of TiCl4 in CDCl3 under a reflux condition for 1 day, but
toluene did not react at all because the activator of p-methyl is not
as strong as p-hydroxy. The reaction route of electrophilic sub-
stitution was also found when aniline was used as a nucleophile,
but it was much slower than the nucleophilic substitution with
aniline as a nitrogen nucleophile.
OH
OTiCl3
TiCl4
..
MeO
+ HCl
MeO
5b
6b
MeO
OCH3
..
For the above TiCl4-activated nucleophilic substitution reactions
CH3OH
MeO
of tert-butyl alcohol and benzyl alcohols with
p-donating sub-
stituents, the increasing amount of TiCl4 shortened the reaction
time of the nucleophilic substitution reactions and increased the
yields. The minimum amount of TiCl4 for the TiCl4-activated nu-
cleophilic substitutions of tert-butyl alcohol and benzyl alcohols
MeO
with p-donating substituents was around 0.1 equiv Residual water
in the solvent slowed down the nucleophilic substitution reactions
and decreased the yields, so molecular sieves were usually used in
the reactions.
To test TiCl4-activated selective nucleophilic substitutions of
alcohols, we mixed primary or secondary alcohol with tert-butanol
Scheme 3.
Other Lewis acids like SnCl4 and FeCl3 were used to replace TiCl4
in the TiCl4-activated nucleophilic substitution reaction of benzyl
alcohol 5b with methanol in CDCl3 with activated 4 A molecular
sieves at room temperature or a reflux condition. No substitution
product 6b was formed at all. These experimental results confirm
that TiCl4 as a Lewis acid is a good choice for the selective nucle-
ophilic substitutions of tert-butanol and benzyl alcohols with
ꢀ
or benzyl alcohol with
p-donating substituent, and treated the
mixture with excess of various oxygen, nitrogen or carbon nucle-
ophile in the presence of 0.1e0.3 equiv of TiCl4 in CDCl3 under
a reflux condition for 1e2 days. Selective nucleophilic substitution
of t-butanol or benzyl alcohol with
p-donating substituent was
p
-donating substituents.
performed in a good yield. The results were similar to those shown
in Table 1.
To figure out which one activates benzyl alcohol in the TiCl4-
activated nucleophilic substitution reactions of benzyl alcohols
3. Conclusion
In conclusion, TiCl4 may selectively activate tert-butanol and
benzyl alcohols with p-donating substituents for their nucleophilic
substitution reactions with various oxygen, nitrogen, and carbon
nucleophiles in the presence of primary and secondary alcohols.
with
p-donating substituents, TiCl4 or HCl, we compared two
reactions, which were run at the same condition. In the first re-
action, we treated 5b (1 mmol) with CH3OH (2 mmol) and TiCl4
ꢀ
(0. 1 mmol) in CDCl3 with activated 4 A molecular sieves. In the first
hour at room temperature, the reaction produced 6b (5%) and
p-methoxybenzyl chloride (12%). After 9 h at a reflux condition, the
reaction generated 6b (82%) and p-methoxybenzyl chloride (10%).
In the second reaction, we treated 5b (1 mmol) with CH3OH
4. Experimental section
4.1. General procedure for TiCl4-activated nucleophilic
substitutions of alcohols
ꢀ
(2 mmol) and concd HCl (0.4 mmol) in CDCl3 with activated 4 A
ꢀ
molecular sieves. For this reaction, we used activated 4 A molecular
ꢀ
sieves to remove water in the reaction system. In the first hour at
room temperature, the reaction produced 6b (4%) and p-methoxy-
benzyl chloride (14%). After 9 h at a reflux condition, the reaction
generated 6b (52%) and p-methoxybenzyl chloride (48%). Because
more p-methoxybenzyl chloride was generated in the second
reaction than in the first reaction, it strongly suggests that TiCl4 is
the major species in activating benzyl alcohol in the TiCl4-activated
nucleophilic substitution reactions of benzyl alcohols with
To an alcohol (1 mmol) and 4 A molecular sieves (0.5 g) in CHCl3
(2 mL) at room temperature was added TiCl4 (0.1e0.3 mmol, 10% in
CHCl3). The mixture was stirred at room temperature for 1 min. A
suitable nucleophile (2 mmol) was added into the mixture, fol-
lowed by stirring at a reflux condition for 1e3 days. The product
was purified by column chromatography with silica gel as sta-
tionary phase and hexane/EtOAc as mobile phase.
According to the procedure, the following products were
obtained with the yields shown in Table 1. The products are known
and their characterization by 1H and 13C NMR spectroscopic data.
p-donating substituents. However, HCl that was generated from
ligand-exchange of TiCl4 with alcohols also activates alcohols for
further nucleophilic substitutions.
The mechanism for the TiCl4-activated nucleophilic substitution
reaction of benzyl alcohol 5b with methanol in CDCl3 with activated
4.1.1. 1-(3-Phenylpropyl)-1-(1,1-dimethylethyl) ether (4)9. 1H NMR
(300 MHz, CDCl3):
d
7.21e7.33 (m, 5H), 3.40 (t, J¼6.5 Hz, 2H), 2.73 (t,

6872
C.-Y. Tsai et al. / Tetrahedron 66 (2010) 6869e6872
J¼7.6 Hz, 2H), 1.90 (m, 2H), 1.23 (s, 9H); 13C NMR (75 MHz, CDCl3):
3.97 (t, J¼7.5 Hz, 0.6H), 3.55 (s, 0.8H), 3.06 (d, J¼7.5 Hz, 1.2H), 2.91
(s, 6H), 2.09 (s, 6H); 13C NMR (75 MHz, CDCl3):
204.2, 191.9, 149.4,
d
142.2, 128.4, 128.1, 125.6, 72.4, 60.6, 32.4, 32.1, 27.5.
d
149.3, 129.2, 128.0, 127.4, 125.5, 113.0, 112.9, 108.8, 70.4, 40.8, 40.6,
33.5, 31.8, 29.7, 23.2.
4.1.2. Benzyl methyl ether (6a)10
d
.
1H NMR (300 MHz, CDCl3):
7.30e7.39 (m, 5H), 4.41 (s, 2H), 3.34 (s, 3H); 13C NMR (75 MHz,
CDCl3):
d
138.0, 128.0, 127.3, 127.2, 74.2, 57.6.
4.1.14. 4-(4-Methoxybenzyl)phenol (6m)17 1H NMR (300 MHz,
.
CDCl3):
d 6.24e7.10 (m, 8H), 4.78 (b, OH), 3.85 (s, 2H), 3.79
4.1.3. 4-Methoxybenzyl methyl ether (6b)11. 1H NMR (300 MHz,
(s, 3H); 13C NMR (75 MHz, CDCl3):
129.9, 129.7, 115.2, 113.8, 55.3, 40.1.
d 157.9, 153.7, 133.8, 133.7,
CDCl3):
d
7.27 (d, J¼8.5 Hz, 2H), 6.90 (d, J¼8.5 Hz, 2H), 4.40 (s, 2H),
3.80 (s, 3H), 3.37 (s, 3H); 13C NMR (75 MHz, CDCl3):
129.21, 113.63, 74.19, 57.61, 55.06.
d 159.1, 130.16,
4.1.15. 4-(4-N,N-Dimethylaminobenzyl)phenol (6n)17 1H NMR (300
.
MHz, CDCl3):
d 6.67e7.14 (m, 8H), 4.74 (b, OH), 3.90 (s, 2H), 2.91
4.1.4. N-(4-Methoxybenzyl)butan-1-amine (6c)12
.
1H NMR (300 MHz,
(s, 6H); 13C NMR (75 MHz, CDCl3):
120.8, 115.9, 113.2, 40.7, 35.8.
d 154.1, 145.1, 130.8, 129.3, 127.7,
CDCl3):
d
7.23 (d, J¼8.6 Hz, 2H), 6.86 (d, J¼8.6 Hz, 2H), 3.79 (s, 3H),
3.74 (s, 2H), 2.64 (t, J¼7 Hz, 2H), 1.5 (m, 2H), 1.35 (m, 2H), 0.9
(t, J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 158.7, 131.7, 129.5,
Acknowledgements
113.8, 55.2, 53.2, 48.8, 31.8, 20.4, 13.9.
4.1.5. N-Ethyl-N-(4-methoxybenzyl)ethanamine (6d)12
.
1H NMR
Financial support from National Science Council of Taiwan (NSC
98-2113-M-006-001-MY3) is gratefully acknowledged.
(300 MHz, CDCl3):
d
7.23 (d, J¼8.6 Hz, 2H), 6.84 (d, J¼8.6 Hz,
2H), 3.80 (s, 3H), 3.51 (s, 2H), 2.50 (q, J¼7.2 Hz, 4H), 1.04
(t, J¼7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3):
d 158.5, 131.6, 130.1,
Supplementary data
113.5, 56.7, 55.2, 46.4, 11.6.
4.1.6. N-(4-Methoxybenzyl)aniline (6e)13
d
.
1H NMR (300 MHz, CDCl3):
6.62e7.31(m,9H),4.25(s,2H),3.80(s, 3H);13CNMR(75 MHz,CDCl3):
158.9, 148.2, 131.4, 129.2, 128.8, 117.5, 114.0, 112.8, 55.3, 47.8.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.06.046.
d
References and notes
4.1.7. 3-(4-Methoxybenzyl)pentane-2,4-dione (6f)14 (keto and enol
forms). 1H NMR (300 MHz, CDCl3):
6.79e7.07 (m, 4H), 3.96 (t,
J¼7.5 Hz, 0.6H), 3.77 (s, 3H), 3.58 (s, 0.8H), 3.09 (d, J¼7.5 Hz, 1.2H),
2.08 (s, 6H); 13C NMR (75 MHz, CDCl3):
203.8, 191.9, 158.4, 158.1,
131.6, 129.9, 129.6, 128.3, 114.1, 114.0, 108.6, 70.2, 55.3, 55.2, 33.5,
32.0, 29.7, 23.2.
d
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d
4.1.8. 2-Methoxybenzyl methyl ether (6)15 1H NMR (300 MHz,
.
CDCl3):
d 6.90e7.42 (m, 4H), 4.52 (s, 2H), 3.84 (s, 3H), 3.43 (s, 3H);
13C NMR (75 MHz, CDCl3):
69.5, 58.3, 55.3.
d 157.2, 129.1, 128.7, 126.4, 120.3, 110.2,
4.1.9. 4-N,N-Dimethylaminobenzyl methyl ether (6h)16
(300 MHz, CDCl3):
7.21 (d, J¼8.3 Hz, 2H), 6.71 (d, J¼8.3 Hz, 2H),
4.36 (s, 2H), 3.34 (s, 3H), 2.94 (s, 6H); 13C NMR (75 MHz, CDCl3):
150.3, 129.3, 125.9, 112.4, 74.6, 57.5, 40.6.
.
1H NMR
d
d
4.1.10. 4-((Butylamino)methyl)-N,N-dimethylaniline (6i)12
.
1H NMR
(300 MHz, CDCl3):
d
7.26 (d, J¼8.7 Hz, 2H), 6.64 (d, J¼8.7 Hz, 2H),
7. Hassner, A.; Fibiger, R.; Andisik, D. J. Org. Chem. 1984, 49, 4237e4244.
8. (a) Smith, M. B.; March, J. March’s Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure, 5th ed.; John-Wiley: New York, NY, 2001; (b) King,
R. B. Encyclopedia of Inorganic Chemistry; John-Wiley: New York, NY, 1994; Vol.
8; p 4203.
9. Kopecky, D. J.; Rychnovsky, S. D. J. Org. Chem. 2000, 65, 191.
10. Imrie, C.; Modro, T. A.; Rohwer, E. R.; Wagener, C. C. P. J. Org. Chem. 1993, 58,
5643e5649.
11. Rathore, R.; Kochi, J. K. J. Org. Chem. 1995, 60, 7479e7490.
12. Brooke, G. M.; Mohammed, S. J. Chem. Soc., Perkin Trans. 1 1997, 3371e3379.
13. Fujita, K. I.; Enoki, Y. Tetrahedron 2008, 64, 1943e1954.
14. (a) Christoffers, J. Synth. Commun. 1999, 29, 117e122; (b) Sakai, T.; Miyata, K.;
Tsuboi, S.; Utaka, M. Bull. Chem. Soc. Jpn. 1989, 62, 4072e4074.
15. (a) Heravi, M. M.; Ahari, N. Z.; Ahari, N. Z.; Oskooie, H. A.; Ghassemzadeh,
M. Phosphorus, Sulfur, and Silicon and the Related Elements 2005, 180,
3.94 (s, 2H), 2.89 (s, 6H), 2.83 (t, J¼7.9 Hz, 2H), 1.62 (m, 2H), 1.30 (m,
2H), 0.86 (t, J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 150.7, 130.8,
118.6, 112.3, 51.2, 46.3, 40.2, 28.3, 19.9, 13.5.
4.1.11. 4-((Diethylamino)methyl)-N,N-dimethylaniline
(6j)12 1H
.
NMR (300 MHz, CDCl3):
d
7.18 (d, J¼8.3 Hz, 2H), 6.69 (d, J¼8.3 Hz, 2H),
3.55(s, 2H), 2.93 (s, 6H), 2.56 (q, J¼7.1 Hz, 4H),1.07 (t, J¼7.1 Hz, 6H); 13C
NMR (75 MHz, CDCl3): d 149.8,130.1,129.6,112.4, 56.5, 46.2, 40.7,11.3.
4.1.12. N,N-Dimethyl-4-((phenylamino)methyl)-aniline (6k)13. 1H NMR
(300 MHz, CDCl3):
d 6.64e6.75 (m, 7H), 7.04e7.08 (m, 2H),
1701e1712; (b) Wan, P.; Chak, B. J. Chem. Soc., Perkin Trans.
2 1986,
4.21 (s, 2H), 2.95 (s, 6H); 13C NMR (75 MHz, CDCl3):
129.4, 128.7, 127.0, 117.3, 113.0, 112.8, 47.9, 40.9.
d 150.0, 148.4,
1751e1756.
16. Smith, J. R. L.; Linford, J. M.; McKeer, L. C.; Morris, P. M. J. Chem. Soc., Perkin Trans.
2 1984, 1099e1105.
17. Torii, S.; Tanaka, H.; Taniguchi, M.; Kameyama, Y.; Sasaoka, M.; Shiroi, T.;
Kikuchi, R.; Kawahara, I.; Shimabayashi, A.; Nagao, S. J. Org. Chem. 1991, 56,
3633e3637.
4.1.13. 3-(4-(Dimethylamino)benzyl)pentane-2,4-dione (6l)14 (keto
and enol forms). 1H NMR (300 MHz, CDCl3):
6.64e7.04 (m, 4H),
d