Efficient synthesis of Bis(4-Dimethaminophenyl)arylmethanes and Bis(4-Diamethaminophenyl)alkanes using iodine reagent

Article abstract of DOI:10.1080/00397911.2012.680569

A novel synthetic utility of NaICl₂ for the preparation of bis(4-dimethaminophenyl)arylmethanes and bis(4-dimethaminophenyl)alkanes is described. In the presence of an aqueous solution of NaICl₂, the reaction of arenes with aromatic aldehydes gives corresponding triarylmethane derivatives regioselectively in moderate to good yields. The method is also useful for the preparation of diarylalkane derivatives by using aliphatic aldehydes. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.

Full text of DOI:10.1080/00397911.2012.680569

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Efficient Synthesis of Bis(4-
Dimethaminophenyl)arylmethanes and
Bis(4-Diamethaminophenyl)alkanes Using
Iodine Reagent
Harshal M. Bachhav a , Balaram S. Takale a & Vikas N. Telvekar a
a Department of Pharmaceutical Sciences and Technology, Institute
of Chemical Technology, Matunga, Mumbai, India
Version of record first published: 05 Apr 2013.
To cite this article: Harshal M. Bachhav , Balaram S. Takale & Vikas N. Telvekar (2013): Efficient
Synthesis of Bis(4-Dimethaminophenyl)arylmethanes and Bis(4-Diamethaminophenyl)alkanes Using
Iodine Reagent, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 43:14, 1909-1914
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Synthetic Communications1, 43: 1909–1914, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.680569
EFFICIENT SYNTHESIS OF BIS(4-DIMETHAMINOPHENYL)
ARYLMETHANES AND BIS(4-DIAMETHAMINOPHENYL)
ALKANES USING IODINE REAGENT
Harshal M. Bachhav, Balaram S. Takale, and Vikas N. Telvekar
Department of Pharmaceutical Sciences and Technology,
Institute of Chemical Technology, Matunga, Mumbai, India
GRAPHICAL ABSTRACT
Abstract A novel synthetic utility of NaICl2 for the preparation of bis(4-dimethamino-
phenyl)arylmethanes and bis(4-dimethaminophenyl)alkanes is described. In the presence
of an aqueous solution of NaICl2, the reaction of arenes with aromatic aldehydes gives cor-
responding triarylmethane derivatives regioselectively in moderate to good yields. The method
is also useful for the preparation of diarylalkane derivatives by using aliphatic aldehydes.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Bis(4-dimethaminophenyl)alkanes; bis(4-dimethaminophenyl)arylmethane;
carbon–carbon coupling; sodium dichloroiodate
INTRODUCTION
During the past three decades, diaminotriphenylmethane (DTM) compounds
have received considerable attention because of their applications in biological
and analytical fields, where these compounds are used as dyes for the detection of
hydrogen peroxide in medical diagnostic kits and biotechnology process control.
In the medicinal field, these compounds are used as antifungal,[1,2] antitubercular,[3]
antiinfective, and antimicrobial agents.[4] Different vmethods have been reported
for the preparation of 4,40-diaminotriphenylmethane compounds such as from
4,40-diaminodiphenylmethanes and amines, by condensation of amines and anilines
Received January 25, 2012.
Address correspondence to Vikas N. Telvekar, Department of Pharmaceutical Sciences and
Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India. E-mail: vikastelvekar@
rediffmail.com
1909

1910
H. M. BACHHAV, B. S. TAKALE, AND V. N. TELVEKAR
Scheme 1. Reaction of aryl and alkyl aldehydes with N,N-dimethylaniline in presence of NaICl2.
in an acidic medium, using zeolites;[5] with a metal catalyst,[6] or clay-mediated
by microwave irradiation.[7] Most of these protocols, however, suffer from various
drawbacks.
Sodium dichloroiodate is a commercially available iodine reagent in a 50%
water solution and has been reported for the iodination of the aromatic ring at
40–70 ꢀC for 72 h.[8,9] More recently we used this reagent for the transformations
of alcohol to aldehyde and aldehyde to corresponding nitriles.[10,11]
While working on this reagent, we found that it can be used for the regio-
selective carbon–carbon bond-forming reaction. We observed that in the presence
of an aqueous solution of sodium dichloroiodate, N,N-dimethylaniline and aromatic
or aliphatic aldehydes converted into either 4,40-arylmethylene-bis-(N,N-dimethy-
laniline) or 4,40-alkylmethylene-bis-(N,N-dimethylaniline) (Scheme 1).
RESULTS AND DISCUSSION
For our initial study we selected N,N-dimethylaniline as a model substrate to
explore suitable reaction conditions with benzaldehyde in the presence of aqueous
NaICl2 at room temperature. In this case, the reaction afforded the corresponding
Table 1. Reaction of benzaldehyde and N,N-dimethylaniline with different iodine
reagents
No.
Reagenta
Time (h)
Yield %b
1
2
3
4
5
6
7
I2
ICl
8
7
65
70
25
85
20
30
10
DIB
NaICl2
IBX
12
4
12
12
12
DMP
NaIO4
aReaction was conducted in acetonitrile and aqueous NaICl2 at room temperature.
bIsolated yield of 4,40-(phenylmethylene)bis(N,N-dimethylaniline) after column
chromatography.

SYNTHETIC UTILITY OF NaICl2
1911
a
Table 2. Reaction of N,N-dimethylaniline with aldehydes in the presence of aqueous NaICl2
Entry
R-CHO
Product
Time (h)
Yield %b
1
4
85
2
5
85
3
4
3
6
82
80
5
6
82
6
7
4
6
80
85
85
8
9
6
4
75
(Continued )

1912
Entry
10c
H. M. BACHHAV, B. S. TAKALE, AND V. N. TELVEKAR
Table 2. Continued
R-CHO
Product
Time (h)
Yield %b
2
65
11c
2
5
60
55
12
aReaction conditions: N,N0-dimethylaniline (2 equiv), NaICl2 (2 equiv), and aldehyde (1 equiv) in
acetonitrile.
bIsolated yields after column chromatography and structures were confirmed by comparison of IR,
1H NMR, and mp with literature reports.
cReflux temperature.
4,40-(phenylmethylene)bis(N,N-dimethylaniline) as a major product. Further investi-
gation observed that 2 equivalents of NaICl2 are required to furnish the reaction.
With our interest in iodine reagents, we explored the conversion of N,N-
dimethylaniline to 4,40-(phenylmethylene)bis(N,N-dimethylaniline) using different
iodine reagents such as I2, ICl, diacetoxyiodo(benzene) (DIB), iodoxybenzoic acid
(IBX), Dess–Martin periodonane (DMP), and NaIO4 (Table 1) under varied reac-
tion conditions. This study shows that all these reagents can be successfully used
for the aforementioned conversion, but lower reaction rates were observed compared
to that obtained using NaICl2.
Herein, we report an efficient and versatile methodology for synthesizing
diaminotriphenylmethanes as well as diamininodiphenylalkanes by using aqueous
sodium dichloroiodate. Next, to evaluate the scope of this new protocol, these con-
ditions were applied to a variety of aromatic and aliphatic aldehydes, and the results
are presented in Table 2. The results clearly indicate that this method is suitable for
electron-withdrawing as well as electron-donating substituted aromatic substrates
(Table 2, entries 2–5). In each case, good to excellent yields of the desired 4,40-
arylmethylene-bis-(N,N-dimethylaniline) products were isolated. Heterocyclic
aromatic aldehydes are also suitable for this transformation (Table 2, entries 6–8). It
was noteworthy that in the case of aliphatic aldehydes at room temperature
no reaction was observed, whereas this reaction under reflux condition proceeds
well with lower yield (Table 2, entries 10 and 11). Further investigations indicate
that a,b-unsaturated aldehydes can also be suitable for this reaction (Table 2, entry
12) without affecting the double bond.

SYNTHETIC UTILITY OF NaICl2
1913
Scheme 2. Reaction of paraformaldehyde with N,N-dimethylaniline in the presence of NaICl2.
During the reaction, it was observed that N,N-dimethylaniline reacts with para-
formaldehyde at 50 to 60 ꢀC in the presence of an aqueous solution of sodium
dichloiodate, resulting in the formation of 4,40-methylene-bis(N,N-dimethylaniline)
and thus provides an interesting route for the synthesis of diphenylmethane com-
pounds (Scheme 2). No reaction was observed at room temperature.
In conclusion, a new reaction system using NaICl2 for C–C coupling has been
developed, which is capable of converting various aldehydes into corresponding
triphenyl and diphenyl compounds. The developed method is mild and gives mode-
rate to good yields of the product for both aliphatic as well as aromatic substrates.
EXPERIMENTAL
Typical Procedure for Synthesis of Lucomalachite Green
(Table 2, Entry 1)
In a stirred solution of benzaldehyde (4.7 mmol, 0.5 g) and 10mL of N,N-dimethy-
laniline (9.4 mmol, 1.15 g), aqueous NaICl2 (2 M, 9.4mmol) was added. The reaction
mixture was stirred at room temperature. After completion of the reaction [as monitored
by thin-layer chromatography (TLC)], the reaction mixture was quenched in water
(10 mL) and further diluted with dichloromethane (30 mL). The organic layer was
separated and washed successively with 10% aqueous solution of Na2S2O3(2 ꢁ 20 mL),
10% aqueous solution of NaHCO3(2 ꢁ 15 mL), and finally with H2O (2 ꢁ 20 mL). Then
organic layer was dried over anhydrous Na2SO4 and concentrated under reduced
pressure to give the crude product. Pure diaminotriphenylmethane (DTM) as a green
solid was obtained after silica-gel column chromatography (EtOAc–hexane, 1:9); mp.
1
92–93ꢀC (lit.[12] mp 91–92 ꢀC); H NMR (CDCl3): d 2.93 (s, 12H), 5.40 (s, 1H), 6.66
(d, J ¼ 8.7 Hz, 2H), 6.69 (d, J ¼ 8.7 Hz, 2H), 7.04 (m, 4H), 7.14 (d, J ¼ 7 Hz, 2H), 7.25
(m, 3H); IR (KBr, cmꢂ1): 3075, 1611, 1532, 1459, 1347; 13C NMR (CDCl3): d 148.91,
145.41, 132.81, 129.98, 129.86, 129.32, 128.02, 112.54, 112.41, 55.04, 40.79, 40.65.
Complete experimental details are available online in the Supplemental Material.
ACKNOWLEDGMENT
V. N. T. thanks the Institute of Chemical Technology, Mumbai (ICT), for
providing financial support under the Golden Jubilee Fund.
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