A general approach to substituted diphenyldiazenes

Article abstract of DOI:10.1016/j.tet.2016.02.011

A general and practical synthetic method for the construction of unsymmetrically substituted diphenyldiazenes based on classical azo coupling reaction has been developed. A key feature of this method is the use of N,N-diallyl protected aniline derivatives

Full text of DOI:10.1016/j.tet.2016.02.011

Tetrahedron xxx (2016) 1e11
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A general approach to substituted diphenyldiazenes
*
Toni A. Lutz, Patrick Spanner, Klaus T. Wanner
€
€
Ludwig-Maximilians-Universitat Munchen, Department of Pharmacy e Center for Drug Research, Butenandtstr. 5e13, D e 81377 Munich, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A general and practical synthetic method for the construction of unsymmetrically substituted diphe-
nyldiazenes based on classical azo coupling reaction has been developed. A key feature of this method is
the use of N,N-diallyl protected aniline derivatives as coupling components. The N,N-diallyl moiety of the
coupling component warrants sufficient reactivity and allows to avoid formation of constitutional iso-
mers resulting from intermediate triazene formation. Furthermore, subsequent to the coupling reaction,
the N,N-diallyl aminofunction, can be replaced by other substituents including hydrogen via diazonium
ion intermediates. In general, following this approach target compounds can be obtained in reasonable to
good yields.
Received 15 December 2015
Received in revised form 1 February 2016
Accepted 3 February 2016
Available online xxx
Dedicated to Professor Dr. Eberhard Re-
imann with warmest wishes on the occa-
sion of his 80th birthday
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Substituted diphenyldiazenes
Azo coupling
N,N-Diallyl protection group
Cleavage of N,N-diallyl groups (deallylation)
Photoswitchable ligands
1. Introduction
preparative methods have been reported such as the reductive
coupling of aromatic nitro derivatives28 or the oxidative coupling of
Aromatic azo compounds have found widespread application in
chemical and pharmaceutical industry. They are classically used for
instance as dyes and pigments,1 food additives, indicators for pH-
measurements,2 initiators for radical reactions,3 as therapeutic
agents4,5 or as part of drug delivery systems.6 Meanwhile a major
focus of azobenzenes is on their use as light sensitive molecular
switches,7e9 as for example, for photoresponsive liquid
crystals.10e12 But in recent time, many papers appeared in partic-
ular on the use of photoswitchable ligands for photopharmacology,
e.g., for the optical control of epithelial sodium channels,13 insulin
aniline derivatives.29 However, the substitution pattern of the ar-
omatic azo compounds accessible by these methods is in general
quite limited. Thus, when dimerization reactions such as the re-
ductive coupling of nitro compounds are applied to establish the
respective phenyl azo derivatives, homo and hetero coupling will
inevitably lead to symmetrically and unsymmetrically substituted
azo compounds and as a consequence thereof to poor yields.
Clearly, the well known azo coupling reactions in which diazonium
salts are reacted with aromatic systems give access to a broad array
of differently substituted target compounds. But this approach
suffers from distinct limitations as well. In this case the coupling
component to be reacted with the diazonium salt must display
a sufficiently high electron density, typically achieved by the
presence of a hydroxy- or an amino group to undergo the desired
conversion.
In the context with the development of new photoswitchable
ligands for GABA transporters, we sought for a very specific sub-
stitution pattern of the diphenyldiazene unit, that is, exhibiting two
main features (Scheme 1): There should be a halogen function at
one of the two phenyl moieties allowing the assembly of the final
photosensitive target compounds or precursors by cross coupling
reactions like Suzuki, Sonogashira or Heck reactions. The second
phenyl moiety should exhibit substituents such as halogens or alkyl
groups preferentially in the ortho or the para position or in both
receptors,14 the acetylcholinesterase,15
m
-opioid receptors,16
TRPV1-channels,17 glutamate receptors,18 NMDA receptors,19
AMPA receptors,20 local anesthetics21 and cell division.22 We re-
cently described the use of this method to control the activity of
a
neurotransmitter transporter, the GABA transporter GAT1,
employing a photoswitchable ligand.23
Because of the broad interest in azo compounds, several
methods have been developed for their synthesis in the past.24
Classical approaches comprise azo coupling reaction,25 the Mills
reaction,26 and the Wallach reaction.27 Recently, additional
* Corresponding author. Tel.: þ49 0 89 2180 77249; fax: þ49 0 89 2180 77247;
e-mail address: klaus.wanner@cup.uni-muenchen.de (K.T. Wanner).
http://dx.doi.org/10.1016/j.tet.2016.02.011
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
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2
T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
Scheme 1. Design of the desired target compounds.
since due to former results substituents in these positions were
expected to improve binding affinities to GABA transporters.30
Moreover, particularly substituents in the ortho or para position
might also allow to tune the kinetics of the E/Z-isomerization of the
photosensitive compounds as well as the wavelength of the nec-
essary light used for isomerization which is often a decisive factor
for the use of photoswitchable compounds in organic tissues.
We considered azo coupling reactions as the most efficient and
versatile synthetic approach to the desired azo compounds 3
(Scheme 2). For such coupling reactions, the diazonium salt 1
should be used exhibiting an iodine substituent that should allow
to use the target compound for Palladium catalyzed coupling re-
actions. The main problem, however, to solve was the question
which reactant might be employed as nucleophile in the azo cou-
pling reaction. Benzene derivatives with halogen function but de-
void of any activating groups such as an OH or an NH2 group
increasing electron density of the aromatic system like 2 do not
come into consideration as they are known to fail in azo coupling
reactions. Given the fact that primary aromatic amino groups can
be efficiently exchanged by e.g., halogene substituents by Sand-
meyer or Schiemann reactions, the use of aniline derivatives 4, the
electron density of which should be high enough to undergo the
desired coupling reaction, appears quite tempting. But in that case,
an exchange of the azo and the amino group may occur between
the coupling reagents via triazenes as intermediates which would
It appeared to us that this problem could be easily solved, if the
aniline derivatives 4 displaying a primary amino function were
replaced by benzene derivatives 6 exhibiting a tertiary amino
function carrying suitable protecting groups. Due to the protecting
groups, triazene formation and side reactions resulting therefrom
could be ruled out whereas compounds 6 should be still amenable
to azo coupling reactions owing to the positive mesomeric effect of
the amino group. Given its easy introduction and efficient removal
without a significant effect on the electron donor ability of amino
groups, we considered allyl residues as the most appropriate pro-
tecting groups for the purpose of this study. In the present paper,
we wish to report on the results of our study utilizing N,N-diallyl
protected aniline derivatives 6 for azo coupling reactions and the
subsequent transformation of the primary coupling products 7 into
azo benzene derivatives 5 exhibiting a primary amino group by N-
deprotection and further on the replacement of the primary amino
group by various substituents (/3). To the best of our knowledge,
the above outlined synthetic concept has not been reported before.
2. Results and discussions
The primary step of our synthetic sequence that should give
access to a broad variety of differently substituted azo benzenes 3
and 5, the coupling reaction between a diazonium salt and N,N-
diallyl substituted aniline derivative was in general performed as
follows. The diazonium salts of anilines 1, i.e., 1a and 1b, were
generated right before their use by treating the respective iodo
ultimately result in
compounds.
a
variety of structurally isomeric azo
not activating
substituent
3
1
2
activating
substituent
5
1
4
activating
N-protected
substituent
7
1
6
Scheme 2. Synthesis of substituted diphenyldiazenes by azo coupling.
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T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
3
aniline in a mixture of EtOH and 2 M HCl (3 equiv) with NaNO2
(1.1 equiv in H2O; excess NaNO2 destroyed by addition of
H2NSO3H). For the azo coupling reactions, the resulting solution
was then added to a solution of the respective N,N-diallylaniline (in
EtOH/H2O) at 0 ꢀC, in which, where indicated, also NaOAc or a fur-
ther amount of 2 M HCl was present. The reaction mixture, the pH
of which was estimated by means of indication paper, was finally
stirred at 0 ꢀC for the time given, before the product was isolated by
extraction and purified by flash chromatography.
The next step aimed at the deprotection of the tertiary amino
function in 9aed and 10aed which should be accomplished by
isomerization of the two allyl residues and subsequent hydrolysis
of the thus formed aminovinyl units.
First attempts were performed with 9a employing Pd/C,
Rh(PPh3)3Cl2 or Ru(PPh3)3Cl2 in EtOH or THF also in presence of
additives such as ethanolamine or trimethylamine, or the use of
potassium tert-butoxide in DMSO or toluene remained un-
successfully as either no reaction occurred or a complex mixture of
products was formed. Finally, the transition metal catalyst
RuClH(CO) (PPh3)3 reported by Krompiec et al.31 to effect CeC
double bond isomerization in N-allylamines was found to be well
suited for our purposes, i.e., the isomerization of 9a to 11a. Thus
when 9a was heated with 1 Mol % of RuClH(CO) (PPh3)3 in CH2Cl2 to
60 ꢀC in a microwave reactor, a clean reaction to the divinylamine
11a occurred, which was complete within 2 h. Product 11a was
found to be labile. Therefore, neither 11a nor the related products
11bed and 12aed were isolated, instead the solutions from the
isomerization containing these compounds directly used for the
next step.
The conditions required for the hydrolysis of the divinylamine
function to liberate the primary amino group were exemplarily
examined for 11a to which end the solution of this compound
resulting from the isomerization reaction was used without any
purification. Treatment of 11a with HCl, HOAc, NH4Cl or water did
not provide the desired amine or only as part of a complex reaction
mixture. However, upon treatment of the CH2Cl2 solution of 11a,
obtained from the isomerization reaction, with NHþ3 OHClꢁ
(10 equiv) and NEt3 (5 equiv) at 60 ꢀC for 3 h, a procedure de-
veloped for the cleavage of pyrrols,32 a clear conversion to the free
amino derivative occurred delivering 13a in 96% yield.
When diazonium salt 1 was reacted with N,N-diallylaniline (8a)
under weak acidic pH conditions (pHz4), the reaction was com-
plete within 4 h providing 9a in 94% yield (Table 1, entry 1). For the
coupling reaction of 1a with the m-chloro substituted aniline de-
rivative 8b, longer reaction times were required. After 4 h as in the
aforementioned reaction with 8a, only 53% of 9b were obtained
which could be raised to 61% and 64% upon extension of the re-
action time to 16 and 36 h, respectively (Table 1, entries 2e4).
When the compounds were allowed to react for 36 h but at
a higher pH (z5e6, adjusted by extra NaOAc), the yield lowered to
32% whereas 71% of 9b could be isolated by running the reaction at
a lower pH (Table 1, entry 6, pHz2e3, adjusted by omission of
NaOAc). But when the pH was further reduced (to z1e2 by addi-
tion of 2 equiv of 2 M HCl) instead of an additional increase in yield
a slight reduction occurred (Table 1, entry 7) indicating the pH
optimum for the reaction to be z2e3. In case of the coupling re-
action of 1a with the m-fluoro substituted aniline derivative 8c
yields amounted to 55% (Table 1, entry 8) and 56% (Table 1, entry 9)
only performed at the pH values of z4 and z2e3 that had so far
appeared to be the most rewarding. For the more electron-rich 3-
methyl substituted aniline derivative 8d, the coupling reaction
proceeded again quite smoothly. At both pH values, z4 and z2e3,
the reaction was complete within 4 h yielding the coupling product
in 92% and 85%, respectively (Table 1, entries 10e11).
The same procedure for the removal of the allyl protecting
groups comprising isomerization and hydrolysis worked also well
for 9be9d and the regioisomers regarding the iodo substituted
10aed, for the latter of which the reaction times for both steps had,
however, to be extended to 4 h and 6 h, respectively, providing the
target compounds 13bed and 14aed in yields from 87 to 95%.
The respective results that could be achieved for the cleavage of
the N,N-diallylaniline protection group in these cases are shown in
Table 3.
The reaction conditions that had turned out best for the prep-
aration of the diazobenzenes 9aed were finally also applied to the
synthesis of regioisomers 10aed exhibiting the iodo substituent in
meta position. That way, by coupling 8aed with meta iodo
substituted diazonium salt 1b, the corresponding diazobenzenes
10aed could be obtained in reasonable to good yields (51e84%,
Table 2, entries 1e4).
Table 1
Formation of diphenyldiazenes 9aed from diazotized 4-iodoaniline 1a and N,N-diallylanilines 8aeda
1a
8a-d
Additivesb
9a-d
Entry
Educt
X
pH rangec
Reaction time [h]
Product
Yield:
1
2
3
4
5
6
7
8
8a
8b
8b
8b
8b
8b
8b
8c
8c
8d
8d
H
NaOAc, 2 equiv
NaOAc, 2 equiv
NaOAc, 2 equiv
NaOAc, 2 equiv
NaOAc, 4 equiv
d
z4
z4
z4
z4
z5e6
z2e3
z1e2
z4
z2e3
z4
4
4
9a
9b
9b
9b
9b
9b
9b
9c
9c
9d
9d
94%
53%
61%
64%
32%
71%
68%
55%
56%
92%
85%
Cl
Cl
Cl
Cl
Cl
Cl
F
F
Me
Me
16
36
36
36
36
36
36
4
2M HCl, 2 equiv
NaOAc, 2 equiv
d
9
10
11
NaOAc, 2 equiv
d
z2e3
4
a
A solution of 1a was freshly generated from 4-iodoaniline by addition of NaNO2 (1.1 equiv) and 2M HCl (3.0 equiv) in EtOH/H2O (2:1). This solution was then added to
a separate solution of 8aed in EtOH/H2O (2:1).
b
Further additives added to the solution of the coupling component 8aed where indicated.
Determined from the reaction mixture directly after the addition of the solution of 1a to the solution of 8aed.
c
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T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
Table 2
Formation of diphenyldiazenes 10aed from diazotated 3-iodoaniline 1b and N,N-diallylanilines 8aeda
1b
10a-d
8a-d
Entry
Educt
X
Additivesb
pH rangec
Reaction time [h]
Product
Yield:
1
2
3
4
8a
8b
8c
8d
H
Cl
F
NaOAc, 2 equiv
d
z4
4
36
36
4
10a
10b
10c
10d
80%
63%
51%
84%
z2e3
z2e3
z4
d
Me
NaOAc, 2 equiv
a
A solution of 1b was freshly generated from 4-iodoaniline by addition of NaNO2 (1.1 equiv) and 2M HCl (3.0 equiv) in EtOH/H2O (2:1). This solution was then added to
a separate solution of 8aed in EtOH/H2O (2:1).
b
Further additives added to the solution of the coupling component 8aed where indicated.
Determined from the reaction mixture directly after the addition of the solution of 1b to the solution of 8aed.
c
To demonstrate the synthetic utility of the thus obtained
diphenyldiazenes, prototypic reactions for the replacement of the
amino group in 13aed by hydrogen, chlorine, and fluorine have
been performed.
Substitution of the amino group in the aniline derivatives ob-
tained in this study by chlorine or fluorine in a Sandmeyer and
Schiemann reaction is feasible as well, as shown for 13a. Treatment
of 13a with tert-BuONO and 4-dodecylbenzenesulfonic acid in
tetrachloromethane and subsequent heating with triethylamine
following a literature procedure33 provided the chloroderivative 16
in 52%. For this transformation, it occurred crucial that CCl4 was
employed as solvent as with other organic solvent which were
required because of the poor solubility of 13a in water, partial
Reductive removal of the amino group in 13aed could be ac-
complished following
a standard procedure. Treatment with
NaNO2 (3 equiv) and H3PO2 (20 equiv) of 13aed in THF provided
the desired desamino derivatives 15aed in reasonable to good
yields (Table 4, 66e75%).
Table 3
Deallylation of diphenyldiazenes 9 and 10 via isomerization and subsequent hydrolysis
9a-d, 10a-d
11a-d, 12a-d
13a-d, 14a-d
Entry
1
Educt
X
Isomerization time [h]
Hydrolysis time [h]
3
Product
Yield:
96%
9a
H
2
13a
2
3
4
9b
9c
9d
Cl
F
Me
2
2
2
3
3
3
13b
13c
13d
93%
91%
95%
5
10a
H
4
6
14a
92%
6
7
8
10b
10c
10d
Cl
F
Me
4
4
4
6
6
6
14b
14c
14d
88%
87%
90%
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T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
5
Table 4
Reductive removal of the amino group in aniline derivatives 13aed
15a-d
Product
13a-d
Entry
Educt
X
Yield:
1
2
3
4
13a
13b
13c
13d
H
Cl
F
15a
15b
15c
15d
75%
66%
68%
71%
Me
replacement of the amino substituent by hydrogen occurred lead-
ing to diminished yields.
reaction could possibly also be performed with 1-
aminonaphthalene in either N-protected or even unprotected form.
Interestingly, in this case a protection of the primary amino
group was not required. When the diazonium salts 1a and 1b de-
rived from 4-iodoaniline and 3-iodoaniline were reacted with 1-
aminonaphtalene (18) the corresponding azo coupling products
19a and 19b were formed without any sign of isomeric products
that could have resulted from intermediate triazene formation. Also
the yields for the products amounting to 91% and 93% for 19a and
19b, respectively, were very high. As in the case of the amino
substituted diphenyldiazenes the reductive elimination of the
amino group in 19aeb employing NaNO2 and H3PO2 worked here
well, too, providing the desaminated phenylnaphtyl diazenes
20aeb in good yields (20a: 72%; 20b: 68%).
Similarly, the fluorine derivative 17 could be prepared in
a
Schiemann reaction treating 13a with tert-BuONO and
BF3$Et2O (followed by heating to 120 ꢀC) the yield amounting
to 63% (Scheme 3). According to these results, the synthetic
sequence of azo coupling with N,N-diallyl protected aniline
derivatives, subsequent deprotection and substitution of the
amino group represents a highly efficient and versatile access
to differently substituted diphenyldiazene derivatives (see
Scheme 4).
Having successfully accomplished the formation of amino
substituted diphenyldiazenes by azo coupling reactions with N-
protected aniline derivatives, we wondered whether an analogous
1) tBuONO, CCl4,
4-docecylbenzenesulfonic acid
25 °C, 2 h
2) Et3N, 60 °C, 2 h
13a
16
1) tBuONO, BF3 Et2O
0 °C, 16 h
.
2) 120 °C, 2 h
13a
17
Scheme 3. Replacement of the amino group in 13a by a chlorine and fluorine substituent.
19a
20a
18
1a
91%
72%
19b
20b
18
1b
68%
93%
Scheme 4. Azo coupling of diazotated iodoaniline 1aeb with 1-aminonaphthaline (18).
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6
T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
Of these compounds, the naphtylphenyl diazene derivative 20b
extracted with CH2Cl2 (3ꢂ). The combined organic layers were
dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude product was purified by flash chromatography
(eluting with pentane) to give the diallylated derivatives.
has already successfully been used as a building block for the
construction of a valuable photoswitchable ligand of the GABA
transporter GAT1.23
3. Conclusion
4.3. General procedure for the azo coupling (GP2)
Based on diazonium chemistry, a highly versatile synthetic
route to substituted diphenyldiazenes exhibiting an iodo sub-
stituent on one of the two aromatic rings and additional sub-
stituents on the other has been established.
The corresponding iodo aniline (1.0 equiv) was dissolved in of
EtOH (3 mL/mmol) und 2N HCl (1.5 mL/mmol, 3.0 equiv) was
added. The mixture was cooled to 0 ꢀC and a pre-cooled solution of
NaNO2 (1.1 equiv) in H2O (1.5 mL/mmol) was added dropwise over
a period of 10 min. After the end of the addition, the solution was
stirred for further 10 min at 0 ꢀC. Then the excess of NaNO2 was
removed by the addition of amidosulfuric acid (0.2 equiv) once
again followed by stirring for 10 min at 0 ꢀC (suspension A).
The corresponding N,N-diallyl aniline derivative (1.0 equiv) was
dissolved in EtOH (20 mL/mmol) and 10 mL/mmol water was added
(solution B). If indicated, to this solution is also added either NaOAc
(2.0 equiv) or a further amount of 2N HCl (1 mL/mmol, 2.0 equiv)
additionally.
The method comprises the coupling of diazonium salts derived
from iodo substituted aniline derivatives on the one with N,N-
diallyl protected anilines on the other side. The key feature of this
approach is to be seen in the use of the temporary protection of the
amino group of the aniline derivative with two N-allyl residues. The
N,N-diallyl residue warrants sufficient reactivity of the benzene
derivatives for azo coupling reactions whereas the N-protection of
the amino group rules out side reaction that would otherwise arise
from intermediate triazene formation. Further, the primary amino
group accessible by deprotection of the N,N-diallyl moiety after the
azo coupling reaction has the advantage to provide the opportunity
for a broad array of transformation reactions as exemplified by its
replacement by hydrogen, chlorine or fluorine substituents
employing common methods. Overall the synthetic method out-
lined in this paper provides a broadly applicable and flexible ap-
proach to differently substituted diphenyl diazenens derivatives
which equipped with a suitable functional group, such as an iodine
substituent for metal catalyzed coupling reactions, can be re-
warding building blocks for the construction of photoswitchable
bioactive compounds.
Suspension A was then added to solution B at 0 ꢀC, the pH was
determined of the resulting mixture (indicator paper) and it was
stirred for the indicated time at 0 ꢀC. Afterwards it was allowed to
warm up to rt slowly followed by the addition of both CH2Cl2
(20 mL/mmol) and H2O (20 mL/mmol). The aqueous phase was
made alkaline (pH 10e12) by the addition of NaOH and the product
was extracted with CH2Cl2 (3ꢂ). The combined organic layers were
dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude product was purified by flash chromatography
(eluting with pentane/CH2Cl2¼8/2) to give the clean azo
compound.
4. Experimental section
4.1. General methods
4.4. General procedure for the deallylation of the diallyl-
amines (GP3)
For all reactions only distilled solvents were used. THF and NEt3
were dried over sodium and distilled under nitrogen. CH2Cl2 was
distilled from CaH2 under nitrogen. Commercial available reagents
were used without further purification. Flash column chromatog-
Under nitrogen the corresponding N,N-diallyl amine (1.0 equiv)
and RuClH(CO) (PPh3)3 (0.01 equiv) were introduced in a pressure
tube and dissolved in of CH2Cl2 (5 mL/mmol). The tube was sealed
air tightly and the solution was heated to 60 ꢀC for the indicated
time. After cooling to rt both H2NOHꢂHCl (10 equiv) and Et3N
(5 equiv) were added and the mixture was heated to 80 ꢀC for the
indicated time. After cooling to rt, once again H2O (5 mL/mmol) was
added and the product was extracted with CH2Cl2 (3ꢂ). The com-
bined organic layers were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude product was
purified by flash chromatography (eluting with pentane/
dichloromethane¼1/1) to give the corresponding primary aromatic
amine.
raphy was performed using silica gel (40e60 mm). NMR spectra
were measured with a Jeol Eclipse þ400 (400 MHz) and a Jeol
Eclipse þ500 (500 MHz) spectrometer or an Avance III HD 400 MHz
Bruker BioSpin and an Avance III HD 500 MHz Bruker BioSpin
spectrometer. 1H NMR chemical shifts were referenced to TMS and
13C NMR chemical shifts were referenced to CHCl3. The coupling
constants were stated with an accuracy of 0.5 Hz. MestreNova
software was used for further analysis of the spectra. IR spectra
were recorded with an FT-IR spectrometer Paragon 1000 (Perki-
nElmer). Samples were measured either as KBr pellets or as films on
NaCl plates. Spectrum v2.00 software (PerkinElmer) was used for
analysis. Mass spectra were measured with a mass spectrometer
59827A with 59980 particle beam LC/MS interface (Hew-
lettePackard). High resolution mass spectrometry was carried out
with an LTQ FT (ThermoFinnigan), FAB (Xenon, 6 kV, MBA, refer-
ence PEG), or a JMS GCmate II (Jeol).
4.5. General procedure for the reductive dediazoniation of
the aromatic amines (GP4)
The corresponding primary aromatic amine derivative
(1.0 equiv) was dissolved in THF (20 mL/mmol), cooled to 0 ꢀC and
hypophosphorous acid (50% solution in water, 20 equiv) was added.
Sodium nitrite (3.0 equiv) was added and the mixture was stirred
for 4 h at 0 ꢀC and then at rt for further 12 h. Afterwards there were
added CH2CL2 (20 mL/mmol) and water (20 mL/mmol) and the
aqueous phase was made alkaline (pH 10e12) with 2N NaOH. The
product was extracted with CH2Cl2 (3ꢂ). The combined organic
layers were dried over Na2SO4 and the solvent was removed under
reduced pressure. The crude product was purified by flash chro-
matography (eluting with pentane) to give the corresponding re-
duced species.
4.2. General procedure for the allylation of aniline derivatives
(GP1)
The corresponding aniline was dissolved in EtOH (2 mL/mmol)
and H2O (0.5 mL/mmol) was added. Ally bromide (2.4 equiv) and
Na2CO3 (1.2 equiv) were added and the mixture was heated to
reflux for the indicated time. After the end of the reaction, the main
part of the alcohol was removed by distillation. CH2Cl2 (5 mL/
mmol) and H2O (5 mL/mmol) were added and the product was
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T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
7
4.6. Characterization data of new products
time was 4 h at 0 ꢀC. 9a was obtained as red solid (3.80 g, 94%). TLC:
Rfz0.4 (pentane/CH2Cl2¼8/2). Mp: 41 ꢀC. IR (KBr): ṽ¼3075, 3006,
2974, 2864,1596,1512,1401,1383,1350,1310,1234,1158,1137,1001,
4.6.1. N,N-Diallylaniline (8a). According to GP1 from aniline (4.7 g,
50 mmol), allylbromide (14.8 g, 120 mmol) and K2CO3 (6.4 g,
60 mmol). The reaction time was 3 h 8a was obtained as colorless
oil (8.20 g, 95%). TLC: Rfz0.3 (pentane). IR (NaCl): ṽ¼3084, 3062,
2979, 2912, 2858,1642,1599,1574,1505,1388,1357,1233,1181, 988,
938, 919, 829 cmꢁ1. 1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d¼3.98
(dt, J¼4.0/1.6 Hz, 4H), 5.13e5.22 (m, 4H), 5.84 (ddt, J¼17.1/10.1/
4.7 Hz, 2H), 6.70e6.74 (m, 2H), 7.53e7.58 (m, 2H), 7.75e7.79 (m,
2H), 7.79e7.84 (m, 2H) ppm 13C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
918, 746, 691 cmꢁ1. 1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d
¼3.90
d
¼52.89 (2C), 95.36, 111.87 (2C), 116.65 (2C), 124.05 (2C), 125.30
(dt, J¼4.6/1.6 Hz, 4H), 5.10e5.21 (m, 4H), 5.84 (ddt, J¼17.2/10.1/
(2C), 132.83 (2C), 138.15 (2C), 143.76, 151.41, 152.64 ppm. M
(C18H18IN3)¼403.26. MS (ESIþ): m/z: 404.1 ([MþH]þ). HRMS
(ESIþ): Mþ calcd for C18H19IN3 404.0545; found 404.0617.
4.9 Hz, 2H), 6.63e6.72 (m, 3H), 7.14e7.23 (m, 2H) ppm 13C NMR
(126 MHz, CDCl3, 21 ꢀC, TMS):
d
¼52.81 (2C), 112.41 (2C), 116.06
(2C), 116.38, 129.16 (2C), 134.12 (2C), 148.78 ppm. M (C12H15N)¼
173.25. MS (EIþ): m/z: 173.1 (Mþ). HRMS (EIþ): Mþ calcd for
4.6.6. N,N-Diallyl-3-chloro-4-[(E)-(4-iodophenyl)azo]aniline
(9b). According to GP2 solution A was made of 4-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 mL,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8b (2.12 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) without
any further additions. The resulting pH was between 2 and 3. The
reaction time was 36 h at 0 ꢀC. 9b was obtained as red solid (3.12 g,
71%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/2). Mp: 81 ꢀC. IR (KBr):
ṽ¼3429, 3078, 3004, 2975, 2885, 1590, 1503, 1381, 1344, 1322, 1300,
C
12H15N: 173.1204; found 173.1205.
4.6.2. N,N-Diallyl-3-chloroaniline (8b). According to GP1 from 3-
chloro-aniline (6.4 g, 50 mmol), allylbromide (14.8 g, 120 mmol)
and K2CO3 (6.4 g, 60 mmol). The reaction time was 4 h 8b was
obtained as colorless oil (9.60 g, 92%). TLC: Rfz0.3 (pentane). IR
(NaCl): ṽ¼3083, 3008, 2981, 2910, 2865, 1642, 1594, 1560, 1493,
1417, 1385, 1357, 1235, 1180, 1101, 985, 920, 830, 759, 681 cmꢁ1. 1H
NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d
¼3.89 (dt, J¼4.0/1.7 Hz, 4H),
5.14 (dq, J¼8.8/1.7 Hz, 2H), 5.17 (m, 2H), 5.82 (ddt, J¼16.8/10.7/
1229, 1191, 1176, 1126, 1043, 1002, 925, 835, 802 cmꢁ1
.
1H NMR
4.8 Hz, 2H), 6.54 (ddd, J¼8.4/2.4/0.9 Hz, 1H), 6.63 (m, 2H), 7.07 (t,
(500 MHz, CDCl3, 21 ꢀC, TMS):
d
¼3.97 (dt, J¼4.7/1.8 Hz, 4H), 5.16
J¼8.0 Hz, 1H) ppm 13C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
d
¼52.81
(dq, J¼17.1/1.6 Hz, 2H), 5.21 (dq, J¼10.3/1.4 Hz, 2H), 5.83 (ddt,
J¼17.1/10.2/4.7 Hz, 2H), 6.58 (dd, J¼9.3/2.8 Hz, 1H), 6.77 (d,
J¼2.8 Hz, 1H), 7.59e7.62 (m, 2H), 7.74 (d, J¼9.2 Hz, 1H), 7.77e7.81
(2C), 110.48, 112.19, 116.20, 116.36 (2C), 130.08, 133.36 (2C), 135.07,
149.85 ppm. M (C12H14ClN)¼207.7. MS (EIþ): m/z: 207.1 (Mþ).
HRMS (EIþ): Mþ calcd for C12H14ClN 207.0815; found 207.0808.
(m, 2H) ppm 13C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
d¼52.92 (2C),
96.09, 111.01, 112.30, 116.95 (2C), 118.59, 124.45 (2C), 132.28 (2C),
138.25 (2C), 138.87, 139.21, 151.82, 152.70 ppm. M (C18H17IClN3)¼
437.70. MS (EIþ): m/z: 437.0 (Mþ). HRMS (EIþ): Mþ calcd for
4.6.3. N,N-Diallyl-3-fluoroaniline (8c). According to GP1 from 3-
fluoro-aniline (5.6 g, 50 mmol), allylbromide (14.8 g, 120 mmol)
and K2CO3 (6.4 g, 60 mmol). The reaction time was 4 h 8c was
obtained as colorless oil (9.01 g, 94%). TLC: Rfz0.3 (pentane). IR
(NaCl): ṽ¼3083, 3008, 2981, 2912, 2866, 1642, 1619, 1578, 1500,
1418, 1389, 1357, 1333, 1257, 1184, 1158, 991, 960, 922, 822, 753,
C18H17IClN3 437.0156; found 437.0146.
4.6.7. N,N-Diallyl-3-fluoro-4-[(E)-(4-iodophenyl)azo]aniline
(9c). According to GP2 solution A was made of 4-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 mL,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8c (1.95 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) without
any further additions. The resulting pH was between 2 and 3. The
reaction time was 36 h at 0 ꢀC. 9c was obtained as red solid (2.36 g,
56%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/2). Mp: 72 ꢀC. IR (KBr):
ṽ¼3078, 3003, 2976, 2923, 1610, 1560, 1511, 1395, 1381, 1350, 1330,
681 cmꢁ1. 1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d
¼3.89 (dt, J¼3.8/
1.7 Hz, 4H), 5.14 (dq, J¼5.1/1.7 Hz, 2H), 5.16e5.18 (m, 2H), 5.82 (ddt,
J¼17.7/9.8/4.8 Hz, 2H), 6.32e6.38 (m, 2H), 6.43 (ddd, J¼8.4/2.3/
0.9 Hz, 1H), 7.04e7.14 (m, 1H) ppm 13C NMR (126 MHz, CDCl3, 21 ꢀC,
2
TMS):
d
¼52.93 (2C), 99.34 (d, JCF¼26.1 Hz), 102.77 (d,
2JCF¼21.6 Hz), 107.91 (d, JCF¼2.0 Hz), 116.32 (2C), 130.13 (d,
4
3JCF¼10.4 Hz), 133.49 (2C), 150.54 (d, JCF¼10.7 Hz), 164.24 (d,
3
1JCF¼241.5 Hz) ppm. M (C12H14FN)¼191.2. MS (EIþ): m/z: 191.1
(Mþ). HRMS (EIþ): Mþ calcd for C12H14FN 191.1110; found 191.1108.
1232, 1184, 1108, 1001, 919, 828 cmꢁ1
.
1H NMR (500 MHz, CDCl3,
21 ꢀC, TMS):
d
¼3.94e3.98 (m, 4H), 5.16 (dq, J¼17.2/1.6 Hz, 2H), 5.21
4.6.4. N,N-Diallyl-3-methylaniline (8d). According to GP1 from 3-
methyl-aniline (5.4 g, 50 mmol), allylbromide (14.8 g, 120 mmol)
and K2CO3 (6.4 g, 60 mmol). The reaction time was 4 h 8d was
obtained as colorless oil (8.12 g, 87%). TLC: Rfz0.3 (pentane). IR
(NaCl): ṽ¼3079, 3042, 3006, 2978, 2916, 2861, 1641, 1601, 1581,
1497, 1417, 1385, 1357, 1333, 1249, 1179, 990, 954, 917, 837, 764,
(dq, J¼10.4/1.6 Hz, 2H), 5.82 (ddt, J¼17.0/10.0/4.7 Hz, 2H), 6.41e6.48
(m, 2H), 7.55e7.60 (m, 2H), 7.70e7.75 (m, 1H), 7.75e7.80 (m, 2H)
13
ppm C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
d¼53.00 (2C), 95.83,
98.85 (d, J¼24.9 Hz), 108.22 (d, J¼1.5 Hz), 116.94 (2C), 118.71 (d,
J¼2.2 Hz), 124.23 (2C), 131.64 (d, J¼7.1 Hz), 132.27 (2C), 138.18 (2C),
152.72, 153.00 (d, J¼11.6 Hz), 162.49 (d, J¼255.5 Hz) ppm. M
(C18H17IFN3)¼421.25. MS (EIþ): m/z: 421.0 (Mþ). HRMS (EIþ): Mþ
calcd for C18H17IFN3 421.0451; found 421.0450.
691 cmꢁ1. 1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d
¼2.28 (s, 3H),
3.89 (dt, J¼4.5/1.6 Hz, 4H), 5.12e5.19 (m, 4H), 5.84 (ddt, J¼17.2/10.0/
4.9 Hz, 2H), 6.46e6.55 (m, 3H), 7.03e7.12 (m, 1H) ppm 13C NMR
(126 MHz, CDCl3, 21 ꢀC, TMS):
116.00 (2C), 117.36, 129.05, 134.21 (2C), 138.82, 148.89 ppm. M
(C13H17N)¼187.28. MS (EIþ): m/z: 187.1 (Mþ). HRMS (EIþ): Mþ
calcd for C13H17N 187.1361; found 187.1355.
d
¼22.05, 52.75 (2C), 109.66, 113.11,
4.6.8. N,N-Diallyl-3-methyl-4-[(E)-(4-iodophenyl)azo]aniline
(9d). According to GP2 solution A was made of 4-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 ml,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8d (1.91 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) and an
addition of sodium acetate (1.70 g, 20.0 mmol). The resulting pH
was about 4. The reaction time was 4 h at 0 ꢀC. 9d was obtained as
red solid (3.84 g, 92%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/2). Mp:
68 ꢀC. IR (KBr): ṽ¼3075, 3002, 2974, 2920, 2886, 1596, 1565, 1503,
1378, 1347, 1324, 1298, 1232, 1190, 1102, 1001, 957, 920, 835, 821,
4.6.5. N,N-Diallyl-4-[(E)-(4-iodophenyl)azo]aniline (9a). According
to GP2 solution A was made of 4-iodoaniline (2.24 g, 10.0 mmol) in
EtOH (30 mL) and 2 N HCl (15 ml, 30 mmol), sodium nitrite (0.76 g,
11.0 mmol) in H2O (10 mL) and amidosulfuric acid (0.20 g,
2.0 mmol). Solution B was obtained from 8a (1.77 g, 10.0 mmol) in
EtOH (200 mL) and H2O (100 mL) and an addition of sodium acetate
(1.70 g, 20.0 mmol). The resulting pH was about 4. The reaction
802 cmꢁ1. 1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d¼2.66 (s, 3H),
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8
T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
3.94e3.99 (m, 4H), 5.13e5.20 (m, 4H), 5.84 (ddt, J¼17.0/9.9/4.7 Hz,
2H), 6.51e6.56 (m, 2H), 7.53e7.57 (m, 2H), 7.68e7.73 (m, 1H),
7.74e7.78 (m, 2H) ppm 13C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
2JCF¼24.9 Hz), 108.07 (d, 4JCF¼1.5 Hz), 116.82 (2C), 117.07, 118.63 (d,
3
3JCF¼2.2 Hz), 122.82, 130.28, 130.43, 131.45 (d, JCF¼7.2 Hz), 132.09
2
(2C), 138.10, 152.98 (d, JCF¼11.6 Hz), 154.10, 162.42 (d,
d¼18.36, 52.70 (2C), 94.99, 110.39, 112.84, 116.54 (2C), 117.11, 124.14
1JCF¼255.9 Hz) ppm. M (C18H17IN3F)¼421.3. MS (EIþ): m/z: 421.0
(Mþ). HRMS (EIþ): Mþ calcd for C18H17IN3F 421.0451; found
421.0450.
(2C), 132.96 (2C), 138.09 (2C), 141.58, 141.94, 151.39, 153.03 ppm. M
(C19H20IN3)¼417.29. MS (EIþ): m/z: 417.1 (Mþ). HRMS (EIþ): Mþ
calcd for C19H20IN3 417.0702; found 417.0694.
4.6.12. N,N-Diallyl-3-methyl-4-[(E)-(3-iodophenyl)azo]aniline
(10d). According to GP2 solution A was made of 3-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 ml,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8d (1.91 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) and an
addition of sodium acetate (1.70 g, 20.0 mmol). The resulting pH
was about 4. The reaction time was 4 h at 0 ꢀC. 10d was obtained as
red solid (3.52 g, 84%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/2). Mp:
65 ꢀC. IR (KBr): ṽ¼3070, 3061, 3006, 2979, 2920, 1598, 1503, 1381,
1354, 1228, 1177, 1107, 991, 915, 804, 782 cmꢁ1. 1H NMR (500 MHz,
4 . 6 . 9 . N , N - D i a l l yl - 4 - [ ( E ) - ( 3 - i o d o p h e n yl ) a z o ] a n i l i n e
(10a). According to GP2 solution A was made of 3-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 ml,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8a (1.77 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) and an
addition of sodium acetate (1.70 g, 20.0 mmol). The resulting pH
was about 4. The reaction time was 4 h at 0 ꢀC. 10a was obtained as
red high vicious oil (3.22 g, 80%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/
2). IR (KBr): ṽ¼3070, 3060, 3006, 2980, 2920, 1642, 1599, 1565,
1512, 1420, 1387, 1354, 1334, 1312, 1233, 1177, 1156, 1138, 1052, 991,
CDCl3, 22 ꢀC, TMS):
d
¼2.68 (s, 3H), 3.97e4.01 (m, 4H), 5.14e5.22 (m,
921, 820, 783, 701 cmꢁ1
.
1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
4H), 5.86 (ddt, J¼17.0/9.8/4.7 Hz, 2H), 6.52e6.57 (m, 2H), 7.18 (t,
J¼7.9 Hz, 1H), 7.66 (d, J¼7.8 Hz, 1H), 7.68e7.71 (m, 1H), 7.79 (d,
J¼8.0 Hz,1H), 8.14 (t, J¼1.7 Hz,1H). 13C NMR (126 MHz, CDCl3, 22 ꢀC,
d
¼3.97e4.04 (m, 4H), 5.13e5.24 (m, 4H), 5.86 (ddt, J¼16.9/9.8/
4.7 Hz, 2H), 6.74 (d, J¼9.1 Hz, 2H), 7.19 (t, J¼7.9 Hz, 1H), 7.67 (d,
J¼7.8 Hz, 1H), 7.78e7.81 (m, 1H), 7.82 (d, J¼9.1 Hz, 2H), 8.16 (t,
TMS):
d
¼18.27, 52.60 (2C), 110.25, 112.72, 116.45 (2C) 117.07, 122.79,
J¼1.6 Hz, 1H) ppm 13C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
d
¼52.78
130.23, 130.41, 132.82 (2C), 137.51, 141.66 ppm. M (C19H20IN3)¼
(2C), 94.60, 111.73 (2C), 116.55 (2C), 122.85, 125.27 (2C), 129.95,
417.3. MS (EIþ): m/z: 417.1 (Mþ). HRMS (EIþ): Mþ calcd for
130.43, 132.68 (2C), 137.78, 143.59, 151.41, 154.08 ppm.
M
C19H20IN3 417.0702; found 417.0704.
(C18H18IN3)¼403.3. MS (EIþ): m/z: 403.1 (Mþ). HRMS (EIþ): Mþ
calcd for C18H18IN3 403.0545; found 403.0546.
4.6.13. 4-[(E)-(4-Iodophenyl)azo]aniline (13a). According to GP3
with N,N-diallyl-4-[(E)-(4-iodophenyl)azo]aniline (9a, 2.02 g,
5.00 mmol) in CH2Cl2 (25 mL) the double bond isomerization was
4.6.10. N,N-Diallyl-3-chloro-4-[(E)-(3-iodophenyl)azo]aniline
(10b). According to GP2 solution A was made of 3-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 ml,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8b (2.12 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) without
any further additions. The resulting pH was between 2 and 3. The
reaction time was 36 h at 0 ꢀC.10b was obtained as red solid (2.75 g,
63%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/2). Mp: 74 ꢀC. IR (KBr):
ṽ¼3070, 3062, 3006, 2980, 2922, 1591, 1501, 1438, 1382, 1353, 1225,
caused by RuClH(CO) (PPh3)3 (48 mg, 50 mmol) and heating for 2 h.
The subsequent hydrolysis was induced by adding of hydroxyl-
amine hydrochloride (3.47 g, 50.0 mmol) and triethylamine (2.53 g,
25.0 mmol) and heating for 3 h 13a was obtained as orange solid
(1.55 g, 96%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp: 164 ꢀC. IR
(KBr): ṽ¼3440, 3359, 1612, 1593, 1561, 1501, 1422, 1387, 1279, 1142,
1131, 1051, 997, 842 cmꢁ1. 1H NMR (500 MHz, CDCl3, 21 ꢀC, TMS):
d
¼4.08 (s, 2H), 6.68e6.77 (m, 2H), 7.53e7.62 (m, 2H), 7.75e7.85 (m,
13
4H) ppm C NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
d
¼96.02, 114.74
1173, 1133, 1040, 991, 923, 782 cmꢁ1
22 ꢀC, TMS):
.
1H NMR (500 MHz, CDCl3,
(2C), 124.18 (2C), 125.46 (2C), 138.27 (2C), 145.45, 150.03,
152.41 ppm. M (C12H10IN3)¼323.1. MS (EIþ): m/z: 323.1 (Mþ).
HRMS (EIþ): Mþ calcd for C12H10IN3 322.9919; found 322.9919.
d
¼3.93e4.00 (m, 4H), 5.16 (d, J¼17.2 Hz, 2H), 5.21 (d,
J¼10.3 Hz, 2H), 5.82 (ddt, J¼18.7/9.4/4.4 Hz, 2H), 6.57 (dd, J¼9.2/
2.1 Hz, 1H), 6.77 (d, J¼2.6 Hz, 1H), 7.18 (t, J¼7.9 Hz, 1H), 7.68 (d,
J¼7.8 Hz, 1H), 7.72 (d, J¼9.2 Hz, 1H), 7.84 (d, J¼8.0 Hz, 1H), 8.19 (t,
4.6.14. 3-Chloro-4-[(E)-(4-iodophenyl)azo]aniline (13b). According
to GP3 with N,N-diallyl-3-chloro-4-[(E)-(4-iodophenyl)azo]aniline
(9b, 2.19 g, 5.00 mmol) in CH2Cl2 (25 mL) the double bond isom-
J¼1.7 Hz, 1H). ppm 13C NMR (126 MHz, CDCl3, 22 ꢀC, TMS):
¼52.75
d
(2C), 94.58,110.80,112.10,116.80 (2C),118.45,122.86,130.45,130.71,
132.08 (2C), 138.23, 138.88, 138.97, 151.74, 154.02 ppm.
M
erization was caused by RuClH(CO) (PPh3)3 (48 mg, 50 mmol) and
(C18H17IN3Cl)¼437.7. MS (EIþ): m/z: 437.0 (Mþ). HRMS (EIþ): Mþ
heating for 2 h. The subsequent hydrolysis was induced by adding
of hydroxylamine hydrochloride (3.47 g, 50.0 mmol) and triethyl-
amine (2.53 g, 25.0 mmol) and heating for 3 h 13b was obtained as
orange solid (1.66 g, 93%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp:
175 ꢀC. IR (KBr): ṽ¼3415, 3328, 3212, 1627, 1595, 1489, 1413, 1301,
calcd for C18H17IN3Cl 437.0156; found 437.0150.
4.6.11. N,N-Diallyl-3-fluoro-4-[(E)-(3-iodophenyl)azo]aniline
(10c). According to GP2 solution A was made of 3-iodoaniline
(2.24 g, 10.0 mmol) in EtOH (30 mL) and 2 N HCl (15 ml,
30 mmol), sodium nitrite (0.76 g, 11.0 mmol) in H2O (10 mL) and
amidosulfuric acid (0.20 g, 2.0 mmol). Solution B was obtained from
8c (1.95 g, 10.0 mmol) in EtOH (200 mL) and H2O (100 mL) without
any further additions. The resulting pH was between 2 and 3. The
reaction time was 36 h at 0 ꢀC. 10c was obtained as red solid (2.16 g,
51%). TLC: Rfz0.4 (pentane/CH2Cl2¼8/2). Mp: 65 ꢀC. IR (KBr):
ṽ¼3082, 3062, 3007, 2981, 2922, 1613, 1566, 1510, 1387, 1355, 1331,
1235, 1182, 1112, 991, 921, 821, 783 cmꢁ1. 1H NMR (500 MHz, CDCl3,
1242, 1187, 1043, 1001, 899, 859, 837 cmꢁ1 1H NMR (500 MHz,
.
CDCl3, 25 ꢀC, TMS):
d
¼4.13 (s, 2H), 6.57 (dd, J¼8.9/2.4 Hz, 1H), 6.81
(d, J¼2.6 Hz, 1H), 7.60e7.65 (m, 2H), 7.71 (d, J¼8.9 Hz, 1H),
7.79e7.84 (m, 2H) ppm 13C NMR (126 MHz, CDCl3, 25 ꢀC, TMS):
d
¼96.57, 113.57, 114.97, 118.87, 124.44 (2C), 138.23 (2C), 138.49,
140.81, 150.37, 152.39 ppm. M (C12H9ClIN3)¼357.6. MS (EIþ): m/z:
357.0 (Mþ). HRMS (EIþ): Mþ calcd for C12H9ClIN3 356.9530; found
356.9523.
22 ꢀC, TMS):
d
¼3.95e4.00 (m, 4H), 5.17 (dd, J¼17.2/1.4 Hz, 2H), 5.22
4.6.15. 3-Fluoro-4-[(E)-(4-iodophenyl)azo]aniline (13c). According
to GP3 with N,N-diallyl-3-fluoro-4-[(E)-(4-iodophenyl)azo]aniline
(9c, 2.11 g, 5.00 mmol) in CH2Cl2 (25 mL) the double bond isom-
(dd, J¼10.4/1.3 Hz, 2H), 5.83 (ddt, J¼17.1/9.9/4.7 Hz, 2H), 6.41e6.50
(m, 2H), 7.18 (t, J¼7.9 Hz, 1H), 7.68 (dt, J¼7.7/1.1 Hz, 1H), 7.72 (m,
1H), 7.81 (dt, J¼8.0/1.3 Hz, 1H), 8.17 (t, J¼1.7 Hz, 1H) ppm 13C NMR
erization was caused by RuClH(CO) (PPh3)3 (48 mg, 50
mmol) and
(126 MHz, CDCl3, 22 ꢀC, TMS):
d¼52.87 (2C), 94.56, 98.69 (d,
heating for 2 h. The subsequent hydrolysis was induced by adding
Please cite this article in press as: Lutz, T. A.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.02.011

T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
9
of hydroxylamine hydrochloride (3.47 g, 50.0 mmol) and triethyl-
amine (2.53 g, 25.0 mmol) and heating for 3 h 13c was obtained as
orange solid (1.55 g, 91%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp:
167 ꢀC. IR (KBr): ṽ¼3438, 1635, 1615, 1587, 1498, 1429, 1245, 1119,
MS (EIþ): m/z: 357.0 (Mþ). HRMS (EIþ): Mþ calcd for C12H9ClIN3
356.9530; found 356.9521.
4.6.19. 3-Fluoro-4-[(E)-(3-iodophenyl)azo]aniline (14c). According
to GP3 with N,N-diallyl-3-fluoro-4-[(E)-(4-iodophenyl)azo]aniline
(10c, 2.11 g, 5.00 mmol) in CH2Cl2 (25 mL) the double bond isom-
1004, 828 cmꢁ1. 1H NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d¼4.19 (s,
2H), 6.42e6.51 (m, 2H), 7.56e7.62 (m, 2H), 7.71 (t, J¼8.8 Hz, 1H),
7.77e7.83 (m, 2H) ppm 13C NMR (126 MHz, CDCl3, 25 ꢀC, TMS):
erization was caused by RuClH(CO) (PPh3)3 (48 mg, 50 mmol) and
d
¼96.34, 101.49 (d, 2JCF¼23.2 Hz), 110.76, 119.05, 124.23 (2C), 133.12
heating for 4 h. The subsequent hydrolysis was induced by adding
of hydroxylamine hydrochloride (3.47 g, 50.0 mmol) and triethyl-
amine (2.53 g, 25.0 mmol) and heating for 6 h 14c was obtained as
orange solid (1.49 g, 87%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp:
107 ꢀC. IR (KBr): ṽ¼3471, 3379, 1621, 1575, 1497, 1427, 1318, 1245,
(d, 3JCF¼6.8 Hz), 138.18 (2C), 151.57 (d, 2JCF¼11.8 Hz), 152.42, 162.21
(d, 1JCF¼257.0 Hz) ppm. M (C12H9FIN3)¼341.1. MS (EIþ): m/z: 341.0
(Mþ). HRMS (EIþ): Mþ calcd for C12H9FIN3 340.9825; found
340.9820.
1161, 1118, 957, 836, 782 cmꢁ1 1H NMR (500 MHz, CDCl3, 25 ꢀC,
.
4.6.16. 3-Methyl-4-[(E)-(4-iodophenyl)azo]aniline (13d). According
to GP3 with N,N-diallyl-3-methyl-4-[(E)-(4-iodophenyl)azo]aniline
(9d, 2.09 g, 5.00 mmol) in CH2Cl2 (25 mL) the double bond isom-
TMS):
d
¼4.21 (s, 2H), 6.39e6.51 (m, 2H), 7.21 (t, J¼7.9 Hz, 1H),
7.63e7.76 (m, 2H), 7.79e7.87 (m, 1H), 8.18 (t, J¼1.7 Hz, 1H) ppm 13
C
NMR (126 MHz, CDCl3, 25 ꢀC, TMS):
d¼94.58, 101.46 (d,
erization was caused by RuClH(CO) (PPh3)3 (48 mg, 50
mmol) and
2JCF¼23.4 Hz), 110.77 (d, 4JCF¼2.2 Hz), 119.13 (d, 3JCF¼1.9 Hz), 123.00,
3
2
heating for 2 h. The subsequent hydrolysis was induced by adding
of hydroxylamine hydrochloride (3.47 g, 50.0 mmol) and triethyl-
amine (2.53 g, 25.0 mmol) and heating for 3 h 13d was obtained as
orange solid (1.60 g, 95%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp:
118 ꢀC. IR (KBr): ṽ¼3457, 3424, 3388, 3331, 3210, 2923, 1616, 1593,
130.55, 133.05 (d, JCF¼6.9 Hz), 138.63, 151.77 (d, JCF¼11.9 Hz),
1
153.94, 162.31 (d, JCF¼257.5 Hz) ppm. M (C12H9FIN3)¼341.1. MS
(EIþ): m/z: 341.0 (Mþ). HRMS (EIþ): Mþ calcd for C12H9FIN3
340.9825; found 340.9828.
1491, 1417, 1385, 1322, 1255, 1227, 1185, 1111, 1001, 826 cmꢁ1
.
1H
4.6.20. 3-Methyl-4-[(E)-(4-iodophenyl)azo]aniline (14d). According
to GP3 with N,N-diallyl-3-methyl-4-[(E)-(3-iodophenyl)azo]aniline
(10d, 2.09 g, 5.00 mmol) in CH2Cl2 (25 mL) the double bond isom-
NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d
¼2.63 (s, 3H), 3.99 (s, 2H), 6.51
(dd, J¼8.7/2.9 Hz, 1H), 6.56 (d, J¼3.1 Hz, 1H), 7.54e7.58 (m, 2H), 7.65
(d, J¼8.7 Hz, 1H), 7.76e7.81 (m, 2H) ppm 13C NMR (126 MHz, CDCl3,
erization was caused by RuClH(CO) (PPh3)3 (48 mg, 50 mmol) and
25 ꢀC, TMS):
d
¼17.68, 95.48, 112.92, 115.78, 117.24, 124.12 (2C),
heating for 4 h. The subsequent hydrolysis was induced by adding of
hydroxylamine hydrochloride (3.47 g, 50.0 mmol) and triethylamine
(2.53 g, 25.0 mmol) and heating for 6 h 14d was obtained as orange
solid (1.52 g, 90%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp: 106 ꢀC. IR
(KBr): ṽ¼3454, 3369, 3051, 1616, 1598, 1591, 1461, 1402, 1308, 1255,
138.06 (2C), 141.67, 143.38, 149.85, 152.67 ppm. M (C13H12IN3)¼
337.2. MS (EIþ): m/z: 337.0 (Mþ). HRMS (EIþ): Mþ calcd for
C
13H12IN3 337.0076; found 337.0081.
4.6.17. 4-[(E)-(3-Iodophenyl)azo]aniline (14a). According to GP3
with N,N-diallyl-4-[(E)-(3-iodophenyl)azo]aniline (10a, 2.02 g,
5.00 mmol) in CH2Cl2 (25 mL) the double bond isomerization was
1218, 1104, 885, 858, 758 cmꢁ1 1H NMR (500 MHz, CDCl3, 25 ꢀC,
.
TMS):
d¼2.65 (s, 3H), 4.01 (s, 2H), 6.51 (dd, J¼8.6/2.7 Hz,1H), 6.57 (d,
J¼2.8 Hz, 1H), 7.20 (t, J¼7.9 Hz, 1H), 7.64 (d, J¼8.8 Hz, 1H), 7.67e7.72
caused by RuClH(CO) (PPh3)3 (48 mg, 50 mmol) and heating for 4 h.
(m, 1H), 7.77e7.85 (m, 1H), 8.15 (t, J¼1.8 Hz, 1H) ppm 13C NMR
The subsequent hydrolysis was induced by adding of hydroxyl-
amine hydrochloride (3.47 g, 50.0 mmol) and triethylamine (2.53 g,
25.0 mmol) and heating for 6 h 14a was obtained as orange solid
(1.48 g, 92%). TLC: Rfz0.3 (pentane/CH2Cl2¼1/1). Mp: 88 ꢀC. IR
(KBr): ṽ¼3447, 3365, 1618, 1597, 1503, 1459, 1427, 1397, 1287, 1218,
(126 MHz, CDCl3, 25 ꢀC, TMS):
d¼17.73, 94.55, 112.89, 115.75, 117.34,
122.92, 130.40, 130.47, 137.99, 141.86, 143.34, 149.97, 154.19 ppm. M
(C13H12IN3)¼337.2. MS (EIþ): m/z: 337.0 (Mþ). HRMS (EIþ): Mþ calcd
for C13H12IN3 337.0076; found 337.0072.
1138, 832 cmꢁ1. 1H NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d¼4.08 (s,
4.6.21. (E)-(4-Iodophenyl)phenyldiazene (15a). According to GP4
starting from 4-[(E)-(4-iodophenyl)azo]aniline (13a, 162 mg,
0.50 mmol) in THF (10 mL), 50% wt solution of hypophosphorous
acid (1.32 g,10.0 mmol) and sodium nitrite (105 mg,1.00 mmol) 15a
was obtained as orange solid (115 mg, 75%). TLC: Rfz0.3 (pentane).
Mp: 105 ꢀC. IR (KBr): ṽ¼3055, 1636, 1561, 1459, 1441, 1403, 1204,
2H), 6.70e6.74 (m, 2H), 7.21 (t, J¼7.9 Hz, 1H), 7.69e7.72 (m, 1H),
7.77e7.83 (m, 3H), 8.17 (t, J¼1.8 Hz, 1H) ppm 13C NMR (126 MHz,
CDCl3, 25 ꢀC, TMS):
130.54, 138.29, 145.28, 150.05, 153.84 ppm. M (C12H10IN3)¼323.1.
MS (EIþ): m/z: 323.0 (Mþ). HRMS (EIþ): Mþ calcd for C12H10IN3
322.9920; found 322.9920.
d
¼94.62,114.60 (2C),123.06,125.46 (2C),130.14,
1148, 1051, 992, 914, 880, 793, 768, 761, 685 cmꢁ1 1H NMR
.
(400 MHz, CDCl3, 25 ꢀC, TMS):
d¼7.46e7.55 (m, 3H), 7.65 (d,
4.6.18. 3-Chloro-4-[(E)-(3-iodophenyl)azo]aniline (14b). According
to GP3 with N,N-diallyl-3-chloro-4-[(E)-(4-iodophenyl)azo]aniline
(10b, 2.19 g, 5.00 mmol) in CH2Cl2 (25 mL) the double bond
J¼8.5 Hz, 2H), 7.86 (d, J¼8.5 Hz, 2H), 7.89e7.94 (m, 2H). 13C NMR
(101 MHz, CDCl3, 25 ꢀC, TMS):
d
¼97.69, 122.99 (2C), 124.49 (2C),
129.16 (2C), 131.36, 138.36 (2C), 151.94, 152.46 ppm. M (C12H9IN2)¼
308.1. MS (EIþ) m/z (%): 308.0 (57, Mþ), 230.0 (11), 203.0 (40), 152.1
(15), 105.0 (52), 77.0 (100), 76.0 (36). HRMS (EIþ): Mþ calcd for
isomerization was caused by RuClH(CO) (PPh3)3 (48 mg, 50 mmol)
and heating for 4 h. The subsequent hydrolysis was induced by
adding of hydroxylamine hydrochloride (3.47 g, 50.0 mmol) and
triethylamine (2.53 g, 25.0 mmol) and heating for 6 h 14b was
obtained as orange solid (1.58 g, 88%). TLC: Rfz0.3 (pentane/
CH2Cl2¼1/1). Mp: 112 ꢀC. IR (KBr): ṽ¼3448, 3434, 3343, 1615, 1593,
1488, 1419, 1407, 1301, 1289, 1238, 1131, 1044, 899, 864, 818, 782,
C12H9IN2 307.9810; found 307.9798.
4 . 6 . 2 2 . ( E ) - ( 2 -C h l o ro p h e nyl ) - ( 4 - i o d o p h e nyl ) d i a z e n e
(15b). According to GP4 starting from 3-chloro-4-[(E)-(4-
iodophenyl)azo]aniline (13b, 180 mg, 0.50 mmol) in THF (10 mL),
50% wt solution of hypophosphorous acid (1.32 g, 10.0 mmol) and
sodium nitrite (105 mg, 1.00 mmol) 15b was obtained as orange
solid (112 mg, 66%). TLC: Rfz0.25 (pentane). Mp: 101 ꢀC. IR (KBr):
ṽ¼3063, 1636, 1577, 1568, 1480, 1469, 1390, 1149, 1050, 1004, 830,
672 cmꢁ1. 1H NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d
¼4.14 (s, 2H),
6.56 (dd, J¼8.9/3.1 Hz, 1H), 6.80 (d, J¼2.9 Hz, 1H), 7.21 (t, J¼7.9 Hz,
1H), 7.69 (d, J¼8.7 Hz, 1H), 7.73 (d, J¼7.9 Hz, 1H), 7.86 (d, J¼7.9 Hz,
13
1H), 8.21 (t, J¼1.6 Hz, 1H) ppm C NMR (126 MHz, CDCl3, 25 ꢀC,
TMS):
d
¼94.55, 113.51, 114.91, 118.88, 123.00, 130.53, 130.94,
760, 717 cmꢁ1
.
1H NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d¼7.32 (t,
138.65, 138.74, 140.70, 150.49, 153.84 ppm. M (C12H9ClIN3)¼357.6.
J¼7.6 Hz, 1H), 7.39 (t, J¼7.6 Hz, 1H), 7.55 (d, J¼7.9 Hz, 1H), 7.65e7.71
Please cite this article in press as: Lutz, T. A.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.02.011

10
T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
(m, 3H), 7.86 (d, J¼8.2 Hz, 2H) ppm 13C NMR (126 MHz, CDCl3, 25 ꢀC,
dissolved in CH2Cl2 (5 mL) and the mixture was cooled to 0 ꢀC.
Boron trifluoride etherate (106 mg, 0.75 mmol, 1.50 equiv) was
added and the mixture was stirred for 5 min at 0 ꢀC. Then tert-butyl
nitrite (103 mg, 1.00 mmol, 2.00 equiv) was added dropwise and
the mixture was stirred for 16 h (0 ꢀC to rt). Afterwards pentane
(10 mL) was added and the precipitated diazonium salt was filtered
off and washed with pentane. The residue was heated to 120 ꢀC for
2 h and the obtained product was directly purified by flash chro-
matography (eluting with pentane) to give 15 as orange solid
(102 mg, 63%). TLC: Rfz0.2 (pentane). Mp: 128 ꢀC. IR (KBr): ṽ¼3059,
1595, 1569, 1498, 1473, 1389, 1229, 1127, 1005, 840 cmꢁ1. 1H NMR
TMS):
d¼98.48, 117.46, 124.83 (2C), 127.25, 130.74, 131.98, 135.59,
138.39 (2C), 148.42, 151.96 ppm. M (C12H8ClIN2)¼342.6. MS (EIþ)
m/z (%): 344.0 (22, Mþ), 343.0 (10, Mþ), 342.0 (66, Mþ), 231.0 (69),
203.0 (100), 152.1 (13), 139.0 (24) 111.0 (56), 76.0 (50), 75.0 (21).
HRMS (EIþ): Mþ calcd for C12H8ClIN2 341.9421; found 341.9413.
4 . 6 . 2 3 . ( E ) - ( 2 - F l u o r o p h e nyl ) - ( 4 - i o d o p h e nyl ) d i a z e n e
(15c). According to GP4 starting from 3-fluoro-4-[(E)-(4-
iodophenyl)azo]aniline (13c, 171 mg, 0.50 mmol) in THF (10 mL),
50% wt solution of hypophosphorous acid (1.32 g, 10.0 mmol) and
sodium nitrite (105 mg,1.00 mmol) 15c was obtained as orange solid
(111 mg, 68%). TLC: Rfz0.25 (pentane). Mp: 115 ꢀC. IR (KBr): ṽ¼3063,
1628, 1605, 1586, 1576, 1567, 1480, 1389, 1264, 1213, 1151, 1103, 1049,
(400 MHz, CDCl3, 21 ꢀC, TMS):
d
¼7.15e7.22 (m, 2H), 7.59e7.65 (m,
2H), 7.82e7.87 (m, 2H), 7.92 (dd, J¼8.2/5.5 Hz, 2H) ppm 13C NMR
(126 MHz, CDCl3, 21 ꢀC, TMS):
d
¼97.85, 116.25 (d, 2JCF¼22.9 Hz, 2C),
1005, 827, 756 cmꢁ1. 1H NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d¼7.20
124.54 (2C), 125.14 (d, JCF¼9.0 Hz, 2C), 138.47 (2C), 149.03 (d,
4JCF¼3.0 Hz), 151.81, 164.66 (d, 1JCF¼252.6 Hz) ppm. M (C12H8FIN2)¼
326.1. MS (EIþ) m/z (%): 326.1 (100, Mþ), 231.0 (24), 203.0 (63),
123.1 (34), 95 (75), 76.1 (44). HRMS (EIþ): Mþ calcd for C12H8FIN2
325.9716; found 325.9716.
3
(t, J¼7.7 Hz, 1H), 7.23e7.29 (m, 1H), 7.42e7.48 (m, 1H), 7.66 (d,
J¼8.5 Hz, 2H), 7.74 (td, J¼7.9/1.6 Hz, 1H), 7.85 (d, J¼8.4 Hz, 2H) ppm
13C NMR (126 MHz, CDCl3, 25 ꢀC, TMS):
d
¼98.30, 117.12 (d,
2JCF¼19.5 Hz), 117.64, 124.29 (d, 3JCF¼3.1 Hz), 124.66 (2C), 132.85 (d,
2
3JCF¼8.6 Hz), 138.36 (2C), 140.42 (d, JCF¼7.3 Hz), 152.01, 160.19 (d,
1JCF¼258.4 Hz) ppm. M (C12H8FIN2)¼326.1. MS (EIþ) m/z (%): 326.0
(65, Mþ), 231.0 (73), 203.0 (100), 123.0 (14), 95.1 (30), 76.1 (53), 75.0
(17). HRMS (EIþ): Mþ calcd for C12H8FIN2 325.9716; found 325.9716.
4.6.27. 4-[(E)-(4-Iodophenyl)azo]naphthalen-1-amine
(19a). According to GP2 solution A was made of 4-iodoaniline
(1.12 g, 5.00 mmol) in EtOH (15 mL) and 2 N HCl (7.5 mL,
15.0 mmol), sodium nitrite (0.38 g, 5.50 mmol) in water (5 mL) and
amidosulfuric acid (0.10 g, 1.0 mmol). Solution B was obtained from
1-naphthylamine (0.73 g, 5.0 mmol) in EtOH (100 mL) and H2O
(50 mL) and an addition of 2 N HCl (5.0 ml, 10 mmol). The resulting
pH was between 1 and 2. The reaction time was 1 h at 0 ꢀC. 19a was
obtained as dark red solid (1.78 g, 95%). TLC: Rfz0.4 (pentane/
CH2Cl2¼1/1). Mp: 204 ꢀC. IR (KBr): ṽ¼3416, 3298, 3186, 3012, 1638,
1571,1514,1464,1385,1336,1191,1142, 1052, 999, 826, 755 cmꢁ1. 1H
4 . 6. 24 . (E ) - ( 2 - M e t hylp h e nyl) - ( 4 - i od o p h e nyl ) d i a z e n e
(15d). According to GP4 starting from 3-methyl-4-[(E)-(4-
iodophenyl)azo]aniline (13d, 168 mg, 0.50 mmol) in THF (10 mL),
50% wt solution of hypophosphorous acid (1.32 g, 10.0 mmol) and
sodium nitrite (105 mg,1.00 mmol) 15d was obtained as orange solid
(116 mg, 72%). TLC: Rfz0.25 (pentane). Mp: 105 ꢀC. IR (KBr): ṽ¼3063,
2923, 1576, 1564, 1477, 1459, 1427, 1390, 1058, 1052, 1003, 832, 764,
721 cmꢁ1
7.22e7.28 (m, 1H), 7.29e7.39 (m, 2H), 7.59e7.66 (m, 3H), 7.79e7.87
(m, 2H) ppm 13C NMR (101 MHz, CDCl3, 25 ꢀC, TMS):
.
1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d¼2.70 (s, 3H),
NMR (400 MHz, CDCl3, 21 ꢀC, TMS):
d
¼4.66 (s, 2H), 6.82 (d,
J¼8.3 Hz, 1H), 7.56 (ddd, J¼8.3/6.8/1.3 Hz, 1H), 7.66 (ddd, J¼8.4/6.8/
1.2 Hz, 1H), 7.70e7.73 (m, 2H), 7.82 (d, J¼8.5 Hz, 1H), 7.84e7.87 (m,
2H), 7.94 (d, J¼8.3 Hz, 1H), 9.02 (d, J¼8.5 Hz, 1H) ppm 13C NMR
d¼17.52, 97.34,
115.36, 124.51 (2C), 126.42, 131.30 (2C), 138.27 (2C), 138.41, 150.46,
152.24 ppm. M (C13H11IN2)¼322.1. MS (EIþ) m/z (%): 322.0 (59, Mþ),
231.0 (11), 203.0 (42), 195.1 (15), 119.1 (19), 91.1 (100), 76.0 (21), 65.0
(16). HRMS (EIþ): Mþ calcd for C13H11IN2 321.9967; found 321.9957.
(101 MHz, CDCl3, 21 ꢀC, TMS):
d
¼95.90, 109.26, 114.31, 120.73,
122.53, 124.17, 124.44 (2C), 125.59, 127.41, 133.38, 138.35 (2C),
140.37, 146.81, 153.04 ppm. M (C16H12IN3)¼373.2. MS (ESIþ) m/z:
374.1 ([MþH]þ). HRMS (EIþ): calcd for C16H12IN3, 373.0076; found
373.0069.
4.6.25. (E)-(4-Chlorophenyl)-(4-iodophenyl)diazene (16). 4-[(E)-(4-
Iodophenyl)azo]aniline (13a, 162 mg, 0.50 mmol, 1.00 equiv) was
dissolved in CCl4 (10 mL). 4-dodecylbenzenesulfonic acid (163 mg,
0.50 mmol, 1.00 equiv) was added and the mixture was stirred for
5 min at room temperature. Then tert-butyl nitrite (310 mg,
3.00 mmol, 6.00 equiv) was added and the reaction mixture was
stirred at room temperature until the initial aromatic amine dis-
appeared (TLC, pentane/ethyl acetate¼8/2; the reaction was com-
plete after about 2 h). Triethylamine (51 mg, 0.50 mmol, 1.00 equiv)
was added and the reaction mixture was heated to 80 ꢀC for 2 h
resulting in an instant nitrogen evolving. After cooling to room
temperature again, H2O (10 mL) was added and the product was
extracted with CH2Cl2 (3ꢂ). The combined organic layers were
dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude product was purified by flash chromatography
(pentane) to give 14 as orange solid (90 mg, 52%). TLC: Rfz0.2
(pentane). Mp: 178 ꢀC. IR (KBr): ṽ¼3064, 1575, 1565, 1472, 1389,
1088, 1050, 1003, 835 cmꢁ1. 1H NMR (400 MHz, CDCl3, 21 ꢀC, TMS):
4.6.28. 4-[(E)-(3-Iodophenyl)azo]naphthalen-1-amine
(19b). According to GP2 solution A was made of 3-iodoaniline
(1.12 g, 5.00 mmol) in EtOH (15 mL) and 2 N HCl (7.5 mL,
15.0 mmol), sodium nitrite (0.38 g, 5.50 mmol) in water (5 mL) and
amidosulfuric acid (0.10 g, 1.0 mmol). Solution B was obtained from
1-naphthylamine (0.73 g, 5.0 mmol) in EtOH (100 mL) and H2O
(50 mL) and an addition of 2 N HCl (5.0 mL, 10 mmol). The resulting
pH was between 1 and 2. The reaction time was 1 h at 0 ꢀC. 19b was
obtained as dark red solid (1.76 g, 94%). TLC: Rfz0.4 (pentane/
CH2Cl2¼1/1). Mp: 123 ꢀC. IR (KBr): ṽ¼3396, 3328, 3235, 3054, 1647,
1619, 1574, 1515, 1466, 1400, 1339, 1213, 1159, 992, 880, 845, 832,
790, 756 cmꢁ1. 1H NMR (400 MHz, CDCl3, 21 ꢀC, TMS):
d¼4.66 (s,
2H), 6.79 (d, J¼8.4 Hz, 1H), 7.25 (t, J¼7.9 Hz, 1H), 7.52e7.58 (m, 1H),
7.63e7.69 (m, 1H), 7.73 (dt, J¼8.0/1.3 Hz, 1H), 7.80 (d, J¼8.5 Hz, 1H),
7.90e7.97 (m, 2H), 8.30 (t, J¼1.7 Hz, 1H), 9.03 (d, J¼8.4 Hz, 1H) ppm
13C NMR (101 MHz, CDCl3, 21 ꢀC, TMS):
d
¼94.67 (s, 1C), 109.02 (d,
d
¼7.46e7.51 (m, 2H), 7.61e7.67 (m, 2H), 7.82e7.90 (m, 4H) ppm 13
C
1C), 114.29 (d, 1C), 120.56 (d, 1C), 122.27 (s, 1C), 123.28 (d, 1C),
124.01 (d, 1C), 125.44 (d, 1C), 127.35 (d, 1C), 130.35 (d, 1C), 130.56 (d,
1C), 133.24 (s, 1C), 138.16 (d, 1C), 140.06 (s, 1C), 146.82 (s, 1C), 154.32
(s, 1C) ppm. M (C16H12IN3)¼373.19. MS (ESIþ) m/z: 374.1 ([MþH]þ).
HRMS (EIþ): calcd for C16H12IN3, 373.0076; found 373.0069.
NMR (126 MHz, CDCl3, 21 ꢀC, TMS):
d
¼98.20, 124.36 (2C), 124.63
(2C), 129.55 (2C), 137.43, 138.54 (2C), 150.87, 151.83 ppm. M
(C12H8ClIN2)¼342.6. MS (EIþ) m/z (%): 344 (33), 342.0 (100, Mþ),
231.0 (42), 203.0 (90), 139.1 (32), 113 (20), 111.1 (65), 76.1 (45).
HRMS (EIþ): Mþ calcd for C12H8ClIN2 341.9421; found 341.9421.
4.6.29. (E)-(4-Iodophenyl)-(1-naphthyl)diazene (20a). According to
GP4 starting from 16a (1.50 g, 4.00 mmol) in THF (80 mL), 50% wt
solution of hypophosphorous acid (10.6 g, 80.0 mmol) and sodium
4.6.26. (E)-(4-Fluorophenyl)-(4-iodophenyl)diazene (17). 4-[(E)-(4-
Iodophenyl)azo]aniline (13a, 162 mg, 0.50 mmol, 1.00 equiv) was
Please cite this article in press as: Lutz, T. A.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.02.011

T.A. Lutz et al. / Tetrahedron xxx (2016) 1e11
11
7. Feringa, B. L.; van Delden, R. A.; Koumura, N.; Geertsema, E. M. Chem. Rev. 2000,
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nitrite (0.56 g, 8.00 mmol) 20a was obtained as red solid (1.03 g,
72%). TLC: Rfz0.2 (pentane). Mp: 116 ꢀC. IR (KBr): ṽ¼3045, 2999,
1577, 1564, 1508, 1473, 1391, 1343, 1297, 1213, 1094, 1054, 1002, 862,
823, 797, 768 cmꢁ1 1H NMR (400 MHz, CDCl3, 21 ꢀC, TMS):
.
10. Tazuke, S.; Kurihara, S.; Ikeda, T. Chem. Lett. 1987, 16, 911.
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Giesselmann, F.; Laschat, S. Phys. Chem. Chem. Phys. 2015, 17, 8382.
d
¼7.52e7.60 (m, 2H), 7.64 (ddd, J¼8.4/6.8/1.3 Hz, 1H), 7.72e7.77 (m,
2H), 7.81 (dd, J¼7.5/1.0 Hz, 1H), 7.85e7.89 (m, 2H), 7.91 (d, J¼8.2 Hz,
1H), 7.98 (d, J¼8.1 Hz, 1H), 8.89 (d, J¼8.4 Hz, 1H) ppm 13C NMR
€
13. Schonberger, M.; Althaus, M.; Fronius, M.; Clauss, W.; Trauner, D. Nat. Chem.
(101 MHz, CDCl3, 21 ꢀC, TMS):
d
¼97.89, 112.09, 123.46, 124.84 (2C),
2014, 6, 712.
14. Broichhagen, J.; Podewin, T.; Meyer-Berg, H.; von Ohlen, Y.; Johnston, N. R.;
125.72, 126.66, 127.10, 128.10, 131.47, 131.89, 134.43, 138.52 (2C),
147.60, 152.55 ppm. M (C16H11IN2)¼358.18. MS (ESIþ) m/z: 359.0
([MþH]þ). HRMS (EIþ): calcd for C16H11IN2, 357.9967; found
357.9963.
€
Jones, B. J.; Bloom, S. R.; Rutter, G. A.; Hoffmann-Roder, A.; Hodson, D. J.;
Trauner, D. Angew. Chem., Int. Ed. 2015, http://dx.doi.org/10.1002/anie.
201506384
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4.6.30. (E)-(3-Iodophenyl)-(1-naphthyl)diazene (20b). According to
GP4 starting from 16b (1.50 g, 4.00 mmol) in THF (80 mL), 50% wt
solution of hypophosphorous acid (10.6 g, 80.0 mmol) and sodium
nitrite (0.56 g, 8.00 mmol) 20b was obtained as red solid (0.98 g,
68%). TLC: Rfz0.2 (pentane). Mp: 95 ꢀC. IR (KBr): ṽ¼3048, 1562,
1508, 1454, 1403, 1386, 1344, 1206, 990, 909, 888, 800, 789, 768,
Nat. Commun. 2015, 6, 7118.
18. Rullo, A.; Reiner, A.; Reiter, A.; Trauner, D.; Isacoff, E. Y.; Woolley, G. A. Chem.
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19. Laprell, L.; Repak, E.; Franckevicius, V.; Hartrampf, F.; Terhag, J.; Hollmann, M.;
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5b00234
682 cmꢁ1
.
1H NMR (400 MHz, CDCl3, 21 ꢀC, TMS):
d
¼7.29 (t,
J¼7.9 Hz, 1H), 7.53e7.61 (m, 2H), 7.64e7.69 (m, 1H), 7.79e7.83 (m,
2H), 7.93 (d, J¼8.2 Hz, 1H), 7.98e8.03 (m, J¼10.8/5.4/4.5 Hz, 2H),
8.36 (t, J¼1.8 Hz, 1H), 8.91 (d, J¼8.4 Hz,1H) ppm 13C NMR (101 MHz,
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CDCl3, 21 ꢀC, TMS):
d
¼97.89, 112.09, 123.46, 124.84, 125.72, 126.66,
23. Quandt, G.; Hofner, G.; Pabel, J.; Dine, J.; Eder, M.; Wanner, K. T. J. Med. Chem.
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24. Merino, E. Chem. Soc. Rev. 2011, 40, 3835.
127.10, 128.10, 131.47, 131.89, 134.43, 138.52, 147.60, 152.55 ppm. M
(C16H11IN2)¼358.18. MS (ESIþ) m/z: 359.0 ([MþH]þ). HRMS (EIþ):
calcd for C16H11IN2, 357.9967; found 357.9963.
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Please cite this article in press as: Lutz, T. A.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.02.011