On the coupling of aryldiazonium salts with N,N-disubstituted 2-aminothiophenes and some of their carbocyclic and heterocyclic analogues

Article abstract of DOI:10.1039/b006803i

As exemplified with the morpholino derivatives 7, N,N-disubstituted 2-aminothiophenes couple, depending on the substitution pattern at C(5), with aryldiazonium salts 1 either at their C(3) or C(5) position yielding the corresponding 3-arylazo-2-morpholinothiophenes 9 or, under elimination of the substituent at C(5), 5-arylazo-2-morpholinothiophenes 10. This reaction contrasts to the behaviour of 5-morpholinothiazoles 8 and dimethylaniline 13 towards the same diazonium salts 1 which are unable to couple with these compounds if their C(5) or C(4) position, respectively, is not substituted by H, COOH or CHO. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b006803i

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On the coupling of aryldiazonium salts with N,N-disubstituted
2-aminothiophenes and some of their carbocyclic and heterocyclic
analogues
1
Horst Hartmann* and Ines Zug
Fachbereich Chemie, Fachhochschule Merseburg, Geusaer Str. D-06217 Merseburg, Germany
Received (in Cambridge, UK) 21st August 2000, Accepted 27th September 2000
First published as an Advance Article on the web 21st November 2000
As exemplified with the morpholino derivatives 7, N,N-disubstituted 2-aminothiophenes couple, depending on the
substitution pattern at C(5), with aryldiazonium salts 1 either at their C(3) or C(5) position yielding the corresponding
3-arylazo-2-morpholinothiophenes 9 or, under elimination of the substituent at C(5), 5-arylazo-2-morpholinothio-
phenes 10. This reaction contrasts to the behaviour of 5-morpholinothiazoles 8 and dimethylaniline 13 towards the
same diazonium salts 1 which are unable to couple with these compounds if their C(5) or C(4) position, respectively,
is not substituted by H, COOH or CHO.
particular substituted benzimidazoles,4 they have to be
Introduction
prepared by other synthetic routes.5
N,N-Dialkylanilines 2a are known to be highly reactive towards
N,N-Disubstituted 2-aminothiophenes 2b as heterocyclic
electrophilic reagents. For example, with aryldiazonium salts 1
analogues of the N,N-dialkylanilines 2a exhibit a similar
they yield deeply coloured 4-dialkylamino-substituted arylazo-
reactivity towards electrophilic reagents. Thus, with aryldiazo-
benzenes 3a (Scheme 1).1 A few of them are of some practical
nium salts 1 they are transformed, as long as their 5-position
is unsubstituted, into N,N-disubstituted 2-amino-5-arylazo-
thiophenes 3b.6 Otherwise, e.g. if they are substituted by a
phenyl group at C(5), they yield, contrary to the N,N-dialkyl-
anilines 2a, N,N-disubstituted 2-amino-3-arylazothiophenes
4b.7 Obviously, the steric hindrance of an ortho-dialkylamino
substituent to the attack of an electrophilic aryldiazonium salt
1 is significantly lower for the five-membered thiophene moiety
than for the six-membered benzene ring.
A surprising result which contrasts this finding was
reported by Russian authors. They observed the formation of
2-amino-5-arylazothiophenes 3b if the 5-formyl derivatives
of N,N-disubstituted 2-aminothiophenes 2b (R1 = CH᎐O) were
᎐
allowed to react with aryldiazonium salts.6a Obviously, the 5-
formyl group in the starting material 2b split off in the course
of the coupling reaction.
To see if this finding is peculiar to a particular substituted
2-dialkylaminothiophene derivative or a more general one
the reaction of some aryldiazonium salts 1 towards a series of
2-dialkylaminothiophenes 2b with different substituents at
their 5-position was studied. As model compounds for this
study the nitro-substituted benzenediazonium salts 1a and 1b8
as well as the 2-morpholinothiophenes 7a–7p are used. The
2-morpholino-substituted thiophenes 7b–7p were prepared by
known routes either from their corresponding parent com-
pound 7a9 or from acyclic precursors, such as from the
Scheme 1
N-[3-amino(thioacryloyl)]morpholines 510 and the halomethyl-
carbonyl compounds 6 (Scheme 2).11
interest, e.g. as acid–base indicators (C.I. Acid Orange 52)
To check the results of the reaction of the aryldiazonium
salts 1 with the 5-substituted 2-morpholinothiophenes 7, e.g. to
see if isomeric products or mixtures of products were formed,
not only were the products isolated and structurally character-
ised but the reaction mixture that resulted from the mixing of
the components which were then left to stand for some time at
room temperature was also monitored by TLC.
or as disperse dyes for dyeing synthetic fibres or plastics (C.I.
Disperse Blue 354).2 Very recently, 4-dialkylamino-substituted
arylazobenzenes 3a have been used as model compounds for
materials with non-linear optical properties.3
The coupling reaction of aryldiazonium salts 1 with dialkyl-
anilines 2a giving rise to the formation of 4-dialkylamino-
substituted diarylazobenzenes 3a occurs only if the 4-position
of 2a is unsubstituted. Otherwise, no reaction occurs, meaning
that the isomeric 2-dialkylamino-substituted diarylazobenzenes
4a, which would be the alternative coupling products, are not
available by this method. Because these 2-aminoazo com-
pounds are of interest, e.g. as starting materials for preparing
Results and discussion
Of the 5-substituted 2-morpholinothiophenes 7 studied not
all reacted with the aryldiazonium salts 1. Thus, a reaction
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J. Chem. Soc., Perkin Trans. 1, 2000, 4316–4320
This journal is © The Royal Society of Chemistry 2000
DOI: 10.1039/b006803i

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However, from compounds 7b and 7c mixtures of two prod-
ucts are formed. Whereas from 7b the 5-arylazo-substituted
2-morpholinothiophenes 10 are formed as the main products,
from 7c the 3-arylazo-substituted 5-acetyl-2-morpholinothio-
phenes 9c are mainly formed. In the reaction of compound
7b with the aryldiazonium salts 1 the corresponding 3-arylazo
compound 9b was obtained as a by-product. These products
could be, as exemplfied with the 3-(4-nitrophenylazo)-
substituted compound 9b, isolated and unambiguously charac-
terised. In the reaction of compound 7c with the aryldiazonium
salts 1 the corresponding 5-arylazo-substituted compounds
10a are formed as by-products. Because they were only
formed in trace amounts they were identified by TLC. Neither
with compounds 7b and 7c nor with the other 5-substituted 2-
morpholinothiophenes 7 studied, the conceivable bisarylazo-
substituted 2-morpholinothiophenes 11 formed. Obviously,
the introduction of one arylazo moiety in the thiophene ring
prevents, similarly to an acceptor-substituted phenyl or vinyl
moiety as mentioned before, a further coupling reaction giving
rise to the formation of 3,5-bisarylazo-substituted thiophenes,
even if the highly reactive 2,4-dinitrophenyl diazonium salt 1b is
used as diazo compound.
An interesting result was obtained, however, by studying the
reaction of some of the 5-arylazo-substituted 2-morpholino-
thiophenes 10 prepared towards the nitrophenydiazonium
salts 1. Whereas no reaction was observed, as indicated by
TLC, by allowing the 5-(2,4-dinitrophenylazo)-substituted
2-morpholinothiophene 10aЈ to react with the 4-nitrophenyl-
diazonium salt 1a a reaction was observed between the 5-(4-
nitrophenylazo)-substituted 2-morpholinothiophene 10a and
the 2,4-dinitrophenyldiazonium salt 1b. In this case the 5-(2,4-
dinitrophenylazo)-substituted 2-morpholinothiophene 10aЈ
was formed. Obviously, the 4-nitrophenylazo moiety at C(5) of
the starting thiophene derivative 10a can be replaced by the
more electrophilic 2,4-dinitrophenylazo moiety and not the
2,4-dinitrophenylazo moiety at the same position of compound
10aЈ by the less electrophilic 4-nitrophenylazo moiety.
The formation of the above mentioned 3,5(bisarylazo)-
substituted 2-morpholinothiophenes 11 was never observed.
This means that an arylazo group at C(5) of a 2-morpholino-
thiophene moiety completely prevents the further attack of an
aryldiazonium salt at C(3) of these products 10, even if the
reagents used are substituted by two strong electron accepting
nitro groups.
Scheme 2
was observed only with the 5-acyl- and 5-cyano-substituted
2-morpholinothiophenes 7b–7l as well as with the 5-phenyl-
substituted 2-morpholinothiophene 7m. No reaction was
observed with the 2-morpholinothiophenes 7n–7p which are
substituted at their C(5) position by an acceptor-substitued aryl
or vinyl moiety, such as a 4-nitrophenyl or a dicyanovinyl
moiety (Scheme 3).
Whereas from 7c–7j as well as from 7l and 7m the corre-
sponding 3-arylazo-substituted 2-morpholinothiophenes 9c–9j,
9l, and 9m, respctively, are formed, from 7a–7c and 7k, which
was prepared from the corresponding alkyl 5-carboxylates 7i or
7j by saponification with sodium hydroxide in methanolic solu-
tion, the 5-arylazo-substituted 2-morpholinothiophenes 10 are
formed. The latter compounds are also available from the
parent 2-morpholinothiophene 7a and the same aryldiazonium
salts 1. Due to the synthetic procedure for obtaining the corre-
sponding azo compounds, namely allowing the required com-
ponents to react in acetic acid containing some sulfuric acid
and subsequent addition of methanol after the reaction, some
azo compounds precipitate as hydrogen sulfates.
The previous results stimulated us to check the reactivity of
some 5-substituted 2-morpholinothiazoles 8 and 4-substituted
N,N-dimethylanilines 13 towards the aryldiazonium salts 1. As
model compounds the 2-morpholinothiazole derivatives 8a–8d,
8o, and 8p, as well as the N,N-dimethylaniline derivatives 13a,
13b, 13k, and 13l were used. These heterocyclic thiazole deriv-
atives were prepared in close analogy to the 5-substituted
2-morpholinothiophenes 7 from the halomethyl compounds 6
By checking the reaction mixtures by TLC it was found that
from compounds 7a and 7k the corresponding 5-arylazo-
substituted 2-morpholinothiophenes 10 are formed exclusively.
Scheme 3
J. Chem. Soc., Perkin Trans. 1, 2000, 4316–4320
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and the corresponding azaanalogues of the aminothioacryl-
amides 5.12
either as previously described in the reported literature (7a,9c
7b,9d 7i and 7j,15 7k,16 7m,17 7n–7p,11a 8a,18 8b,19 8d,12a 8o,11e and
8p11a) or as follows.
The reactions were monitored by TLC as well as performed
on a preparative scale. It was found that no reactions occur with
the 2-morpholinothiazole derivatives 8b–8d, 8o, and 8p, or with
the 4-cyano-substituted dimethylaniline dervatives 13l. In con-
trast, coupling reactions occur with the 2-morpholinothiazole
derivatives 8a and with the dimethylaniline derivatives 13a,
13b, and 13k. Thus, in this way the 5-nitrophenyl-substituted
2-morpholinothiazoles 12 and the 4-dimethylamino-4Ј-nitro-
azobenzenes 14 are available. These compounds have been pre-
viously prepared from their unsubstituted parent compound 8a
or 13a, respectively, by coupling with the nitrophenyldiazonium
salts 1 (Scheme 4).6c
5-Substituted 2-morpholinothiophenes 7c–7h and 7l–7p (general
procedure)
A mixture of 3-[dimethylamino(thioacryloyl)]morpholide 5
(R = CH3)20 (10 mmol, 2.0 g) and the appropriate halomethyl
compound 6 (10 mmol) in acetonitrile (25 mL) was refluxed for
2 min and subsequently mixed with triethylamine (10 mL).
After cooling and dilution of the reaction mixture with water
(5 mL) the precipitate formed was isolated by filtration and
recrystallised.
The following 2-morpholinothiophenes 7 were so prepared.
5-Acetyl-2-morpholinothiophene 7c. (1.7 g, 80%) from chloro-
acetone 6c; mp 114–116 ЊC (Found: C, 56.5; H, 6.2; N, 6.7.
C10H13NO2S requires C, 56.9; H, 6.4; N, 6.7%); δH(300 MHz;
CDCl3; Me4Si) 2.41 (3H, s, CH3CO), 3.25 (4H, t, NCH2), 3.81
(4H, t, OCH2), 6.03 (1H, d, CH), 7.43 (1H, d, CH).
5-Benzoyl-2-morpholinothiophene 7d. (2.3 g, 84%) from
phenacyl bromide 6d; mp 127–129 ЊC (Found: C, 66.0; H, 5.5;
N, 5.3. C15H15NO2S requires C, 65.9; H, 5.5; N, 5.1%); δH(300
MHz; CDCl3; Me4Si) 3.32 (4H, t, NCH2), 3.85 (4H, t, OCH2),
6.09 (1H, d, CH), 7.39 (1H, d, CH), 7.42–7.52 (3H, m, CH),
7.75–7.77 (2H, m, CH).
5-(4-Methylbenzoyl)-2-morpholinothiophene 7e. (1.5 g, 52%)
from 4-methylphenacyl bromide 6e; mp 169–172 ЊC (Found: C,
66.5, H, 6.0; N, 4.7. C16H17NO2S requires C, 66.9; H, 5.9; N,
4.9%); δH(300 MHz; CDCl3; Me4Si) 2.40 (3H, s, CH3), 3.29 (4H,
t, NCH2), 3.83 (4H, t, OCH2), 6.07 (1H, d, CH), 7.24 (2H, d,
CH), 7.39 (1H, d, CH), 7.66 (2H, d, CH).
Scheme 4
The results obtained with the dimethylaniline derivatives 13
agree in some aspects with findings in the literature. Thus, it
was reported that 4-dimethylaminobenzaldehyde 13b13 and
4-dimethylaminobenzoic acid 13k14 are able, analogously to
their unsubstituted parent compound 13a, to couple with
(het)aryldiazonium salts.
All the prepared arylazo-substituted 2-morpholinothio-
phenes 9 and 10 are, similarly to the known 5-nitrophenyl-
substituted 2-morpholinothiazoles 12 and 4-dimethylamino-4Ј-
nitroazobenzene 14a, deeply coloured compounds which exhibit
intense absorptions in the visible range. Whereas the 3-aryl-
azo-substituted thiophenes 9 are orange coloured products
which absorb at about 500 nm, the 5-arylazo-substituted
2-morpholinothiophenes 10 are deeply magenta coloured com-
pounds which exhibit, depending on the substitution pattern at
their arylazo moiety and on the polarity of the solvent, intense
absorption maxima at about 550 nm.6c
5-(4-Chlorobenzoyl)-2-morpholinothiophene 7f. (2.2 g, 72%)
from 4-chlorophenacyl bromide 6f; mp 168 ЊC (Found: C, 58.3;
H, 4.7; N, 4.4. C15H14ClNO2S requires C, 58.6; H, 4.6; N, 4.6%);
δH(300 MHz; CDCl3; Me4Si) 3.33 (4H, t, NCH2), 3.85 (4H, t,
OCH2), 6.09 (1H, d, CH), 7.35 (1H, d, CH), 7.43 (2H, d, CH),
7.70 (2H, d, CH).
5-(4-Bromobenzoyl)-2-morpholinothiophene 7g. (2.9 g, 82%)
from 4-bromophenacyl bromide 6g; mp 170–171 ЊC (Found: C,
50.9; H, 4.0; N, 4.2. C15H14BrNO2S requires C, 51.1; H, 4.0; N,
4.0%); δH(300 MHz; CDCl3; Me4Si) 3.33 (4H, t, NCH2), 3.85
(4H, t, OCH2), 6.09 (1H, d, CH), 7.35 (1H, d, CH), 7.57–7.66
(4H, m, CH).
The structures of the arylazo compounds 9 and 10 were
unambiguously confirmed by their analytical and spectral data.
Thus, in all the H NMR spectra of the 3-arylazo-substituted
2-morpholinothiophenes 9 a sharp singlet at about 7.00 ppm
1
5-(4-Nitrobenzoyl)-5-morpholinothiophene 7h. (2.5 g, 79%)
from 4-nitrophenacyl bromide 6h; mp 205–206 ЊC (Found: C,
56.4; H, 4.4; N, 8.7. C15H14N3O4S requires C, 56.6; H, 4.4; N,
8.8%); δH(300 MHz; DMSO-d6; Me4Si) 3.37 (4H, t, NCH2),
3.76 (4H, t, OCH2), 6.35 (1H, d, CH), 7.44 (1H, d, CH), 7.92
(2H, d, CH), 8.32 (2H, d, CH).
could be detected. This signal is attributed to the H(4) in the
1
thiophene moiety. In contrast, in the H NMR spectra of the
5-arylazo-substituted 2-morpholinothiophenes 10 two signals
at about 7.00 and 8.00 ppm were detected. Both signals appear
as doublets with coupling constants of 10–12 Hz indicating
the presence of two adjacent protons at the corresponding
thiophene moieties.
5-Cyano-2-morpholinothiophene 7l. (1.0 g, 52%) from chloro-
acetonitrile 6l; mp 129 ЊC (Found: C, 55.2; H, 5.2; N, 14.2; S,
16.2. C9H10N2OS requires C, 55.7; H, 5.2; N, 14.4; S, 16.5%);
δH(300 MHz; CDCl3; Me4Si) 3.21 (4H, t, NCH2), 3.84 (4H, t,
OCH2), 6.01 (1H, d, CH), 7.34 (1H, d, CH).
Experimental
Melting points were determined by means of a heating table
microscope (Boetius). The 1H NMR spectra were recorded with
a Varian 300 MHz spectrometer Gemini 300 or with a JEOL
200 MHz spectrometer JNM FX 200. The UV/Vis spectra were
recorded with a Perkin-Elmer spectrometer Lambda 900. The
elemental analytical data were determined by means of a
LECO analyser CHNS 932. The 2-morpholinothiophenes and
2-morpholinothiazoles 7 and 8, respectively were prepared
5-Acetyl-2-morpholinothiazole. Analogously, by starting from
2-aza-3-morpholinothioacylmorpholide11 and chloroacetone
6c, 5-acetyl-2-morpholinothiazole 8c (1.1 g, 56%) was prepared;
mp 147 ЊC (Found: C, 55.3; H, 6.0; N, 14.1. C9H12N2OS
requires C, 55.1; H, 6.1; N, 14.3%); δH(300 MHz; CDCl3;
Me4Si) 2.43 (3H, s, CH3), 3.58 (4H, t, NCH2), 3.80 (4H, t,
OCH2), 7.80 (1H, s, CH).
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Coupling of the 2-morpholinothiophenes 7, 2-morpholino-
thiazoles 8, and N,N-dimethylanilines 13 with nitro-substituted
benzenediazonium salts 1 (general procedure)
thiophene 7g; mp 260–265 ЊC (Found: C, 50.2; H, 3.5; N,
10.9. C21H17BrN4O4S requires C, 50.3; H, 3.4; N, 11.2%);
λmax(CH2Cl2)/nm 498 (ε/dm3 molϪ1 cmϪ1 = 23400); δH(300
MHz; DMSO-d6; Me4Si) 3.87 (4H, t, NCH2), 4.05 (4H, t,
OCH2), 7.76 (7H, m, CH), 8.29 (2H, d, CH).
To a mixture of the appropriate 2-morpholinothiophene 7, 2-
morpholinothiazole 8 (10 mmol), or N,N-dimethylaniline 13
(10 mmol) in methanol or acetonitrile (25 mL) a solution of the
nitro-substituted benzediazonium salt 1, prepared by diazotis-
ation of the appropriate nitroaniline (10 mmol) dissolved in a
mixture of acetic acid (50 mL) and sulfuric acid (10 mL) with
sodium nitrite (0.7 g, 10 mmol), was added dropwise at room
temperature. After standing at room temperature for 2 h the
resulting mixture was diluted with methanol (50 mL) and water
(100 mL) and the product formed was isolated by filtration. The
dried solution was evaporated and the remaining product was
purified by column chromatography.
2-Morpholino-5-(4-nitrobenzoyl)-3-(4-nitrophenylazo)thio-
phene 9h. (1.3 g, 28%) from 2-morpholino-5-(4-nitrobenzoyl)-
thiophene 7h; mp 262–264 ЊC (Found: C, 53.6; H, 4.1; N, 14.6.
C21H17N5O6S requires C, 54.0; H, 3.6; N, 15.0%); λmax(CH2Cl2)/
nm 498 (ε/dm3 molϪ1 cmϪ1 = 22400); δH(300 MHz; DMSO-d6;
Me4Si) 3.87 (4H, t, NCH2), 4.06 (4H, t, OCH2), 7.75 (1H, s,
CH), 7.80 (2H, d, CH), 7.99 (2H, d, CH), 8.29 (2H, d, CH),
8.38 (2H, d, CH).
5-(Ethoxycarbonyl)-2-morpholino-3-(4-nitrophenylazo)thio-
phene 9i. (2.5 g, 64%) from ethyl 2-morpholinothiophene-5-
carboxylate 7i; mp 199–201 ЊC (Found: C, 52.0; H, 4.9; N, 14.0.
C17H18N4O5S requires C, 52.3; H, 4.6; N, 14.4%); λmax(CH2Cl2)/
nm 491 (ε/dm3 molϪ1 cmϪ1 = 19500); δH(300 MHz; DMSO-d6;
Me4Si) 1.29 (3H, t, CH3), 3.84 (4H, t, NCH2), 3.94 (4H, t,
OCH2), 4.27 (2H, q, OCH2), 7.82 (2H, d, CH), 7.89 (1H, s,
CH), 8.31 (2H, d, CH).
4-Nitrophenyldiazonium hydrogen sulfate 1a as diazo compon-
ent. By using 4-nitrophenyldiazonium hydrogen sulfate 1a as
diazo component the following azo compounds or their hydro-
gen sulfates were prepared.
5-Formyl-2-morpholino-3-(4-nitrophenylazo)thiophene
9b.
(0.7 g, 20%), plus 2-morpholino-5-(4-nitrophenylazo)thiophene
10a, from 5-formyl-2-morpholinothiophene 7b; mp 218–220 ЊC
(Found: C, 52.2; H, 4.0; N, 16.3. C15H14N4O4S requires C, 52.0;
5-Cyano-2-morpholino-3-(4-nitrophenylazo)thiophene 9l. (2.5
g, 73%) from 5-cyano-2-morpholinothiophene 7l; mp 260–
262 ЊC (Found: C, 52.2; H, 3.9; N, 20.0; S, 9.3. C15H13N5O3S
requires C, 52.5; H, 3.8; N, 20.4; S, 9.3%); λmax(CH2Cl2)/nm 479
(ε/dm3 molϪ1 cmϪ1 = 19500); δH(300 MHz; DMSO-d6; Me4Si)
3.84 (4H, t, NCH2), 3.94 (4H, t, NCH2), 7.81 (2H, d, CH), 8.01
(1H, s, CH), 8.32 (2H, d, CH).
H, 4.1; N, 16.2%); λmax(CH2Cl2)/nm 492 (ε/dm3 molϪ1 cmϪ1
=
17000); δH(300 MHz; DMSO-d6; Me4Si) 3.85 (4H, t, NCH2),
4.02 (4H, t, OCH2), 7.82 (2H, d, CH), 8.14 (1H, s, CH), 8.32
(2H, d, CH), 9.73 (1H, s, CH).
5-Acetyl-2-morpholino-3-(4-nitrophenylazo)thiophene hydro-
gen sulfate 9cؒH2SO4. (2.6 g, 57%), plus 2-morpholino-5-(4-
nitrophenylazo)thiophene 10a, from 5-acetyl-2-morpholino-
thiophene 7c; mp 217 ЊC (Found: C, 41.6, H, 4.1; N, 11.9; S,
13.6. C16H16N4O4SؒH2SO4 requires C, 41.9; H, 3.5; N, 12.1;
S, 14.0%); λmax(CH2Cl2)/nm 493 (ε/dm3 molϪ1 cmϪ1 = 21800);
δH(300 MHz; DMSO-d6; Me4Si) 2.46 (3H, s, CH3CO), 3.84
(4H, t, NCH2), 3.99 (4H, t, OCH2), 7.82 (2H, d, CH), 8.01
(1H, s, CH), 8.31 (2H, d, CH).
2-Morpholino-3-(4-nitrophenylazo)-5-phenylthiophene hydro-
gen sulfate 9mؒH2SO4. (3.2 g, 65%) from 5-phenyl-2-
morpholinothiophene 7m; mp 228–230 ЊC (Found: C, 47.4;
H, 4.2; N, 10.7; S, 13.2. C20H18N4O3SؒH2SO4 requires C, 48.8;
H, 3.7; N, 11.4; S, 13.0%); λmax(CH2Cl2)/nm 536 (ε/dm3 molϪ1
cmϪ1 = 27000); δH(300 MHz; DMSO-d6; Me4Si) 3.86 (4H, t,
NCH2), 4.10 (4H, t, OCH2), 7.44–7.86 (8H, m, CH), 8.22 (1H,
d, CH), 8.30 (1H, d, CH).
5-Benzoyl-2-morpholino-3-(4-nitrophenylazo)thiophene
9d.
2-Morpholino-5-(4-nitrophenylazo)thiophene 10a. (1.3 g, 41%)
from 2-morpholinothiophene 7a, (0.7 g, 22%) from 5-formyl-
2-morpholinothiophene 7b, (in a trace) from 5-acetyl-2-
morpholinothiophene 7c, (1.3 g, 41%) from 2-morpholino-
thiophene-5-carboxylic acid 7k; mp 231 ЊC (lit.,6c 231 ЊC);
λmax(CH2Cl2)/nm 536 (ε/dm3 molϪ1 cmϪ1 = 15800).
(2.2 g, 52%), from 5-benzoyl-2-morpholinothiophene 7d; mp
222–224 ЊC (Found: C, 59.7; H, 4.7; N, 13.1. C21H18N4O4S
requires C, 59.7; H, 4.7; N, 13.3%); λmax(CH2Cl2)/nm 498
(ε/dm3 molϪ1 cmϪ1 = 17400); δH(300 MHz; DMSO-d6; Me4Si)
3.87 (4H, t, NCH2), 4.04 (4H, t, OCH2), 7.55–7.66 (3H, m,
CH), 7.76–7.82 (4H, m, CH), 7.81 (1H, s, CH), 8.29 (2H, d,
CH).
2-Morpholino-5-(4-nitrophenylazo)thiazole 12a. (1.0 g, 31%)
from 2-morpholinothiazole 7a, (1.8 g, 56%) from 2-morphol-
inothiazole-5-carboxylic acid; mp 248–250 ЊC (lit.,6c 248–
250 ЊC); λmax(CH2Cl2)/nm 473 (ε/dm3 molϪ1 cmϪ1 = 13800).
2-Morpholino-3-(4-nitrophenylazo)-5-(4-methylbenzoyl)thio-
phene 9e. (2.9 g, 67%) from 2-morpholino-5-(4-methylbenzoyl)-
thiophene 7e; mp 225–227 ЊC (Found: C, 60.2, H, 4.5; N, 12.8.
C22H20N4O4S requires C, 60.6; H, 4.6; N, 12.8%); λmax(CH2Cl2)/
nm 498 (ε/dm3 molϪ1 cmϪ1 = 18600); δH(300 MHz; DMSO-d6;
Me4Si) 2.42 (3H, s, CH3), 3.86 (4H, t, NCH2), 4.03 (4H, t,
OCH2), 7.38 (2H, d, CH), 7.68 (2H, d, CH), 7.77 (2H, d, CH),
7.81 (1H, s, CH), 8.30 (2H, d, CH).
N,N-Dimethyl-4-(4-nitrophenylazo)aniline 14a. (2.0 g, 74%)
from N,N-dimethylaniline 13a, (2.2 g, 82%) from 4-dimethyl-
aminobenzoic acid 13k; mp 225–228 ЊC (lit.,6c 225–228 ЊC);
λmax(CH2Cl2)/nm 482 (ε/dm3 molϪ1 cmϪ1 = 11000).
2,4-Dinitrophenyldiazonium hydrogen sulfate 1b as diazo com-
ponent. By using 2,4-dinitrophenyldiazonium hydrogen sulfate
the following azo compounds were prepared.
5-(4-Chlorobenzoyl)-2-morpholino-3-(4-nitrophenylazo)thio-
phene 9f. (2.5 g, 55%) from 5-(4-chlorobenzoyl)-2-morpholino-
thiophene 7f; mp 235–239 ЊC (Found: C, 54.9; H, 4.2; N,
12.1. C21H17ClN4O4S requires C, 55.2; H, 3.7; N, 12.3%);
λmax(CH2Cl2)/nm 497 (ε/dm3 molϪ1 cmϪ1 = 19000); δH(300 MHz;
DMSO-d6; Me4Si) 3.87 (4H, t, NCH2), 4.04 (4H, t, OCH2),
7.63 (2H, d, CH), 7.76 (1H, s, CH), 7.78–7.82 (4H, m, CH),
8.29 (2H, d, CH).
5-Acetyl-3-(2,4-dinitrophenylazo)-2-morpholinothiophene 9cЈ.
(2.0 g, 50%) from 5-acetyl-2-morpholinothiophene 7c; mp
229 ЊC (Found: C, 47.1; H, 3.7; N, 17.1; S, 7.9. C16H15N5O6S
requires C, 47.5; H, 3.7; N, 17.3; S, 7.9%); λmax(CH2Cl2)/nm 523
(ε/dm3 molϪ1 cmϪ1 = 25100); δH(300 MHz; CDCl3; Me4Si) 2.45
(3H, s, CH3CO), 3.85 (4H, t, NCH2), 4.02 (4H, t, OCH2), 7.80
(1H, s, CH), 8.45 (1H, d, CH), 8.47 (1H, d, CH), 8.78 (1H, d,
CH).
5-(4-Bromobenzoyl)-2-morpholino-3-(4-nitrophenylazo)thio-
phene 9g. (4.2 g, 84%) from 5-(4-bromobenzoyl)-2-morpholino-
J. Chem. Soc., Perkin Trans. 1, 2000, 4316–4320
4319

View Article Online
3-(2,4-Dinitrophenylazo)-2-morpholino-5-(4-toluoyl)thiophene
hydrogen sulfate 9eЈؒ2/3 H2SO4. (2.3 g, 42%) from 2-morphol-
ino-5-(4-toluoyl)thiophene 7e; mp 215–220 ЊC (Found: C, 48.5;
H, 3.6; N, 12.6. C22H19N5O6Sؒ2/3 H2SO4 requires C, 48.3; H,
N,N-Dimethyl-4-(2,4-dinitrophenylazo)aniline 14aЈ. (1.6 g,
51%) from N,N-dimethylaniline 13a, (1.3 g, 41%) from
4-dimethylaminobenzoic acid 13k; mp 211 ЊC (lit.,6c 211 ЊC);
λmax(CH2Cl2)/nm 527 (ε/dm3 molϪ1 cmϪ1 = 18600).
3.7; N, 12.8%); λmax(CH2Cl2)/nm 528 (ε/dm3 molϪ1 cmϪ1
=
22400); δH(300 MHz; DMSO-d6; Me4Si) 2.42 (3H, s, CH3), 3.87
(4H, t, NCH2), 4.05 (4H, t, OCH2), 7.37 (2H, d, CH), 7.62 (1H,
s, CH), 7.66 (2H, d, CH), 7.79 (1H, d, CH), 8.44 (1H, dd, CH),
8.76 (1H, d, CH).
References
1 K. H. Schindehütte, in Houben-Weyl, Methoden der Organischen
Chemie, ed. E. Müller, Georg Thieme, Stuttgart, 1965, vol. X/3,
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5-(Ethoxycarbonyl)-3-(2,4-dinitrophenylazo)-2-morpholino-
thiophene hydrogen sulfate 9iЈؒH2SO4. (2.6 g, 49%) from ethyl
2-morpholinothiophene-5-carboxylate 7i; mp 192–195 ЊC
(Found: C, 38.5; H, 3.4; N, 12.9. C17H17N5O7SؒH2SO4 requires
C, 38.3; H, 3.6; N, 13.1%); λmax(CH2Cl2)/nm 523 (ε/dm3 molϪ1
cmϪ1 = 21400); δH(300 MHz; DMSO-d6; Me4Si) 1.28 (3H, t,
CH3), 3.84 (4H, t, NCH2), 4.00 (4H, t, OCH2), 4.27 (2H, q,
OCH2), 7.70 (1H, s, CH), 7.80 (1H, d, CH), 8.44 (1H, q, CH),
8.79 (1H, d, CH).
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3-(2,4-Dinitrophenylazo)-5-(methoxycarbonyl)-2-morpholino-
thiophene hydrogen sulfate 9jЈؒH2SO4. (2.0 g, 48%) from methyl
2-morpholinothiophene-5-carboxylate 7j; mp 199–202 ЊC
(Found: C, 45.3; H, 3.7; N, 16.5. C16H15N5O7SؒH2SO4 requires
C, 45.6; H, 3.6; N, 16.6%); λmax(CH2Cl2)/nm 520 (ε/dm3 molϪ1
cmϪ1 = 30200); δH(300 MHz; DMSO-d6; Me4Si) 3.81 (3H, s,
OCH3), 3.85 (4H, m, NCH2), 3.99 (4H, m, OCH2), 7.71 (1H, s,
CH), 7.80 (1H, d, CH), 8.43 (1H, q, CH), 8.78 (1H, d, CH).
3-(2,4-Dinitrophenylazo)-5-cyano-2-morpholinothiophene 9lЈ.
(3.3 g, 85%) from 5-cyano-2-morpholinothiophene 7l; mp 231–
233 ЊC (Found: C, 46.5; H, 3.2; N, 21.5; S, 8.3. C15H12N6O5S
requires C, 46.4; H, 3.1; N, 21.7; S, 8.3%); λmax(CH2Cl2)/nm 508
(ε/dm3 molϪ1 cmϪ1 = 21800); δH(300 MHz; DMSO-d6; Me4Si)
3.84 (4H, t, NCH2), 3.97 (4H, t, OCH2), 7.84 (1H, s, CH), 8.45
(1H, d, CH), 8.48 (1H, d, CH), 8.79 (1H, d, CH).
5-(2,4-Dinitrophenylazo)-2-morpholinothiophene 10aЈ. (1.8 g,
50%) from 2-morpholinothiophene 7a, (0.7 g, 19%) from
5-formyl-2-morpholinothiophene 7b, (1.8 g, 50%) from
2-morpholinothiophene-5-carboxylic acid 7k, (0.9 g, 25%)
from 2-morpholino-5-(4-nitrophenylazo)thiophene 10a; mp 205–
207 ЊC (lit.,6c 205–207 ЊC); λmax(CH2Cl2)/nm 581 (ε/dm3 molϪ1
cmϪ1 = 56800).
5-(2,4-Dinitrophenylazo)-2-morpholinothiazole 12aЈ. (1.7 g,
38%) from 2-morpholinothiazole 8a, (1.8 g, 41%) from
2-morpholinothiazole-5-carboxylic acid 8k; mp 240 ЊC (lit.,6c
240 ЊC); λmax(CH2Cl2)/nm 498 (ε/dm3 molϪ1 cmϪ1 = 16600).
4320
J. Chem. Soc., Perkin Trans. 1, 2000, 4316–4320