Conversion of coumarins accompanied by opening and recyclization of the lactone ring. 1. Study of the reaction of 3-ethoxycarbonyl(3-acyl)coumarins with cyanoacetylhydrazine and its derivatives

Article abstract of DOI:10.1023/B:COHC.0000014410.73636.dd

A stepwise sequence for the interaction of 3-ethoxycarbonyl(acyl)coumarins with cyanoacetylhydrazine, its N-acetyl and N-isopropylidene derivatives, leading to the formation of 3-cyanocoumarins, is proposed and demonstrated. It was established that the 3-cyanocoumarins formed are also able to participate in further conversions by a type of Michael reaction.

Full text of DOI:10.1023/B:COHC.0000014410.73636.dd

Chemistry of Heterocyclic Compounds, Vol. 39, No. 11, 2003
CONVERSION OF COUMARINS ACCOMPANIED
BY OPENING AND RECYCLIZATION OF THE
LACTONE RING. 1. STUDY OF THE REACTION OF
3-ETHOXYCARBONYL(3-ACYL)COUMARINS WITH
CYANOACETYLHYDRAZINE AND ITS DERIVATIVES
M. P. Nemeryuk1, V. D. Dimitrova1, O. S. Anisimova2, A. L. Sedov2, N. P. Solov'eva2,
and V. F. Traven1
A stepwise sequence for the interaction of 3-ethoxycarbonyl(acyl)coumarins with cyanoacetylhydrazine,
its N-acetyl and N-isopropylidene derivatives, leading to the formation of 3-cyanocoumarins, is
proposed and demonstrated. It was established that the 3-cyanocoumarins formed are also able to
participate in further conversions by a type of Michael reaction.
Keywords: cyanoacetylhydrazine derivatives, 3-ethoxycarbonyl(acyl)coumarins, mass spectrometry,
Michael reaction, recyclization of coumarin lactone rings.
It is known that coumarins substituted in position 3 with electron-withdrawing groups enter into the
Michael reaction with compounds containing an active methylene group. Products of addition at position 4 of
the initial coumarin are formed in this way [1]. In a series of cases this reaction does not stop at the addition
stage but leads to the product of opening of the coumarin lactone ring [2]. We have also discovered that the
reaction between 3-ethoxycarbonyl(acetyl)coumarins [3], their 5,6-benzo analogs, and 7-methoxy-substituted
derivatives [4], and cyanoacetylhydrazine, its N-acetyl and N-isopropylidene derivatives in the presence of a
secondary amine (piperidine), i. e. under Michael reaction conditions, does not stop at the two stages indicated
above, but unexpectedly leads to the formation of the corresponding 3-cyanocoumarins. In developing these
studies we established that 6-(8)-methoxy-, 3-ethoxycarbonyl-6-methylcoumarins, and 3-acetyl-8-
methoxycoumarin are subject to an analogous conversion (see Scheme 1).
It is obvious that the observed conversion is the result of a series of sequentially occurring steps leading
finally to the formation of the corresponding 3-cyanocoumarins. We propose the following scheme for this
process. The initially formed product of addition at position 4 of the initial coumarin A is subject to opening of
the lactone ring with the formation of anion B, which may be transformed into the final 3-cyanocoumarin in two
directions, differing in the sequence of removal of a molecule of hydrazine and the appropriate β-dicarbonyl
compounds. Route 1 is the recyclization of anion B with the intermediate formation of the 3-cyano-3,4-
dihydrocoumarin C, fission from which of a molecule of malonic or acetoacetic (benzoylacetic) ester leads to
__________________________________________________________________________________________
1
D. I. Mendeleev Russian Chemical Engineering University, Moscow 125047; e-mail: traven@main-
2
gw.muctr.edu.ru. Center for Drug Chemistry – All Russian Chemical and Pharmaceutical Research Institute,
Moscow 119815, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1652-1664,
November, 2003. Original article submitted October 11, 2000.
1454
0009-3122/03/3911-1454$25.00©2003 Plenum Publishing Corporation

Scheme 1
R1
R4
1
R
2
R
R2
R3
COR
O
CN
O
CONHX
C5H10NH
ethanol
+
R3
CN
O
O
R4
2a–c
1a–l
3a–g
1a,d,f,h-j,l R = OEt, b,e,g,k R = Me, c R = Ph; a-c,f-l R1 = H, d,e R1 + R2 = o-C6H4;
a-c,f,g,j,k R2 = H, h R2 = OMe, i R2 = Me, l R2 = Br; a-e,h-l R3 = H, f,g R3 = OMe;
a-i,l R4 = H, j,k R4 = OMe; 3 a,c-g R1 = H, b R1+R2 = o-C6H4; a,c,d R2 = H, e R2 = Me, f R2 = OMe, g R2 = Br;
a,b,d-g R3 = H, c R3 = Me; a-c,e-g R4 = H, d R4 = OMe; 2 a X = NH2, b X = NHCOMe, c X = N=CMe2
the final 3-cyanocoumarins. Route 2 is the conversion of anion B into the benzylidene derivative D, also
recyclizing subsequently into 3-cyanocoumarins (see Scheme 2). It should be kept in mind that all the
intermediate compounds shown in the Scheme in the form of anions exist in the reaction mixture in equilibrium
with the corresponding neutral molecules.
Scheme 2
O
O
O
R
NC
NC
NC
+
NHX
..
_
NHX
O
O
2a–c
1a–l
H
H
NC
CONHX
CONHX
COR
EtOH
_
COR
.
.
H
H
_
O
O
O
O
A
H
H
H
NC
ROC
NC
CONHX
CONHX
COR
COOEt
COR
CN
H
CONHX
H
H
H
H
_
_
COOEt
_
OH
OEt
O
O
O
B
route 1
route 2
–NH2X
COOEt
–EtOCOCH2COR
H
ROC
_
CN
CONHX
CN
.
.
H
_
O
O
O
C
_
_
D
–EtOCOCHCOR
3a–g
–NHX
1455

With the aim of investigating the conversion of 3-ethoxycarbonyl(3-acyl)coumarins into
3-cyanocoumarins by mass spectrometry, reaction mixtures formed by the interaction of 1a-c,f,l with 2a, 1a,c
with 2c, and also 1a-c,f,h-j with 2c were studied. The corresponding 3-cyanocoumarins 3 were separated first in
the precipitate. Then preparative resolution of the mixture was carried out by TLC and the mass spectra of the
isolated fractions were studied.
According to the data obtained, the initial coumarins 1, cyanoacetylhydrazines 2, and the final reaction
products, the 3-cyanocoumarins 3, were present in the mixtures investigated. In addition a significant number of
compounds were observed, probably existing as intermediates and byproducts in the formation of
3-cyanocoumarins and as products of further conversions of the 3-cyanocoumarins*. Compounds identified by
us are given in Tables 1 and 2, however it must be stressed that the reaction mixtures proved to be so complex
that the identification of the separated components has been unsuccessful up to the present.*2
As expected the interaction of 3-substituted coumarins with cyanoacetylhydrazines begins with a
Michael reaction with addition of the latter at position 4 of the lactone ring (structure A) with its subsequent
opening (structure B). The presence of the neutral forms of anions A and B was successfully recorded in the
reaction mixtures formed in the interaction of the coumarins 1 with N-acetylcyanoacetylhydrazine 2b and
N-isopropylidenecyanoacetylhydrazine 2c. This is indicated by the presence in the electron capture mass spectra
of peaks for the corresponding molecular ions (see Table 1). In addition, in the chemical ionization mass
spectrum of the reaction mixture formed on interacting 1a + 2c, peaks were observed for the protonated
molecular ions MH+ at 358 (A), 404 (B).
The preferred direction for the fragmentation of the molecular ions of compounds B is caused by the
elimination from them of –OEt, EtOH, and –COOEt. The fragments [M-EtOH]+ naturally have the same mass
number as the molecular ions of the unopened structure A. It was concluded that compounds having structure A
were present in the mixture together with compounds B on the basis of the significant redistribution of the
+
intensities of the peaks for MA+ and MB during the evaporation of specimens.
Compounds A were not recorded in reaction mixtures obtained using cyanoacetylhydrazine 2a in
several cases (1a + 2a, 1b + 2a, 1c + 2a, 1f + 2a). When using 2a compound B was not recorded practically
anywhere in the reaction, which is evidently linked with the high recyclization rate of the latter into
cyanocoumarins 3. In addition, in the case of the interaction of 2a with 3-ethoxycarbonylcoumarins 1a,f,h,j, an
additional route is possible for the further conversion of structure A linked with cyclization into tricyclic
structures through the elimination of ethanol*3.
An additional route emerges in the case of the reactions of 2a with 3-acylcoumarins 1b,c for the
cyclization of structure A through interaction with the carbonyl of the acyl group*4 (Scheme 3).
In this case the appropriate peaks for the molecular ions at 269 (1b + 2a) and 331 (1c + 2a) were
observed in the spectra, but compound A was not recorded. It is interesting to note that, judging by the mass
spectrometric decomposition, the molecular ions of E were found partially in the open form E'. This is indicated
by the ease of the breaking away of 40 m. u. (NCCH2 group) from the molecular ions at the same time as
elimination of a CONH group seemingly corresponding to the tricyclic form E of the molecular ions.
_______
* Further analysis showed that products isolated during the reaction interact with one another, with the initial
reactants, and with the final 3-cyanocoumarins.
*2 Since the reaction masses were multicomponent mixtures analysis of the evaporation curves of separate
characteristic ions was widely used when considering the mass spectra. This significantly facilitated assignment
of peaks to the spectrum of one or another component of the mixture being considered.
*3 This route will be considered in more detail below.
*4 The problem of which center (carbonylacyl group or the position 4 of the coumarin ring) initiates the
interaction of the cyanoacetylhydrazine with 3-acylcoumarins remains.
1456

TABLE 1. Mass Spectra of the Main Coumarin-containing Products
Molecular masses of reaction products
No.
Initial mixture
K and
I-2Н
M
А
B
C
3
E
F
G
I
J
А-2Н
C-2Н
N
1
2
3
4
5
6
7
8
9
10
11
12
13*2
14
171
171
171
171
171
171
171
201
201
—*
185
201
249/251
204
250
269
268
1а+2а
1b+2а
1c+2а
1a+2b
1b+2b
1b+2c
1a+2c
1f+2а
1k+2c
1h+2c
1i+2c
1j+2c
1l+2a
1c+2c
269
331
267
329
359
329
327
357
246
292
280
357
327
325
355
311
299
310
310
308
308
298
338
403
331
361
244
234
274
310
340
284
329
387
387
371
387
395/397
389
433
433
417
433
314
314
298
314
385
258
322
361
363
282/284 328/330
393/397 407/409
387
346/348
308
435
_______
* The presence of 3-cyanocoumarin was not recorded mass spectrometrically in the reaction mixture after separating it in
the precipitate.
*2 The masses of ions containing 79Br/81Br are indicated.

TABLE 2. Mass Spectra of the Main Hydrazine Derivatives in the Reaction
Molecular masses of products
Reaction products
1а+2а
1b+2а
1c+2а
1а+2b
1b+2b
1b+2c
1a+2c
1f+2a
1f+2c
1h+2c
1i+2c
1j+2c
1l+2a
1c+2c
NH2X
XNHCOCH2COOEt
Pyrazolidine-3,5-dione
3-Methyl(phenyl)pyrazol-5-one
Me2NNHCOCH2COPh
74
188
74
72
72
186
72
186
72
186
72
186
72
186
72
146
100
146
100
146
100
98
160
218

Scheme 3
CN
O
H
N
H
NC
NC
CONHNH2
COR
CONHN
N
H
R
R
–H2O
O
O
O
O
O
O
A
E
E'
R = Me, Ph
The fact that recyclization of structures B into cyanocoumarins 3 occurs with the separation of
hydrazines and β-keto esters (malonic, acetoacetic, or benzoylacetic) is confirmed by the presence in the mass
spectra of the reaction mixtures with 2b and 2c of intense peaks for the corresponding molecular ions
+
NH2NHCOMe+ (74) and NH2N=CMe2 (72) (see Table 2). In the spectra of the mixtures obtained in reactions
+
with cyanoacetylhydrazine 2a the molecular peak of hydrazine NH2NH2 (32) is outside the range of recording
mass spectra (50-800 m. u.), however there is no doubt that hydrazine is formed since products of its interaction
with β-keto esters formed in the course of the reaction are observed. In the interaction of cyanoacetylhydrazines
2a-c with 3-ethoxycarbonylcoumarins 1a,f intense peaks were observed in the mass spectra belonging to the
spectrum of malonic ester monohydrazide. The values of the mass numbers of the molecular ions (146 for the
interaction with 2a, 188 with 2b, and 186 with 2c) and the daughter ions [M-OEt]+, [M-EtOH]+, and
[M-NHNH2]+ completely confirm the structure of the hydrazides. Judging by the intensity of the peaks the
monohydrazides of malonic ester are one of the main components of the reaction mixtures after the separation
of the 3-cyanocoumarins*.
On using hydrazine 2a in the reaction, formed malonic ester monohydrazide unsubstituted at the
terminal nitrogen atom is partially cyclized into pyrazolidine-3,5-dione, which is indicated by the significant
redistribution of intensities of the molecular ions of the monohydrazide (M+ 146) and pyrazolidine-3,5-dione
(100) during the temperature fractionation of the sample.
On interacting 2a with 3-acetyl- and 3-benzoylcoumarins 1b,c an analogous reaction takes place
between the unsubstituted hydrazine separated on recyclization and acetoacetic (benzoylacetic) ester, however
the hydrazides formed in this way readily cyclize with the formation of the corresponding pyrazolones (see
Scheme 4).
Scheme 4
(Ph)Me
NH2NH2
X = NH2
– H2O
Me(Ph)COCH2CONHX
Me(Ph)COCH2COOEt
N
N
H
O
In the mass spectra of the mixtures mentioned above intense peaks were observed for the appropriate
molecular ions at 98 (1b + 2a) and 160 (1c + 2a) and also peaks for the daughter ions [M-HCO]+ and
[M-CH2CO]+ characteristic of the decomposition of pyrazolones [5]. The structure of the isopropylidene-
substituted hydrazide of benzoylacetic acid ester (see Table 2) is observed in the mixture formed on interaction
of 3-benzoylcoumarin 1c with hydrazine 2c.*2
_______
* Malonic acid dihydrazide is most probably formed in minor amounts since peaks for the corresponding ions
are of low intensity in all cases.
*2 Hydrazides were not recorded in the reaction mixtures obtained on interacting 3-acetylcoumarin 1b with
N-substituted hydrazines 2b,c.
1459

Hydrazines split off in the process of recyclization also react with the initial 3-ethoxycarbonylcoumarins
1a,f-l, and the interaction proceeds both at the carbethoxy group with the formation of the corresponding
hydrazides of coumarin-3-carboxylic acid F, and by way of addition of hydrazines at the 4 position of the
lactone ring (structure G) (see Scheme 5).
Scheme 5
NHX
CONHX
COOEt
NH
NH2X
X = NH2,
N=CMe2
NH2X
H
1
H
O
O
O
R = OEt
G
F
The formation of hydrazides is evidently the conversion preferred since the corresponding products are
observed in almost all reaction mixtures, it is confirmed by the presence of molecular ion peaks in the electron
impact spectra*, and by the characteristic decomposition direction with the formation of the [M-NHX]+ ion.
Products of addition of hydrazine at position 4 of the lactone ring were observed in mixtures of 1a + 2a,
1a + 2b, 1f + 2a, and 1l + 2a. The corresponding peaks for the molecular ions of G have mass numbers 250,
292, 280, and 328/330*2. Although the molecular mass of ions F coincide with that of the [MG-EtOH]+ ion
formed on mass spectrometric decomposition of the molecular ion of G, the conclusion as to the formation of
compounds F follows from the temperature redistribution of the intensities of the peaks for the MF and MG ions.
In addition, structure F was observed in the spectra of the reaction mixtures obtained using 2c, where, by virtue
of the presence of the isopropylidene-substituent at the terminal nitrogen atom of the hydrazine, elimination of
EtOH from the molecular ion of G is impossible.
It is interesting to note that the N-unsubstituted malonic acid hydrazide formed in the reactions of
1a + 2a, 1f + 2a, and 1l + 2a also reacts with the initial 3-ethoxycarbonylcoumarin at the ethoxycarbonyl group
with the formation of the corresponding hydrazides (see Scheme 6).
Scheme 6
COOEt
O
CONHNH
COOEt
H2NNHCOCH2COOEt
O
O
O
Peaks were observed in the mass spectra for the molecular ions at 318 (1a + 2a), 348 (1f + 2a), and
396/398 (1l + 2a).
As already mentioned above the recyclization into 3-cyanocoumarin may be effected with a different
sequence of splitting away molecules of hydrazine and β-keto esters. Consideration of the mass spectra of all the
mixtures studied shows that the intermediate structure C (route 1) is present in the reaction mixtures obtained on
_______
* In the chemical ionization spectrum of the reaction mixture obtained on interacting 1a + 2c a peak was
recorded for the corresponding structure F as the quasimolecular ion MH+ 245.
*2 Here and subsequently the masses of the ions containing 79Br/81Br are indicated.
1460

interacting 1a + 2c (MC 331), 1f + 2c (MC 361), and 1j + 2c (MC 361). Finally it is impossible to exclude that
structure C is not the direct product of the recyclization of B, as shown in Scheme 2, but is formed on further
interaction of the isolated 3-cyanocoumarin 3 with the malonic ester split off at a previous stage. However this
hypothesis seems less probable, since neither the free malonic ester nor the product of its addition to the initial
3-ethoxycarbonylcoumarin were recorded in these mixtures. Probably the malonic ester is mainly linked with
the separated hydrazine.
Concerning the second possible reaction route through the formation of the intermediate benzylidene
derivative D, structure D was not recorded in any mixture. Either this route does not occur or this structure has a
short life span. It is possible that compound D, due to intramolecular cyclization involving the nitrile group and
the phenolic hydroxyl, is readily converted into the 2-imino derivative of coumarin-3-carboxylic acid hydrazide
H, and subsequent hydrolysis of H under the reaction conditions leads to the formation of the corresponding
hydrazide of coumarin-3-carboxylic acid F, as shown in Scheme 7 [6, 7]. At the same time, the fact that
hydrazides F are observed only in mixtures where the initial coumarin had an ethoxycarbonyl group in position
3 permits the assumption that the formation of F is linked preferably with the interaction of the hydrazine with
the ethoxycarbonyl group, as was considered above. An unequivocal answer to the problem of the occurrence of
the second pathway may only be obtained by studying the reaction dynamics with recording of the intermediate
structures D and H.
Scheme 7
CN
CONHX
CN
O
NHX
OH
OH
D
CONHX
CONHX
NH
O
O
O
H
F
The resulting 3-cyanocoumarins 3 are also obviously capable of undergoing a Michael reaction with the
initial cyanoacetylhydrazines 2. In the case of reaction mixtures obtained on interacting 1a + 2c and 1f + 2c the
molecular ions corresponding to structure I were successfully recorded at 310 and 340. The Michael adducts
formed are probably capable of recyclization proceeding by a mechanism analogous to that considered above in
Scheme 1. Recyclization leads to the formation of hydrazine, cyanoacetic ester, 3-cyanocoumarin and adduct J
(see Scheme 8).
Cyanoacetic ester was not recorded in the mass spectra of the reaction mixtures investigated, however in
the case of the interaction of N-isopropylidenecyanoacetylhydrazine 2c with coumarins 1a,f,h-j peaks for
molecular ions were observed in the spectra corresponding to structure J at 284 (1a + 2c), 298 (1i + 2c), and
314 (1f,h,j + 2c).
As was shown in [1] using 3a as example, adduct J is readily formed on interacting 3-cyanocoumarins
with cyanoacetic ester in the presence of catalytic amounts of piperidine. The absence of compounds J from
reaction mixtures obtained involving hydrazine 2a is possibly linked with additional stabilization of adduct I as
a result of cyclization into the tricyclic structure I' [8] with subsequent dehydrogenation into structure K
1461

(Scheme 8). A similar dehydrogenation was noted when obtaining benzopyranopyrimidine and pyridocoumarin
derivatives, when during the synthesis compounds were also isolated having a molecular mass 2 m. u. lower
than expected [9].
Scheme 8
H
NC
CONHX
CN
3
+
2
H
H
O
I
O
EtOH
X = N=CMe2
X = NH2
H
NC
O
CONHNCMe2
CN
H
N
NC
H
NH
H
H
COOEt
NH
O
H
OH
H
O
I'
– NH2N=CMe2
– 2H
H
O
NC
COOEt
CN
H
N
NC
H
NH
H
H
NH
O
O
O
J
O
– NCCH2COOEt
K
3
The ability to dehydrogenate is evidently a property of products with an unsaturated 3-4 bond formed in
the given mixtures. Dehydrogenation proceeds especially readily in tricyclic systems. This relates to structures
E (in the interaction of 2a with acylcoumarins), I', and also the tricyclic structures L, which are formed from
adduct A (in the interaction of 2a with ethoxycarbonyl-substituted coumarins) by way of cyclization with
elimination of EtOH (Scheme 6).
Essentially, when both compounds E and the dehydrogenation products M are successfully observed in
the case of acyl coumarins, then structures I' and L are not recorded when 2a interacts with
ethoxycarbonylcoumarins 1a,h-j. Only the dehydrogenated products K and N* are observed (see Scheme 9).
To a lesser extent dehydrogenation is natural for Michael adducts by virtue of their structures being
incapable of cyclization. Dehydrogenation probably has a thermal character. In the process of evaporating
samples in all mixtures with 2c, where compounds A, C, and I are recorded, the intensity of their molecular ion
_______
* It is impossible to exclude the fact that the formation of tricyclic structures may occur as a result of the
interaction of not only the terminal NH2 group but also the amide N atom of the hydrazine fragment, which will
lead to the formation of isomeric K and N tricyclic structures containing a six-membered ring with an exocyclic
NH2 group.
1462

peaks M+ is reduced, peaks for [M-2H]+ ions appear, and their intensity grows in proportion to the degree of
heating of the sample.
Scheme 9
O
H
–EtOH
N
NC
H
R = OEt
A
1
NH
O
R = Ph, Me
– H2O
H
H
O
O
O
H
N
NC
H
L
N
– 2H
Me(Ph)
H
O
H
H
N
NC
H
O
E
O
NH
– 2H
O
O
H
N
O
NC
O
N
N
H
Me(Ph)
O
O
M
It should be noted that, as already mentioned above, all the products of the interaction of cyanoacetyl
hydrazines with 3-substituted coumarins with the structures represented have not been exhausted. The large
number of reactive centers and the possibility of interaction with hydrazines and β-keto esters formed during the
reaction does not exclude the probability of forming dimeric and more complex structures.
To confirm the data of mass spectrometry given above with the aid of 1H NMR spectroscopy, the course
of the reaction of 3-ethoxycarbonylcoumarin 1a with cyanoacetylhydrazine 2a was studied directly in the
ampule by recording the NMR spectra of the reaction mixture formed at definite time intervals. The reaction
was carried out in CD3OD and CH3OD at an equimolar ratio of the initial reactants in the presence of a catalytic
amount of piperidine. In the first step of the reaction it was established that directly after mixing 1a and 2a, even
without adding piperidine, the formation of trace amounts of 3-cyanocoumarin 3a was observed, as was shown
by the appearance in the NMR spectrum of a low intensity signal for C(4)–H at 8.66 ppm. In addition signals
were observed corresponding to the protons of the COOEt fragment of malonic ester and its monohydrazide
(triplet at 1.28 (CH3) and quartet at 4.18 ppm (CH2)). After adding piperidine the process accelerates sharply
and leads to an increase of up to 36-40% in the content of 3-cyanocoumarin 3a (10 min after adding piperidine).
Simultaneously the intensity of the multiplet for aromatic protons at 6.7-7.3 ppm in the spectrum increased and
new signals appeared for the COOEt group. At the present time a paper on the study of this reaction by NMR
spectroscopy is being prepared.
1463

EXPERIMENTAL
The mass spectra were recorded on a Finnigan SSQ-710 chromato-mass spectrometer with direct
insertion of samples into the ion source. Energy of ionizing electrons was 70 eV, ion source temperature 150°C.
Chemical ionization spectra were obtained using isobutane as reactant gas. The IR spectra were taken in nujol
on a Perkin–Elmer 457 instrument. The NMR spectra were recorded on a Varian Unity 400 (400 MHz)
spectrometer, internal standard was TMS.
Reaction masses 1-14 (see Table 1), the compositions of which were studied by mass spectrometry,
were obtained by the interaction of hydrazines 2a-c with the appropriate coumarins under the conditions
indicated previously in [4], after separating the precipitated 3-cyanocoumarins 3 and evaporating the obtained
filtrate from the ethanol used as reaction medium.
3-Cyano-8-methoxycoumarin (3d, C11H7NO3). A. Piperidine (3 drops) was added to a suspension of
coumarin 1j (0.5 g, 2 mmol) and hydrazine 2c (0.28 g, 2 mmol) in ethanol (20 ml). The reaction mixture was
stirred for 1 h at 20°C. The precipitated solid was filtered off, washed with chilled ethanol (5 ml), and air-dried.
Cyanocoumarin 3d (0.3 g: 74%) was obtained; mp 221-223°C (ethanol). IR spectrum, ν, cm-1: 2225 (CN), 1720
(C=O).
B. Cyanocoumarin 3d (0.32 g, 65%) was obtained from coumarin 1k (0.5 g, 2.3 mmol) and hydrazine 2c
(0.32 g, 2.3 mmol) under the conditions of method A and was identical both in mp and in spectral characteristics
to the product synthesized by method A. According to [10] mp 222-223°C.
3-Cyano-6-methoxycoumarin (3f) was obtained under the conditions of synthesis of 3d by method A
on interacting coumarin 1h (0.3 g, 1.2 mmol) with 2c (0.17 g, 1.2 mmol). The yield of 3f was 0.23 g (94%) of a
bright yellow crystalline substance; mp 218-220°C (ethanol). IR spectrum, ν, cm-1: 2225 (CN), 1725 (CO).
Found, %: C 65.92; H 3.61; N 6.73. M+ 201. C11H7NO3. Calculated, %: C 65.67; H 3.48; N 6.96. M 201.
3-Cyano-6-methylcoumarin (3e, C11H7NO2) was obtained under the conditions of synthesis of 3d by
method A on interacting coumarin 1i (0.4 g, 1.7 mmol) with 2c (0.24 g, 1.7 mmol). The yield of 3e was 0.1 g
(40%) of white thread-like crystals; mp 203-205°C (ethanol). IR spectrum, ν, cm-1: 2225 (CN), 1720 (CO).
According to [11] mp 205-206°C.
In order to study the dynamics of the interaction of 3-ethoxycarbonylcoumarin 1a with
1
cyanoacetylhydrazines 2a,c the H NMR spectra were taken of both the initial components and of mixtures of
these compounds (in CD3OD and DMSO-d6). The mixtures were taken both in the absence of catalyst and in its
presence (drop of piperidine).
Plottings were made at the following time intervals: directly after mixing the reactants, after 10, 20, 30,
40 min, 1, 2, 4 h, 1, 2, 3 days, and finally 7 d after the beginning of the reaction.
For the purpose of identifying the products formed the NMR spectra of samples mixed with
3-cyanocoumarin 3a were taken.
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