hydrazide 4a; compound 4b, which exists in solution in the form of a mixture of the isomeric forms with relative
contents of 2:1, is characterized by the singlet signals of the N=C(CH3)2 fragment at 1.99, 2.00, 2.06, and 2.07
and signals for the protons of the CO2C2H5 group at 1.27, 1.30 (t, 3J = 7.2) and 4.18, 4.21 (q, 3J = 7.2 Hz). From
analysis of the relative concentrations of the main components given in Table 2 it is seen that components 3 and
4a,b are already present in significant amounts at the beginning of the reaction (spectrum No. 1): 15% of 3 and
16.5% of 4a for the 1 + 2a reaction and 30% of 3 and 39% of 4b for 1 + 2b*. The first stage of the Michael
reaction is quite fast. The intermediate products A, B, and C are short-lived and are practically undetectable in
the case of the reaction of compounds 1 + 2b (~1%); for the reaction of 1 + 2a the total concentration of these
compounds amounts to ~4.5%.*2 A high rate of transformation of the intermediate structures A → B → C into
the final reaction product 3 was also observed during mass-spectrometric investigation of the reaction [2].
As soon as the cyanocoumarin 3 was formed in the solution the second stage of the reaction, in which
compound 3 reacts with the initial cyanohydrazines 2a,b, began. Addition of 2a,b takes place at position 4 of the
coumarin ring (as also in the case of compound 1) with the formation of the intermediate dihydropyran adduct
.
D, which is transformed fairly quickly into a tricyclic structure of the E
E' type. In the 1H NMR spectra the
E (E') structures are characterized by a multiplet for the aromatic protons in the region of 7.0-7.4 ppm; for
structures D it is shifted upfield to 6.70-6.95 ppm. The signals of the methine protons H-4 are observed at
4.6-4.9 ppm; on account of deuteroexchange the signals of the H-3 and H-4' protons are observed in the
spectrum in the form of strongly broadened and weak signals in the region of 3.40-3.65 ppm.
The respective adducts 5 (see the experimental section) and 6*3 [1], in the 1H NMR spectra of which the
signals of the aromatic protons are represented by multiplets at 6.70-7.10 for 5 and 7.00-7.40 ppm for 6, were
used as model compounds for the reaction products D and E.
In addition, the reaction of the cyanocoumarin 3 with the monohydrazides of malonic ester 4a,b takes
place in parallel, leading to the formation of the dihydropyran adducts G, which are easily transformed into the
1
tricyclic compounds H (H'). Like compounds D and E, in the H NMR spectra compounds G and H are
characterized by multiplets for the aromatic protons in the regions of 6.70-7.00 and 7.00-7.40 ppm respectively
and also by the presence of signals for the protons of the ester groups CO2CH2CH3: (like C) 0.85-1.10 (t,
3
3J = 7.2, СН3), 3.70-3.90 (m, СН2) for G; 1.02–1.18 (t, J = 7.2 Hz, СН3), ~ 4.05 ppm (narrow m, СН2) for H.
The complicated form of the signals for the methylene protons of the ester groups results from the presence of
asymmetric carbon atoms in the molecule, and in the dihydropyran structures C, G the multiplet for the protons
of the CH2 group of the ester groups (δ 3.70-3.90) is largely extended, whereas for the tricyclic structures H the
methylene protons form a narrow sharp multiplet centered at ~4.05 ppm. An overall estimate of the relative
content of the dihydropyran compounds with two CN groups D and of the tricyclic structures E was made on the
basis of the integral intensity of the signals for the aromatic protons in the region of 6.70-7.40 ppm, from which
the integral intensity of the aromatic protons corresponding to the structures of the dihydro adducts of types A,
C, and G and the tricyclic structure H was deducted. The last two values were calculated from the integral area
of the multiplets for the methylene protons of the CO2CH2CH3 fragment at 3.70-3.90 and 4.05 ppm respectively.
_______
* Here and subsequently the relative concentrations of the main reaction components, determined without regard
to the concentration of compounds 2a,b, are presented and compared (see Table 2, notes).
*2 The relative concentrations of compounds A, B, and C were determined on the basis of comparison of the
intensities of the signals of the ester groups and the multiplets of the aromatic protons with the analogous signals
of the initial compound 1. For forms A, B, and C: 0.85-1.10 (bt, СН3СН2О), 3.70-3.90 (m, СН3СН2О),
6.70-7.00 ppm (m, СН arom.).
2
3
*
3 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.40, 3.09 (1H each, dd, JHA,HB = 15.7, JCHA,CH = 13.6,
3JCHB,CH = 4.6, CH2); 4.00 (1H, dd, JCHA,CH = 13.6, JCHB,CH = 4.6, H-10b); 7.00-7.40 (4H, m, H arom.); 8.00
3
3
(2H, bs, 2NH); 10.2 (1H, s, OH).
41