Reactivity of Cross-Conjugated Enynones in Cyclocondensations with Hydrazines: Synthesis of Pyrazoles and Pyrazolines

with Hydrazines: Synthesis of Pyrazoles and Pyrazolines

Article

Reactivity of Cross-Conjugated Enynones in Cyclocondensations

Alexander A. Golovanov,* Ivan S. Odin, Dmitry M. Gusev, Anna V. Vologzhanina, Ilya M. Sosnin,

and Stanislav A. Grabovskiy

Cite This: J. Org. Chem. 2021, 86, 7229 −7241

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sı Supporting Information

ABSTRACT: The cyclocondensation of cross-conjugated eny-

nones, dienynones, and trienynones (easily available due to low-

cost starting compounds) with arylhydrazines leads to the

regioselective synthesis of pyrazole derivatives (dihetaryl-substi-

tuted ethens, buta-1,3-diens, and hexa-1,3,5-triens) or results in

,5-dihydro-1H-pyrazoles in good yield. The reaction path is

controlled by the character of the substituent in enynone: the

pyrazoles are obtained from the reaction of substrates that contain

ﬁve-membered heteroaromatic substituents with arylhydrazines,

and the 4,5-dihydro-1H-pyrazoles are obtained from the reaction of

,5-diphenylpent-1-en-4-yn-3-one with arylhydrazines consistently.

Despite the presence of a substituent, cyclocondensation of 2-hydrazinylpyridine with all of examined cross-conjugated enynones

leads to the formation of pyrazoles. The reaction does not require special conditions (temperature, catalyst, inert atmosphere). The

cyclocondensation pathways are determined by the electronic eﬀect of an electron-rich ﬁve-membered heteroaromatic ring in the

substrate. The synthesis allows use of various substituents and functional groups in enynone and hydrazine. The present method

features high yields and simplicity of the product puriﬁcation. The obtained pyrazoles possess ﬂuorescent properties with a quantum

yield up to 31%.

INTRODUCTION

cyclocondensation with hydrazine derivatives 2. Such type of

cyclocondensation may proceed in two ways: ﬁrst, when the

enynone 1 CC bond takes part, resulting in alkynylsub-

stituted 4,5-dihydro-1H-pyrazoles 3, and second, when the

triple bond provides formation of alkenyl pyrazoles isomers 4

and 5 (Scheme 1).

■

The polycentric cross-conjugated motif of pent-1-en-4-yn-3-

ones is applied quite successfully as a building block for the

synthesis of heterocycle complex functional derivatives which

are too impractical to be obtained by other methodologies.

The point is that the multiple bond electron-deﬁcient character

increases reactivity of pent-1-en-4-yn-3-ones toward mono-

and polynucleophiles. Moreover, regioselective processing of

corresponding reactions is provided by imbalance of three

Data literature shows that the direction of reaction with

arylhydrazines 2 is mostly determined by substituents R and

R at positions 1 and 5 of enynones 1; if the substituents are

identical, there are 4,5-dihydro-1H-pyrazoles 3 forming. The

electrophilic centers of cross-conjugated enynones. Combin-

ing the factors of high activity and selectivity allows

development of eﬀective methods for synthesis of a variety

reaction of arylhydrazines 2 with 5-phenylpent-1-en-4-yn-3-

one proceeds in the same way. But, if the substrate 1 contains

substituted double and terminal triple carbon−carbon bonds

simultaneously, then cyclocondensation proceeds with the

terminal triple one; according to pH of the reaction medium,

of heterocycles, such as for pyrrolone, 4-oxodihydrothiopyr-

an, indole, pyrazole, pyrimidine, and other compounds

with more complex structures. Just recently, the expansion of

pent-1-en-4-yn-3-ones was balanced with operation of current

methods of metal complex catalysis

application of superelectrophilic activation. Finally, the

potential of the enynone building blocks is obviously featured

by the multistep synthesis of complex natural products. There

have been cross-conjugated enynone chemical transformations

resulting in various interesting heterocycles extended and

pyrazoles 4 or 5 form. It is evident also that the CC bond

is more active than triple one when R and R are identical.

There is also the obvious possibility to vary the reaction

as well as with

Received: March 10, 2021

Published: May 6, 2021

summarized in reviews recently.

Among the variety of cross-conjugated enynone hetero-

cyclization examples, a special position is taken by the

2021 American Chemical Society

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Article

Scheme 1. Pyrazole and 4,5-Dihydro-1H-pyrazole Synthesis Based on Pent-1-en-4-yn-3-ones According to Literature Data

Figure 1. Starting cross-conjugated enynones 1 and aryl-(hetaryl-)hydrazines 2.

Scheme 2. Possible Interactions of Enynones 1a,o with Hydrazines 2a,d

direction by intentional entry of the combination of donor and

acceptor substituents into the conjugated enynone positions 1

progress on development of common synthesis methods and

for the functionalization of polysubstituted pyrazoles.

and 5 (R and R ) as well as by electronic character selection

of Ar in the reagent 2. Such approaches provide easy access to

eﬀectively obtain 1,3,5-trisubstituted pyrazoles with deﬁnite

types of substituents. That approach is speciﬁcally topical due

to the yearly increasing signiﬁcance of the pyrazole sequence

The present work was devoted to researching the inﬂuence

of structures of cross-conjugated enynone substrates 1 and

arylhydrazines 2 (Figure 1) on the reaction direction.

The object of this work was to discover conditions providing

the direct synthesis of alkenyl-substituted pyrazoles which will

increase the synthetic potential of cross-conjugated enynones.

It is necessary to admit that recently the possibility of the

selective implication of the synthesis of the double or triple

chemical variety for pharmaceutics, coordination chemis-

try, supramolecular chemistry, liquid crystals, polymers,

and agricultural chemistry. Therefore, there has been much

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in Figure 2 ) according to calculations; in addition, the ω_k

Article

bond of 1,5-disubstituted pent-1-en-4-yn-3-ones into the

pyrrolo[2,1-α]isoquinolines was demonstrated successfully.

hydrazine 2 attack at the carbon C is presumed by the ω

value, but it is much less proﬁtable thermodynamically than

attack at the carbon C or C . Therefore, the formation of 1,2-

disubstituted hydrazines A and thus 2,3-dihydro-1H-pyrazoles

3′, as the reaction end products, is incredible. The present

point corresponds quite well with character of the reactions of

RESULTS AND DISCUSSION

The simple approach allows a presumption about the possible

addition products in the reaction of cross-conjugated enynones

■

with arylhydrazines 2 (by the example of compounds 1a, o

hydrazines with chalcones, as reported in the literature data.

and 2a, d), depending on the electronic nature of the reactant

Thus, these calculations are consistent with the available

literature data, and it can be assumed that the pyrrole type

substituent has a signiﬁcant reducing eﬀect on the activity of

the CC bond in the conjugated enynone 1a. It would be

reasonable to presume the formation of pyrazoles 4 in

reactions of similar substrates with any of the hydrazines 2.

The reaction of enynone 1o with phenylhydrazine 2a may

provide the formation of 4,5-dihydro-1H-pyrazoles 3 or

pyrazoles 5, and the same reaction with electron-deﬁcient

hydrazine 2d may result in pyrazole 4.

(

moiety X = CH or N) and substituent R in the substrate

Scheme 2); that approach is supposed to use global

electrophilicity indices. It is a well-known fact that

nucleophilicity of α- and β-nitrogen diﬀers signiﬁcantly in

monosubstituted hydrazines; in the case of arylhydrazines 2, β-

nitrogen is the most preferable reaction center.

On the other hand, enynones 1 are moderately active

polyelectrophiles (see index ω, HOMO and LUMO energies

Then, we performed preparative reactions of enynones 1

with hydrazines 2. The reaction of enynone 1c with 2-

hydrazinylpyridine 2d was chosen as the optimization model.

11,12

In previous works,

it was described that alcohols are

supposed to be the most preferable solvents for the

cyclocondensation of cross-conjugated enynones with arylhy-

drazines; therefore, the ﬁrst experiment was performed by

ethanol reﬂuxing of reagents. Under those conditions, the

reaction completed in 4 h. To our delight, optimization was

not needed because the product was isolated in 90% yield

(Table 2). In accordance with its H and C NMR spectra, as

well as with the elemental analysis data, the product was

identiﬁed as (E)-2-(5-(2-(5-bromofuran-2-yl)vinyl)-3-phenyl-

Figure 2. Selected electronic characteristics of enynones 1a,o

calculated at the M06-2X/6-31G(d,p) level of theory ( natural

+ c

charges; local electrophilicity index ω = ωf ; global electrophilicity

index ω = (E_H_O_M_O+ E_L_U_M_O) /8(E

− E_H_O_M_O)).

LUMO

values aﬃrm positive charge localization on the C , C , and C

H-pyrazol-1-yl)pyridine 4h. The direction of hydrazine 2d β-

atoms of the π-conjugated system, and these atoms are

supposed to be the substrate reaction centers (Figure 2). It

points presumably that the reaction proceeds preferentially

with the formation of 1,2-disubstituted hydrazine A and

hydrazones B1 and B2, the subsequent cyclization of which

may result in products 3′, 4, 5, and 3 consistently. Comparison

nitrogen nucleophilic attack to the carbon C of enynone 1c

i.e., the formation of isomer 4 as end-product exactly, not 5;

(

see Scheme 2) was conﬁrmed by NOESY correlations and X-

ray analysis (see Figures 3 and 4 and the Supporting

Information for details). So, the structure of the product 4h

compares well with our suggestions based on quantum

chemical calculations.

of ω indices shows that the reaction direction may depend on

substituent R : in reaction with enynone 1o, nucleophilic

attack is directed to the carbon C (providing formation of

After that, we carried out a series of experiments with

various hetaryl-substituted enynones 1a−k and hydrazines 2a−

d (Table 2). The reactions proceeded in a regioselective way,

and expected pyrazoles 4a−s were isolated in yields of 59−

90%. All pyrazoles 4 are crystalline products, they are obtained

easily by common ﬁltration after cooling of the reaction

mixture; also, they do not need chromatography for

puriﬁcation. The data in Table 2 demonstrate that in enynones

1g−i, pyrrol-2-yl, thiophen-2-yl, and thiophen-3-yl substituents

(entries 13−16), in common with furan-2-yl substituent in

enynones 1a−f and 1j, decrease the CC bond activity. It is

obvious that such a situation is supposed to be a result of the

electron density increasing on the CC bond due to electron-

hydrazone B2 and its cyclization into 4,5-dihydro-1H-pyrazole

or pyrazole 5), whereas the similar reaction with enynone 1a

must proceed by the carbon C (providing formation of

hydrazone B1 and its succeeding cyclization into pyrazole 4).

Additionally, we calculated thermodynamic parameters of

the interactions of enynones 1a,o with phenylhydrazine 2a and

more electron-deﬁcient 2-hydrazinylpyridine 2d consistently

(

Table 1). The Gibbs free energy values demonstrate that the

hydrazone B1 formation is the most proﬁtable method for

reactions of enynone 1a with hydrazines 2a,d as well as in

reactions of enynone 1o with hydrazine 2d. The hydrazone B2

formation is supposed to be preferable only in the reaction of

enynone 1o with hydrazine 2a (R = Ph, X = CH). The

rich furan, thiophene, etc. Consequently, the carbon C (triple

Table 1. Thermodynamic Characteristics for Reactions of Enynones 1a,o with Hydrazines 2a,d Calculated at the M06-2X/6-

1G(d,p) Level of Theory

−

ΔH , kcal/mol

−ΔS , cal/(mol K)

−ΔG₂₉₈, kcal/mol

enynone

hydrazine

14.41

16.21

14.56

16.18

50.32

1.85

50.92

50.42

4.95

29.91

7.90

4.40

38.53

40.96

40.26

41.24

46.27

3.78

48.61

48.86

4.67

16.44

6.51

8.77

2.91

4.00

2.56

4.03

36.51

0.23

36.43

35.86

3.52

25.01

5.96

1.78

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Table 2. Reactions of Ketones 1 with Hydrazines 2

entry

enynone

hydrazine

reaction time,

pyrazole

yield, %

1.5

Reaction conditions: stirring with reﬂux of 1a−k (1 mmol) and 2a−d (1.1 mmol) in 4 mL of solvent. The time of complete conversion of

enynone 1a−k, in accordance with TLC. Preparative yields. Used MeOH as solvent. According to TLC and H NMR spectra, the reaction

mixtures contained traces of hydrazones 6.

10a

obtained in past work. It is necessary to admit that even the

entry of electron-rich 5-bromofuran-2-yl substituent, being

adjacent to the triple bond (enynone 1k), does not vary the

reaction regioselectivity; in this case, the only reaction product

is pyrazole 4s (80% yield, entry 19). The present example

shows that in enynones 1a−k, their CC bond is supposed to

be a better electronic eﬀect conductor than the triple one.

The (E)-conﬁguration of the CC bond persisted during

the reaction, which was conﬁrmed by high values of the spin−

Figure 3. Selected NOESY correlation (arrow) proving the formation

of isomer 4 .

spin coupling constant of vinyl protons ( J ∼ 16 Hz).

However, in the reaction of pyrrole enynone 1g, which was

available in form of the (E)- and (Z)-isomer mixture, only (E)-

isomer 4m was able to be isolated (entry 13). Unfortunately,

we did not manage to isolate (Z)-isomer 4m by chromatog-

raphy or by fractional crystallization. It would be appropriate to

admit that we obtained enynones 1a−k and 1m−o by the

condensation of aryl(hetaryl)but-3-yn-2-ones with aldehydes,

in which a double bond has the (E)-conﬁguration, except for

compound 1g. This situation is representative for other pyrrol

substituted α,β-unsaturated ketones.

Furthermore, we demonstrated that extension of the

conjugated system in the substrate allows obtaining of

pyrazoles containing diene and triene bridges in heterocyclic

moieties. As a result of the reactions of enynones 1l, m with

hydrazines 2a, d, we isolated compounds 4t−v in good to

excellent yields (Table 3).

Figure 4. Overlay of UV−vis spectra for 5.0 × 10⁻M solution of

pyrazole 4l in EtOH.

The structure of each of the obtained pyrazoles 4 was

proven by H and C NMR spectra. In additional two-

bond) is the most preferable reaction center in such enynones;

dimensional experiments (by means of the H NOESY NMR

thus, pyrazoles 4 form instead of 4,5-dihydro-1H-pyrazoles 3

spectra), we conﬁrmed the formation of regioisomers 4, not 5

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Table 3. Reactions of Ketones 1l, m with Hydrazines 2a, d

entry

enynone

hydrazine

reaction time,

pyrazole

yield, %

Reaction conditions: stirring with reﬂux of 1l, m (1 mmol) and 2a, d (1.1 mmol) in 4 mL of EtOH. The time of complete conversion of enynone

l, m, in accord with TLC. Preparative yields. According to TLC and H NMR spectra, the reaction mixtures contained traces of hydrazones 6.

(

see Figure 3 and the Supporting Information for details). We

Table 4. Reaction of Enynones 1a, b, e, f, h, i with

Phenylhydrazine 2a in Acidiﬁed Ethanol

conducted X-ray analysis for compounds 4d, h, k, which

showed the direction of the cyclocondensation of enynones 1

with hydrazines 2 as well as the retention of the double bond

(

E)-conﬁguration (see the Supporting Information for details).

It is necessary to admit that, except for main products 4,

there are corresponding traces of arylhydrazones 6 (B2 in

Scheme 2) formed in reaction with arylhydrazines 2a−c

reaction product

(

entries 1, 2, 4, 6, 7, 9−11, 13, 14, 16, 18, and 19 in Table 2

entry

starting enynone

reaction time, min

compound

yield, %

and entries 1 and 3 in Table 3); it aﬃrms a certain competition

_o_f_t_h_e_r_e_a_c_t_i_o_n_c_e_n_t_e_r_s_C3 _a_n_d_C5 of enynone 1 for a

nucleophile. However, as we might expect by the ΔG values

comparison (Table 1), 2-hydrazinylpyridine 2d (entries 3, 5, 8,

2, 15, 17 in Table 2; entry 2 in Table 3) provides pyrazoles

4c, e, h, l, o, q as the only end products under the same

conditions.

Reaction conditions: stirring with reﬂux of 1 (1 mmol) and 2a (1.1

mmol) in 4 mL of a EtOH−AcOH mixture. The time of complete

Next studied was selection of substrates and conditions that

direct the hydrazine attack on the reaction centers of other

enynones. By means of the reaction medium acidiﬁcation, it is

conversion of enynone 1, according to TLC. Preparative yields.

possible to vary relative activity of the carbons C and C in

substrate 1 triple bond, e.g. by the introduction of a sterically

hindered substituent.

substrates 1. Therewith, protonation of the carbonyl group

oxygen lead objectively to the carbon C electrophilicity

Actually, the interaction of (E)-1-(furan-2-yl)-5-(trimethyl-

silyl)pent-1-en-4-yn-3-one 1n with phenylhydrazine 2a results

in expected 5-(furan-2-yl)-1-phenyl-3-((trimethylsilyl)-

ethynyl)-4,5-dihydro-1H-pyrazole 3a under the conditions

determined above (see Table 2).

increasing; under such conditions, it would be correct to

expect inverted direction of the hydrazine 2 nucleophilic attack

that provides formation of hydrazones B2 (see Scheme 2),

pyrazoles 5, or 4,5-dihydro-1H-pyrazoles 3 mostly. Thus, we

operated the reaction by reﬂuxing in ethanol containing about

However, we did not manage to reach full conversion of

compound 1n, even by extended reﬂux, and the highest yield

of product 3a was 46% only. It is important to mark the

retention of the TMS group during the reaction; it is

3% of acetic acid (based on examples of enynones 1a, b, e, f,

h, i and phenylhydrazine 2a). In these experiments, the only

products we isolated from the reaction mixture were

phenylhydrazones 6a−f (Table 4). In additional experiments,

we demonstrated intentionally that the application of stronger

acids (HCl) or hydrazines 2 hydrochlorides leads mostly to

resin formation.

Our attempts to cyclize the isolated phenylhydrazones 6 by

extended reﬂuxing in acidiﬁed ethanol or AcOH did not cause

any desired eﬀect. After the experiments ﬁnished, all reaction

solutions contained starting phenylhydrazone 6 only. The

present experiments demonstrate that the CC and CC

bonds are not active enough for intramolecular cyclization in

phenylhydrazones, and the reaction directed toward hetero-

cycles 5 is not realized on the basis of enynones 1.

determined by the phenylhydrazine 2a basicity that is

insuﬃcient to deprotect the triple bond (Scheme 3).

Obviously, formation of the product 3a can follow the

intermediate phenylhydrazone B2 cyclization stage only, and

that is an exception to the rule described for similar

phenylhydrazones 6a−f; presumably, that depends on the

speciﬁc combination of electronic and steric eﬀects of the TMS

group and furan ring.

It can be noticed that 4,5-dihydro-1H-pyrazoles 3a, b are

stable and do not decompose during storage. This is a general

property of 1,3-disubstituted 4,5-dihydro-1H-pyrazoles (for

example, see page 51 of Desenko’s monograph ). The

enynone cyclizations, proceeding with retention of the triple

bond, are of certain practical interest as a method for the

Considering the discovered competition of the reaction

centers C and C of enynone 1, it would be correct to expect

that varying of substituents in the substrate leads to formation

of mostly 4,5-dihydro-1H-pyrazoles 3, not pyrazoles 4.

Apparently, it is necessary to decrease relative activity of the

7a,24

practicable ethynylated heterocycle synthesis.

Depending on quantum calculations data, the enynone 1o

which contains two phenyl substituents in positions 1 and 5

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Scheme 3. Reaction of Enynone 1n with Phenylhydrazine 2a

Scheme 4. Reaction of Enynone 1a with Hydrazines 2a−d

must interact with arylhydrazines in some other way.

According to Gibbs free energy values (see Table 1), the

reaction direction is determined by the electronic character of

the substituent in hydrazine 2 in that case; thus, by varying

diﬀerent hydrazines 2, we can obtain 4,5-dihydro-1H-pyrazoles

Previously, the authors of a patent informed about

practical photophysical properties of pyrazoles with alkenyl

substituents. Therefore, we studied some certain photophysical

properties of the obtained pyrazoles 4. The ﬂuorescence occurs

in the greatest number of the pyrazoles 4 variety solutions in

EtOH under UV light. For example, we revealed absorption

and emission spectra for some certain compounds (see Figure

4 and the Experimental Section).

0,11

as well as pyrazoles 4. Considering that, we additionally

studied the reactions of enynone 1o with hydrazines 2a−d

(Scheme 4).

The enynone 1o reacted with hydrazines 2a−d by reﬂuxing

The emission peaks have maxima in the range λ_e_m332−401

nm. Among the observed range of pyrazoles, the compound 4l

has the most ﬂuorescent emission maximum (λ_e_m401 nm); the

compound possesses the most intensive ﬂuorescence ability as

well. Its relative quantum yield was calculated, which is Φ = 31

± 10%. Certain ﬂuorescent properties of pyrazole 4l can be

explained by speciﬁc interaction in planar π-system, which is

formed from the benzofuran cycle, pyrazole cycle, and ethylene

bridge. It is necessary to admit that ﬂuorescence does not

occur in the cases of nitrofuryl derivative 4i or diene and triene

derivatives 4t−v. In the last example, ﬂuorescence quenching is

probably linked with domination of energy nonradiative

dissipation, which is caused by intramolecular rotations and

vibrations. That kind of eﬀect is typical of some various

in ethanol. In all cases, the reaction time was 3 h, and the

products precipitated after acidiﬁcation of solution by acetic

acid. As expected, in the case of phenylhydrazine 2a, the

carbonyl group and the substrate CC bond take part in the

cyclocondensation proceeding which results in mixture of 4,5-

dihydro-1H-pyrazole 3b with starting enynone 1o in the ratio

.5:1. In the case of more electron deﬁcient hydrazines 2b−d,

the pyrazoles 4w−y were obtained in good yields consistently.

The arylhydrazones 6g, h was isolated independently in the

good yield. It is necessary to admit that the product formation

proceeds under more mild reaction conditions than the

phenylhydrazones 6a−f synthesis does; once again, that

represents the deactivating inﬂuence of electron-rich ﬁve-

membered heteroaromatic rings in enynones 1a−n.

polyenes.

Thus, the obtained experimental and calculation data reveal

compliant polarizability of the conjugated π-system of the

cross-conjugated enynones. Through that, it would be possible

to vary reactivity of similar unsubstituted poly systems within

certain limits (by the entering of electron-rich ﬁve-membered

donor heteroaromatic rings); then, the process of cyclo-

condensation with hydrazines will be oriented to needed

reaction centers. We have observed and marked that use of the

eﬀective combination of substituents, being adjacent to the

extreme carbons in a polyconjugated chain, provides possibility

of the CC or CC bond cyclization; further, that leads to

the required heterocycle closure and the retention of reaction

centers which are supposed to be practical for further synthesis

procedures. We presume that a similar approach would help to

extend the synthetic potential of the cross-conjugated enynone

moiety.

In common with chalcone and dibenzylideneacetone, the

initial enynones 1a−k, n, o as well as their similarities with the

extended π-system of 1l, m do not ﬂuoresce because of high

probability of the intersystem crossing of S into the T_π_π_*

nπ*

state.

CONCLUSIONS

■

In conclusion, we revealed that the direction of interaction

with arylhydrazines is determined by the electronic character

of the substituent in cross-conjugated enynones. Combination

of substrates with the electron-rich ﬁve-membered hetero-

aromatic rings provides interaction with arylhydrazines

oriented with the carbonyl group and triple carbon bond.

Based on the discovered pattern, we developed a practical and

highly eﬀective method for ﬂuorescent pyrazole synthesis.

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High yields and simplicity of obtaining the object products

demonstrate that the method is a suitable technique for

synthesis of compounds with practical photophysical proper-

ties.

In contrast, by using the 1,5-diarylsubstituted cross-

conjugated enynones or enynones with TMS group adjacent

to the triple bond, we obtained 3-alkynylsubstituted 4,5-

dihydro-1H-pyrazoles which seemed to be eﬀective in organic

synthesis.

157.1, 149.3, 133.9, 132.9, 130.5, 128.6, 124.4, 120.4, 119.2, 109.9,

−

0.8, 86.8, 14.0; IR (CHCl , cm ) ν 2112 (CC), 1614 (CO);

Anal. Calcd for C H O : C, 81.34; H, 5.12. Found: C, 81.07; H,

16 12

.09.

(

E)-1-(5-Iodofuran-2-yl)-5-phenylpent-1-en-4-yn-3-one (1d).

Light brown prisms; yield 2.58 g (74%); mp 115−116 °C (EtOH−

H O); H NMR (400 MHz, CDCl ): δ 7.67−7.64 (m, 2H), 7.54 (d, J

15.8 Hz, 1H), 7.51−7.47 (m, 1H), 7.45−7.40 (m, 2H), 6.76 (d, J =

15.8 Hz, 1H), 6.72 (d, J = 3.5 Hz, 1H), 6.68 (d, J = 3.5 Hz, 1H);

C{ H} NMR (101 MHz, CDCl ): δ 177.2, 155.9, 133.0, 131.8,

30.7, 128.7, 126.5, 123.6, 120.2, 118.9, 94.2, 91.4, 86.8; IR (CHCl ,

−

cm ) ν 2212 (CC), 1622 (CO); Anal. Calcd for C H IO : C,

EXPERIMENTAL SECTION

■

51.75; H, 2.61; I, 36.45. Found: C, 51.69; H, 2.79; I, 36.61.

General Experimental Methods. All reagents and solvents were

used directly as purchased or puriﬁed according to standard

procedures when necessary. Analytical thin-layer chromatography

was carried out using Sorbﬁl commercial silica gel plates (EtOAc/

hexane solvent system), visualized with iodine vapor, or detected by

using UV light. Melting points of substances were measured in open

capillaries and are uncorrected.

(E)-1-(5-Nitrofuran-2-yl)-5-phenylpent-1-en-4-yn-3-one (1e).

Concentrated sulfuric acid (98%, 100 mg) was added to a solution

of 4-phenylbut-3-in-2-one (1.44 g, 10 mmol) and 5-nitrofurfural (1.41

g, 10 mL) in 5 mL of AcOH and stirred at room temperature for 3

days. After that, precipitate was ﬁltered, washed with cold EtOH (3

mL), and dried in air. Yellow needles; yield 1.07 g (40%); mp 203−

204 °C (EtOH); H NMR (400 MHz, CDCl ): 7.7069−7.67 (m,

The NMR spectra of the solutions of compounds 1b, d−g, i, j, k, l,

2H), 7.60 (d, J = 16.0 Hz, 1H), 7.55−7.51 (m, 1H), 7.48−7.43 (m,

n, 3, 4, and 6a, d, j, k, n, p in CDCl or DMSO-d were recorded on a

2H), 7.41 (d, J = 3.8 Hz, 1H), 7.05 (d, J = 16.0 Hz, 1H), 6.93 (d, J =

Bruker Avance III 400 spectrometer at 400 and 101 MHz for H and

C NMR, respectively, at 25 °C. The residual proton-solvent peak

CDCl (δ 7.26 ppm) for H NMR spectra and the carbon signal of

CDCl (δ 77.16 ppm) for C NMR spectra were used as references.

.8 Hz, 1H); C{ H} NMR (101 MHz, CDCl ): δ 176.2, 152.6,

152.1, 133.2, 131.2, 131.1, 130.2, 128.8, 119.6, 116.6, 113.1, 92.9.

−1

86.7; ν IR (CHCl , cm ) 2212 (CC), 1614 (CO); Anal. Calcd

for C H NO : C, 67.42; H, 3.39. Found: C, 67.35; H, 3.44.

NMR spectra of compound 1m were recorded on a Bruker AM-300

spectrometer (300 and 75 MHz for H and C NMR respectively);

(E)-1-(Benzofuran-2-yl)-5-phenylpent-1-en-4-yn-3-one (1f). Yel-

low needles; yield 2.04 g (75%); mp 127−128 °C (EtOH−H O); H

the spectra of compounds 4x and 6g, h were recorded on a Jeol ECX-

NMR (400 MHz, CDCl ): δ 7.76 (d, J = 15.7 Hz, 1H), 7.70−7.67

00A spectrometer (400 and 100 MHz for H and C NMR

(m, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.55−7.49 (m, 2H), 7.47−7.41 (m,

3H), 7.31−7.27 (m, 1H), 7.13 (s, 1H), 7.03 (d, J = 15.7 Hz, 1H);

respectively). IR spectra of compounds in CHCl were taken on a

Shimadzu IRTracer-100 Fourier spectrometer in the range of 4000−

C{ H} NMR (101 MHz, CDCl ): δ 177.3, 156.0, 152.0, 133.6,

−

00 cm . Elemental microanalysis for C, H, Cl, Br, I, S, and Si was

33.0, 130.7, 128.7, 128.5, 128.4, 127.2, 123.6, 122.0, 120.2, 113.3,

−

carried out by express gravimetry according to the methods described

11.6, 91.7, 86.9; IR (CHCl , cm ) ν 2212 (CC), 1625 (CO);

in the handbook. Additionally, HRMS for pyrazoles 4r, t was carried

out on a Bruker maXis HRMS-ESI-QTOF instrument. UV−vis

absorption spectra of the solutions of pyrazoles in EtOH were

obtained on a Shimadzu UV-2600 spectrophotometer in quartz cells;

ﬂuorescence spectra were measured on a Shimadzu RF-6000

instrument. The ﬂuorescence intensity of all products was determined

for solutions of the same concentration (5.0 × 10⁻M). The

procedure for measuring the relative quantum yield (by quinine

Anal. Calcd for C H O : C, 83.81; H, 4.44. Found: C, 83.54; H,

.38.

Mixture of 5-Phenyl-1-(1H-pyrrol-2-yl)-pent-1-en-4-yn-3-one (E)-

and (Z)-Isomers (1g). Yellow needles; yield 0.73 g (33%); mp 138−

139 °C (EtOH−H O); H NMR (400 MHz, CDCl ): δ 12.86 (s,

0.24H), 9.88 (s, 1H), 7.87 (d, J = 15.7 Hz, 1H), 7.65−7.60 (m,

2.60H), 7.57−7.53 (m, 0.30H), 7.49−7.34 (m, 4.96H), 7.17−7.12

(m, 1.28H), 6.84 (d, J = 11.9 Hz, 0.27H), 6.77−6.67 (m, 2.38H),

sulfate) for compound 4l is described in our previous article.

6.42−6.37 (m, 1.27H), 6.22 (d, J = 11.9 Hz, 0.27H); C{ H} NMR

X-ray Analysis. Single crystals of pyrazoles 4d, h, k were grown

from EtOH. Intensities of reﬂections were measured at 120.0(2) K on

Bruker Apex II diﬀractometer. Crystal structures were solved and

(101 MHz, CDCl ): δ 178.4, 175.8, 138.9, 138.8, 135.0, 133.2, 133.0,

132.9, 130.6, 130.5, 130.4, 128.6, 125.5, 124.9, 122.1, 121.7, 120.5,

120.4, 118.0, 116.6, 112.3, 111.9, 91.4, 91.3, 90.4, 86.6; IR (CHCl ,

−1

reﬁned using Olex2 and ShelXL packages. All nonhydrogen atoms

cm ) ν 2214 (CC), 1616 (CO); Anal. Calcd for C H NO: C,

were reﬁned in anisotropic approximation against F (hkl). Riding

81.43; H, 5.01. Found: C, 81.74; H, 5.18.

hydrogens were reﬁned in isotropic approximation.

(E)-5-Phenyl-1-(thiophen-3-yl)-pent-1-en-4-yn-3-one (1i). Light

DFT Calculations. All geometry optimizations were carried out at

yellow needles; yield 2.21 g (93%); mp 97−98 °C (EtOH−H O); H

the M06-02X level in conjunction with the 6-31G(d,p) basis set.

NMR (400 MHz, CDCl ): δ 7.92 (d, J = 16.0 Hz, 1H); 7.68−7.65

All studied structures were optimized without constraints. Optimized

structures were veriﬁed as true minima with no imaginary frequencies.

Vibrational frequencies and zero-point vibrational energies were

obtained at the same levels of theory. Estimation of thermodynamic

parameters was carried out using the Hessian matrix calculation.

Gibbs free energies were calculated for 25 °C. Solvent-phase

(m, 3H), 7.51−7.37 (m, 5H), 6.72 (d, J = 16.0 Hz, 1H); C{ H}

NMR (101 MHz, CDCl ): δ 178.4, 141.5, 137.4, 132.9, 130.6, 129.9,

−

128.7, 128.4, 127.4, 125.4, 120.3, 91.4, 86.6; IR (CHCl , cm ) ν

2214 (CC), 1624 (CO); Anal. Calcd for C H OS: C, 75.60; H,

4.23; S, 13.45. Found: C, 75.37; H, 4.38; S, 13.26.

(E)-1-(5-Bromofuran-2-yl)-5-(p-tolyl)pent-1-en-4-yn-3-one (1j).

calculations used the polarizable continuum model (PCM). All

calculations were carried out with the aid of the Gaussian 09 suite of

Light yellow needles; yield 2.81 g (89%); mp 123−124 °C

(EtOH−H O); H NMR (400 MHz, CDCl ): δ 7.55−7.50 (m,

programs.

3H), 7.23 (d, J = 7.9 Hz, 1H), 6.78−6.74 (m, 2H), 6.49 (d, J = 3.5

Hz, 1H), 2.42 (s, 3H); C{ H} NMR (101 MHz, CDCl ): δ 177.3,

Starting 1,5-Disubstituted Pent-1-en-4-yn-3-ones 1a−o.

Enynones 1a−d, f−m, o were prepared by condensation of 4-

arylbut-3-yn-2-ones with aromatic and heteroaromatic aldehydes in

152.6, 141.4, 133.0, 131.8, 129.5, 126.9, 126.3, 118.7, 117.0, 114.8,

−

92.1, 86.6, 21.8; IR (CHCl , cm ) ν 2210 (CC), 1612 (CO);

the presence of NaOH using a known method. Enynones 1a, c, h, o

Anal. Calcd for C H BrO : C, 60.98; H, 3.52; Br, 25.35. Found: C,

are described in the reports.

E)-1-(5-Methylfuran-2-yl)-5-phenylpent-1-en-4-yn-3-one (1b).

60.97; H, 3.74; Br, 25.20.

(E)-1,5-Bis(5-bromofuran-2-yl)pent-1-en-4-yn-3-one (1k). A 2.5

(

Yellow needles; yield 1.79 g (76%); mp 64−65 °C (EtOH−H O);

M solution of BuLi in hexane (28 mL, 0.07 mol) was added dropwise

H NMR (400 MHz, CDCl ): δ 7.65−7.63 (m, 2H), 7.58 (d, J = 15.6

to a solution of 2-bromo-5-ethynylfuran (14.43 g, 0.084 mol) in 60

Hz, 1H), 7.49−7.39 (m, 3H), 6.73−6.68 (m, 2H), 6.18 (d, J = 3.3 Hz,

mL of Et O (abs.) at −30 °C under argon atmosphere. The resulting

H), 2.39 (s, 3H); C{ H} NMR (101 MHz, CDCl ): δ 177.6,

solution of lithium acetylenide was warmed to room temperature and

235

J. Org. Chem. 2021, 86, 7229−7241

The Journal of Organic Chemistry

Article

added portionwise with stirring to a solution of freshly distilled Ac O

General Method for the Synthesis of Pyrazoles. Arylhy-

drazine 2a−d (1.1 mmol, 1.1 equiv) was added to a solution of

enynone 1a−m (1 mmol, 1.0 equiv) in 4 mL of 96% EtOH. The

solution was reﬂuxed (water bath) with stirring until complete

conversion of the starting enynone 1 (the duration of reﬂux for each

example is indicated in Tables 2 and 3). After cooling to room

temperature, the reaction mass was stirred for another 15 min, and the

precipitated crystals were ﬁltered oﬀ, washed with 1 mL of cold

(below 0 °C) EtOH, dried in air for 2 h, and then in a desiccator over

(

17.2 g, 0.17 mol) in 50 mL of Et O (abs.), maintaining the

temperature of the reaction mixture at the range of −70 to −65 °C.

After this, the reaction mixture was stirred while cooling for another

5 min, heated to 0 °C, and then both solution of NH Cl (25 g in 170

mL) and 25% solution of NH OH (10 mL) were added to it. The

product was extracted three times with ether; the extract was washed

with water, then with brine, and thereafter dried with Na SO . After

removal of the solvent, the residue was puriﬁed by ﬂash

chromatography on silica gel (EtOAc/hexane 1:50) to give 4-(5-

CaCl (24 h).

bromofuran-2-yl)but-3-yn-2-one. Colorless needles; yield: 7.75 g

(E)-5-(2-(Furan-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole (4a). Light

(

52%); mp 72−73 °C. H NMR (400 MHz, CDCl ): δ 6.91 (d, J =

yellow crystals; yield 184 mg (59%); mp 88−89 °C (EtOH−H O);

.6 Hz, 1H), 6.44 (d, J = 3.6 Hz, 1H), 2.45 (s, 3H); C{ H} NMR

H NMR (400 MHz, DMSO-d ): δ 7.91−7.89 (m, 2H), 7.689−7.686

(

101 MHz, CDCl ): δ 183.3, 136.7, 126.7, 123.8, 113.9, 94.5, 79.1,

(m, 1H), 7.64−7.57 (m, 4H), 7.55−7.50 (m, 1H), 7.48−7.44 (m,

2H), 7.38−7.34 (m, 2H), 7.21 (d, J = 16.1 Hz, 1H), 6.72 (d, J = 16.1

−

2.2; IR (CHCl , cm ) ν 2189 (CC), 1666 (CO); Anal. Calcd

for C H BrO : C, 45.11; H, 2.37; Br 37.51. Found: C, 45.06; H, 2.40;

Hz, 1H), 6.62 (d, J = 3.4 Hz, 1H), 6.56−6.55 (m, 1H); C{ H}

35b

Br 37.46. According to a previous method,

enynone 1k was

NMR (101 MHz, DMSO-d ): δ 152.1, 151.5, 144.3 (CH), 142.5,

synthesized from 4-(5-bromofuran-2-yl)but-3-yn-2-one and 5-bromo-

139.5, 133.2, 129.9 (CH), 129.2 (CH), 128.8 (CH), 128.5 (CH),

furan-2-carbaldehyde. Light gray needles; yield 1.94 g 52%; mp >150

126.0 (CH), 125.8 (CH), 120.4 (CH), 113.0 (CH), 112.7 (CH),

−1

C (with decomposition) (EtOH−H O). H NMR (400 MHz,

111.5 (CH), 101.6 (CH); IR (CHCl , cm ) ν 1591, 1541, 1487,

CDCl ): δ 7.47 (d, J = 15.8 Hz, 1H), 6.94 (d, J = 3.5 Hz, 1H), 6.78

1471, 1458; Anal. Calcd for C H N O: C, 80.75; H, 5.16. Found: C,

21 16

d, J = 3.5 Hz, 1H), 6.73 (d, J = 15.8 Hz, 1H), 6.50 (d, J = 3.5 Hz,

80.79; H, 5.29.

H), 6.46 (d, J = 3.5 Hz, 1H); C{ H} NMR (101 MHz, CDCl ): δ

(E)-5-(2-(Furan-2-yl)vinyl)-1-(4-nitrophenyl)-3-phenyl-1H-pyra-

76.0, 152.4, 136.9, 132.1, 127.4, 126.3, 125.5, 123.5, 119.4, 115.1,

zole (4b). Yellow powder; yield 264 mg (81%); mp 193−194 °C

−

14.0, 93.2, 80.0; IR (CHCl , cm ) ν 2191 (CC), 1618 (CO);

(with decomposition) (EtOH−Me CO−H O); H NMR (400 MHz,

DMSO-d ): δ 8.47−8.43 (m, 2H), 7.93−7.87 (m, 4H), 7.739−7.735

(m, 1H), 7.50−7.46 (m, 3H), 7.42−7.37 (m, 1H), 7.27 (d, J = 16.1

Hz, 1H), 6.83 (d, J = 16.1 Hz, 1H), 6.69 (d, J = 3.4 Hz, 1H), 6.60−

Yellow needles; yield 2.04 g (82%); mp 125−126 °C (EtOH−

6.58 (m, 1H); C{ H} NMR (101 MHz, DMSO-d ): δ 152.8, 152.0,

H O); H NMR (300 MHz, CDCl ): δ 7.66−7.57 (m, 3H), 7.48−

146.6, 144.5, 144.4, 143.2, 132.6, 129.3, 129.0, 126.0, 125.8, 125.6,

−

.37 (m, 4H), 6.92−6.79 (m, 2H), 6.54 (d, J = 3.5 Hz, 1H), 6.47−

.45 (m, 1H), 6.40 (d, J = 15.2 Hz, 1H); C{ H} NMR (75 MHz,

121.5, 112.8, 112.7, 111.9, 103.4; IR (CHCl , cm ) ν 1597, 1527,

1501; Anal. Calcd for C H N O : C, 70.58; H, 4.23. Found: C,

CDCl ): δ 177.7, 152.1, 147.6, 144.3, 132.8, 131.5, 130.5, 129.0,

70.39; H, 4.58.

−

28.6, 124.5, 120.3, 113.2, 112.4, 91.1, 86.8. IR (KBr, cm ) ν 2190

(E)-2-(5-(2-(Furan-2-yl)vinyl)-3-phenyl-1H-pyrazol-1-yl)pyridine

(CC), 1621 (CO); Anal. Calcd for C H O : C, 82.24; H, 4.87.

(4c). Light yellow needles; yield 276 mg (88%); mp 144−145 °C

Found: C, 82.11; H, 4.69.

(EtOH−Me

CO−H

O); H NMR (400 MHz, DMSO-d

): δ 8.60−

(

4E,6E,8E)-9-(Furan-2-yl)-1-phenylnona-4,6,8-trien-1-yn-3-one

8.58 (m, 1H), 8.06−8.02 (m, 1H), 7.99−7.96 (m, 3H), 7.85 (d, J =

16.3 Hz, 1H), 7.743−7.740 (m, 1H), 7.50−7.45 (m, 3H), 7.43−7.36

(m, 2H), 7.22 (d, J = 16.3 Hz, 1H), 6.63 (d, J = 3.4 Hz, 1H), 6.58−

(

1m). Orange prisms; yield 1.12 g (41%); mp 60−61 °C (hexane); H

NMR (300 MHz, CDCl ): δ 7.66−7.58 (m, 3H), 7.51−7.40 (m, 4H),

.88−6.80 (m, 2H), 6.64−6.50 (m, 2H), 6.47−6.45 (m, 2H), 6.36 (d,

6.57 (m, 1H); C{ H} NMR (101 MHz, DMSO-d ): δ 153.3, 152.6,

J = 15.2 Hz, 1H); C{ H} NMR (75 MHz, CDCl ): δ 177.9, 152.6,

152.0, 148.3 (CH), 144.2 (CH), 143.7, 139.8 (CH), 132.7, 129.2

(CH), 128.9 (CH), 126.0 (CH), 122.7 (CH), 120.3 (CH), 117.4

(CH), 115.6 (CH), 112.7 (CH), 111.3 (CH), 103.3 (CH); IR

47.9, 143.6, 142.9, 132.9, 131.3, 130.5, 130.4, 128.6, 126.4, 124.8,

−

20.4, 112.3, 111.4, 91.1, 86.9; IR (CHCl , cm ) ν 2212 (CC),

−

618 (CO); Anal. Calcd for C H O : C, 83.19; H, 5.14. Found:

(CHCl , cm ) ν 1591, 1580, 1541, 1487, 1471, 1447; Anal. Calcd for

C, 83.15; H, 5.23.

C H N O: C, 76.66; H, 4.83. Found: C, 76.49; H, 4.98; UV−vis

−

(

E)-1-(Furan-2-yl)-5-(trimethylsilyl)pent-1-en-4-yn-3-one (1n). A

(ε × 10 ) 322 (1.32) nm; emission λ 389 nm.

max max

.5 M solution of BuLi in hexane (3.8 mL, 9.5 mmol) was added

(E)-5-(2-(5-Methylfuran-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole

dropwise to a solution of trimethylsilylacetylene (990 mg, 10.1 mmol)

in 8 mL of THF (abs.) with stirring under argon atmosphere, and a

temperature below −40 °C was maintained. The solution was heated

to 0 °C, then cooled again, and subsequently, a solution of trans-3-(2-

furyl)acrolein (1.17 g, 9.58 mmol) in 12 mL of THF was added

dropwise in the range of −65 to −60 °C. The reaction mixture was

(4d). Light yellow crystals; yield 212 mg (65%); mp 113−114 °C

(petroleum ether); H NMR (400 MHz, DMSO-d ): δ 7.91−7.89

(m, 2H), 7.63−7.55 (m, 4H), 7.54−7.50 (m, 1H), 7.47−7.44 (m,

2H), 7.38−7.33 (m, 2H), 7.13 (d, J = 16.1 Hz, 1H), 6.61 (d, J = 16.1

Hz, 1H), 6.50 (d, J = 3.3 Hz, 1H), 6.18−6.16 (m, 1H), 2.26 (s, 3H);

C{ H} NMR (101 MHz, DMSO-d ): δ 153.5, 151.5, 150.8, 142.8,

heated to 0 °C and poured into a solution of NH Cl (4.4 g) in 13 mL

139.6, 133.2, 129.9 (CH), 129.2 (CH), 128.7 (CH), 128.5 (CH),

126.0 (CH), 125.8 (CH), 120.6 (CH), 112.9 (CH), 111.4 (CH),

of water. The product was extracted three times with CH Cl (20

−

mL), and the extract was washed with water. Then, the extract was

dried with Na SO ; the solvent was removed, and the remaining

109.1 (CH), 101.3 (CH), 13.9 (CH); IR (CHCl , cm ) ν 1636,

1597, 1525, 1501, 1458; Anal. Calcd for C H N O: C, 80.96; H,

22 18

−

viscous yellowish liquid (1.95 g) was dissolved in 70 mL of CH Cl₂

5.56. Found: C, 80.99; H, 5.72; UV−vis λ (ε × 10 ) 327 (2.37)

max

and treated with MnO (18.9 g, 217 mmol) for 1.5 h. The precipitate

nm; emission λ 332 nm.

max

was ﬁltered and washed with small portions of CH Cl (about 150 mL

(E)-2-(5-(2-(5-Methylfuran-2-yl)vinyl)-3-phenyl-1H-pyrazol-1-yl)-

in total). Removal of the solvent gave 1.44 g (66%) of an orange

viscous liquid. The resulting product, containing about 8% impurity of

pyridine (4e). Light yellow needles; yield 203 mg (62%); mp 92−93

°C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ

trans -3-(2-furyl)acrolein (see H NMR spectrum in the Supporting

8.62−8.60 (m, 1H), 8.09−8.05 (m, 1H), 7.97−7.92 (m, 3H), 7.66 (d,

J = 16.2 Hz, 1H), 7.50−7.37 (m, 5H), 7.14 (d, J = 16.2 Hz, 1H), 6.51

Information ), was used in subsequent syntheses without further

puriﬁcation. H NMR (400 MHz, CDCl ): δ 7.59−7.55 (m, 2H),

(d, J = 3.2 Hz, 1H), 6.21−6.20 (m, 1H), 2.34 (s, 3H); C{ H} NMR

.80 (d, J = 3.5 Hz, 1H), 6.68 (d, J = 15.8 Hz, 1H), 6.57−6.54 (m,

H), 0.31 (s, 9H); C{ H} NMR (101 MHz, CDCl ): δ 177.4,

(101 MHz, DMSO-d ): δ 153.4, 153.3, 151.9, 151.1, 148.4 (CH),

144.0, 139.9 (CH), 132.8, 129.3 (CH), 128.9 (CH), 126.0 (CH),

50.6, 145.9, 134.1, 125.8, 117.0, 112.9, 100.7, 98.3, − 0.6; IR

122.9 (CH), 120.5 (CH), 117.6 (CH), 113.9 (CH), 112.7 (CH),

−

−1

(

CHCl , cm ) ν 2154 (CC), 1649 (CO); Anal. Calcd for

109.0 (CH), 103.0 (CH), 14.1 (CH); IR (CHCl , cm ) ν 1591,

C H O Si: C, 66.02; H, 6.46. Found: C, 66.24; H, 6.33.

1528, 1506, 1472, 1449; Anal. Calcd for C H N O: C, 77.04; H,

21 17

236

J. Org. Chem. 2021, 86, 7229−7241

The Journal of Organic Chemistry

Article

−

.23. Found: C, 76.80; H, 5.34. UV−vis λ (ε × 10 ) 294 (2.39)

(E)-2-(5-(2-(Benzofuran-2-yl)vinyl)-3-phenyl-1H-pyrazol-1-yl)-

max

nm; emission λ 390 nm.

pyridine (4l). Colorless needles; yield 331 mg (91%); mp 195−196

max

(

E)-5-(2-(5-Bromofuran-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole

°C (EtOH−Me

CO−H

O); H NMR (400 MHz, DMSO-d

): δ

(

4f). Light orange crystals; yield 286 mg (73%); mp 108−109 °C

8.66−8.64 (m, 1H), 8.12−7.96 (m, 5H), 7.67−7.58 (m, 3H), 7.52−

EtOH−H O); H NMR (400 MHz, CDCl ): δ 7.93 (d, J = 7.1 Hz,

7.47 (m, 3H), 7.43−7.33 (m, 3H), 7.28−7.25 (m, 1H), 7.07 (s, 1H);

H), 7.61−7.53 (m, 4H), 7.50−7.44 (m, 3H), 7.39−7.35 (m, 1H),

C{ H} NMR (101 MHz, DMSO-d ): δ 154.9, 154.5, 153.2, 152.1,

.94 (s, 1H), 6.86−6.81 (m, 2H), 6.37−6.35 (m, 2H); C{ H} NMR

48.5 (CH), 143.2, 140.0 (CH), 132.6, 129.3 (CH), 129.1, 129.0

101 MHz, CDCl ): δ 154.2, 152.0, 142.1, 139.4, 132.8, 129.4, 128.7,

(CH), 126.0 (CH), 125.8 (CH), 123.8 (CH), 123.0 (CH), 121.8

CH). 120.3 (CH), 118.7 (CH), 117.5 (CH), 111.5 (CH), 107.6

28.2, 128.1, 125.9, 125.6, 122.8, 118.7, 114.2, 113.7, 112.3, 101.1; IR

(

−

CHCl , cm ) ν 1598, 1491, 1468; Anal. Calcd for C H BrN O: C,

3 21 15 2

(CH), 104.1 (CH); IR (CHCl , cm ) ν 1591, 1528, 1506, 1472,

4.47; H, 3.99; Br, 20.42. Found: C, 64.55; H, 3.95; Br, 20.31; UV−

449; Anal. Calcd for C H N O: C, 79.32; H, 4.72. Found: C,

24 17 3

−4

vis λ (ε × 10 ) 330 (1.73) nm; emission λ 382 nm.

−4

max

79.27; H, 4.60; UV−vis λ (ε × 10 ) 343 (3.93) nm; emission λ

max

(

E)-2-(5-(2-(5-Bromofuran-2-yl)vinyl)-1-(4-bromophenyl)-3-phe-

01 nm.

nyl-1H-pyrazole (4g). Light brown needles; yield 381 mg (81%); mp

(

E)-5-(2-(1H-Pyrrol-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole (4m).

27−128 °C (EtOH−Me CO−H O); H NMR (400 MHz, CDCl ):

Light yellow crystals; yield 190 mg (61%); mp 128−129 °C (with

δ 7.89−7.87 (m, 2H), 7.82−7.79 (m, 2H), 7.56−7.53 (m, 2H), 7.48−

decomposition) (EtOH−H O); H NMR (400 MHz, DMSO-d ): δ

.44 (m, 2H), 7.39−7.35 (m, 2H), 7.15 (d, J = 16.0 Hz, 1H), 6.71−

(

1.31 (s, 1H), 7.91−7.88 (m, 2H), 7.63−7.55 (m, 4H), 7.53−7.43

.66 (m, 3H); ¹³C{ H} NMR (101 MHz, CDCl ): δ 154.4, 151.9,

m, 3H), 7.37−7.33 (m, 1H), 7.23 (s, 1H), 7.13 (d, J = 16.2 Hz, 1H),

42.4, 138.7, 132.9, 132.9, 129.3, 128.7, 127.7, 125.8, 123.1, 121.6,

19.8, 114.8, 113.9, 113.4, 102.4; IR (CHCl , cm ) ν 1593, 1559,

54, 1516, 1495, 1481, 1458; Anal. Calcd for C H BrN O: C, 53.65;

H, 3.00; Br, 33.99. Found: C, 53.66; H, 3.19; Br, 33.79; UV−vis λ

.84−6.84 (m, 1H), 6.68 (d, J = 16.2 Hz, 1H), 6.28−6.26 (m, 1H),

−

.09−6.07 (m, 1H); C{ H} NMR (101 MHz, DMSO-d ): δ 151.3,

43.9, 139.8, 133.4, 130.1, 129.8, 129.2, 128.4, 128.3, 125.8, 125.7,

max

−1

24.1, 121.3, 111.6, 109.6, 109.1, 100.7; IR (CHCl , cm ) ν 1636,

−

(ε × 10 ) 330 (3.01) nm; emission λ 387 nm.

max

599, 1501, 1456; Anal. Calcd for C H N : C, 81.00; H, 5.50.

(

E)-2-(5-(2-(5-Bromofuran-2-yl)vinyl)-3-phenyl-1H-pyrazol-1-yl)-

Found: C, 80.84; H, 5.62.

(E)-1,3-Diphenyl-5-(2-(thiophen-2-yl)vinyl)-1H-pyrazole (4n).

pyridine (4h). Light brown needles; yield 353 mg (90%); mp 93−94

C (EtOH−H O); H NMR (400 MHz, CDCl ): δ 8.60−8.58 (m,

Light yellow needles; yield 250 mg (76%); mp 112−113 °C

H), 8.02 (d, J = 8.2 Hz, 1H), 7.96−7.84 (m, 4H), 7.49−7.45 (m,

(

EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ 7.90

H), 7.40−7.37 (m, 1H), 7.30−7.27 (m, 1H), 6.98 (s, 1H), 7.87 (d, J

(d, J = 7.6 Hz, 2H), 7.64−7.45 (m, 9H), 7.38−7.35 (m, 2H), 7.26 (d,

16.3 Hz, 1H), 6.40−6.38 (m, 2H); C{ H} NMR (101 MHz,

J = 3.6 Hz, 1H), 7.09−7.07 (m, 1H), 6.67 (d, J = 16.0 Hz, 1H);

CDCl ): δ 154.7, 153.4, 152.4, 147.9, 143.3, 138.6, 132.7, 128.7,

C{ H} NMR (101 MHz, DMSO-d ): δ 151.5, 142.4, 141.6, 139.5,

(

28.3, 125.9, 122.5, 121.7, 118.5, 117.1, 116.7, 113.6, 111.9, 102.7; IR

CHCl , cm ) ν 1591, 1580, 1485, 1470, 1447; Anal. Calcd for

C H BrN O: C, 61.24; H, 3.60; Br, 20.37. Found: C, 61.19; H, 3.71;

Br, 20.31; UV−vis λ (ε × 10 ) 331 (2.75) nm; emission λ 394

nm.

E)-5-(2-(5-Iodofuran-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole (4i).

−

133.1, 129.9, 129.3, 128.7 (2C), 128.5, 128.3, 126.9, 126.0, 125.80,

−1

25.76, 114.5, 101.9; IR (CHCl , cm ) ν 1599, 1541, 1501, 1458;

−

Anal. Calcd for C H N S: C, 76.80; H, 4.91; S, 9.76. Found: C,

21 16 2

max

−

6.93; H, 4.70; S, 9.71; UV−vis λ (ε × 10 ) 326 (2.40) nm;

emission λ 332 nm.

max

(

max

(

E)-2-(3-Phenyl-5-(2-(thiophen-2-yl)vinyl)-1H-pyrazol-1-yl)-

Light brown needles; yield 342 mg (78%); mp 108−109 °C

pyridine (4o). Colorless needles; yield 273 mg (83%); mp 100−101

(

EtOH−H O); H NMR (400 MHz, CDCl ): δ 7.94−7.91 (m,

C (EtOH−Me CO−H O); H NMR (400 MHz, CDCl ): δ 8.57−

H), 7.62−7.55 (m, 4H), 7.50−7.43 (m, 3H), 7.39−7.35 (m, 1H),

.55 (m, 1H), 8.05 (d, J = 8.2 Hz, 1H), 7.97−7.95 (m, 2H), 7.91−

.94 (s, 1H), 6.88−6.79 (m, 2H), 6.60 (d, J = 3.4 Hz, 1H), 6.31 (d, J

₃_.₄_H_z_,₁_H₎_;1 C{ H} NMR (101 MHz, CDCl ): δ 157.7, 152.0,

7.87 (m, 2H), 7.49−7.45 (m, 2H), 7.41−7.37 (m, 1H), 7.33−7.26

(

m, 3H), 7.16 (d, J = 3.5 Hz, 1H), 7.06−7.04 (m, 1H), 7.02 (s, 1H);

42.0, 139.5, 132.9, 129.4, 128.7, 128.13, 128.07, 125.8, 125.6, 122.6,

18.4, 114.5, 112.6, 101.2, 88.7; IR (CHCl , cm ) ν 1599, 1501,

472, 1458; Anal. Calcd for C H IN O: C, 57.55; H, 3.45; I, 28.96.

Found: C, 57.45; H, 3.52; I, 28.73.

E)-5-(2-(5-Nitrofuran-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole (4j).

−

C{ H} NMR (101 MHz, CDCl ): δ 153.5, 152.3, 147.7, 143.6,

42.4, 138.6, 132.7, 128.7, 128.3, 127.7, 126.9, 125.9, 125.2, 124.9,

−

21.6, 117.5, 117.0, 102.7; IR (CHCl , cm ) ν 1591, 1580, 1547,

506, 1472, 1449; Anal. Calcd for C H N S: C, 72.92; H, 4.59; S,

(

20 15

.73. Found: C, 72.88; H, 4.52; S, 9.66.

Brown needles; yield 214 mg (60%); mp 165−166 °C (with

(

E)-1,3-Diphenyl-5-(2-(thiophen-3-yl)vinyl)-1H-pyrazole (4p).

decomposition) (EtOH−Me CO−H O); H NMR (400 MHz,

Light yellow needles; yield 217 mg (66%); mp 127−128 °C

DMSO-d ): δ 7.91−7.88 (m, 2H), 7.74 (d, J = 3.9 Hz, 1H), 7.66−

(

EtOH−H O); H NMR (400 MHz, DMSO-d ): δ 7.92−7.89 (m,

.53 (m, 6H), 7.49−7.45 (m, 2H), 7.40−7.35 (m, 1H), 7.32 (d, J =

H), 7.65−7.55 (m, 6H), 7.53−7.44 (m, 3H), 7.38−7.32 (m, 4H),

.83 (d, J = 16.1 Hz, 1H); C{ H} NMR (101 MHz, DMSO-d ): δ

6.1 Hz, 1H), 7.07−7.03 (m, 2H); C{ H} NMR (101 MHz,

DMSO-d ): δ 155.2, 151.7, 151.6, 141.5, 139.2, 132.8, 130.1 (CH),

51.4, 143.0, 139.6, 139.5, 133.2, 129.9 (CH), 129.2 (CH), 128.5

(CH), 127.8 (CH), 127.4 (CH), 125.88 (CH), 125.80 (CH), 125.63

(CH), 125.57 (CH), 125.2 (CH), 115.4 (CH), 101.9 (CH); IR

(

29.3 (CH), 129.1 (CH), 128.7 (CH), 126.0 (CH), 125.8 (CH),

19.8 (CH), 118.4 (CH), 116.0 (CH), 113.8 (CH), 103.3 (CH); IR

CHCl , cm ) ν 1597, 1528, 1501, 1472; Anal. Calcd for

−

C H N O : C, 70.58; H, 4.23. Found: C, 70.79; H, 4.31; UV−vis

(CHCl

, cm ) ν 1599, 1541, 1501, 1458, 1439; Anal. Calcd for

C H N S: C, 76.80; H, 4.91; S, 9.76. Found: C, 76.73; H, 4.98; S,

21 16 2

−

max

(ε × 10 ) 267 (2.72).

−

(

E)-5-(2-(Benzofuran-2-yl)vinyl)-1,3-diphenyl-1H-pyrazole (4k).

9.62; UV−vis λmax (ε × 10 ) 297 (3.25) nm; emission λmax 336 nm.

Colorless needles; yield 319 mg (88%); mp 140−141 °C (EtOH−

(E)-2-(3-Phenyl-5-(2-(thiophen-3-yl)vinyl)-1H-pyrazol-1-yl)-

pyridine (4q). Colorless needles; yield 201 mg (61%); mp 99−100 °C

Me CO−H O); H NMR (400 MHz, DMSO-d ): δ 7.94−7.91 (m,

(

EtOH−H O); H NMR (400 MHz, DMSO-d ): δ 8.61−8.59 (m,

H), 7.66−7.59 (m, 5H), 7.57−7.52 (m, 2H), 7.49−7.45 (m, 3H),

.40−7.35 (m, 2H), 7.32−7.28 (m, 1H), 7.25−7.21 (m, 1H), 7.05 (s,

H), 8.09−8.05 (m, 1H), 7.99−7.94 (m, 3H), 7.81 (d, J = 16.4 Hz,

H), 7.66−7.65 (m, 1H), 7.62−7.60 (m, 1H), 7.51−7.34 (m, 7H);

H), 6.98 (d, J = 16.0 Hz, 1H); C{ H} NMR (101 MHz, DMSO-

d₆): δ 154.9, 154.1, 151.6, 142.2, 139.4, 133.1, 130.0 (CH), 129.3

CH), 129.0, 128.9 (CH), 128.6 (CH), 126.1 (CH), 125.85, 125.84

CH), 123.8 (CH), 121.8 (CH), 120.3 (CH), 116.1 (CH), 111.5

C{ H} NMR (101 MHz, DMSO-d

): δ 153.2, 151.9, 148.5 (CH),

(

144.1, 139.89, 139.86(CH), 132.8, 129.3 (CH), 128.9 (CH), 127.8

(CH), 126.9 (CH), 126.0 (CH), 125.6 (CH), 124.9 (CH), 122.7

−

−1

CH), 107.8 (CH), 102.4 (CH); IR (CHCl , cm ) ν 1600, 1533,

(CH), 117.8 (CH), 117.3 (CH), 103.2(CH); IR (CHCl , cm ) ν

499, 1458; Anal. Calcd for C H N O: C, 82.85; H, 5.01. Found: C,

1591, 1580, 1472, 1449; Anal. Calcd for C H N S: C, 72.92; H,

20 15

−

2.64; H, 5.12; UV−vis λ (ε × 10 ) 340 (3.96) nm; emission λ

4.59; S, 9.73. Found: C, 72.90; H, 4.48; S, 9.65. UV−vis λ (ε ×

max

−4

91 nm.

10 ) 286 (3.47) nm; emission λ 376 nm.

max

237

J. Org. Chem. 2021, 86, 7229−7241

The Journal of Organic Chemistry

Article

(

E)-5-(2-(5-Bromofuran-2-yl)vinyl)-1-phenyl-3-(p-tolyl)-1H-pyra-

Calcd for C H N OSi: C, 70.09; H, 6.54; Si, 9.11. Found: C, 69.82;

18 20 2

H, 6.59; Si, 9.02.

zole (4r). Light yellow needles; yield 316 mg (78%); mp 109−110 °C

(

EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ 7.77 (d,

General Procedure for the Preparation of 5-Phenyl-1-

hetarylpent-1-en-4-yn-3-ones Phenylhydrazones 6a−f. Phe-

nylhydrazine 2a (119 mg, 1.1 mmol, 1.1 equiv) and AcOH (0.4 mL)

were added successively to a solution of enynone 1a, b, e, f, h, i (1

mmol, 1.0 equiv) in 3.5 mL of EtOH. The solution was reﬂuxed

(water bath) with stirring (the duration of reﬂux for each example is

indicated in the Table 4) and cooled; the precipitated crystals were

ﬁltered oﬀ. The product was dried in vacuo (40 mmHg) for 1 h.

1-((E)-1-(Furan-2-yl)-5-phenylpent-1-en-4-yn-3-ylidene)-2-phe-

nylhydrazine (6a). Orange needles; yield 234 mg (76%); mp 108−

J = 8.2 Hz, 2H), 7.64−7.60 (m, 2H), 7.58−7.51 (m, 3H), 7.33 (s,

(

H), 7.26 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 16.2 Hz, 1H), 6.68−6.64

m, 3H), 2.34 (s, 3H); C{ H} NMR (101 MHz, DMSO-d ): δ

54.4, 151.6, 142.1, 139.4, 137.9, 130.3, 130.0, 129.8, 128.8, 125.9,

25.7, 122.9, 119.3, 114.8, 113.7, 113.6, 101.7, 21.3; IR (CHCl ,

−

cm ) ν 1599, 1501, 1481; Anal. Calcd for C H BrN O: C, 65.20;

H, 4.23; Br, 19.72. Found: C, 65.16; H, 4.54; Br, 19.34; HRMS (ESI)

m/z calcd for C H BrN O [M + H] 406.0596, found 406.0619.

(

E)-3-(5-Bromofuran-2-yl)-5-(2-(5-bromofuran-2-yl)vinyl)-1-phe-

nyl-1H-pyrazole (4s). Colorless needles; yield 368 mg (80%); mp

109 °C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ

38−139 °C (EtOH−Me CO−H O); H NMR (400 MHz, CDCl ):

10.06 (s, 1H), 7.85−7.80 (m, 2H), 7.72−7.71 (m, 1H), 7.53−7.48

(m, 3H), 7.35−7.26 (m, 4H), 6.95−6.86 (m, 3H), 6.68 (d, J = 3.3 Hz,

δ 7.58−7.53 (m, 4H), 7.51−7.46 (m, 1H), 6.85 (s, 1H), 6.83−6.74

(

m, 3H), 6.42 (d, J = 3.4 Hz, 1H), 6.37−6.35 (m, 2H); C{ H}

1H), 6.57−6.56 (m, 1H); C{ H} NMR (101 MHz, DMSO-d ): δ

NMR (101 MHz, CDCl ): δ 154.0, 150.4, 143.7, 142.0, 139.0, 129.4,

152.7, 144.3, 143.8 (CH), 132.7 (CH), 130.2 (CH), 129.5 (CH),

129.1 (CH), 126.5, 125.6 (CH), 121.7, 121.2 (CH), 118.9 (CH),

28.5, 125.7, 123.0, 121.5, 119.1, 113.7, 113.6, 113.2, 112.6, 108.6,

00.7; IR (CHCl , cm ) ν 1593, 1495, 1481, 1458; Anal. Calcd for

−

114.3 (CH), 112.7 (CH), 110.4 (CH), 103.1, 78.6; IR (CHCl ,

−

C H Br N O : C, 49.60; H, 2.63; Br, 34.73. Found: C, 49.80; H,

cm ) ν 3308 (NH), 2189 (CC), 1601 (CN); Anal. Calcd for

−

.88; Br, 34.41; UV−vis λ (ε × 10 ) 327 (3.58) nm; emission λ

93 nm.

C H N O: C, 80.75; H, 5.16. Found: C, 80.69; H, 5.36.

21 16

max

1-((E)-1-(5-Methylfuran-2-yl)-5-phenylpent-1-en-4-yn-3-yli-

-((1E,3E)-4-(Furan-2-yl)buta-1,3-dien-1-yl)-1,3-diphenyl-1H-

dene)-2-phenylhydrazine (6b). Orange needles; yield 222 mg (68%);

pyrazole (4t). Orange needles; yield 277 mg (82%); mp 141−142 °C

mp 112−113 °C (EtOH−Me CO−H O); H NMR (400 MHz,

(

EtOH−H O); H NMR (400 MHz, DMSO-d ): δ 7.91−7.88 (m,

DMSO-d ): δ 10.00 (s, 1H), 7.84−7.80 (m, 2H), 7.53−7.49 (m, 3H),

H), 7.671−7.668 (m, 1H), 7.62−7.49 (m, 5H), 7.47−7.44 (m, 2H),

7.35−7.26 (m, 4H), 6.90−7.84 (m, 2H), 6.80 (d, J = 15.9 Hz, 1H),

.38−7.34 (m, 1H), 7.31 (s, 1H), 7.11 (dd, J = 15.5, 10.9 Hz, 1H),

6.54 (d, J = 3.1 Hz, 1H), 6.18−6.17 (m, 1H), 2.33 (s, 3H); C{ H}

.83 (dd, J = 15.5, 10.9 Hz, 1H), 6.65 (d, J = 15.5 Hz, 1H), 6.58−6.53

NMR (101 MHz, DMSO-d ): δ 152.9, 151.3, 144.4, 132.6 (CH),

(

m, 3H); ¹³C{ H} NMR (101 MHz, DMSO-d ): δ 152.9, 151.5,

130.2 (CH), 129.5 (CH), 129.1 (CH), 126.7, 124.2 (CH), 121.7,

43.9, 143.0, 139.5, 133.2, 133.1, 129.9, 129.22, 128.6, 128.5, 127.4,

25.81, 125.80, 122.3, 119.0, 112.7, 110.3, 101.8; IR (CHCl , cm ) ν

599, 1537, 1501, 1479, 1358; Anal. Calcd for C H N O: C, 81.63;

H, 5.36. Found: C, 81.49; H, 5.62; HRMS (ESI) m/z calcd for

121.0 (CH), 119.0 (CH), 114.2 (CH), 111.8 (CH), 109.1 (CH),

−

−1

102.9, 78.6, 14.0 (CH); IR (CHCl , cm ) ν 3310 (NH), 2187 (C

C), 1601 (CN); Anal. Calcd for C H N O: C, 80.96; H, 5.56.

22 18

Found: C, 81.01; H, 5.36.

C H N O [M + H] 339.1497, found 339.1486.

1-((E)-1-(5-Nitrofuran-2-yl)-5-phenylpent-1-en-4-yn-3-ylidene)-

-(5-((1E,3E)-4-(Furan-2-yl)buta-1,3-dien-1-yl)-3-phenyl-1H-pyr-

2-phenylhydrazine (6c). Red powder; yield 311 mg (87%); mp 141−

azol-1-yl)pyridine (4u). Yellow needles; yield 255 mg (75%); mp

142 °C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ

33−134 °C (EtOH−H O); H NMR (400 MHz, DMSO-d ): δ

10.46 (s, 1H), 7.86−7.81 (m, 2H), 7.77 (d, J = 4.0 Hz, 1H), 7.54−

7.50 (m, 3H), 7.42−7.40 (m, 2H), 7.34−7.25 (m, 3H), 7.09 (d, J =

.59−8.58 (m, 1H), 8.08−8.03 (m, 1H), 7.96−7.93 (m, 3H), 7.699−

.696 (m, 1H), 7.55 (d, J = 15.6 Hz, 1H), 7.51−7.37 (m, 5H), 7.14

.0 Hz, 1H), 6.98−6.94 (m, 2H); C{ H} NMR (101 MHz, DMSO-

(

dd, J = 15.6, 11.0 Hz, 1H), 6.87 (dd, J = 15.4, 11.0 Hz, 1H), 6.67 (d,

d ): δ 156.4, 151.4, 143.8, 133.0 (CH), 132.7 (CH), 130.3 (CH),

J = 15.4 Hz, 1H), 6.61 (d, J = 3.3 Hz, 1H), 6.56−6.55 (m, 1H);

C{ H} NMR (101 MHz, DMSO-d ): δ 153.2, 153.0, 151.9, 148.4,

44.0, 143.9, 139.8, 132.9, 132.7, 129.3, 128.9, 127.6, 126.0, 122.8,

22.1, 121.4, 117.4, 112.7, 110.4, 103.4; IR (CHCl , cm ) ν 1599,

537, 1501, 1458; Anal. Calcd for C H N O: C, 77.44; H, 5.21.

Found: C, 77.68; H, 5.33.

29.6 (CH), 129.1 (CH), 125.4, 122.1 (CH), 121.6, 116.4 (CH),

116.0 (CH), 114.9 (CH), 112.9 (CH), 103.7, 78.0; IR (CHCl ,

−

cm ) ν 3365 (NH), 1597 (CN); Anal. Calcd for C H N O : C,

−

70.58; H, 4.23. Found: C, 70.63; H, 4.34.

1-((E)-1-(Benzofuran-2-yl)-5-phenylpent-1-en-4-yn-3-ylidene)-2-

phenylhydrazine (6d). Yellow needles; yield 330 mg (91%); mp

-((1E,3E,5E)-6-(Furan-2-yl)hexa-1,3,5-trien-1-yl)-1,3-diphenyl-

148−149 °C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-

H-pyrazole (4v). Orange needles; yield 255 mg (81%); mp 129−130

d ): δ 10.24 (s, 1H), 7.88−7.84 (m, 2H), 7.63 (d, J = 7.4 Hz, 1H),

C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ

7.58 (d, J = 8.1 Hz, 1H), 7.55−7.51 (m, 3H), 7.41−7.38 (m, 2H),

7.34−7.29 (m, 3H), 7.26−7.22 (m, 1H), 7.18 (d, J = 15.9 Hz, 1H),

.91−7.88 (m, 2H), 7.671−7.668 (m, 1H), 7.62−7.49 (m, 5H),

.47−7.43 (m, 2H), 7.38−7.34 (m, 1H), 7.32 (s, 1H), 7.10−7.04 (m,

H), 6.76−6.70 (m, 1H), 6.63−6.56 (m, 3H), 6.54−6.51 (m, 2H),

7.09−7.05 (m, 2H), 6.95−6.90 (m, 1H); C{ H} NMR (101 MHz,

DMSO-d ): δ 154.9, 154.8, 144.1, 132.70 (CH), 130.3 (CH), 129.5

.45 (d, J = 15.4 Hz, 1H); C{ H} NMR (101 MHz, DMSO-d ): δ

(CH), 129.3, 129.2 (CH), 129.0 (CH), 126.0, 125.43 (CH), 123.6

53.1, 151.5, 143.8, 143.0, 139.5, 135.3, 133.47, 133.40, 133.2, 129.9,

29.2, 128.6, 128.5, 127.4, 125.87, 125.80, 121.5, 118.6, 112.8, 110.3,

01.6; IR (CHCl , cm ) ν 1598, 1537, 1500, 1458; Anal. Calcd for

(CH), 121.7, 121.57 (CH), 121.53 (CH), 118.3 (CH), 114.5 (CH),

−

111.3 (CH), 106.5 (CH), 103.33, 78.50; IR (CHCl , cm ) ν 3321

−

(NH), 2187 (CC), 1603 (CN); Anal. Calcd for C H N O: C,

25 18

C H N O: C, 82.39; H, 5.53. Found: C, 82.40; H, 5.62.

82.85; H, 5.01. Found: C, 82.59; H, 5.29.

-(Furan-2-yl)-1-phenyl-3-((trimethylsilyl)ethynyl)-4,5-dihydro-

1-Phenyl-2-((E)-5-phenyl-1-(thiophen-2-yl)pent-1-en-4-yn-3-

H-pyrazole (3a). A solution of enynone 1n (218 mg, 1 mmol) and

ylidene)hydrazine (6e). Orange needles; yield 279 mg (85%); mp

phenylhydrazine 2a (119 mg, 1.1 mmol) in EtOH (2 mL) was

reﬂuxed for 10 h. After the solution was cooled, the crystalline

precipitate was ﬁltered oﬀ, washed with a minimal amount of cold

41−143 °C (with decomposition) (EtOH−Me CO−H O);

NMR (400 MHz, CDCl ): δ 8.69 (s, 1H), 7.69−7.65 (m, 2H), 7.52−

.45 (m, 3H), 7.36−7.32 (m, 2H), 7.26−7.19 (m, 4H), 7.12 (d, J =

13 1

EtOH, and dried in air. Light gray needles; yield 142 mg (46%); mp

.6 Hz, 1H), 7.05−7.03 (m, 1H), 6.99−6.93 (m, 2H); C{ H} NMR

28−129 °C (with decomposition) (EtOH−H O); H NMR (400

(101 MHz, CDCl ): δ 143.2, 142.4, 132.0, 129.7, 129.40, 129.40,

MHz, DMSO-d ): δ 7.574−7.567 (m, 1H), 7.21−7.16 (m, 2H),

128.7, 127.8, 127.4, 126.4, 125.0, 124.6, 121.4, 121.2, 113.5, 103.5,

−

.07−7.04 (m, 2H), 6.82−6.78 (m, 1H), 6.42 (d, J = 3.0 Hz, 1H),

7.5; IR (CHCl , cm ) ν 3308 (NH), 2187 (CC), 1603 (CN);

.38−6.36 (m, 1H), 5.64 (dd, J = 12.5, 5.6 Hz, 1H), 3.53 (dd, J =

Anal. Calcd for C H N S: C, 76.80; H, 4.91; S, 9.76. Found: C,

7.4, 12.5 Hz, 1H), 2.99 (dd, J = 17.4, 5.6 Hz, 1H), 0.24 (s, 9H);

7.11; H, 5.22; S, 9.59.

1-Phenyl-2-((E)-5-phenyl-1-(thiophen-3-yl)pent-1-en-4-yn-3-

C{ H} NMR (101 MHz, DMSO-d ): δ 152.6, 143.5, 143.4, 131.7,

29.4, 120.4, 114.2, 110.8, 108.7, 101.0, 99.0, 56.9, 42.1, 0.1; Anal.

ylidene)hydrazine (6f). Orange needles; yield 269 mg (82%); mp

238

J. Org. Chem. 2021, 86, 7229−7241

The Journal of Organic Chemistry

https://pubs.acs.org/doi/10.1021/acs.joc.1c00569.

Article

25−126 °C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-

2H), 8.10−8.02 (m, 2H), 7.99−7.96 (m, 1H), 7.58−7.55 (m, 2H),

7.50−7.46 (m, 2H), 7.42−7.37 (m, 3H), 7.34−7.26 (m, 2H), 7.20 (d,

d ): δ 9.98 (s, 1H), 7.86−7.82 (m, 2H), 7.71−7.70 (m, 1H), 7.58−

.50 (m, 5H), 7.35−7.26 (m, 4H), 7.13 (d, J = 16.0 Hz, 1H), 7.01 (d,

J = 16.6 Hz, 1H), 7.07 (s, 1H); C{ H} NMR (101 MHz, DMSO-

d₆): δ 153.6, 152.3, 147.7 (CH), 144.0, 138.6 (CH), 137.0, 132.8,

132.0 (CH), 128.72 (CH), 128.69 (CH), 128.3 (CH), 128.1 (CH),

126.9 (CH), 126.0 (CH), 121.6 (CH), 118.1 (CH), 117.1 (CH),

J = 16.0 Hz, 1H), 6.90−6.86 (m, 1H); C{ H} NMR (101 MHz,

DMSO-d ): δ 144.4, 139.9, 132.7 (CH), 130.2 (CH), 129.5 (CH),

(

29.2 (CH), 127.46 (CH), 127.42 (CH), 127.1, 125.9 (CH), 125.8

CH), 124.3 (CH), 121.8, 121.0 (CH), 114.2 (CH), 103.0, 78.9; IR

−

102.9 (CH); IR (CHCl , cm ) ν 1591, 1580, 11545, 1472, 1447;

Anal. Calcd for C22H N : C, 81.71; H, 5.30. Found: C, 81.95; H,

17 3

−

CHCl , cm ) ν 3310 (NH), 2187 (CC), 1603 (CN); Anal.

−

Calcd for C H N S: C, 76.80; H, 4.91; S, 9.76. Found: C, 77.45; H,

5.47; UV−vis λmax (ε × 10 ) 289 (2.68) nm; emission λmax 372 nm.

5.64; S, 9.70.

General Procedure for the Preparation of 1,5-Diphenyl-

ASSOCIATED CONTENT

sı Supporting Information

The Supporting Information is available free of charge at

■

pent-1-en-4-yn-3-ones Phenylhydrazones 6g, h. To a solution

of enynone 1o (232 mg, 1 mmol, 1.0 equiv) in EtOH (2 mL),

acidiﬁed with one drop conc. HCl, arylhydrazine 2a or 2c (1.1 mmol,

.1 equiv) was added. The reaction mixture was stirred for 10 min at

room temperature, and the product was isolated as described in the

previous procedure.

¹H, ¹³C{1H} NMR spectra of compounds, X-ray data,

computational details (PDF)

-((E)-1,5-Diphenylpent-1-en-4-yn-3-ylidene)-2-phenylhydrazine

FAIR data, including the primary NMR FID ﬁles, for

compounds 1b, d−g, i−n, 4-(5-bromofuran-2-yl)but-3-

yn-2-one, 4a−y, 3a, 6a−h, and mixture of 3b and 1o

(

6g). Orange needles; yield 242 mg (70%); mp 136−137 °C (EtOH−

Me CO−H O); H NMR (400 MHz, DMSO-d ): δ 8.67 (s, 1H),

(

.66−7.63 (m, 2H), 7.52−7.50 (m, 2H), 7.47−7.43 (m, 3H), 7.37−

(ZIP)

.24 (m, 5H), 7.18−7.15 (m, 2H), 7.09−7.07 (m, 2H), 6.95−6.91

m, 1H); ¹³C{ H} NMR (100 MHz, DMSO-d ): δ 143.3, 137.0,

Accession Codes

32.0, 131.8, 129.8, 129.5, 128.8, 128.8, 127.94, 127.91, 126.9, 126.8,

CCDC 2016001−2016003 contain the supplementary crys-

tallographic data for this paper. These data can be obtained

free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by

emailing data_request@ccdc.cam.ac.uk, or by contacting The

Cambridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

21.5, 121.3, 113.6, 103.6, 77.8; Anal. Calcd for C H N : C, 85.68;

H, 5.63. Found: C, 85.59; H, 5.70.

-((E)-1,5-Diphenylpent-1-en-4-yn-3-ylidene)-2-(4-nitrophenyl)-

hydrazine (6h). Orange needles; yield 316 mg (86%); mp 198−199

(

C (EtOH−Me CO−H O); H NMR (400 MHz, DMSO-d ): δ

0.74 (s, 1H), 8.18−8.15 (m, 2H), 7.85−7.82 (m, 2H), 7.66−7.64

m, 2H), 7.54−7.43 (m, 5H), 7.36 (t, J = 7.4 Hz, 2H), 7.30−7.26 (m,

13 1

H), 7.21 (d, J = 16.2 Hz, 1H), 7.15 (d, J = 16.2 Hz, 1H); C{ H}

AUTHOR INFORMATION

Corresponding Author

■

NMR (100 MHz, DMSO-d ): δ 150.0, 140.4, 136.5, 134.4, 133.0,

31.9, 130.7, 129.4, 129.3, 129.0, 127.7, 127.1, 126.3, 121.4, 113.8,

03.9, 78.5; Anal. Calcd for C H N O: C, 75.19; H, 4.66. Found: C,

Alexander A. Golovanov − Togliatti State University, 445020

Togliatti, Russia; orcid.org/0000-0001-7133-3070;

Email: aleksandgolovanov@yandex.ru

5.28; H, 4.71.

Reaction of Enynone 1o with Hydrazines 2a−d. A solution

containing enynone 1o (232 mg, 1 mmol, 1.0 equiv) and the

corresponding hydrazine 2a−d (1.1 mmol, 1.1 equiv) in EtOH (2

mL) was reﬂuxed (water bath) for 3−4 h until complete conversion of

the starting enynone (TLC monitoring). The solution was cooled and

acidiﬁed with AcOH (0.4 mL). After 10−15 min, a precipitate was

formed and ﬁltered oﬀ. The product was isolated as described in the

procedure for the synthesis of compounds 4.

Authors

Ivan S. Odin − Togliatti State University, 445020 Togliatti,

Russia

Dmitry M. Gusev − Togliatti State University, 445020

Togliatti, Russia

Anna V. Vologzhanina − A. N. Nesmeyanov Institute of

Organoelement Compounds of the Russian Academy of

Science, 119991 Moscow, Russia; orcid.org/0000-0002-

A Mixture of 1,5-Diphenyl-3-(phenylethynyl)-4,5-dihydro-1H-

pyrazole 3b and Starting Enynone 1o. Orange needles; total yield

77 mg; 3b:1o ratio 4.5:1 ( H NMR spectrum, see Supporting

6228-303X

Information for details). Individual compound 3b was synthesized

10a

Ilya M. Sosnin − Togliatti State University, 445020 Togliatti,

Russia

Stanislav A. Grabovskiy − Ufa Institute of Chemistry, UFRS

of the Russian Academy of Science, 450054 Ufa, Russia

and characterized earlier.

E)-1-(4-Bromophenyl)-3-phenyl-5-styryl-1H-pyrazole (4w). Col-

(

orless powder; yield 217 mg (54%); mp 159−160 °C (EtOH−

Me CO−H O); H NMR (400 MHz, DMSO-d ): δ 7.93−7.90 (m,

H), 7.81−7.77 (m, 2H), 7.59−7.53 (m, 4H), 7.49−7.44 (m, 2H),

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.1c00569

.41−7.35 (m, 5H), 7.34−7.30 (m, 1H), 7.00 (d, J = 16.2 Hz, 1H);

C{ H} NMR (101 MHz, DMSO-d ): δ 152.8, 146.5, 144.6, 143.7,

36.6, 134.1, 132.7, 129.41, 129.40, 129.2, 129.1, 127.6, 126.1, 125.69,

25.66, 115.5, 104.0; Anal. Calcd for C H BrN : C, 68.84; H, 4.27;

Notes

The authors declare no competing ﬁnancial interest.

Br, 19.91. Found: C, 68.77; H, 4.37; Br, 19.85.

E)-1-(4-Nitrophenyl)-3-phenyl-5-styryl-1H-pyrazole (4x). Yellow

powder; yield 224 mg (61%); mp 158−159 °C (EtOH−Me CO−

(

ACKNOWLEDGMENTS

The reported study was funded by RFBR, project number 20-

3-80004. X-ray diﬀraction studies were performed using the

■

H O); H NMR (400 MHz, DMSO-d ): δ8.43−8.39 (m, 2H), 7.92−

.86 (m, 4H), 7.58−7.56 (m, 2H), 7.47−7.43 (m, 3H), 7.41−7.34

13 1

(

m, 4H), 7.32−7.27 (m, 1H), 7.09 (d, J = 16.3 Hz, 1H); C{ H}

equipment of the Center for Molecular Composition Studies

of INEOS RAS. S.A.G. thanks the state program for the

ﬁnancial support (state registration no. AAAA-A20-

NMR (100 MHz, DMSO-d ): δ 152.8, 146.5, 144.6, 143.7, 136.6,

34.1, 132.7, 129.41, 129.40, 129.2, 129.1, 127.6, 126.1, 125.69,

25.66, 115.5, 104.0; Anal. Calcd for C H N O: C, 75.19; H, 4.66.

20012090025-2). The authors are grateful to Kareem V.

Found: C, 75.31; H, 4.58.

Gordon for help in preparing this manuscript and also to Ivan

A. Kolyada and Evgeny A. Zatynatskiy for their help with the

experiments.

(

E)-2-(3-Phenyl-5-styryl-1H-pyrazol-1-yl)pyridine (4y). Colorless

powder; yield 165 mg (51%); mp 97−98 °C (EtOH−H O); H

NMR (400 MHz, DMSO-d ): δ 8.58−8.56 (m, 1H), 8.07−8.03 (m,

239

J. Org. Chem. 2021, 86, 7229−7241

The Journal of Organic Chemistry

V. V.; Vologzhanina, A. V.; Voronova, E. D. Synthesis of Isoxazole

Article

Derivatives of 4,5-Dihydro-1 H -pyrazole. Russ. J. Org. Chem. 2017 , 53 ,

REFERENCES

■

1) (a) Golovanov, A. A.; Odin, I. S.; Zlotskii, S. S. Conjugated

664 −1668. (c) Thomson, C. J.; Barber, D. M.; Dixon, D. J. One-Pot

Enynones: Preparation, Properties and Applications in Organic

Synthesis. Russ. Chem. Rev. 2019, 88, 280−318. (b) Golovanov, A.

A.; Gusev, D. M.; Odin, I. S.; Zlotskii, S. S. Conjugated 2,4,1- and

,4,3-Enynones as Polycentric electrophiles in Synthesis of Hetero-

cyclic Compounds. Chem. Heterocycl. Compd. 2019, 55 , 333 −348.

2) Golubev, P. V.; Pankova, A. S.; Kuznetsov, M. A. Regioselective

Catalytic Enantioselective Synthesis of 2-Pyrazolines. Angew. Chem.,

Int. Ed. 2019, 58, 2469−2473.

(

11) Golovanov, A. A.; Zatynatskiy, E. A.; Odin, I. S.; Dorogov, M.

V.; Vikarchuk, A. A. Condensation of 5-Phenylpent-1-en-4-yn-3-one

with Arylhydrazines. Russ. J. Org. Chem. 2018 , 54 , 662 −663.

(12) Miller, R. D.; Reiser, O. The Synthesis of Electron Donor-

Transition-Metal-Free Synthesis of 2-(Trimethylsilylmethylene)-

pyrrol-3-ones by Thermal Cyclization of Acetylenic Enamines. J.

Org. Chem. 2015, 80, 4545−4552.

Acceptor Substituted Pyrazoles. J. Heterocycl. Chem. 1993, 30, 755−

63.

13) (a) Bennani, F. E.; Doudach, L.; Cherrah, Y.; Ramli, Y.;

(

3) (a) Rosiak, A.; Christoffers, J. Synthesis of Unsymmetrically 2,6-

Karrouchi, K.; Ansar, M.; Faouzi, M. E. A. Overview of Recent

Developments of Pyrazole Derivatives as an Anticancer Agent in

Different Cell Line. Bioorg. Chem. 2020, 97, 103470. (b) Karrouchi,

K.; Radi, S.; Ramli, Y.; Taoufik, J.; Mabkhot, Y. N.; Al-Aizari, F. A.;

Ansar, M. Synthesis and Pharmacological Activities of Pyrazole

Derivatives: A Review. Molecules 2018 , 23 , 134 −219. (c) Ansari, A.;

Ali, A.; Asif, M.; Shamsuzzaman. Review: Biologically Active Pyrazole

Derivatives. New J. Chem. 2017, 41, 16−41. (d) Khan, F. M.; Alam,

M. M.; Verma, G.; Akhtar, W.; Akhter, M.; Shaquiquzzaman, M. The

therapeutic voyage of pyrazole and its analogs: A review. Eur. J. Med.

Chem. 2016, 120, 170 −201. (e) Kasiotis, K. M.; Tzanetou, E. N.;

Haroutounian, S. A. Pyrazoles as potential anti-angiogenesis agents: a

contemporary overview. Front. Chem. 2014, 2, 78. (f) Balbi, A.;

Anzaldi, M.; Maccio, C.; Aiello, C.; Mazzei, M.; Gangemi, R.;

Castagnola, P.; Miele, M.; Rosano, C.; Viale, M. Synthesis and

Biological Evaluation of Novel Pyrazole Derivatives with Anticancer

Activity. Eur. J. Med. Chem. 2011, 46, 5293−5309. (g) Saleh, N. M.;

El-Gazzar, M. G.; Aly, H. M.; Othman, R. A. Novel Anticancer Fused

Pyrazole Derivatives as EGFR and VEGFR-2 Dual TK Inhibitors.

Front. Chem. 2020 , 7 , 917. (h) Ran, F.; Liu, Y.; Zhang, D.; Liu, M.;

Zhao, G. Discovery of Novel Pyrazole Derivatives as Potential

Anticancer Agents in MCL. Bioorg. Med. Chem. Lett. 2019, 29, 1060−

Disubstituted 2,3-Dihydrothiopyran-4-ones. Tetrahedron Lett. 2006 ,

47 , 5095 −5097. (b) Rosiak, A.; Muller, R. M.; Christoffers, J. Studien

zur Synthese von Tetrahydro- und Dihydrothiopyran-4-on-Derivaten.

Monatsh. Chem. 2007 , 138 , 13 −26. (c) Minami, Y.; Kuniyasu, H.;

Kambe, N. One-Pot Syntheses of 2,3-Dihydrothiopyran-4-one

Derivatives by Pd/Cu-Catalyzed Reactions of α ,β -Unsaturated

Thioesters with Propargyl Alcohols. Org. Lett. 2008, 10, 2469−2472.

(4) (a) Heffernan, S. J.; Tellam, J. P.; Queru, M. E.; Silvanus, A. C.;

Benito, D.; Mahon, M. F.; Hennessy, A. J.; Andrews, B. I.; Carbery, D.

R. Double Gold-Catalysed Annulation of Indoles by Enynones. Adv.

Synth. Catal. 2013 , 355 , 1149 −1159. (b) Xie, X.; Du, X.; Chen, Y.;

Liu, Y. One-Pot Synthesis of Indole-Fused Scaffolds via Gold-

Catalyzed Tandem Annulation Reactions of 1,2-Bis(alkynyl)-2-en-1-

ones with Indoles. J. Org. Chem. 2011, 76, 9175 −9181.

(5) (a) Waldo, J. P.; Mehta, S.; Larock, R. C. Room Temperature

ICl-Induced Dehydration/Iodination of 1-Acyl-5-hydroxy-4,5-dihy-

dro-1 H -pyrazoles. A Selective Route to Substituted 1-Acyl-4-iodo-1 H -

pyrazoles. J. Org. Chem. 2008, 73, 6666−6670. (b) Pankova, A. S.;

Golubev, P. R.; Ananyev, I. V.; Kuznetsov, M. A. Synthesis of [2-

Trimethylsilyl)ethynyl]pyrazoles Based on Bis(trimethylsilyl)-

acetylene and Arylacetyl Chlorides. Eur. J. Org. Chem. 2012, 2012,

965−5271.

6) Golubev, P. V.; Pankova, A. S.; Kuznetsov, M. A. Transition-

1064.

(14) (a) Weekes, R. J.; Hawes, C. S. Synthesis, Coordination

Metal-Free Approach to 4-Ethynylpyrimidines via Alkenynones. Eur.

Chemistry and Photophysical Properties of Naphtho-Fused Pyrazole

Ligands. CrystEngComm 2019 , 21 , 5152 −5163. (b) Pearce, B. H.;

Ogutu, H. F.; Luckay, R. C. Synthesis of Pyrazole-Based Pyridine

Ligands and Their Use as Extractants for Nickel(II) and Copper(II):

Crystal Structure of a Copper(II)-Ligand Complex. Eur. J. Inorg.

Chem. 2017, 2017, 1189−1201. (c) Estevan, F.; Hirva, P.; Ofori, A.;

J. Org. Chem. 2014, 2014, 3614−3621.

(

7) (a) Golubev, P. R.; Karpova, E. A.; Pankova, A. S.; Sorokina, M.;

Kuznetsov, M. A. Regioselective Synthesis of 7-(Trimethylsilyl-

ethynyl)pyrazolo[1,5-a ]pyrimidines via Reaction of Pyrazolamines

with Enynones. J. Org. Chem. 2016, 81, 11268−11275. (b) Rode, N.

D.; Arcadi, A.; Chiarini, M.; Marinelli, F.; Portalone, G. Gold-

Catalyzed Synthesis of Dibenzo[1,5]diazocines from β -(2-Amino-

phenyl)-α ,β -ynones. Adv. Synth. Catal. 2017, 359, 3371−3377.

Sanau, M.; Spec, T.; Ubeda, M. Pyrazole and Pyrazolate as Ligands in

the Synthesis and Stabilization of New Palladium(II) and (III)

Compounds. Inorg. Chem. 2016, 55, 2101−2113.

(15) (a) Brewer, G.; Butcher, R. J.; Zavalij, P. Use of Pyrazole

Marinelli, F. Synthesis of 2-Acylindoles via Ag- and Cu-Catalyzed

anti-Michael Hydroamination of β -(2-Aminophenyl)-α ,β -ynones:

Experimental Results and DFT Calculations. J. Org. Chem. 2018,

Hydrogen Bonding in Tripodal Complexes to Form Self Assembled

Homochiral Dimers. Materials 2020, 13, 1595−1613. (b) Ishida, M.;

Fujimoto, H.; Morimoto, T.; Mori, S.; Toganoh, M.; Shimizu, S.;

Furuta, H. Supramolecular Dimeric Structures of Pyrazole-Containing

meso -Oxo Carbaphlorin Analogues. Supramol. Chem. 2017, 29, 8−16.

83 , 6354 −6362. (d) Rode, N. D.; Arcadi, A.; Chiarini, M.; Marinelli,

F. An Improved Environmentally Friendly Approach to 4-Nitro-, 4-

Sulfonyl-, and 4-Aminoquinolines and 4-Quinolones through

Conjugate Addition of Nucleophiles to β -(2-Aminophenyl)-α ,β -

ynones. Synthesis 2017, 49, 2501−2512.

(16) (a) Hariprasad, S.; Srinivasaa, H. T. Symmetric 3,5-Pyrazole

and Isoxazole Heterocycles Comprising a Bent Core Unit: Synthesis

and Mesomorphic Characterization. Liquid Cryst. 2015, 42, 1612−

1620. (b) Soria, L.; Ovejero, P.; Cano, M.; Campo, J. A.; Torres, M.

(8) (a) Saulnier, S.; Lozovskiy, S. V.; Golovanov, A. A.; Ivanov, A.

Yu; Vasilyev, A. V. Brønsted Acid Promoted Cyclization of Cross-

Conjugated Enynones into Dihydropyran-4-ones. Eur. J. Org. Chem.

R.; Nunez, C.; Lodeiro, C. Selecting Pyrazole-Based Silver Complexes

017, 2017, 3635−3645. (b) Aleksandrova, M. I.; Lozovskiy, S. V.;

for Efficient Liquid Crystal and Luminescent Materials. Dyes Pigm.

2014, 110, 159−168. (c) Ovejero, P.; Asensio, E.; Heras, J. V.;

Saulnier, S.; Golovanov, A. A.; Boyarskaya, I. A.; Vasilyev, A. V.

Hydroarylation of Unsaturated Carbon-Carbon Bonds in Cross-

Conjugated Enynones Under the Action of Superacid CF SO H or

Campo, J. A.; Cano, M.; Torres, M. R.; Nunez, C.; Lodeiro, C. Silver-

Pyrazole Complexes as Hybrid Multifunctional Materials with

Metallomesogenic and Photoluminescent Behaviour. Dalton Trans.

2013, 42, 2107−2120.

Acidic Zeolite HUSY. Reaction Mechanism and DFT Study on

Cationic Intermediate Species. Org. Biomol. Chem. 2018, 42, 7891−

902.

(17) (a) Cetin, A.; Korkmaz, A.; Bildirici, I. A Novel Oligo-Pyrazole-

Based Thin Film: Synthesis, Characterization, Optical and Morpho-

logical Properties. Colloid Polym. Sci. 2018, 296, 1249−1257.

(b) Mukundam, V.; Kumar, A.; Dhanunjayarao, K.; Ravi, A.;

Peruncheralathan, S.; Venkatasubbaiah, K. Tetraaryl Pyrazole

Polymers: Versatile Synthesis, Aggregation Induced Emission

Enhancement and Detection of Explosives. Polym. Chem. 2015, 6,

10) (a) Botvinnik, E. V.; Blandov, A. N.; Kuznetsov, M. A. Reaction

9) Am Ende, C. W.; Zhou, Z.; Parker, K. A. Total Synthesis of

±)-Bisabosqual A. J. Am. Chem. Soc. 2013, 135, 582−585.

of 1,5-Diphenyl-1,4-pentadien-3-one and 1,5-Diphenyl-1-penten-4-yn-

-one with Monosubstituted Hydrazines. Russ. J. Org. Chem. 2001, 37,

21−425. (b) Golovanov, A. A.; Odin, I. S.; Anoshina, O. S.; Bekin,

240

J. Org. Chem. 2021, 86, 7229−7241

The Journal of Organic Chemistry

(29) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A.

Article

764 −7770. (c) Wang, S.; Cheng, B. One-Pot Synthesis of

Polypyrazoles by Click Reactions. Sci. Rep. 2017, 7, 12712.

18) (a) Giornal, F.; Pazenok, S.; Rodefeld, L.; Lui, N.; Vors, J.-P.;

Properties of Nicotinonitrile 1,2,3-Triazole Derivatives. Russ. Chem.

Bull. 2018, 67, 1710−1715.

K.; Puschmann, H. OLEX2 : a complete structure solution, refinement

and analysis program. J. Appl. Crystallogr. 2009 , 42 , 339−341.

(30) Sheldrick, G. M. A short history of SHELX . Acta Crystallogr.,

Sect. A: Found. Crystallogr. 2008 , A64 , 112 −122.

(31) Zhao, Y.; Truhlar, D. G. The M06 Suite of Density Functionals

for Main Group Thermochemistry, Thermochemical Kinetics,

Noncovalent Interactions, Excited States, and Transition Elements:

Two New Functionals and Systematic Testing of Four M06-Class

Functionals and 12 Other Functionals. Theor. Chem. Acc. 2008, 120,

(

Leroux, F. R. Synthesis of diversely fluorinated pyrazoles as novel

active agrochemical ingredients. J. Fluorine Chem. 2013 , 152, 2−11.

(b) Lamberth, C. Pyrazole Chemistry in Crop Protection. Heterocycles

19) (a) Metwally, N. H.; Ragab, E. A.; Mohamed, M. S. Synthesis of

007, 71, 1467−1502.

Some Novel N 5-Sulfonylated and N 1-Alkyated Pyrazole Derivatives

and their Antimicrobial Activity in Conjunction with Molecular

Docking Study. J. Heterocycl. Chem. 2020 , 57 , 1698 −1713. (b) Tu, K.

N.; Kim, S.; Blum, S. A. Copper-Catalyzed Aminoboration from

Hydrazones To Generate Borylated Pyrazoles. Org. Lett. 2019 , 21 ,

(

15−241.

32) Hehre, W. J.; Radom, L.; Schleyer, P. V. R.; Pople, J. A. Ab

Initio Molecular Orbital Theory; Wiley & Sons: New York, 1985; p

48.

33) Tomasi, J.; Mennucci, B.; Cammi, R. Quantum Mechanical

Continuum Solvation Models. Chem. Rev. 2005, 105, 2999−3093.

34) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;

283 −1286. (c) Yi, F.; Zhao, W.; Wang, Z.; Bi, X. Silver-Mediated [3

2] Cycloaddition of Alkynes and N -Isocyanoiminotriphenylphos-

phorane: Access to Monosubstituted Pyrazoles. Org. Lett. 2019, 21,

158−3161. (d) Lellek, V.; Chen, C.-Y.; Yang, W.; Liu, J.; Ji, X.;

Faessler, R. An Efficient Synthesis of Substituted Pyrazoles from One-

Pot Reaction of Ketones, Aldehydes, and Hydrazine Monohydro-

chloride. Synlett 2018, 29, 1071−1075. (e) Venkateswarlu, V.; Kour,

J.; Kumar, K. A. A.; Verma, P. K.; Reddy, G. L.; Hussain, Y.;

Tabassum, A.; Balgotra, S.; Gupta, S.; Hudwekar, A. D.; Vishwakarma,

R. A.; Sawant, S. D. Direct N -Heterocyclization of Hydrazines to

Access Styrylated Pyrazoles: Synthesis of 1,3,5-Trisubstituted

Pyrazoles and Dihydropyrazoles. RSC Adv. 2018 , 8 , 26523 −26527.

(

Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr; Vreven, T.;

Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;

Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;

Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.;

Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,

O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J.

B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,

O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P.

Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;

Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas,

O.; Malick, D. K.; Rabuck, D.; Raghavachari, K.; Foresman, J. B.;

Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Cliﬀord, S.; Cioslowski, J.;

Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;

Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;

Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,

W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. GAUSSIAN 03, Revision

D.02; Gaussian, Inc.: Wallingford CT, 2004.

(35) (a) Utekhina, N. V.; Korzhova, N. V.; Kazantseva, V. M.; Surov

Yu, N.; Orlov, V. D.; Korshunov, S. P. 1,5-Diaryl-1-penten-4-yn-3-

ones. Russ. J. Gen. Chem. (J. Gen. Chem. of USSR). 1988, 58, 612−616.

(b) Voronova, E. D.; Golovanov, A. A.; Suponitsky, K. Yu; Fedyanin,

I. V.; Vologzhanina, A. V. Theoretical Charge Density Analysis and

Nonlinear Optical Properties of Quasi-Planar 1-Aryl(hetaryl)-5-

phenylpent-1-en-4-yn-3-ones. Cryst. Growth Des. 2016, 16, 3859−

3868.

(f) Wang, Q.; He, L.; Li, K. K.; Tsui, G. C. Copper-Mediated Domino

Cyclization/Trifluoromethylation/Deprotection with TMSCF : Syn-

thesis of 4-(Trifluoromethyl)pyrazoles. Org. Lett. 2017, 19 , 658 −661.

(g) Zhang, X.; Kang, J.; Niu, P.; Wu, J.; Yu, W.; Chang, J. I -Mediated

Oxidative C-N Bond Formation for Metal-Free One-Pot Synthesis of

Di-, Tri-, and Tetrasubstituted Pyrazoles from α ,β -Unsaturated

Aldehydes/Ketones and Hydrazines. J. Org. Chem. 2014, 79,

(

0170−10178.

20) Matveeva, M.; Golovanov, A.; Borisova, T.; Titov, A.;

Varlamov, A.; Shaabani, A.; Obydennik, A.; Voskressensky, L.

Domino Reactions of Vinyl Ethynyl Ketones with 1-Aryl-3, 4-

Dihydroisoquinolines - Search for Selectivity. Mol. Catal. 2018, 461,

21) (a) Pérez, P.; Domingo, L. R.; Aizman, A.; Contreras, R.

7−72.

Chapter 9 The electrophilicity index in organic chemistry. Theor.

Comput. Chem. 2007 , 19 , 139 −201. (b) Chattaraj, P. K.; Sarkar, U.;

Roy, D. R. Electrophilicity Index. Chem. Rev. 2006, 106, 2065−2091.

(

22) Chebanov, V. A.; Desenko, S. M.; Gurley, T. W. Azaheterocycles

Based on α,β-Unsaturated Carbonyls; Springer-Verlag GmbH:

Amsterdam, 2008.

(36) Vereshchagin, L. I.; Korshunov, S. P.; Skoblikova, V. I.;

Aleksandrova, S. L. Sintez i Nekotorye Svojstva Furilacetilenovyh

Spirtov i Glikolej. Zh. Obshch. Khim. 1964, 34, 1419−1427.

(23) Ushakov, I. A.; Afonin, A. V.; Voronov, V. K.; Stepanova, Z. V.;

Sobenina, L. N.; Mikhaleva, A. I. NMR Study of the Steric and

Electronic Structure of 2-(2-Acylethenyl)pyrroles. Russ. J. Org. Chem.

24) (a) Kumar, R.; Singh, R. M. Metal-Free POCl Promoted

003, 39, 1318−1324.

Stereoselective Hydrochlorination of Ethynylated Azaheterocycles.

Org. Biomol. Chem. 2019, 17, 5990−5996. (b) Li, Y.; Cheng, H.;

Zhang, Z.; Zhuang, X.; Luo, J.; Long, H.; Zhou, Y.; Xu, Y.;

Taghipouran, R.; Li, D.; Patterson, A.; Smaill, J.; Tu, Z.; Wu, D.; Ren,

X.; Ding, K. N -(3-Ethynyl-2,4-difluorophenyl)sulfonamide Derivatives

as Selective Raf Inhibitors. ACS Med. Chem. Lett. 2015, 6, 543−543.

c) Odin, I. S.; Golovanov, A. A.; Bekin, V. V.; Pisareva, V. S.

Synthesis and Acylation of 3-Aryl-5-(2-phenylethynyl)-4,5-dihydro-

H -pyrazoles. Chem. Heterocycl. Compd. 2014, 49, 1687−1689.

25) Yin, B. Blue-light absorbers and its preparation method and

application. Chinese patent CN 107325051, July 11, 2017.

26) Krasovitsky, B. M.; Bolotin, B. M. Organic Luminophores;

Moscow, 1984.

27) Bance, S. Handbook of practical organic micro-analysis:

(

Recommended methods for determining elements and groups (Ellis

Horwood series in analytical chemistry); E. Horwood: New York, 1980.

(28) Rakshin, S. O.; Odin, I. S.; Sosnin, I. M.; Zatynatskiy, E. A.;

Ostapenko, G. I.; Golovanov, A. A. Synthesis and Fluorescence

241