Untitled


 

 

 HUNGARIAN JOURNAL OF 
INDUSTRY AND CHEMISTRY 

Vol. 53(1) pp. 39–42 (2025) 

hjic.mk.uni-pannon.hu 
DOI: 10.33927/hjic-2025-05 

ENANTIOSELECTIVE CATALYTIC THREE-COMPONENT SYNTHESIS OF 

OPTICALLY ACTIVE PROPARGYL AMINO ETHERS 

GULAHMAD MIRAHMAD TALYBOV 1* 

1 Azerbaijan Technical University, Javid Avenue 25, Baku, AZ 1073, AZERBAIJAN 

Catalytic enantioselective three-component aminomethylation of benzaldehyde as well as its methoxy-substituted 
derivatives and propargyl ethers with aniline in the presence of a chiral catalyst – pseudoephedrine – yielded 
previously unknown optically active propargyl amino ethers with high yields and a high degree of 
enantioselectivity. This reaction can also be used to form both C-C and C-N bonds. 

Keywords: enantioselective aminomethylation, enantioselectivity, asymmetric catalysis, three-
component reaction 

1. Introduction 

Optically active propargylamines are important synthetic 

intermediates for the preparation of various natural 

products [1],[2] and biologically active compounds 

[3]-[5]. 

Many Mannich bases have a number of useful 

pharmacological properties, for example, antimicrobial, 

cytotoxic, antitumor and analgesic activity [6],[7]. 

Propargyl-containing chiral organic compounds can 

act as synthons for the targeted synthesis of many natural 

nitrogen-containing compounds as well as optically 

active drugs [8]-[11]. To achieve this goal, the catalytic 

asymmetric Mannich reaction is carried out efficiently. 

This is one of the most convenient methods for 

synthesizing chiral nitrogen-containing compounds [12]. 

Although three-component syntheses of amino ethers 

involving various compounds are found in the literature 

[11], the synthesis of novel compounds No. 1-7 is the first 

time that propargyl ethers have been used. 

Enantioselective reactions using pseudoephedrine as a 

chiral catalyst also exist [12],[13]. 

2. Experimental 

The general methodology for synthesizing target 

compounds was as follows: a mixture of 0.1 mmol of 

aromatic aldehyde, 0.3 mmol of propargyl ether, 

0.1 mmol of aniline as well as 1.5 mg of pseudoephedrine 

and 0.8 mg of CuCl in 18 ml of dry CH2Cl2 was stirred at 

25°C before being heated for 4 hours at 80-90°C. Next, 

3 ml of isopropyl alcohol was added before the 

 

Received: 27 Nov 2024; Revised: 7 Febr 2025; 
Accepted: 7 Febr 2025 
*Correspondence: gtalibov61@gmail.com 

precipitate was filtered off then washed with water (3 ml) 

and isopropyl alcohol (3 ml). 

The purity of the compounds obtained was 

monitored by TLC on Silufol UV-254 plates with a 1:1 

ratio of eluent acetone to hexane. Their melting points 

were determined using a Melting Point M-565 

instrument. The specific optical rotation [α]D20 was 
measured using a Perkin Elmer-341 polarimeter. HPLC 

was performed by a Thermo Scientific TSQ Quantum 

Access™ instrument with a Zorbax CB-C18 (150mm x 

2.1mm, 1.8 µm) designed to carry out reversed phase 

HPLC. 
1H and 13C NMR spectra of the resulting 

compounds in a solution of CDCl3 were recorded by a 

Bruker SF-300 spectrometer with operating frequencies 

of 300 (1H) and 75 MHz (13C) as well as an internal 

standard - HMDS.The data of 1H NMR, 13C NMR 

(CDCl3) and IR spectra can be found in the Supplement. 

In the synthesis described, the following novel 

compounds were obtained: 

No. 1: 

N-[(1R,4R)-4-phenoxy-1-phenylpent-2-yn-1-yl]-aniline 

Yield: 45%. Light yellow powder, m.p.: 156–157°С 
(with decomposition), [α]D22 +55.4 (with 0.1, CHCl3). 

Observed composition (%): C 84.32; H 6.51; N 4.22 - 

С23Н21NO. Calculated composition (%): C 84.37; H 6.46; 

N 4.28.  

No. 2: 

N-[(1R,5R)-4-phenoxy-1-phenylhex-2-yn-1-yl]-aniline 

Yield: 54%. Light yellow powder, m.p.: 158–159°С 
(with decomposition), [α]D22 +56.8 (with 0.1, CHCl3). 

Observed composition (%): C 84.32; H 7.11; N 3.84 - 

https://doi.org/10.33927/hjic-2025-05
mailto:gtalibov61@gmail.com


  TALYBOV 

Hungarian Journal of Industry and Chemistry 

40 

С25Н25NO. Calculated composition (%): C 84.47; H 7.09; 

N 3.94. 

No. 3: 

N-[(1R)-4-(Cyclohexyloxy)-1-phenylbut-2-yn-1-yl]-

aniline 

Yield: 51%. Light yellow powder, m.p.: 124–125°С 
(with decomposition), [α]D22 +36.4 (with 0.1, CHCl3). 

Observed composition (%): C 82.22; H 8.14; N 4.51 - 

С21Н25NO. Calculated composition (%): C 82.04; H 8.20; 

N 4.56. 

No. 4: 

N-[(1R)-4-(Cyclopentyloxy)-1-phenylbut-2-yn-1-yl]-

aniline 

Yield: 56%. Light yellow powder, m.p.: 121–122°С 
(with decomposition), [α]D22 +34.9 (with 0.1, CHCl3). 

Observed composition (%): C 81.23; H 8.21; N 4.87 - 

С19Н23NO. Calculated composition (%): C 81.10; H 8.24; 

N 4.98. 

No. 5: 

N-[(1R,4R)-4-phenoxy-1-(2-(methoxy-phenylpent-2-

in-1-yl]-aniline 

Yield: 53%. Light yellow powder, m.p.: 161–162°С 
(with decomposition), [α]D22 +66.8 (with 0.1, CHCl3). 

Observed composition (%): C 83.87; H 7.21; N 4.21 - 

С24Н25NO. Calculated composition (%): C 83.93; H 7.34; 

N 4.08. 

No. 6: 

N-[(1R,4R)-4-phenoxy-1-(3-(methoxy-phenylpent-2-

yn-1-yl]-aniline 

Yield: 56%. Light yellow powder, m.p.: 160–161°С 
(with decomposition), [α]D22 +64.8 (with 0.1, CHCl3). 

Observed composition (%): C 83.66; H 7.14; N 4.14 - 

С24Н25NO. Calculated composition (%): C 83.93; H 7.34; 

N 4.08. 

No. 7: 

N-[(1R,4R)-4-phenoxy-1-(4-(methoxy-phenylpent-2-

yn-1-yl]-aniline 

Yield: 50%. Light yellow powder, m.p.: 158–159°С 
(with decomposition), [α]D22 +61.8 (with 0.1, CHCl3). 

Observed composition (%): C 83.83; H 7.17; N 4.11 - 

С24Н25NO. Calculated composition (%): C 83.93; H 7.34; 

N 4.08. 

3. Results and analysis 

For the first time, the highly enantioselective three-

component reaction of aldehydes, aniline and propargyl 

ethers was investigated using the chiral catalyst 

pseudoephedrine, where the degree of diastereomeric 

excess (de) was as high as 96 % (Figure 1).  

The starting propargyl ethers were obtained in 

advance [14]. 

Since the methylene protons in compound No. 2 are 

diastereotopic, they exhibit different singlet signals at 

3.46 d (1H, OCH2, J=9.4 Hz), 3.75 d (1H, OCH2, J=9.4 

Hz). 

In the case of R2=Me for compounds No. 1-2 and 

5-7, diastereomers were obtained. The ratio of these 

diastereomeric isomers was determined by 1H NMR 

spectroscopy after the reaction had finished and a 

thermodynamic equilibrium between the 

diastereoisomers (before chromatography) established 

according to the ratio of the integration of doublet signals 

of methine protons 1-2 and 5-7 at 3.46-3.75 ppm. To 

determine the absolute configuration of amino ethers 1-2 

and 5-7, the polarimetric method was used whereby 

similar compounds had previously been studied 

[15],[16]. Therefore, the measured positive optical 

rotation of the synthesized diastereoisomers indicates 

their (R,R)-absolute configuration. 

Reactions of benzaldehyde as well as its methoxy-

substituted derivatives and propargyl ethers with aniline 

in the presence of a chiral catalyst – pseudoephedrine – 

proceeded smoothly to produce the corresponding 

 

 

 

Figure 1: Reaction scheme 



ENANTIOSELECTIVE SYNTHESIS OF OPTICALLY ACTIVE PROPARGYL AMINO ETHERS 

53(1) pp. 39–42 (2025) 

41 

products in yields of 45-56% and with 

enantioselectivities of 90-96% (Table 1).  

The protons of pseudoephedrine interact with the 

hydrogen bonds of propargyl amino ethers, leading to its 

activation (Figure 2).  

The structure and composition of the obtained target 

compounds No. 1-7 were confirmed by 1H and 13C NMR 

spectroscopy as well as elemental analysis (The spectra 

can be found in the Supplementary information, available 

in the Editorial office.). 

4. Conclusions 

Based on the experimental results, the catalytic 

enantioselective three-component synthesis of 

benzaldehyde as well as its methoxy-substituted 

derivatives and propargyl ethers with aniline in the 

presence of a chiral catalyst with high yields and a high 

degree of enantioselectivity was achieved. 

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N

H

CH3

HO CH3

NH

R
1

O

R

R
2

n

 

Figure 2: Scheme of how the protons of 

pseudoephedrine interact with the hydrogen bonds of 

propargyl amino ethers 

Table 1: Enantioselective reactions of benzaldehyde as 

well as its methoxy-substituted derivatives and 

propargyl ethers with aniline in the presence of a chiral 

catalyst – pseudoephedrine 

Entry Time (h) Yield (%) de (%) 

1 1 45 93 

2 1 54 94 

3 1 51 90 

4 1 56 95 

5 1 53 94 

6 1 56 94 

7 1 50 96 

 

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Hungarian Journal of Industry and Chemistry 

42 

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http://doi.org/10.1134/S1070363218100298
http://doi.org/10.1021/ol0268788
http://doi.org/10.1021/ol006614q
https://doi.org/10.1134/S107042802211015X
https://doi.org/10.1039/P19900002301