Addition of azoles to methyl vinyl ketone by the Aza-Michael reaction

Hayotsyan, S. S.; Khachatryan, A. N.; Baltayan, A. O.; Attaryan, H. S.; Hasratyan, G. V.

doi:10.1134/s1070363215040398

Cited by 7 publications

(6 citation statements)

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“…In Table 1, selected examples of such reactions are collected. [6][7][8][9][10][11][12][13][14][15] Besides those few examples purposefully discussing aza-Michael reaction carried out without additives, more examples of such an approach can be found in optimization studies. Therefore, we included such additive-free attempts (if they were reported) in the notes column of the tables.…”

Section: Methodsmentioning

confidence: 99%

Aza-Michael Addition of Imidazole Analogues

2016

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Section: Methodsmentioning

confidence: 99%

Aza-Michael Addition of Imidazole Analogues

2016

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“…8, pp. 1395-1396 We have previously investigated the reactivity of pyrazoles I-III in addition reactions to the carboncarbon double bond conjugated with electronwithdrawing groups [1,2]. In order to verify the possibility of attaching azoles to conjugated systems under mild conditions, we performed reactions of pyrazoles I-III with maleic acid; in the latter molecule the double bond is not polarized due to a mismatched action of two electron-withdrawing groups [3].…”

Section: Letters To the Editormentioning

confidence: 99%

“…The experiments showed that pyrazoles I-III react with maleic acid similarly to the cases of acrylic acid [4] and methyl vinyl ketone [1]: when heated in bulk in the absence of any catalyst, they yielded the corresponding (pyrazol-1-yl)succinic acids IV-VI (Scheme 1).…”

Section: Letters To the Editormentioning

confidence: 99%

“…IR spectrum, ν, cm -1 : 1540 (ring), 1690 (COOH). 1 IR spectra were obtained using a Nexus instrument (Thermo Nicolet Corporation, USA). 1 H NMR spectra of the solutions in DMSO-CCl 4 (1 : 3) were recorded with a Varian Mercury spectrometer (300 MHz).…”

Section: -(35-dimethyl-1h-pyrazol-1-yl)butanedioic Acid (Vi)mentioning

confidence: 99%

“…

The experiments showed that pyrazoles I-III react with maleic acid similarly to the cases of acrylic acid [4] and methyl vinyl ketone [1]: when heated in bulk in the absence of any catalyst, they yielded the corresponding (pyrazol-1-yl)succinic acids IV-VI (Scheme 1).

Yields of aza-Michael adducts IV-VI depended strongly on the azoles basicity.

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Aza-Michael addition of pyrazoles to maleic acid

et al. 2015

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We have previously investigated the reactivity of pyrazoles I-III in addition reactions to the carboncarbon double bond conjugated with electronwithdrawing groups [1,2]. In order to verify the possibility of attaching azoles to conjugated systems under mild conditions, we performed reactions of pyrazoles I-III with maleic acid; in the latter molecule the double bond is not polarized due to a mismatched action of two electron-withdrawing groups [3].The experiments showed that pyrazoles I-III react with maleic acid similarly to the cases of acrylic acid [4] and methyl vinyl ketone [1]: when heated in bulk in the absence of any catalyst, they yielded the corresponding (pyrazol-1-yl)succinic acids IV-VI (Scheme 1).Yields of aza-Michael adducts IV-VI depended strongly on the azoles basicity. When maleic acid reacted with 3,5-dimethylpyrazole III (pK b = 4.38), yield of compound VI was of 96%, whereas in the case of less basic pyrazole I (pK b = 2.53) the reaction proceeded with yield of 65%. In the case of 3(5)methylpyrazole II (pK b = 3.55), the desired product was obtained in yield of 80% as a mixture of two isomers Va and Vb in the ratio of 9 : 1. Isomer 5a was isolated via fractional crystallization from water. 2-(1H-Pyrazol-1-yl)butanedioic acid (IV).A mixture of 1.5 g (0.022 mol) of pyrazole I and 3.0 g (0.024 mol) of maleic acid was heated to 110°C. The reaction temperature spontaneously went up to 130°C. Heating was continued at 110°C for 2.5 h. The resulting mixture was recrystallized from water. Yield 2.6 g (65%), mp 170°C. IR spectrum, ν, cm -1 : 1520 (ring), 1570 (COOH). 1 H NMR spectrum, δ, ppm (J, Hz): 2.99 d.d (1H, CH 2 , J 17.0, 7.6), 3.14 d.d (1H, CH 2 , J 17.0, 6.2), 5.27 d.d (1H, CH, J 7.6, 6.2), 6.18 d.d (1H, =CH, J 2.3, 1.8), 7.37 d.d (1H, =CH, J 1.8, 0.8), 7.65 d.d (1H, =CH, J 2.3, 0.8), 12.20 br.s (2H, COOH). Found, %: C 45.85; H 4.75; N 15.56. C 7 H 8 N 2 O 4 . Calculated, %: C 45.66; H 4.38; N 15.21.R 1 = R 2 = H (I, IV); R 1 = CH 3 , R 2 = H (IIа, Vа); R 1 = H, R 2 = CH 3 (IIb, Vb); R 1 = R 2 = CH 3 (III, VI).

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Weak Nucleophiles in the Aza‐Michael Reaction

Rulev

2023

Adv Synth Catal

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The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes is one of the most significant and widely used reactions in modern synthetic organic chemistry. To date, various protocols for the aza‐Michael reaction have been developed. However, these reports mainly focus on the use of strong Michael donors. In recent years, the conjugate addition of weak nitrogen nucleophiles to various Michael acceptors gained increasing popularity. Impressive progress in this area has been achieved by the use of more efficient catalyst systems. This review aims to provide a critical analysis of the results obtained in reactions of weak nucleophiles (azoles, pyrroles, indoles, carbamates, purines, amides, hydrazides, uraciles etc) with electron‐deficient alkenes which were reported over the past twelve years.

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Addition of azoles to methyl vinyl ketone by the Aza-Michael reaction

Cited by 7 publications

References 19 publications

Aza-Michael Addition of Imidazole Analogues

Aza-Michael Addition of Imidazole Analogues

Aza-Michael addition of pyrazoles to maleic acid

Weak Nucleophiles in the Aza‐Michael Reaction

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