Synthesis of 4‐(trihalomethyl)dipyrimidin‐2‐ylamines from β‐alkoxy‐α,β‐unsaturated trihalomethyl ketones

Zanatta, Nilo; Lopes, Elizandra C. Silva; Fantinel, Leonardo; Bonacorso, Hélio G.; Martins, Marcos A. P.

doi:10.1002/jhet.5570390514

Cited by 19 publications

(7 citation statements)

References 38 publications

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“…16,17 The structure of 4,5-dihydroisoxazole was evidenced by the presence of two doublets in the 1 H NMR spectrum in the range of δ 3.10 to 3.70 assigned to H4'a e H4'b. The observation of a peak around δ 47.0 in the 13 C NMR spectrum from methylene C4', further confirmed the structure of 4,5-dihydroisoxazoles 3 and 4 (Table 3). Compounds 3 and 4 were dehydrated with concentrated sulphuric acid at 45 o C for 3 hours to afford the corresponding 1,2-bis(5'-trihalomethyl-isoxazol-3'-yl) ethanes 5 and 6 in high yields (Scheme 1).…”

Section: Resultssupporting

confidence: 70%

“…The 1 H NMR spectrum of aromatic pyrazoles displays the signal for methylene-3' at δ 3.19 -3.85, for the aromatic H-4' at δ 6.33 -6.85 and for 15 the N-Me appeared at δ 2.97. In the 13 C NMR spectra of 7-15 the signal from C-3' appeared at δ 138.7 -155.3 and signal from C-5' at δ 140.3 -145.0. For the pyrazole 15 they were assigned with two-dimensional correlation spectra HMBC (Heteronuclear Multiple Bond Correlation) by observing a cross peak between the C-5' (142.5 ppm) and the N-methyl hydrogen signal at 3.85 ppm that confirms the 5-ethoxycarbonylpyrazole isomers.…”

Section: Resultsmentioning

confidence: 99%

“…Yields listed in Table 1 and 2 are for isolated compounds. 1 H, 13 C NMR spectra were recorded on a Bruker DPX 400 spectrometer ( 1 H at 400.13 MHz and 13 C at 100.63 MHz) at 298 K, digital resolution of ±0.01 ppm, 0.5 mol L -1 in CDCl 3 , Acetone-d 6 or DMSOd 6 containing TMS as in internal standard. All spectra were acquired in a 5 mm tube, at natural abundance.…”

Section: Methodsmentioning

confidence: 99%

“…The solvent was removed under reduced pressure and the product was recrystallized from a mixture of hexane/ethyl acetate (5:1). (5'-alkoxycarbonylpyrazol-3'-yl) ethanes (11)(12)(13)(14)(15) To a stirred solution 1,1,1,10,10,10-hexachoro-4,7-dimethoxydeca-3,7-dien-2,9-dione (2) (2 mmol) in pyridine (4.2 mmol) was added the appropriate hydrazine hydrochloride (4.2 mmol) in methanol (or ethanol) (15 mL) at room temperature. The mixture was stirred under reflux for 16 hours.…”

Section: 2-bis(5'-trihalomethylpyrazol-3'-yl) Ethanes (7-10)mentioning

confidence: 99%

“…3 We developed a general procedure for preparing 1,1,1-trihalo-4-alkoxy-3-alken-2-ones (β-haloacetylated enol ethers) using halogenated acylating groups CX 3 CO. [4][5][6][7] These compounds are of general interest as precursors for a variety of halomethyl-substituted heterocyclic compounds, e.g. isoxazoles, 8,9 pyrazoles, 10-12 pyrimidines 13,14 and diazepines. 15 …”

Section: Introductionmentioning

confidence: 99%

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Regiospecific synthesis of 1,2-bis(azolyl)ethanes

Martins¹,

Cúnico²,

Siqueira³

et al. 2005

J. Braz. Chem. Soc.

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Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: 2-bis(5'-trihalomethylpyrazol-3'-yl) Ethanes (7-10)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regiospecific synthesis of 1,2-bis(azolyl)ethanes

Martins¹,

Cúnico²,

Siqueira³

et al. 2005

J. Braz. Chem. Soc.

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Synthesis of 4‐(Trihalomethyl)dipyrimidin‐2‐ylamines from β‐Alkoxy‐α,β‐Unsaturated Trihalomethyl Ketones.

et al. 2003

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The synthesis of a novel series of twelve 4-(trihalomethyl)dipyrimidin-2-ylamines, from the cyclocondensation reaction of 4-(trichloromethyl)-2-guanidinopyrimidine, with β-alkoxyvinyl trihalomethyl ketones, of general formula: X 3 C-C(O)-C(R 2 )=C(R 1 )-OR, where: X = F, Cl; R = Me, Et, -(CH 2 ) 2 -, -(CH 2 ) 3 -; R 1 = H, Me; R 2 = H, Me, -(CH 2 ) 2 -, -(CH 2 ) 3 -, is reported. The reactions were carried out in acetonitrile under reflux for 16 hours, leading to the dipyrimidin-2-ylamines in 65-90% yield. Depending on the substituents of the vinyl ketone, tetrahydropyrimidines or aromatic pyrimidine rings were obtained from the cyclization reaction. When X = Cl, elimination of the trichloromethyl group was observed during the cyclization step. The structure of 4-(trihalomethyl)dipyrimidin-2-ylamines was studied in detail by 1 H-, 13 C-and 2D-nmr spectroscopy. J. Heterocyclic Chem., 39, 943(2002).Dipyrimidin-2-ylamines have been the subject of few publications. In a search from the literature only two methods were found for the synthesis of dipyrimidin-2-ylamines. The first method was reported in 1969 and relies on the condensation of 2-guanidinopyrimidine sulfate with diethyl malonate to obtain a series of hydroxydipyrimidin-2-ylamines [1]. Several other alkoxy-and amino-dipyrimidin-2-ylamine derivatives were reported in the same paper and they were obtained by derivatization of hydroxydipyrimidin-2-ylamines. The second method to obtain dipyrimidin-2-ylamines, reported by Akhemerov et al. , consists on the interamination of amnooxypyrimidines with its hydrochloride or another aminooxypyrimidine hydrchloride [2].The applications and biological activities of dipyrimidin-2-ylamines are largely unknown, although several reports have described 2-guanidinopyrimidines and bipyrimidines as metal-cage complexes [3,4] and potential potassium-sparing diuretics [5].In this work, we wish to report the synthesis of a new series of 4-(trihalomethyl)dipirimidin-2-ylamines obtained from the cyclo-condensation reaction of 4-(trichloromethyl)-2-guanidinopyrimidine with a series of β-alkoxyvinyl trihalomethyl ketones. The importance of β-alkoxyvinyl trihalomethyl ketones as potential building blocks for the synthesis of many heterocyclic systems such as isoxazoles [6][7][8][9][10][11][12], pyrazoles [13][14][15][16][17][18], pyrimidines [19][20][21][22][23], diazepines [24,25], and aliphatic compounds [26,27] has been demonstrated in previous publications of our group and by other groups [28].The 4-(trichloromethyl)-2-guanidinopyrimidine (1) was prepared from 4-(trichloromethyl)pyrimidin-2(1H)-one by treatment with phosphorus oxychloride followed by nucleophilic substitution of the 2-chloropyrimidine derivative by guanidine hydrochloride in the presence of potassium t e rtbutoxide in t e rt-butyl alcohol, according to reference [29].The synthesis of dipyrimidin-2-ylamines 4 a -e, 5 a,c,e, and 6a-d, were carried out by refluxing the 4-(trichloromethyl)-2-guanidinopyrimidine (1) with β-alkoxyvinyl trihalomethyl ketones 2a-e and 3a-e ...

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Synthesis and structural study of N‐methyl‐2‐methylthiopyrimidine derivatives from trihalomethylated enones

Zanatta

Madruga

Marisco

et al. 2010

Journal of Heterocyclic Chem

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The synthesis and chemoselective study of a novel series N-methyl-2-methylthio-tetrahydropyrimidines and or N-methyl-2-methylthiodihydropyrimidines, from the cyclocondensation reaction of b-alkoxyvinyl trihalomethyl ketones (enones) with 1,2-dimethylisothiourea sulfate is described. It was found that the chemoselectivity depends on both the reaction conditions and the steric and electronic effects of the substituents on the enones.

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Synthesis of 4‐(trihalomethyl)dipyrimidin‐2‐ylamines from β‐alkoxy‐α,β‐unsaturated trihalomethyl ketones

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 19 publications

References 38 publications

Regiospecific synthesis of 1,2-bis(azolyl)ethanes

Regiospecific synthesis of 1,2-bis(azolyl)ethanes

Synthesis of 4‐(Trihalomethyl)dipyrimidin‐2‐ylamines from β‐Alkoxy‐α,β‐Unsaturated Trihalomethyl Ketones.

Synthesis and structural study of N‐methyl‐2‐methylthiopyrimidine derivatives from trihalomethylated enones

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