Haloacetylated enol ethers. 9. Synthesis of 4-trifluoromethyl-2-methyl[phenyl]pyrimidines and tetrahydro derivatives

The synthesis of 4-trifluoromethyl-2-methyl[phenyl]pyrimidines and the corresponding tetrahydro derivatives from the cyclo-condensation reaction of β-alkoxyvinyl trifluoromethyl ketones 1a-d with acetamidine or benzamidine hydrochloride, is reported. For the cyclo-condensation of 1a-d with acetamidine and benzamidine hydrochloride, two methods were tested: 1 M solution of sodium hydroxide (method A) and sodium alkoxide/alcohol (method B). Depending on the structure of the β-alkoxyvinyl trifluoromethyl ketones and the reactions conditions, pyrimidines or tetrahydropyrimidines or a mixture of both compounds were obtained.     

Haloacetylated enol ethers. 8 [12]. Reaction of β-alkoxyvinyl trihalomethyl ketones with guanidine hydrochloride. Synthesis of 4-trihalomethyl-2-aminopyrimidines

In this work the results of the reaction of β-alkoxyvinyl trihalomethyl ketones 1, 2a-e , with guanidine hydrochloride are reported. Depending on the ketone 1 or 2 and the conditions under which the reactions were carried out, 4-trihalomethyl-2-amino pyrimidines, β-alkoxyvinyl carboxylic acids, or β-acetal carboxylic esters were obtained.     

An efficient and regiospecific preparation of trifluoromethyl substituted 4‐( 1H‐pyrazol‐1 ‐yl)‐7‐chloroquinolines

A new series of 4‐[3‐alkyl(aryl)(heteroaryl)‐5‐hydroxy‐5‐trifluoromethyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]‐7‐chloroquinolines, where [alkyl = CH₃; aryl = C₆H₅, 4‐CH₃C₆H₄, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄, 4‐CH₃OCgH₄, 4‐NO₂CgH₄, 4‐biphenyl, 1‐naphthyl; heteroaryl = 2‐furyl and 2‐thienyl] has been regiospecifi‐caly obtained from the reaction of 7‐chloro‐4‐hydrazinoquinoline with 4‐substituted‐l,1,1‐trifluoro‐4‐methoxybut‐3‐en‐2‐ones in 61 ‐ 96 % yield. Subsequently, dehydration reaction of 4,5‐dihydropyra‐zolylquinolines under acid conditions furnished a new series of 4‐(3‐substituted‐5‐trifluoromethyl‐1H‐pyra‐zol‐1‐yl)‐7‐chloroquinolines in 73 ‐ 96 % yield.     

The regiospecific ω-bromination of 2-trichloroacetylcycloalkanones

Six novel ω-brominated-2-trichloroacetylcycloalkanones were regiospecifically obtained in reactions from four 2-trichloroacetylcycloalkanones and bromine. ¹H and ¹³C NMR data reveal that ω-brominated β-diketones are predominantly in keto-keto form.     

Novel 4,5-bis(trifluoromethyl)-1H-pyrazoles through a concise sequential iodination-trifluoromethylation reaction

An efficient protocol for the assembly of a new series of 1,3-disubstituted 4,5-bis(trifluoromethyl)-1H-pyrazoles – through a concise sequential iodination-trifluoromethylation reaction at the C-4 position of an initial series of 1-aryl-3-(alkyl/aryl)-5-trifluoromethyl-1H-pyrazoles (electronically deactivated heterocycles), using NIS and MFSDA, at good conversion yields and in short reaction times – is reported.     

Chemoselective synthesis of 6-amino(alkoxy)-1,4,5,6-tetrahydropyridines from cyclic β-alkoxyvinyl α-ketoester

The synthetic versatility of ethyl 2-(2-ethoxy-3,4-dihydro-2H-pyran-5-yl)-2-oxoacetate for the synthesis of ethyl 2-oxo-2-(1-alkyl/aryl-6-(amino/ethoxy)-1,4,5,6-tetrahydropyridin-3-yl)acetates, from the reaction with primary amines, is presented. The methodology proposed herein is highly chemoselective, and twenty products were obtained in moderate to good yields (up to 87%).     

One‐pot synthesis of aryl and heteroaroyl‐substituted hydroxypyrazolines from the reactions of β‐alkoxyvinyl trichloromethyl ketones with heteroarylhydrazides

The one‐step regiospecific synthesis of a novel series of 10 trichloromethyl‐, aryl‐, and heteroaroyl‐substituted 5‐hydroxy‐2‐pyrazolines affords 1‐(2‐thenoyl)‐, 1‐(2‐furoyl)‐, and 1‐(isonicotinoyl)‐3‐aryl‐5‐hydroxy‐5‐trichloromethyl‐4,5‐dihydro‐1H‐pyrazoles in 63–92% yields from the cyclocondensation reactions of 1,1,1‐trichloro‐4‐methoxy‐4‐aryl‐3‐buten‐2‐ones (where aryl substituents are –C₆H₅, 4‐CH₃C₆H₄, 4‐OCH₃C₆H₄, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄) with 2‐thiophenecarboxylic hydrazide, furoic hydrazide, and isonicotinic acid hydrazide, respectively. Dehydration reaction of two 2‐pyrazolines with P₂O₅ furnished the corresponding 1H‐pyrazoles in low yields (21–29%). © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:685–691, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20261     

Synthesis and structural study of a new series of 2‐methylsulfanyl‐tetrahydropyrimidines from β‐alkoxyvinyl trihalomethyl ketones

This work describes the synthesis of a novel series of 2‐methylsulfanyl‐tetrahydropyrimidines, from the cyclocondensation reaction of β‐alkoxyvinyl trihalomethyl ketones with 2‐methyl‐2‐thiopseudourea sulfate, in good yields. A detailed ¹H‐ and ¹³C‐NMR study was performed on the 2‐methylsulfanyl‐tetrahydropyrimidines obtained and 3D structures were proposed based on AM1 calculations supported by ¹H NMR coupling constants and NOESY experiments.     

An efficient synthesis of 1-cyanoacetyl-5-halomethyl-4,5-dihydro-1H-pyrazoles in ionic liquid

The synthesis of eleven 1-cyanoacetyl-5-hydroxy-5-halomethyl-4,5-dihydro-1H-pyrazoles from the reaction of 4-alkoxy-3-alken-2-ones f(R ³C(O)C(R ²) = C(R ¹)OR, where R ³ = CF₃, CCl₃, CHCl₂, CO₂ Et; R ²/R ¹ = H/H, H/Me, H/Et, -(CH₂)₄-, Me/H, H/Pr, and R = Me, Et) with cyanoacetohydrazide is reported. The reaction was carried out in the ionic liquid ([bmim][BF₄]) and molecular solvents. The results showed that when the ionic liquid was used as reaction medium, the reaction time was drastically decreased and the yield was improved.     

An ionic liquid as reaction medium for the synthesis of halo-containing β-enaminones at room temperature

A series of twenty halomethylated β-enaminones [RC(O)CH=C(R ¹)NR ³ R ⁴, where R = CF₃,CCl₃, CHCl₂; R ¹ = H, Me, Ph; R ³ = H, Me, Bu, Et; R ⁴ = Me, Et, Bu, allyl, tert-amyl, CH₂CH₂OH, Bn, Ph] were synthesized using the ionic liquid [bmim]BF₄ at room temperature. It is demonstrated that this ionic liquid is a reaction medium suitable for the amination of β-alkoxyvinyl halomethyl ketones. The advantages of this method are the absence of solvents, short reaction times, and good yields. Correspondence: Marcos A. P. Martins, Núcleo de Química de Heterociclos – NUQUIMHE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.