Facile synthesis of 6-organyl-4-(trifluoromethyl)pyridin-2(1H)-ones and their polyfluoroalkyl-containing analogs

The three-component cyclization of 3-polyfluoroalkyl-3-oxopropanoates and methyl ketones with ammonium acetate affords 6-organyl-4-(polyfluoroalkyl)pyridin-2(1H)-ones (organyl is alkyl, aryl, or hetaryl). The synthesized pyridones were evaluated for antifungal, antibacterial, and analgesic activity.

     

Some syntheses using tetrakis(trifluoromethyl)dewar thiophene

Tetrakis(trifluoromethyl)Dewar thiophene ($\text{1}$) is found to be a good dipolarophile and dienophile. Therefore, $\text{1}$ reacts with any kind of azides to give 1,3-dipolar cycloadducts, which are transformed to tetrakis(trifluoromethyl)Dewar pyrroles ($\text{2}$), compounds of a new cyclic ring system. Further, $\text{1}$ reacts with cyclic or acyclic dienes to give Diels-Alder adducts. The adduct ($\text{3}$) of $\text{1}$ with butadiene was transformed to tetrakis(trifluoromethyl)cyclooctatetraene ($\text{4}$) by desulfurization, bromination and dehydrobromination, stepwise. Valence-bond isomerisation of $\text{4}$ will be presented.

     

Reactions of a 4-(trifluoromethyl)thiazole dianion

Treatment of 2-trifluoroacetamido-4-(trifluoromethyl)thiazole with two equivalents of n-butyllithium at -78° produced the thiazole dianion 5 in situ, which reacted preferentially at the 5-position with a variety of electrophiles. These electrophiles include: an aldehyde, ketone, chloroformate, acid chloride, phosphorus oxychloride, silicon chloride, and disulfide. Dianion 5 also combined with dibromodifluoromethane at -98° to give the corresponding 5-(bromodifluoromethyl)thiazole 7 , which is an unusual reaction for an aromatic or heteroaromatic system. Compound 7 was converted to a 4,5-bis-(trifluoromethyl)thiazole 8 using tetrabutylammonium fluoride.     

Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.     

An unusual labilization of a 4-(trifluoromethyl)thiazole

N-Chloro-4-(trifluoromethyl)-5-thiazolyl-N',N'-diethylurea 5 has been found to undergo a facile labilization of the trifluoromethyl group under mild conditions. The reaction relies on the assistance of the nitrogen substitution at the 4-position of the thiazole ring. Treatment of 5 with triethylamine and either methanol or methanethiol replaced the trifluoromethyl group with a methyl ester or a trimethylorthothio ester respectively at room temperature. Combination of 5 with diethylamine led to an unusual thiazolidine with two exocyclic double bonds, 8 .     

One-Pot Three-Component Synthesis of a Series of 2-Amino-4-(4-oxo-4H-chromen-3-yl)-5-(2,2,2-trifluoroacetyl)-6-(trifluoromethyl)-4H-pyrans and 2-Amino-4-(4-oxo-4H-chromen-3-yl)-5-(thiophene-2-carbonyl)-6-(trifluoromethyl)-4H-pyrans as Promising Anticancer Agents

Russian Journal of Organic Chemistry - Novel functionalized 2-amino-4-(4-oxo-4H-chromen-3-yl)-5-(2,2,2-trifluoroacetyl)-6-(trifluoro­methyl)-4H-pyrans and...     

Reaction of 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole with primary amines. Synthesis of 4-substituted-3,5-bis(trifluoromethyl)-4H-1,2,4-triazoles

Reaction of 3,5-bis(trifluoromethyl)-1,3,4-oxadiazole ( 1a ) with primary amines under a variety of conditions conveniently produced 4-substituted-3,5-bis(trifluoromethyl)-4H-1.2,4-triazoles 4a in 26-85% yield. Alkyl amines reacted with 1a in methanol at ?42° to provide hydrogen-bonded monoadduct-methanol complexes 5a , as determined by X-ray. The reaction of 1a with sterically hindered or strongly electron deficient anilines required high temperatures in the absence of solvent.     

Janus Face All-cis 1,2,4,5-tetrakis(trifluoromethyl)- and All-cis 1,2,3,4,5,6-hexakis(trifluoromethyl)- Cyclohexanes

We report the synthesis of all-cis 1,2,4,5-tetrakis (trifluoromethyl)- and all-cis 1,2,3,4,5,6-hexakis (trifluoromethyl)- cyclohexanes by direct hydrogenation of precursor tetrakis- or hexakis- (trifluoromethyl)benzenes. The resultant cyclohexanes have a stereochemistry such that all the CF₃ groups are on the same face of the cyclohexyl ring. All-cis 1,2,3,4,5,6-hexakis(trifluoromethyl)cyclohexane is the most sterically demanding of the all-cis hexakis substituted cyclohexanes prepared to date, with a barrier (ΔG) to ring inversion calculated at 27 kcal mol⁻¹. The X-ray structure of all-cis 1,2,3,4,5,6-hexakis(trifluoromethyl)cyclohexane displays a flattened chair conformation and the electrostatic profile of this compound reveals a large diffuse negative density on the fluorine face and a focused positive density on the hydrogen face. The electropositive hydrogen face can co-ordinate chloride (K≈10³) and to a lesser extent fluoride and iodide ions. Dehydrofluorination promoted decomposition occurs with fluoride ion acting as a base.     

Facile syntheses of 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ)

1-Deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ) were synthesized through a concise and practicable pathway. A strategy of using carbohydrate derivatives bearing two leaving groups in the preparation of azasugars by di-N-alkylation of amines was developed. The strategy involved the selective partial protection of dibromo alditols.     

Rearrangement of 2-amino-4-(trifluoromethyl)oxazoles to hydantoins

Reaction of 2-amino-4-trifluoromethyloxazoles with excess bromine in acetic acid/sodium acetate gives 5-acetoxyhydantoins. The 5-bromooxazoles are intermediates in the reaction.     

Facile syntheses of (−)-montagnetol and (−)-erythrin

A novel synthetic method is introduced to prepare the biologically important montagnetol and erythrin compounds starting from a 1,3-benzodioxin-4-one, synthesized from commercially available orsellinic acid and erythritol.     

Preparative synthesis of 4-methyl-2-(trifluoromethyl)-1,3-oxazin-6-one

Russian Chemical Bulletin -     

Pyridine and pyrimidine ring syntheses from 4-(4-morpholino)-3-pentenone and from ethyl 3-(4-morpholino)-2-butenoate

3-Substituted 2(1H)-pyridones are produced from reaction of 4-(4-morpholino)-3-pentenone 1 with each of the following carbon acids: cyanoacetamide, malononitrile, cyanothioacetamide, acetylacetamide, benzoyl-acetonitrile. Reaction of ethyl 3-(4-morpholino)-2-butenoate 2 with cyanoacetamide gives the corresponding hydroxypyridone. Pyrimidines are formed by reaction of 1 and of 2 with benzamidine and with S-benzylthio-urea; in the last case, the eliminated morpholine displaces the benzylthio group to give the final product.     

2-(4-羟基苯基)-3,3,3-三氟丙酸乙酯的合成研究

报道了以苯酚和三氟丙酮酸乙酯为起始原料,在温和条件下合成高产率的2-(4-羟基苯基)-3,3,3-三氟丙酸乙酯的一条新途径.该途径包括无水碳酸钾催化的苯酚与三氟丙酮酸乙酯间的亲电取代反应、由此形成的产物的选择性侧连羟基的氯代反应和随后的硼氢化钠还原反应.     

New approaches to the synthesis of 2-(trifluoromethyl)indole and 2-amino-3-(trifluoromethyl)quinoline

New synthetic approaches to the preparation of 2-(trifluoromethyl)indole and 2-amino-3-(trifluoromethyl)quinoline have been developed. In both cases, conditions of the Leimgruber-Batcho synthesis of indoles were used in the key step.     

Synthesis of 1-aryl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acids and esters

Ethyl 1-aryl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylates 2 were prepared by the condensation of arylhydrazines with ethyl 3-ethoxy-2-(trifluoroacetyl)-2-propenoate (1a) at low temperature. The corresponding acids were also synthesized. X-ray diffraction analysis of an amide derivative 4 verified the position of the trifluoromethyl group on the pyrazole ring.