Trifluoromethyl derivatives, synthesis

The recent discovery of a convenient synthesis of sulfur tetrafluoride from sulfur dichloride and sodium fluoride in acetonitrile invited the application of this reagent in fluorination reactions. Hasek, Smith and Engelhardt showed that carboxylic acids and their derivatives can be converted into trifluoromethyl derivatives and that aldehydes and ketones are converted into 5 em-difluoro compounds. They also observed that the reaction was acid... 

Trifluoromethyl Derivatives of the Transition Metal Flements 1984 Synthesis and Properties of Aryl... 

Figure 56.2 Synthetic sequence followed by students for the synthesis of catalysts for evaluation. Bis(trifluoromethyl) derivative (6h) was prepared by the procedure ofLeazer etal. ...

The acyclic ADC compounds I and 2 are usually isolable, and reasonably stable, although the trifluoromethyl derivative (1, R = CF3) is reported to be unstable.15 In general, the diesters 2 have found greatest use in synthesis, with DEAZD (2, R = Et) being the most commonly used it is available commercially. 

Azizian J, Mirza B, Mojtahedi MM, Abaee MS, Sargordan M (2008) Biginelli reaction for synthesis of novel trifluoromethyl derivatives of bis(tefrahydropyrimidinone)benzenes. J Fluor Chem 129 1083-1089... 

The first reliable synthesis of an oxetene was that of the 2-ethoxy-4,4-di(trifluoromethyl) derivative in 1965, by reacting di(trifluoromethyl) ketone with ethoxyethyne at -78 °C (Scheme 8.11). At room temperature the product undergoes ring fission to ethyl 3,3-bis(trifluo-romethyl)propenoate. 

The synthesis of 2-(trifluoromethyl) derivatives is more difficult and the compound preferentially obtained depends on the substituents and on the reaction conditions. Thus, the reaction of tryptophan with TFAA gives the 5(47/)-oxazolone without racemization." However, when this optically active product is dissolved in acetonitrile the racemic 5(47/)-oxazolone is obtained. On the other hand, treatment of the optically active compound with hot aqueous dioxane gave the isomeric 5(27/)-oxazolone (see Scheme 7.2). 

This indirect, two-step procedure for the synthesis of trifluoromethyl derivatives of transition metals was developed after it had become evident that the reaction of CF3I with metallate ions such as Mn(CO)5 resulted in the formation of the iodide rather than the expected trifluoromethyl derivative, as indicated in Eq. (3) (16). 

Although no trifluoromethyl derivatives of cadmium had ever been isolated, their attempted synthesis was particularly appealing from several viewpoints. First, alkyl cadmium reagents are typically more... 

The first simple 5(2/f)-oxazolones were the trifluoromethyl derivatives obtained by treating a-amino acids with trifluoroacetic anhydride (equation 156). A general synthesis of 2,2-disubstituted 5(2/f)-oxazolones is the condensation of a- (hydroxylamino) acids with ketones (equation 157) (80S55). The dehydrogenation of 2,2-bis(trifluoromethyl)-5-oxazolidinones affords bis(trifluoromethyl) derivatives (equation 158) (79LA1547). 

An interesting approach for the synthesis of some fused pyrimidines has been reported by Shaaban [102] via reaction of 4,4,4-trifluoro-l-(thien-2-yl)butane-1,3-dione in the presence of triethylorthoformate with 5-aminopyrazole or 1,2,4-aminotriazole or 2-aminobenzimidazole under microwave irradiation. The resulting trifluoromethyl derivatives of pyrazolo[l,5-a]pyrimidine 56, l,2,4-triazolo[l,5-a] pyrimidine 57 and pyrimido[l,2-a]benzimidazoles 58 were obtained in excellent yields and purity (Scheme 42). 

Although these methods did result in the preparation of a number of then new compounds, they are inherently limited by the fact that the amount of material afforded by a typical reaction is often only in the tens of milligrams range, which is ample for product characterization but insufficient for a reasonably thorough examination of the chemistry of the new compounds. Additionally, while metal atom reactions have been successfully utilized on the elements of groups 10-12 (see below), the synthesis, isolation, and characterization of trifluoromethyl derivatives of the elements from earlier periods of the periodic table is yet to be established. 

The synthesis of 4 -C-trifluoromethyl derivatives followed a different scheme. Starting from D-ribose, the key intermediate 48 was obtained in five high yielding steps. The stereoselectivity... 

Direct introduction of the trifluoromethyl group provides another general route. Irradiation of a methanolic solution of trifluoromethyl iodide and imidazole produces a mixture of 2- and 4-trifluoromethylimidazoles and 2,4-bistrifluoromethylimidazole. This can be applied to simple imidazoles and substituted imidazoles. The photochemical procedure provides a convenient synthesis of trifluoromethyl derivatives of histidine and histamine. ... 

Trifluoroacetaldehyde figures in recent work on the synthesis of analogues of nitramine-type explosives, having been used to prepare 2,2,2-trifluoro-1,1-dinitraminoethane (20) by application of the route used to procure Medina itself [CHj(NHNOj)2] (Scheme 19), and to obtain the 2,4,6-tris(trifluoromethyl) derivative (22) of RDX (Scheme 20). Nitration of 2,4,6-tris(trifluoromethyl)hexahydro-sym-triazine (21) yields the heterocyclic nitramine (22) directly. The acetamido-analogue [CF3-CH(NH COMe)2] of the bisformamide (19a) can be prepared by heating anhydrous trifluoroacetaldehyde with acetamide, and the trifluoroacetamido-compound... 

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