Trifluoromethyl isocyanate

Trifluoromethyl isocyanide traps the bis(trifluoromethyI)nitroxyl radical at the terminal carbon atom with the formation of an intermediate radical that decomposes spontaneously to give trifluoromethyl isocyanate as the end product (Table 14).238... 

Hexafluoroacetone and trifluoromethyl isocyanate react to give a system of bicyclic five-membered heterocycles 2 (87AGF921, 81AHC1) (Scheme 11). 

Likewise, trifluoromethyl isocyanate (CXXXI) was obtained from trifluoromethylcarbonimidoyl difluoride by means of water or hydrated fluorides... 

CFaiN RfCOF + hvRr + COF Rr + CFjiN- -> RpN CFj. Extension of this to the bis-acyl fluorides FOC (CF2)3-COF and FOC-(CF2>4-COF, however, gives low yields of perfluoro-(Af-methylpyirolid-2-one) (15 %) and perfluoro-(A -methylplperidin-2-one) ca. 10%), respectively, instead of the imines CFg N-(CF2) N CF2 (a = 3 or 4), presumably via the sequence of events shown in Scheme 39. Fluoride-initiated (CsF) reactions between the formaldazine and these, and other, acyl fluorides leads to novel heterocyclic carbonyl compounds which suffer decarbonylation when irradiated with u.v. light (see Scheme 40). Carbonyl fluoride and oxalyl fluoride react with the formaldazine in the presence of caesium fluoride to yield the acylic and cyclic product (57) (70%) and (58) (ca. 55%), respectively the latter fragments to trifluoromethyl isocyanate when exposed to u.v. light. 

Trimethylsilyl cyanide 296 reacts with trifluoromethyl isocyanate at room temperature... 

Trifluoromethyl isocyanate undergoes an insertion reaction with cyanotrimethylsilane at room temperature to give the insertion product 303 in 70 % yield... 

The trifluoromethyl isocyanide thus formed isomerizes to trifluoromethyl cyanide when heated, reacts with mercuric oxide to yield trifluoromethyl isocyanate, and must be stored at low temperatures otherwise it polymerizes to a yellow solid which possibly has the structure [-C( NCF3)C( NCFj)-]n- Reference has already been made to the preparation of oxazetidines from trifluoronitrosomethane and A AT-bistrifluoromethylamino-substituted allenes (see p. 100). Possibly of greater interest is the preparation in low yield of the flrst perhalogeno oxazetidines bearing no per- or poly-fluoroalkyl substituent on nitrogen (see Scheme 8). Reaction of perfluoro-l, 2-oxazetidine, r. 

C gives the fluoroformyl derivative FOC-N-O-CFa-CFj, pyrolysis of which at 400 °C in glass yields carbonyl fluoride and trifluoromethyl isocyanate (an isomer of the expected CFjrN COF). 

Methylarsine, trifluoromethylarsine, and bis(trifluoromethyl)arsine [371-74-4] C2HAsF, are gases at room temperature all other primary and secondary arsines are liquids or solids. These compounds are extremely sensitive to oxygen, and ia some cases are spontaneously inflammable ia air (45). They readily undergo addition reactions with alkenes (51), alkynes (52), aldehydes (qv) (53), ketones (qv) (54), isocyanates (55), and a2o compounds (56). They also react with diborane (43) and a variety of other Lewis acids. Alkyl haUdes react with primary and secondary arsiaes to yield quaternary arsenic compounds (57). 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

Heptafluoro-4-(trifluoromethyl)-2,3-pentanedione undergoes cycloaddition with phosphorus isocyanate 237 to give a spirocyclic dioxaphospholene 35 (Equation 54) <1997PS419>. 

Chlorotrifluoromethyl aniline (no. 73.) was found in the sediment samples. This compound is used as a reactant with chloro-aniline (no. 72) in the preparation of 4,4 -dichloro-3-(trifluoromethyl)-carbanilide, a disinfectant. Two other related compounds also found in some of the sediments were chlorophenyl isocyanate (no. 74) and chloro(-trifluoromethyl)phenyl isocyanate (no. 75). This suggests that some of the 4,4 -dichloro-3-(trifluoromethyl)-carbanilide may, in fact, exist in the sediment extracts but is decomposed in the injection port of the gas chromatograph, since it is very doubtful that the easily hydrolyzable isocyanates exist as such in the sediments. To strengthen this hypothesis some 3,4,4 -trichlorocarbanilide [none of the 4,4 -dichloro-3-(trifluorome-thyl)-carbanilide was available] was analyzed by GCMS. The injection port temperature was 300°C. As expected, none of the parent compound eluted from the column. However, mass spectra were obtained for chlorophenyl isocyanate, dichlorophenyl isocyanate, chloroaniline, and dichloroaniline. The presence of the carbanilides themselves (no. 76, 77, 78) was confirmed with the help of HPLC and mass spectral identification. 

Ricci and co-workers introduced a new class of amino- alcohol- based thiourea derivatives, which were easily accessible in a one-step coupling reaction in nearly quanitative yield from the commercially available chiral amino alcohols and 3,5-bis(trifluoromethyl)phenyl isothiocyanate or isocyanate, respectively (Figure 6.45) [307]. The screening of (thio)urea derivatives 137-140 in the enantioselective Friedel-Crafts reaction of indole with trans-P-nitrostyrene at 20 °C in toluene demonstrated (lR,2S)-cis-l-amino-2-indanol-derived thiourea 139 to be the most active catalyst regarding conversion (95% conv./60h) as well as stereoinduction (35% ee), while the canditates 137, 138, and the urea derivative 140 displayed a lower accelerating effect and poorer asymmetric induction (Figure 6.45). The uncatalyzed reference reaction performed under otherwise identical conditions showed 17% conversion in 65 h reaction time. 

Thioxo-1,2,4-dithiazolidines can be obtained from thioxo-l,2,4-thiadiazolidines by Dimroth rearrangement (Scheme 47) or reversibly by addition and elimination of acetone (Scheme 22). 1,2,4-Dithiazole type products are also obtained from thiocarbonyl isothiocyanates (154) by reaction with CI2 <84CHEC-I(6)897>, PhMgBr, Sj, or CS2. Other routes include reactions of carbonyl isothiocyanates and thiocarbonyl isocyanates with P4S10 or Sg <84Chec-I(6)897> and sulfonyl isocyanates with dialkyl thioketenes. Phenylisothiocyanate heated with N,C-disubstituted oxaziridines affords 3,5-diimino-l,2,4-dithiazolidines (226, 227). Other miscellaneous syntheses of 1,2,4-dithiazoline derivatives include cyclization of A7-thioacyl hexafluoroacetonimine to 5,5-bis(trifluoromethyl)-... 

In the thermal cyclization of 3-alkoxyphenyl A -(l-aryl-2,2,2-trifluoroethylidene)carbamates 287, obtained from 3-alkoxyphenols 285 and l-aryl-l-chloro-2,2,2-trifluoroethyl isocyanates 286, 2-aryl-2-trifluoromethyl-2,3-dihydro-477-l,3-benzoxazin-4-ones 290 were formed instead of the regioisomeric l,3-benzoxazin-2-ones 288 (Scheme 53). The formation of 290 was explained by a thermal isomerization of 287 involving a skeletal 1,3-rearrangement of the electron-rich aryloxy group to the azomethine carbon, which is electron deficient due to the electron-withdrawing CF3 group <2002JFC(116)97>. 

Many organic and inorganic cyanides, cyanates, isocyanates and thiocyanates react with sulfur tetrafluoride at elevated temperatures with the formation of iminosulfur difluorides. Thus, cyanogen bromide, sodium cyanide, and sodium thiocyanate give (trifluoromethyl)imino-sulfur difluoride (1) in 37 -70% yield.202... 

Chlorine atoms in (trichloromethyl)benzenes which have fluoro, chloro, dichloromethyl, chloroformyl, cyano, isocyanato, jV-phthalimino or methyl substituents in the ring are substituted by fluorine using antimony(III) fluoride (Swarts reaction).3 4 2-(Trifluoromethyl)phen-yl isocyanate, 4-chloro-2-(trifluoromethyl)phenyl isocyanate, 2,4- and 2,5-bis(trifluoro-methyl)phenyl isocyanate, and 2,4-bis(trifluoromethyl)-l,5-phenylenc diisocyanate can be obtained in this way.5... 

Prolonged reflux of 3-methoxy-2,2-bis(trifluoromethyl)-2//-azirine (16) during very slow fractional distillation with a spinning-band column gives isocyanate 17 in 20% purified yield by an alkyl shift from oxygen to carbon.50... 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

Irradiation with Corex filtered ultraviolet light of 65a in the presence of 20 equiv. of 1,1-dimethoxyethene in glyme or benzene solvent results in the formation of a cycloadduct, 6,6-dimethoxy-5-phenyl-4-oxa-l-azabicyclo[3.1.0]heptan-2-one (68a), in 65% yield and no oxiryl isocyanate 67a. Like the photocycloaddition of 3-etho-xyisoindolenone (50) to 1,1-dimethoxyethene, the cycloaddition occurs regiospeci-fically. The methoxy and trifluoromethyl substituted phenyloxazolinones 65 b, c, and d similarly photocycloadd regiospecifically to 1,1-dimethoxyethene. 

Pentafluorosulfanyl isocyanate, SF5NCO and SF5NCS, were first reported in 1964 by Tullock et al. (8). They are obtained from the reaction of pentafluorosulfanyl(trifluoromethyl)amine with benzoic acid and thiobenzoic acid, respectively. An alternative preparative method of F5SNCS involves thiolysis of F5SN=CC12 with H2S in the presence of NaF. 

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