Trifluoroacetic acid, solution preparation

Pyrrolo[l,2-a]azepin-5-one (11), prepared by cyclization of methyl 5-(pyrrol-2-yl)penta-2,4-dienoate (10) with sodium hydride in toluene, in trifluoroacetic acid solution forms the diatropic 5-hydroxypyrrolo[1,2-a]azepinium ion 12.216 6-Methyl-5//-pyrrolo[l,2-tf]azepin-5-one(mp41 -43 C), formed in low yield (20%) by the action of [(ethoxycarbonyl)methylene]triphenylphos-phorane on 4-(pyrrol-2-yl)but-3-en-2-one, behaves similarly. 

Thienopyrrolopyrimidines can be prepared by a photochemical reaction. Upon heating or irradiation of 4-azido-5-(2-thienyl)pyrimidine in trifluoroacetic acid solution, the tricyclic product is formed in good yield <1989CPB2933> (Equation 1). 

In a study of the Hofmann-Loffler reaction, the jV-chloro-amine (8a) was irradiated in trifluoroacetic acid solution and underwent photolysis to yield the pyrrolidine (9a) together with the 205-isomer (9b) in a ratio 8 1. The starting amine (8b) was prepared by hydrogenation of (8c), followed by von Braun demethylation and hydrolysis of the JV-cyano-amine (8d) which was so formed. The n.m.r. spectrum of (8b) and of related amines in the presence of lanthanide shift reagents was discussed.10... 

Several physical properties of amorphous poly-DSP films have been measured64). For the preparation of amorphous films, a trifluoroacetic acid solution containing 10% poly-DSP is cast on a glass plate and dried in vacuo. The resulting film is extracted with triethylamine to remove the last traces of the acid and then extracted with ethanol. 

Propanol recovery solution To prepare 10 ml, mix 6 ml 2-propanol with 4 ml 0.1% trifluoroacetic acid solution. 

Preparation.— Bridgehead positions canying hydrogen in saturated hydrocarbons can be functionalized in high yield by reaction with lead tetra-acetate in methylene chloride-trifluoroacetic acid solution, in the presence of chloride ions, whereas other tertiary positions show low reactivity in this sequence. The bridgehead trifluoroacetates so produced are readily hydrolysed to alcohols (Scheme 1). A hydroxylation process known to be selective for tertiary positions is the reaction... 

A solution of trifluoroacetic acid in toluene was found to be advantageous for cydization of pyruvate hydrazoncs having nitro substituents[4]. p-Toluene-sulfonic acid or Amberlyst-15 in toluene has also been found to give excellent results in preparation of indole-2-carboxylale esters from pyruvate hydra-zoiies[5,6J. Acidic zeolite catalysts have been used with xylene as a solvent to convert phenylhydraziiies and ketones to indoles both in one-flask procedures and in a flow-through reactor[7]. 

Bis(3,4-diethyl-2-pyrrolylmethyl)-3,4-dietliyl-l//-pyrrole (2), prepared in situ from the di-t-butylester of the 5,5 -dicarboxylic acid (/), reacts with 4//-1,2,4-triazole-3,5-dialdehyde (3) in di-chloromethane in the presence of trifluoroacetic acid and 2,3-dichloro-5,6-dicyano-/)-benzoquino-ne as an oxidation reagent. Dark blue crystals are obtained after chromatographic purification. The dark violet chloroform solution fluoresces purple at 360 nm and gives the NMR experiments 39. Which compound and which tautomer of it has been formed ... 

The silver oxide was prepared by adding, with manual stirring, 66 g. of 98% sodium hydroxide (1.62 moles) in 2 1. of water to a solution of 274 g. (1.62 moles) of silver nitrate in 500 ml. of water. The precipitate was collected by filtration and washed with water until free from alkali. The wet cake can be dried or preferably used moist for reaction with trifluoroacetic acid. 

Androst-4-ene-3,17-dione. Testosterone (0.58 g, 2 mmoles) is dissolved in a solution prepared from 3 ml of benzene, 3 ml of dimethyl sulfoxide, 0.16 ml (2 mmoles) of pyridine and 0.08 ml (1 mmole) of trifluoroacetic acid. After addition of 1.24 g (6 mmoles) of dicyclohexylcarbodiimide, the sealed reaction flask is kept overnight at room temperature. Ether (50 ml) is added followed by a solution of 0.54 g (6 mmoles) of oxalic acid in 5 ml of methanol. After gas evolution has ceased ( 30 min) 50 ml of water is added and the insoluble dicyclohexylurea is removed by filtration. The organic phase is then extracted twice with 5 % sodium bicarbonate and once with water, dried over sodium sulfate and evaporated to a crystalline residue (0.80 g) which still contains a little dicyclohexylurea. Direct crystallization from 5 ml of ethanol gives androst-4-ene-3,17-dione (0.53 g, 92%) in two crops, mp 169-170°. 

Braverman and Reisman111 have found that addition of a carbon tetrachloride solution of bromine to bis-y,y-dimethylallenyl sulfone 20 at room temperature unexpectedly resulted in spontaneous and quantitative fragmentation of the sulfone, with formation of the cyclic a, /3-unsaturated sulfmate (y-sultine) 43a and the tribromo products 44 and 45 (equation 38). Analogously, treatment of the same sulfone with trifluoroacetic acid gives rise to y-sultine 43b. It is interesting to note that from a synthetic point of view it is not even necessary to prepare the diallenyl sulfone 20, since one can use its sulfinate precursor (equation 24) to obtain exactly the same results, under the same conditions. The authors suggested that the fragmentation-cyclization of sulfone 20 may take place by the mechanism depicted in equation 39. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

The first widely used intermediates for nucleophilic aromatic substitution were the aryl diazonium salts. Aryl diazonium ions are usually prepared by reaction of an aniline with nitrous acid, which is generated in situ from a nitrite salt.81 Unlike aliphatic diazonium ions, which decompose very rapidly to molecular nitrogen and a carbocation (see Part A, Section 4.1.5), aryl diazonium ions are stable enough to exist in solution at room temperature and below. They can also be isolated as salts with nonnucleophilic anions, such as tetrafluoroborate or trifluoroacetate.82 Salts prepared with 0-benzenedisulfonimidate also appear to have potential for synthetic application.83... 

Preparation of 0.1 % trifluoroacetic acid (TFA) solution from fractionated beeswax... 

For the preparation of N- 2-(methoxyphenyl)cthyl ]-4-mcthylbcn-zenesulfonamide (1) from Ameba resins A and Ba-Bd, 100 mg (0.089 mmol) Ameba resin A was added to a glass peptide reaction vessel, suspended in 3.0 mL 1,2-dichloroethane (DCE note 2), and treated with 26 pL (0.18 mmol, 2.0 Eq.) 2-(4-methoxy-phenyl)ethylamine (note 2) and 38 mg (0.178 mmol, 2.0 Eq.) sodium triacetoxyborohydride (note 2). The suspension was shaken for 1 h treated with 5 mL MeOH filtered on a glass frit and washed with DCM (2x5 mL), DMF (2x5 mL), MeOH (2 x 5 mL), and DCM (2x5 mL). The resin was dried under vacuum (0.5 torr) at room temperature overnight. The resin was suspended in 1.5 mL DCM, treated with 155 pL (0.89 mmol, 10.0 Eq.) N,N-diisopropylethylamine (note 2) and 85 mg (0.445 mmol, 5.0 Eq.) p-toluenesulfonyl chloride (note 2), and shaken for 3.5 h. The reaction mixture was filtered on a glass frit, washed with DCM (2 x 5 mL), DMF (2x5 mL), MeOH (2x5 mL), and DCM (2 x 5 mL), and dried under vacuum (0.5 torr) at room temperature for 2h. The resin was treated with 2.5 mL of a solution of 5% trifluoroacetic acid (note 2) in DCM, shaken for 15 min, filtered on a glass frit, and washed with DCM (3x5 mL). The combined filtrate and washings were concentrated and dried under vacuum (0.5 torr) at room temperature overnight to afford 18.0 mg (66%) N- [2-(methoxyphenyl)ethyl] -4-methylbenzenesulfonamide (1). 

The salt is available from Aldrich Chemical Company Inc. However, the checkers readily prepared it in the following way. To a stirred solution of 8.8 g. (0.22 mole) of sodium hydroxide in 400 ml. of 98% ethanol was added dropwise 26 g. (0.22 mole) of trifluoroacetic acid. 

The procedure described here for the preparation of peroxy-trifluoroacetic acid in methylene chloride has been carried out by the submitters several hundred times without incident and is believed to be the best available. However, it has been pointed out that suspensions of 90% hydrogen peroxide in methylene chloride can be detonated by impact under certain conditions. Accordingly, the use of the recommended safety screen is imperative, and the preparation should not be scaled up without special precautions. The homogeneous solution of peroxytrifluroacetic acid, once obtained, is undoubtedly much safer to handle than the suspension of hydrogen peroxide in methylene chloride. The latter suspension is not transferred, however, and exists for only a brief time period during the preparation. 

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