Dichloromethane, fluorination

When treated with DBU in dichloromethane, fluorinated haloalkanes gave fluorinated alkenes (85MIP2519). 

Primary alkyl chlorides are fairly stable to fluorine displacement. When fluorinated, 1-chloropropane is converted to 1-chloroheptafluoropropane and 1-chloto-2-methylbutane produces 39% l-chlorononafluoro-2-methylbutane and 19% perfluoro-2-methylbutane. Secondary and tertiary alkyl chlorides can undergo 1,2-chlorine shifts to afford perfluonnated primary alkyl chlorides 2-Chloro-2-methylpropane gives l-chlorononafluoro-2-methylpropane, and three products are obtained by the fluorination of 3-chloropentane [7] (equation 1). Aerosol fluorina-tion of dichloromethane produces dichlorodifluoromethane which is isolated in 98% purity [4 (equation 2). If the molecule contains only carbon and halogens, the picture is different. Molecular beam analysis has shown that the reaction of fluorine with carbon tetrachlonde, lodotrichloromethane, or bromotrichloromethane proceeds first by abstraction of halogen to form a trichloromethyl radical [5]... 

Anion-catalyzed phase transfer catalysis in a dichloromethane-aqueous sulfuric acid two-phase system was successfully applied to the diazotization of pen-tafluoroaniline by Iwamoto et al. (1983 a, 1984). If this compound is diazotized in dilute aqueous acid, tetrafluoro-l,4-quinone diazide is obtained, indicating that the diazotization proper is followed by a hydroxy-de-fluorination (Brooke et al., 1965). 

Compounds lb and 2b were the Urst fluorinated ligands tested in Mn-catalyzed alkene epoxidation [5,6]. The biphasic Uquid system perfluorooc-tane/dichloromethane led to excellent activity and enantioselectivity (90% ee) in the epoxidation of indene with oxygen and pivalaldehyde (Scheme 1, Table 1). In addition, the fluorous solution of the catalyst was reused once and showed the same activity and selectivity. This represents a considerable improvement over the behavior in the homogeneous phase, where the used catalyst was bleached and reuse was impossible. Unfortunately, indene was the only suitable substrate for this system, which failed to epoxidize other alkenes (such as styrene or 1,2-dihydronaphthalene) with high enantioselectivity. The system was also strongly dependent on the oxidant and only 71% ee was obtained in the epoxidation of indene with mCPBA at - 50 °C. 

To visualize bond formation by an outer atom other than hydrogen, recall the bond formation in HF. One valence p orbital from the fluorine atom overlaps strongly with the hydrogen 1 S orbital to form the bond. We can describe bond formation for any outer atom except H through overlap of one of its valence p orbitals with the appropriate hybrid orbital of the inner atom. An example is dichloromethane, CH2 CI2, which appears in Figure 10-11. We describe the C—H bonds by 5 -I S overlap, and we describe the C—Cl bonds by 5 - 3 p... 

The choice of solvent may have a critical impact on efficiency too. In metathesis, dichloromethane, 1,2-dichloroethane and toluene are the solvents most commonly used. There are examples that show much higher yields in ring closing metathesis (RCM) when using fluorinated solvents [150]. An impressive effect of hexafluorobenzene as a solvent for CM is the modification of the steroid 93 the use of 1,2-dichloroethane leads to a very low yield and significant amounts of dimerisa-tion while the same reaction proceeds in 90% yield in C F (Scheme 3.14) [151]. 

Though a powerful oxidant, the difluoride is not explosively unstable. Safe procedures for the use of xenon difluoride in fluorination reactions are detailed. Residual traces of the fluoride are rapidly destroyed by dichloromethane at ambient temperatures. 

Mixtures of the tetraoxide with dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, trichloroethylene and tetrachloroethylene are explosive when subjected to shock of 25 g TNT equivalent or less [1], Mixtures with trichloroethylene react violently on heating to 150°C [2], Partially fluorinated chloroalkanes were more stable to shock. Theoretical aspects are discussed in the later reference [2,3], The effect of pressure on flammability limits has been studied [4],... 

Mixtures of liquid oxygen with dichloromethane, 1,1,1-trichloroethane, trichloroethylene and chlorinated dye penetrants 1 and T exploded violently when initiated with a blasting cap. Carbon tetrachloride exploded only mildly, and a partly fluorinated chloroalkane not at all. Trichloroethylene has been used for degreasing metallic parts before use with liquid oxygen, but is not safe. 

Displacement of the 3-hydroxyl group of 74 was carried out with Et2NSF3 (DAST) (DAST - diethylaminosulfur trifluoride) in dichloromethane. The expected fluorinated product 75 on treatment with aqueous perchloric acid led to regioselective epoxide ring opening to give 76, which on treatment with hydrazine hydrate at 100 °C for 18 h yielded 3,4-dihydroxy-8-oxo-octahydropyridazino[l,6-r/][l,2,4]triazine-l-carboxylic acid phenylamide 77 (Scheme 3) <1997T9357>. 

The incorporation of fluorine atoms improves the solubility of aromatic condensation polymers without causing them to lose their high thermal stability and modifies the processability. Hexafluoroisopropylidene-unit-containing poly-(azomethine)s and copoly(azomethine)s are readily soluble in highly polar solvents such as DMAc, HMPA, and NMP, and they also dissolve completely in dichloromethane, chloroform, and THF, whereas poly(azomethine)s derived from 21 and 22 and having no fluorine atom are insoluble in these solvents.20 Accordingly, the solubility of aromatic poly(azomethine)s is remarkably improved by substituting isopropylidene units with fluorine atoms. 

A detailed study of the formation of n-octyl ethers under solidrliquid two-phase conditions in the absence of an added solvent has been reported [10], Potassium alkoxides tend to produce higher yields of the ethers than do the corresponding sodium derivatives, but octene is the major product in the reaction of 1-bromooctane with potassium t-butoxide. High temperatures also tend to promote the preferential formation of octene and slightly higher yields of the ethers are obtained using n-octyl tosylate in preference to n-octyl bromide. p-Fluorinated acetals have been prepared either under basic catalytic liquidrliquid or solidrliquid conditions from the fluori-nated alcohol and dichloromethane [11] with displacement of the fluorine atoms. 

Partial fluorination of 4-arylthio-l,3-dioxolan-2-ones occurs preferentially at the carbon atom adjacent to the thio group [67]. However, a remarkable solvent effect is encountered. In the more polar solvent, dimethoxyethane substitution occurs, while in the less polar dichloromethane a larger portion of the desulfurization with cleavage of the phenylthio group takes place. This is attributed to the fact that the intermediate radical cation is more stable in the polar solvent and undergoes deprotonation, while in the less polar solvent, the less stabilized radical cation dissociates into a dioxolane cation and a phenylthio radical. 

Bromo [ F]fluoride is different from the other electrophilic radiolabelling agents discussed so far in the sense that the electrophilic part of the molecule is not fluorine but bromine. This is reflected by its synthesis from nucleophilic p F]fluoride and it can be obtained in high specific radioactivity. Bromo p F]fluoride was developed for fluorine-18 labelling of steroids (see Section 3.2) [64-66]. It was prepared (Scheme 11) in situ by reaction of dried p Fjfluoride with 1,3-dibromo-5,5-dimethylhydantoin and sulphuric acid in dichloromethane containing also the substrate. 

Table 14. (Phenylselanyl)fluorination at C = C Bonds by. V-(Phenylselanyl)phthalimidc/Triethylamine Tris(hydrogen Fluoride) in Dichloromethane at 25 C216...

Until recently, halogen substituted alkanes were thought to be inert to xenon difluoride, but detailed examination has shown that common solvents such as dichloromethane (3) and chloroform (4) undergo fluorine-chlorine and fluorine-hydrogen exchange at room temperature due to hydrogen fluoride catalysis.15... 

The treatment of tran.v-l-phenylpropene and /rans-stilbene with xenon difluoride in dichloromethane catalyzed by trifluoroacetic acid leads to an approximately equimolar mixture of fluorination and fluorotrifluoroacetoxylation products, the latter process proceeds regio-spccifically.34... 

Methyl groups arc stable to xenon difluoride exposure. Mesitylene reacts with xenon difluoride in dichloromethane in the presence of hydrogen fluoride at room temperature to form 2,4-difluoromesitylene in 30% yield.64 The hydrogen fluoride catalyzed fluorination of 1,2,3-... 

The fluorination of heterocyclic compounds with xenon difluoride has received much less attention. Pyridine reacts readily with xenon difluoridc in dichloromethane without a catalyst to form 2-fluoropyridine (35 %), 3-fluoropyridine (20 %) and 2,6-difluoropyridine (11 %).80 8-Hydroxyquinoline treated with xenon difluoride forms 5-fluoro-8-hydroxyquinoline at room temperature in 35% yield.80 Uracil reacts with xenon difluoride to give 5-fluorouracil in 10% yield.81 Only one example exists of a highly substituted pyrrole fluorinated with xenon difluoride in acetonitrile in 35% yield.82... 

Alkyl fluorides have been generated from the reaction of carboxylic acids with one equivalent of xenon difluoride in dichloromethane or chloroform solution. The process has been named fluorodecarboxylation", the fluorine analog of the Hunsdieckerand Kochi reaction.8384 Both primary and tertiary acids react very well, but secondary acids react less readily. A possible scheme involves a free-radical mechanism including an unstable fluoroxenon ester of an appropriate acid.84... 

An amine with labile fluorine atoms, A -(l,l,2,3,3,3-hexafluoropropyl)diethylamine, generated in situ by the interaction of perfluoroprop-l-ene and diethylamine, was found to work well as a source of fluorine in the reactions of 1,3-dithiolanes with 1,3-dibromo-5,5-dimethylhydan-toin or A -iodosuccinimide. The reactions run in dichloromethane at — 78 to — 20 C give gem-difluorides in 50-70% yield.76... 

Iodine pentafluoride can be employed for mild selective oxidative fluorination. Aryl- and al-kylphosphanes R3P, R2PF, R2PC1, and RPC12 are oxidized by iodine pentafluoride to the corresponding fluorophosphoranes at or below 0 C.138 In dichloromethane, the fluorination proceeds more readily than in acetonitrile which is prone to coordination. The yields of the products are 50-70%. 

Cesium fluoroxysulfate in acetonitrile medium at 35 C converts primary alcohols and alkyl and aryl aldehydes into acid fluorides in high yields.i" Hammett correlation analysis of the fluorination of various benzene-substituted aldehydes gives the reactivity constant31 q = —0.38. It has been shown that solvent polarity plays an extremely important role in the conversion of aldehydes into fluorides the conversion is almost quantitative in acetonitrile, but completely stopped in dichloromethane, hexane or tetrahydrofuran. The presence of ni-... 

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