Halides activations

Triethylbenzylammonium chloride and potassium fluoride containing 1% water can provide chlorine-fluorine exchange of activated halides in the absence of a solvent. This mixture also can displace the chlorine of a chlorodifluoromethyl group to form a trifluoromethyl group [62] (equation 36). 

The behavior of such activated halides as alkylating agents under Friedel-Crafts conditions expands the scope of the synthesis. Aluminum chloride enhances the electrophilic character of the a,/S-unsaturated carbonyl system and permits the nucleophilic attachment of the aromatic addendum (Y ) to the carbon bearing the positive charge, with displacement of halogen [Eq. (5)]. Thus,... 

Primary amines can be prepared from alkyl halides by the use of hexamethylenetetramine followed by cleavage of the resulting salt with ethanolic HCl. The method, called the Delepine reaction, is most successful for active halides such as allylic and benzylic halides and a-halo ketones, and for primary... 

The Delepine reaction Involves nucleophilic displacement of active halides by hexamethylenetetramine, followed by hydrolysis of Intermediate quaternary ammonium salt to release the amine. 

Route A 1- is very convenient for the substitution of OH groups by bromide or iodide. The reaction conditions are relatively mild (acetonitrile, room temperature, and reflux for 1—3 h, neutral medium). The activating halide (methyl iodide, ally or benzyl bromide) is added in excess (5 equivalents) or in large excess (10 equivalents) when the resultant halide is nearly as reactive as the activating halide. The imidazolium-iV-carboxylates are the important intermediates, which undergo a displacement reaction to give the halides,... 

This is, of course, the Wurtz reaction, and support for such a mechanism involving carbanions (radicals may be involved under some conditions, however) is provided by the observation that in some cases it is possible, with optically active halides, to demonstrate inversion of configuration at the carbon atom undergoing nucleophilic attack. The carbanion, e.g. (61), can also act as a base and promote elimination ... 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

Cardillo et al. (1976) have used dicyclohexyl-18-crown-6 ([20] + [21]) and dibenzo-18-crown-6 [11] to solubilize K2Cr04 in hexamethylphosphoramide. The complex reacts with activated halides to produce aldehydes, according to (39). 

This reaction involves the two reactants carbon monoxide and alcohol and produces esters, or lactones. The starting material, which will be considered here, is an alkene or an alkyne but it is also possible to start from activated halides (aryl- or allyl- iodides and bromides) to produce the same kind of organic products. 

An alternative route to sulphones utilizes the reaction of the appropriate activated halide with sodium dithionite or sodium hydroxymethanesulphinite [6], This procedure is limited to the preparation of symmetrical dialkyl sulphones and, although as a one-step reaction from the alkyl halide it is superior to the two-step oxidative route from the dialkyl sulphides, the overall yields tend to be moderately low (the best yield of 62% for dibenzyl sulphoxide using sodium dithionite is obtained after 20 hours at 120°C). The mechanism proposed for the reaction of sodium hydroxymethanesulphinite is shown in Scheme 4.20. The reaction is promoted by the addition of base and the best yield is obtained using Aliquat in the presence of potassium carbonate. It is noteworthy, however, that a comparable yield can be obtained in the absence of the catalyst. The reaction of phenacyl halides with sodium hydroxy-methane sulphinite leads to reductive dehalogenation [7]. 

The Friedel-Crafts alkylation of 2,5-dimethylthiophene was also studied (57). In contradistinction to thiophene itself, it was reported that this substituted thiophene alkylated readily with only a minor amount of polymerization when an active halide such as t-butyl chloride was used. With less reactive halides, e.g. n-butyl chloride, some replacement of the methyl groups in 2,5-dimethylthiophene occurred and polymerization increased. 

Figure 15. Synthesis of directly copolymerized wholly aromatic sulfonated poly(arylene ether sulfone), BPSH-ax, where XX is the ratio of sulfonated/unsulfonated activated halide.

Cf. Gabriel synthesis, where the product is also amine and Sommelet reaction, where the product is aldehyde. The Delepine works well for active halides such as benzyl, allyl halides, and a-halo-ketones. 

Thus. S 2 reactions of optically active halides are accompanied by Inversion of configuration. 

The title reagent (prepared by the reaction of sodium hydrogen telluride with chlorotriph-enylstannane) reacts easily with the more active halides such as benzyl bromides whereas common halides need to be activated by cesium fluoride. 

Starting from Difluoroallylic and Difluoropropargylic Derivatives Just like the esters of bromodifluoroacetic acids, difluoroallylic and difluoropropargylic bromides (via organometallic derivatives) can add onto aldehydes and couple with activated halides (Figure 2.17). ... 

Fig.1 Surface concentration of adsorbed ions versus rational electrode potential curves for the Cd(OOOl) electrode in aqueous solution with constant ionic strength O.lx M KA + 0.1 (1 - x) M KF, where A is the surface-active halide ion (Br curves 1-3) and (1 curves 4-6), and x is its mole fractions, x = 0.1 (curves 1,4) ...

Deprotonation of the enantiomerically pure AT-to-f-butoxycarbonyl-5,6-diphenyl-2,3,5,6-tetra-hydro-4//-l, 4-oxazin-2-onc (4) with sodium hexamethyldisilazanide at —100 °C with subsequent alkylation of the enolate with active halides gave good yields of 6 and with high diastereoselec-tivity91. Attempts to deprotonate 4 with bases other than sodium or lithium hexamethyldisilazanide effected only decomposition and no trace of alkylation. 

A camphor-based 3-acyl-2-oxazolidinone has also been used for diastereoselective alkylations66. The A-acylated auxiliary 18 is prepared in three steps from 7,7-dimethyl-2-oxobicy-clo[2.2.1]heptane-l-carboxylic acid (ketopinic acid, 17)67. Deprotonation by lithium diiso-propylamide in tetrahydrofuran at — 78 °C and subsequent alkylation with activated halides [(bromo- or (iodomethyl)benzene, 3-bromo- or 3-iodopropene] furnished moderate to good yields of alkylation products in high diastereomeric ratios (>97 3 by H NMR). With added hexamethylphosphoric triamide the alkylation yields are increased and bromoalkanes also give satisfactory yields. The diastereomeric ratios are, however, much lower (d.r. 70 30 to 85 15)67. 

The racemic C2-symmetric l,3-diacyl-1,3-imidazolidinones 1 and 2 can be obtained from either rra/t.v-l,2-diaminocyclohexane or nwM-l,2-diphenyl-l,2-ethanediamineu 13. On deprotona-tion with potassium hexamethyldisilazide in THF at —78 C these furnish dianions which are alkylated by activated halides or iodomethane (R2X) to give mixtures of diastereomeric dialky-lated products 3-5 and 6-812,13. 

The basic amino group of the 1-position in semicarbazide or thiosemi-carbazide may be used to react by a substitution reaction with activated halides [52], ethers [51], hydroxy [53], phenoxy [54], and amino groups [55] to yield substituted 1-semicarbazides or thiosemicarbazides. In addition, the amino group of the 1-position may add to electron-deficient double bonds [56]. Formaldehyde and other aldehydes may add to all the available free NH groups to give methylol, alkylol, or polymeric products under basic conditions [57]. Aldehydes or ketenes usually give semicarbazone derivatives, and these in turn are used analytically to identify the purity or structure of a known aldehyde [3]. 

The coupling reaction with active halides such as allyl halides or acid chlorides catalyzed by cuprous halides afforded the corresponding alkenylated compounds [131,167,168] (Scheme 57). 

The synthesis of other poly(arylene ether)s containing thiophene units concerned the reaction of two activated halides containing thiophene (structures 8 and 9) with bisphenol A [44,45]. The polymers from the monomers of structures 8 and 9 and bisphenol A had intrinsic viscosities (NMP, 25 °C) of 1.23 and 0.43 dL/g and Tgs of 158 and 120°C, respectively. 

Regardless of which reagent is used, a catalyst is nearly always required.231 Aluminum chloride and boron trifiuoride are the most common, but many other Lewis acids have been used, and also proton acids such as HF and H2S04.232 For active halides a trace of a less... 

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