Direct halogenation

The tnhahdes of phosphoms usually are obtained by direct halogenation under controlled conditions, eg, in carbon disulfide solution in the case of the triiodide. Phosphoms trifluoride [7647-19-0] is best made by transhalogenation of PCl using AsF or Cap2. AH of the phosphoms tnhahdes are both Lewis bases and acids. The phosphoms tnhahdes rapidly hydroly2e in water and are volatile. Examination by electron diffraction has confirmed pyramidal stmctures for the gaseous tnhahde molecules (36). Physical properties and heat of formation of some phosphoms hahdes are hsted in Table 7. 

A/-Chloro fatty acid amides have been synthesized from the direct halogenation of the amide in boiling water (28). They are useful as reactive intermediates for further synthesis. Fluorination has also been reported by treating the fatty amide with fluorine-containing acid reagents at 200 °C to reach a fluorinated amide with less reactivity toward fluorocarbon polymers (29). 

Direct halogenation of S-hydroxyquiaoline has been used as a route to 5,7-dihalo derivatives. Compounds of this type reported iaclude... 

Direct halogenation of sahcyhc acid is generally carried out ia glacial acetic acid. As expected, the main product is the 5-halo-sahcyhc acid with small quantities of the 3-halo and 3,5-dihalosahcyhc acids. 

Direct halogenation of sucrose has also been achieved using a combination of DMF—methanesulfonyl chloride (88), sulfuryl chloride—pyridine (89), carbon tetrachloride—triphenylphosphine—pyridine (90), and thionyl chloride—pyridine—1,1,2-trichloroethane (91). Treatment of sucrose with carbon tetrachloride—triphenylphosphine—pyridine at 70°C for 2 h gave 6,6 -dichloro-6,6 -dideoxysucrose in 92% yield. The greater reactivity of the 6 and 6 primary hydroxyl groups has been associated with a bulky halogenating complex formed from triphenylphosphine dihaUde ((CgH )2P=CX2) and pyridine (90). 

The best known of the hahdes are the trialkyldihalo- and triaryldihaloantimony compounds. The dichloro, dibromo, and diiodo compounds are generally prepared by direct halogenation of the corresponding tertiary stibiaes. The difluoro compounds are obtained by metathasis from the dichloro or dibromo compounds and silver fluoride. The diiodo compounds are the least stable and are difficult to obtain ia a pure state. The tri alkyl- and triaryldichloro- and dibromoantimony compounds are all crystalline soHds which are stable at room temperature that but decompose on heating ... 

Direct halogenation of quinoxaline appears to be of limited value but pyrazine may be chlorinated in the vapor phase to give monochloropyrazine at 400 °C or at lower temperatures under catalytic conditions 72AHC(14)99, and at higher temperatures tetra-chloropyrazine formation occurs in high yields. Mention has already been made of direct chlorination (see Section 2.14.2.1) of phenazine. 

In contrast to the 3-substituted products above, 4-chloro-, 4-bromo- and 4-iodo-isoxazoles are readily prepared by direct halogenation of the corresponding isoxazoles, from 4-isoxazolediazonium salts by the Sandmeyer reaction, or by reaction of hydroxylamine with a-halo- 8-dicarbonyl compounds (62HC(l7)l, p. 66, 63AHC(2)365). 3,5-Bis(dimethyl-amino)-4-fluoroisoxazole has been synthesized by reaction of (Me2NCO)2CHF with hydroxylamine (78BSB391). 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

Direct halogenation of a 20-ketopregnane (lacking an hydroxyl at C-17) generally does not give satisfactory yields of the 21-bromo derivative, unless the presence of a C-16 substituent e.g., methoxyl or methyl) inhibits formation of the usual 17-bromo primary product. However, an indirect method has been devised. If the 20-ketaI is first prepared, it can be brominated satisfactorily at C-21 using trimethylphenylammonium tribromide as halo-... 

Direct halogenation at C-21 of a A -20-ketopregnane with the common reagents e.g., bromine) is ordinarily not possible. However, by the use of cupric bromide as halogenating agent, a modest yield of the 21-bromo compound can be obtained ... 

BCI3 and BBr3 are prepared on an industrial scale by direct halogenation of the oxide in the presence of C, e.g. ... 

Nitrogen forms two series of oxohalides — the nitrosyl halides XNO and the nitryl halides XNO2. There are also two halogen nitrates FONO2 (bp -46°) and CIONO2 (bp 22.3°), but these do not contain N-X bonds and can be considered as highly reactive derivatives of nitric acid, from which they can be prepared by direct halogen ation ... 

The nitrosyl halides are reactive gases that feature bent molecules they can be made by direct halogenation of NO with X2, though fluorination of NO with Agp2 has also been used and CINO can be more conveniently made by passing N2O4 over moist KCl ... 

All 4 trihalides are volatile reactive compounds which feature pyramidal molecules. The fluoride is best made by the action of CaF2, Znp2 or Asp3 on PCI3, but the others are formed by direct halogenation of the element. PF3 is colourless, odourless and does not fume in air, but is very hazardous due to the formation of a complex with blood haemoglobin (cf. 

The SH, SCHs, and weakly directing halogens cause small shifts, which to a large extent are determined by magnetic anisotropy effects, especially in the case of the halogens. Attempts have been made to estimate these effects for the other thiophenes. Except for orthohydrogens, these effects are usually very small. 

While the direct halogenation of toluene gives a mixture of isomers that is difficult to separate into the pure isomers, the isomeric o- and /r-nitrotoluenes 6a and 6b, formed by nitration, are easy to separate from each other. Thus reduction of the single o- or /j-nitrotoluene 6 to the o- or /j-toluidine 7a or 7b respectively, followed by conversion into the corresponding diazonium salt 8 and a subsequent Sandmeyer reaction leads to the pure o- or /j-halotoluene 9. 

Despite several attractive features in this method of direct halogen introduction and the obvious applications in the synthesis of deoxy sugars, its uses have not been further exploited by other groups of workers. Some new related methods have become available which reportedly eliminate the difficulties previously encountered such as rearrangement, unreactivity due to steric hindrance, and phosphonate ester formation. The reaction is based on the observation (28) that triethylphosphine reacts with ethanol and carbon tetrachloride to give ethyl chloride, chloroform, and triethylphosphite. In a new adaptation (76, 77) of this... 

One further point inductive effects and resonance effects don t necessarily act in the same direction. Halogen, hydroxyl, alkoxyl, and amino substituents, for instance, have electron -withdrawing inductive effects because of the electronegativity of the -X, -O, or —N atom bonded to the aromatic ring but have resonance effects because of the lone-pair electrons on those same —X, -O, or —N atoms. When the two effects act in opposite directions, the stronger of the two dominates. 

Most electrophilic substitutions in benzimidazole (31 R = H) occur primarily in the 5-position. In multiple bromination the order followed, 5 > 7 > 6,4 > 2, parallels molecular orbital calculations. In benzimidazole itself the 4(7)- and 5(6)-positions are tautomerically equivalent. Fusion of a benzene ring deactivates C-2 to electrophilic attack to such an extent that it is around 5000 times less reactive than the 2-position of imidazole. Strong electron donors at C-5 direct halogenation to the 4-position, whereas electron-withdrawing groups favor C-4 or C-6 substitution (84MI21). 

An electron donor in the 5-position directs halogenation to carbon-4 (63JGU223, 63JGU1714). 

Most halogenoalkyl- and halogenoarylquinoxalines have been made by primary synthesis (see Chapter 1) or by direct halogenation of alkyl- or arylquinoxalunes (see Section 2.2.4). However, other minor procedures may be used, as illustrated in the following classified examples. 

The second type oiPd lV) andPt(/F) complexes have the general stoichiometry M(R2C fc)3X 117). These compounds are isostructural with Ni(Bu2rftc)3Br 118). However, in contrast to the preparation of the latter complex, the former complexes cannot be obtained by the direct halogenation of the divalent metal dithiocarbamates, so other preparative routes, as given in Table 1 must be followed. 

Instead of direct halogenation of ketones, reactions with more reactive derivatives such as silyl enol ethers and enamines have advantages in certain cases. 

Aryl Halides from Diazonium Ion Intermediates. Replacement of diazonium groups by halides is a valuable alternative to direct halogenation for the preparation of aryl halides. Aryl bromides and chlorides are usually prepared by a reaction using the appropriate Cu(I) salt, which is known as the Sandmeyer reaction. Under the classic conditions, the diazonium salt is added to a hot acidic solution of the cuprous halide.99 The Sandmeyer reaction occurs by an oxidative addition reaction of the diazonium ion with Cu(I) and halide transfer from a Cu(III) intermediate. 

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