Directed halogenation directive

Ordinary commercial camphor is (-i-)-cam phor, from the wood of the camphor tree. Cinnamonum camphora. Camphor is of great technical importance, being used in the manufacture of celluloid and explosives, and for medical purposes, /t is manufactured from pinene through bornyl chloride to camphene, which is either directly oxidized to camphor or is hydrated to isoborneol, which is then oxidized to camphor. A large number of camphor derivatives have been prepared, including halogen, nitro and hydroxy derivatives and sulphonic acids. 

Halogen derivatives of silanes can be obtained but direct halogena-tion often occurs with explosive violence the halogen derivatives are usually prepared by reacting the silane at low temperature with a carbon compound such as tetrachloromethane, in the presence of the corresponding aluminium halide which acts as a catalyst. 

Nitrogen does form a number of binary compounds with the halogens but none of these can be prepared by the direct combination of the elements and they are dealt with below (p. 249). The other Group V elements all form halides by direct combination. 

A complete set of trihalides for arsenic, antimony and bismuth can be prepared by the direct combination of the elements although other methods of preparation can sometimes be used. The vigour of the direct combination reaction for a given metal decreases from fluorine to iodine (except in the case of bismuth which does not react readily with fluorine) and for a given halogen, from arsenic to bismuth. 

Sulphur is less reactive than oxygen but still quite a reactive element and when heated it combines directly with the non-metallic elements, oxygen, hydrogen, the halogens (except iodine), carbon and phosphorus, and also with many metals to give sulphides. Selenium and tellurium are less reactive than sulphur but when heated combine directly with many metals and non-metals. 

None of the halogens reacts directly with oxygen but all form oxides by indirect methods. 

Halides of non-metals are usually prepared by the direct combination of the elements. If the element exhibits more than one oxidation state, excess of the halogen favours the formation of the higher halide whilst excess of the element favours the formation of the lower halide (e.g. PCI5 and PCI3). 

A point in case is provided by the bromination of various monosubstituted benzene derivatives it was realized that substituents with atoms carrying free electron pairs bonded directly to the benzene ring (OH, NH2, etc) gave 0- and p-substituted benzene derivatives. Furthermore, in all cases except of the halogen atoms the reaction rates were higher than with unsubstituted benzene. On the other hand, substituents with double bonds in conjugation with the benzene ring (NO2, CHO, etc.) decreased reaction rates and provided m-substituted benzene derivatives. 

A halogen atom directly attached to a benzene ring is usually unreactive, unless it is activated by the nature and position of certain other substituent groups. It has been show n by Ullmann, however, that halogen atoms normally of low reactivity will condense with aromatic amines in the presence of an alkali carbonate (to absorb the hydrogen halide formed) and a trace of copper powder or oxide to act as a catalyst. This reaction, known as the Ullmant Condensation, is frequently used to prepare substituted diphenylamines it is exemplified... 

The reaction must be carried out in the absence of direct sunlight, since sunlight causes direct addition of the halogen to the hydrocarbon, particularly if the latter is warm benzene, for example, yields the hexahalide ... 

The direct introduction of a halogen atom (usually bromine) by means of V-haloamine (generally iV-bromosuccinimide) in the allyl position is known as the Wohl-Ziegler reaction ... 

The metal reacts directly with elemental carbon, nitrogen, boron, selenium, silicon, phosphorus, sulfur, and with halogens. 

Hafnium is resistant to concentrated alkalis, but at elevated temperatures reacts with oxygen, nitrogen, carbon, boron, sulfur, and silicon. Halogens react directly to form tetrahalides. 

That looks simple and direct don t it If safrole was used as the alkene one would get safrole-azide as product. Just one teensy little reduction away from MDA. Strike also found some azide papers that, with a little work, will get safrole-azide in a totally different way. Strike came across a lot of work where groups were using dinucleophilic addition to get an azide and a halogen added across a double bond. The azide would always go to the beta secondary carbon and the halogen to the primary carbon (just what one would want if safrole was the substrate). 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Carbocyclic substitution can also be achieved by first introdueing a reactive organomelallic substituent. Preparation of organolithium reagents can be done by one of the conventional melhods. especially halogen-metal exchange or directed lithiation. Table 14.2 gives examples. 

The O-S exchange method in presence of a-halogenated carbonyl compound is a very good one for thiazole compounds. The thioamide is prepared in situ by the action of amide upon phosphorus pentasulphide with solvent. The a-halogenated aldehyde reacts directly. But the O-Se exchange cannot be performed with a-halogenated carbonyl compounds because of the apparition of phosphoric acid. (Scheme 3), The C-Se bond is very sensitive to add pH. 

All possible dichloro- or dibromothiazoles are known. The 2.5-dihalogeno derivatives can be prepared from the 5-halogeno-2-aminothiazoles by diazotization/decomposition with CuCl or CuBr (3, 12, 13, 18, 75). The 5-halogeno-2-aminothiazoles can be easily prepared by halogenation of 2-aminothiazole (65, 76-79) 2,5-dibromothiazole can also be prepared by direct bromination of 2-bromothiazole (5). 

Substitutive nomenclature of alkyl halides treats the halogen as a halo—(fluoro chloro bromo or lodo ) substituent on an alkane chain The carbon chain is numbered m the direction that gives the substituted carbon the lower number... 

Hydroxyl groups take precedence over ( outrank ) alkyl groups and halogen substituents m determining the direction m which a carbon chain is numbered The OH group is assumed to be attached to C 1 of a cyclic alcohol and is not numbered... 

The reactivity of the halogens decreases m the order F2 > CI2 > Br2 > I2 Fluo rme is an extremely aggressive oxidizing agent and its reaction with alkanes is strongly exothermic and difficult to control Direct fluonnation of alkanes requires special equip ment and techniques is not a reaction of general applicability and will not be discussed further... 

Carbon-carbon double bonds take precedence over alkyl groups and halogens in determining the mam carbon chain and the direction in which it is numbered... 

Halogen substituents are slightly deactivating but are ortho para directing... 

Activating Standard of comparison Deactivating —R —Ar —CH=CR —H —X (X = F Cl —CH2X (alkyl) (aryl) 2 (alkenyl) (hydrogen) (halogen) Br 1) (halomethyl) Ortho para directing Ortho para directing... 

Returning to Table 12 2 notice that halogen substituents direct an incoming electrophile to the ortho and para positions but deactivate the ring toward substitution Nitration of chlorobenzene is a typical example of electrophilic aromatic substitution m a halobenzene... 

Because we have come to associate activating substituents with ortho para directing effects and deactivating substituents with meta the properties of the halogen substituents appear on initial inspection to be unusual... 

The mix of inductive and resonance effects varies from one halogen to another but the net result is that fluorine chlorine bromine and iodine are weakly deactivating ortho para directing substituents... 

Like aldehydes ketone functions take precedence over alcohol functions double bonds halogens and alkyl groups m determining the parent name and direction of numbering Aldehydes outrank ketones however and a compound that contains both an aldehyde and a ketone carbonyl group is named as an aldehyde In such cases the carbonyl oxy gen of the ketone is considered an 0x0 substituent on the mam chain... 

Aryl halides are compounds m which a halogen substituent is attached directly to an aro matic ring Representative aryl halides include... 

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