Substitution reaction hydrogen halides

Aromatic substitution, a quantitative treatment of directive effects in, 1, 35 Aromatic substitution reactions, hydrogen isotope effects in, 2, 163 Aromatic systems, planar and non-planar, 1, 203 Aryl halides and related compounds, photochemistry of, 20, 191 Arynes, mechanisms of formation and reactions at high temperatures, 6, I A-Se2 reactions, developments in the study of, 6,63... 

For reaction with hydrogen halides, the substitution reaction with halide ion easily occurs when a cuprous or cupric compound is used as the catalyst (23) and yields a halogenated allyl compound. With a cuprous compound as the catalyst at 18 °C, the reaction is completed in 6 h. Zinc chloride is also a... 

Most 8 2 reactions are faster in aprotic solvents and slower in protic solvents. Water tends to promote ionization. In pro-tic media, particularly aqueous media, ionization of tertiary halides occurs to give a carbocation intermediate (more slowly with secondary halides) 9,10,11,12,49, 55,69, 70, 77,86. Carbocation intermediates can be trapped by nucleophiles in what is known at an 8 1 reaction. An 8 1 reaction proceeds by ionization to a planar carbocation containing an sp hybridized carbon, follows first-order kinetics, and proceeds with racem-ization of a chiral center. Carbocations are subject to rearrangement to a more stable cation via 1,2 hydrogen or alkyl shifts 24, 25, 26, 27, 29, 50, 65, 67, 76, 77, 78, 79, 80, 81, 83, 84, 85,87,88, 89. A variety of nucleophiles can be used in the substitution reactions, including halides, alkoxides, amines, phosphines, azides, cyanide, acetylides, and enolate anions 2,3,13,14,36,62,63,88, 89,105. 

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 majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The reaction of an alcohol with a hydrogen halide is a substitution A halogen usually chlorine or bromine replaces a hydroxyl group as a substituent on carbon Calling the reaction a substitution tells us the relationship between the organic reactant and its prod uct but does not reveal the mechanism In developing a mechanistic picture for a par ticular reaction we combine some basic principles of chemical reactivity with experi mental observations to deduce the most likely sequence of steps... 

Section 4 9 The potential energy diagrams for separate elementary steps can be merged into a diagram for the overall process The diagram for the reac tion of a secondary or tertiary alcohol with a hydrogen halide is charac terized by two intermediates and three transition states The reaction is classified as a ummolecular nucleophilic substitution, abbreviated as SnI... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

We first encountered nucleophilic substitution in Chapter 4, in the reaction of alcohols with hydrogen halides to fonn alkyl halides. Now we ll see how alkyl halides can themselves be converted to other classes of organic compounds by nucleophilic substitution. 

Two kinds of starting materials have been examined in nucleophilic substitution reactions to this point. In Chapter 4 we saw that alcohols can be converted to alkyl halides by reaction with hydrogen halides and pointed out that this process is a nucleophilic substitution taking place on the protonated fonm of the alcohol, with water serving as the... 

Another method for preparing alkyl halides from alkenes is by reaction with jV-brotnosuccinimide (abbreviated NBS) in the presence of light to give products resulting from substitution of hydrogen by bromine at the allylic position—the position next to the double bond. Cyclohexene, for example, gives 3-bromo-cyclohexene. 

We said at the beginning of this chapter that two kinds of reactions can happen when a nucleophile/Lewis base reacts with an alkyl halide. The nucleophile can either substitute for the halide by reaction at carbon or cause elimination of HX by reaction at a neighboring hydrogen ... 

Common reactions are the anodic substitution of hydrogen atoms in organic compounds by halide or other functional groups ... 

Entries 3 to 6 are examples of ester enolate alkylations. These reactions show stereoselectivity consistent with cyclic TSs in which the hydrogen is eclipsed with the enolate and the larger substituent is pseudoequatorial. Entries 4 and 5 involve SN2 substitutions of allylic halides. The formation of the six- and five-membered rings, respectively, is the result of ring size preferences with 5 > 7 and 6 > 8. In Entry 4, reaction occurs through a chairlike TS with the tertiary C(5) substituent controlling the conformation. The cyclic TS results in a trans relationship between the ester and vinylic substituents. 

Finally it should be mentioned that a number of nucleophilic substitution reactions of unactivated halides can be made to proceed in bipolar non-protic solvents such as dimethyl sulphoxide (DMSO), Me2S —Oe. No hydrogen-bonded solvent envelope, as in for example MeOH, then needs to be stripped from Ye before it can function as a nucleophile AG is thus much lower and the reaction correspondingly faster. Rate differences of as much as 109 have been observed on changing the solvent from MeOH to Me2SO. Chlorobenzene will thus react readily under these conditions with Me3COe ... 

Isomerically pure 1 is obtained when HMes2SiSiPh2SiPh2SiMes2H (Mes = mesityl) 5 is used as a starting material, because bonds between silicon and methyl substituted aryl groups like p-tolyl or mesityl are cleaved much faster by hydrogen halides than Si-Ph bonds [3], Further reaction of I with HCl or HBr leads to the formation of the corresponding halo-derivatives 2 and 3 ... 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

Remarks on 1 and 2.—These two reactions are special cases of a general change, namely, the substitution of an alcoholic hydroxyl group by a halogen atom. This substitution can be carried out in two ways first, as in the preparation of ethyl bromide, 1, by acting on alcohols with hydrogen halides, e.g. 

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