Substitution reaction types

To simplify the discussion, we will classify simple chemical reactions into five types Type 1 combination reactions Type 2 decomposition reactions Type 3 substitution reactions Type 4 double-substitution reactions Type 5 combustion reactions... 

Discuss (a) the acidity and (b) the substitution reactions of metal hexa-aquo cations. [MfH O) ]" (where n = 2 or 3), giving two examples of each type of reaction. Discuss the effect upon the stabilities of the -t- 2 and -f- 3 oxidation states of... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

The most widely studied electrophilic substitution reactions are haloge-nation and nitration. Two main types of substrates are possible alkyl-thiazoles and arylthiazoles. 

Section 8 1 Nucleophilic substitution is an important reaction type m synthetic organic chemistry because it is one of the mam methods for functional group transformations Examples of synthetically useful nucleophilic sub stitutions were given m Table 8 1 It is a good idea to return to that table and review its entries now that the details of nucleophilic substitution have been covered... 

Alkynes of the type RC CH may be prepared by nucleophilic substitution reactions in which one of the starting matenals is sodium acetyhde (Na" C=CH)... 

Reduction of arenes by catalytic hydrogenation was described m Section 114 A dif ferent method using Group I metals as reducing agents which gives 1 4 cyclohexadiene derivatives will be presented m Section 1111 Electrophilic aromatic substitution is the most important reaction type exhibited by benzene and its derivatives and constitutes the entire subject matter of Chapter 12... 

Electrophilic aromatic substitution (Section 12 1) Fundamen tal reaction type exhibited by aromatic compounds An electrophilic species (E" ) attacks an aromatic ring and re places one of the hydrogens... 

Iron Porphyrins. Porphyrias (15—17) are aromatic cycHc compouads that coasist of four pyrrole units linked at the a-positions by methine carbons. The extended TT-systems of these compounds give rise to intense absorption bands in the uv/vis region of the spectmm. The most intense absorption, which is called the Soret band, falls neat 400 nm and has 10. The TT-system is also responsible for the notable ring current effect observed in H-nmr spectra, the preference for planar conformations, the prevalence of electrophilic substitution reactions, and the redox chemistry of these compounds. Porphyrins obtained from natural sources have a variety of peripheral substituents and substitution patterns. Two important types of synthetic porphyrins are the meso-tetraaryl porphyrins, such as 5,10,15,20-tetraphenylporphine [917-23-7] (H2(TPP)) (7) and P-octaalkylporphyrins, such as 2,3,7,8,12,13,17,18-octaethylporphine [2683-82-1] (H2(OEP)) (8). Both types can be prepared by condensation of pyrroles and aldehydes (qv). 

In a simple pyrometaHurgical reduction, the reduciag agent, R, combines with the nonmetal, X, ia the metallic compound, MX, according to a substitution reaction of the foUowiag type ... 

These effects can be attributed mainly to the inductive nature of the chlorine atoms, which reduces the electron density at position 4 and increases polarization of the 3,4-double bond. The dual reactivity of the chloropteridines has been further confirmed by the preparation of new adducts and substitution products. The addition reaction competes successfully, in a preparative sense, with the substitution reaction, if the latter is slowed down by a low temperature and a non-polar solvent. Compounds (12) and (13) react with dry ammonia in benzene at 5 °C to yield the 3,4-adducts (IS), which were shown by IR spectroscopy to contain little or none of the corresponding substitution product. The adducts decompose slowly in air and almost instantaneously in water or ethanol to give the original chloropteridine and ammonia. Certain other amines behave similarly, forming adducts which can be stored for a few days at -20 °C. Treatment of (12) and (13) in acetone with hydrogen sulfide or toluene-a-thiol gives adducts of the same type. 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

Halogen atoms in the 2-position of imidazoles, thiazoles and oxazoles (542) undergo nucleophilic substitution reactions. The conditions required are more vigorous than those used, for example, for a- and y-halogenopyridines, but much less severe than those required for chlorobenzene. Thus in compounds of type (542 X = Cl, Br) the halogen atom can be replaced by the groups NHR, OR, SH and OH (in the last two instances, the products tautomerize see Sections 4.02.3.7 and 4.02.3.8.1). 

Although some of the oxidative ring closures described above, e.g. reactions with lead tetraacetate (Section 4.03.4.1.2), may actually involve radical intermediates, little use has been made of this reaction type in the synthesis of five-membered rings with two or more heteroatoms. Radical intermediates involved in photochemical transformations are described in Section 4.03.9. Free radical substitutions are described in the various monograph chapters. 

The stereochemistry of the most fundamental reaction types such as addition, substitution, and elimination are described by terms which specify the stereochemical relationship between the reactants and products. Addition and elimination reactions are classified as syn or anti, depending on whether the covalent bonds which are made or broken are on the same face or opposite faces of the plane of the double bond. 

Although different reaction types exhibit large quantitative differences, and there are exceptions, the order 5>6>3>7>4> 8-10 is a rough guide of relative reactivity for many systems. Some quantitative data on typical reactions involving nucleophilic substitution or participation are shown in Scheme 3.4. 

The caibonyl group in aldehydes, ketones, acids, esters, and amides is deactivating and wcto-directing. There are distinct limitations on the types of substitution reactions that are satisfiictory for these deactivating substituents. In general, only those electrophiles in category A in Scheme 10.1 react readily. 

It was noted early by Smid and his coworkers that open-chained polyethylene glycol type compounds bind alkali metals much as the crowns do, but with considerably lower binding constants. This suggested that such materials could be substituted for crown ethers in phase transfer catalytic reactions where a larger amount of the more economical material could effect the transformation just as effectively as more expensive cyclic ethers. Knbchel and coworkers demonstrated the application of open-chained crown ether equivalents in 1975 . Recently, a number of applications have been published in which simple polyethylene glycols are substituted for crowns . These include nucleophilic substitution reactions, as well as solubilization of arenediazonium cations . Glymes have also been bound into polymer backbones for use as catalysts " " . 

Photochemical substitution reactions of this type which involve selective hydrogen abstractions from intramolecular sites by the m.tt ketone oxygen, are reviewed in chapter 12. ... 

Three skeleton atoms of a hetero-l,3-diene are incorporated into a five-membered ring system on reaction with 1,2 [n,n] compounds (e.g., hydrazines, reaction type 4, equation 10). On further heating in the presence of azobisiso-butyronitrile (AIBN), the bis(trifluoromethyl)-substituted 1,2,4-triazolines are transformed into 5-tnfluoromethyl-l,2,4-triazoles in high yield [t02 (equation 22). 

Semicarbazide hydrochloride [705] and amidrazones [106] react with trifluo-ropyruvates to give six-membered heterocycles A variety of trifliioromethyl substituted heterocyclic systems is available, starting from the hydrate of trifluoropy-ruvicacid, a versatile 1,2-bielectrophihc building block (reaction type 2, equation 10) [107] (equation 24). 

Sulfides, compounds of the type RSR, are prepared by nucleophilic substitution reactions. Treatment of a primary or secondary alkyl halide with an alkanethiolate ion (RS ) gives a sulfide ... 

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