Cyclic, from alkyl halides

If, oil the other hand, R- is unsaturated and can undergo cyclization rapidly, it will do so. This competition between reduction of the first formed radical R and its cyclization to a new cyclic radical R - is the same as discussed for the formation of free radicals from alkyl halides and tributyltin radicals. The only difference is in the way in which the carbon-centered radical is produced. 

The preparation of tertiary amines from alkyl halides and a secondary amine, or a primary amine in which both TV-hydre en atoms are to be replaced by identical alkyl groups, can be carried out with favourable yields in many cases, as evidenced by preparations of diethyl-n-hexadecylamine (from diethylamine) and of dimethyl-n-docosylamine (from dimethylamine) . Alkyl sulphonates have similarly been used, and the reaction extended to the preparation of cyclic tertiary amines from primary amines and appropriate terminal di-sulphonates (reaction 38) . Satisfactory conditions have been reported... 

The lithiated oxathiolan dioxide (19) has been used as a carbonyl anion equivalent to give high yields of aldehydes from alkyl halides and acyloins from cyclic ketones.The /8-acyl anion equivalent (20 X = Li), which can be prepared from the stannylated diene (20 X = SnRs) by metal exchange, reacts with a variety of electrophiles (E ) to give dienes (20 X = E) in good to excellent yields.The thiophosphate (21) gives a,/3-unsaturated esters in 48—68% yield... 

Sheppard N and De La Cruz C 1998 Vibrational spectra of hydrocarbons adsorbed on metals. Part II. Adsorbed acyclic alkynes and alkanes, cyclic hydrocarbons including aromatics and surface hydrocarbon groups derived from the decomposition of alkyl halides, etc Adv. Catal. 42 181-313... 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

Electrophilic attack on the sulfur atom of thiiranes by alkyl halides does not give thiiranium salts but rather products derived from attack of the halide ion on the intermediate cyclic salt (B-81MI50602). Treatment of a s-2,3-dimethylthiirane with methyl iodide yields cis-2-butene by two possible mechanisms (Scheme 31). A stereoselective isomerization of alkenes is accomplished by conversion to a thiirane of opposite stereochemistry followed by desulfurization by methyl iodide (75TL2709). Treatment of thiiranes with alkyl chlorides and bromides gives 2-chloro- or 2-bromo-ethyl sulfides (Scheme 32). Intramolecular alkylation of the sulfur atom of a thiirane may occur if the geometry is favorable the intermediate sulfonium ions are unstable to nucleophilic attack and rearrangement may occur (Scheme 33). 

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

The numerous straightforward examples of internal displacement reactions leading to isolable cyclic products will not be discussed here, but only, for the most part, those ionization reactions in which a cyclic intermediate or transition state is deduced from the rearranged structure of the product. A well-known example is mustard gas and other alkyl chlorides with sulfur on the /3-carbon atom. Although mustard gas is a primary and saturated alkyl chloride, its behavior is like that of a typical tertiary alkyl chloride. It reacts so fast by a first order ionization that the rate of the usual second order displacement reaction of primary alkyl halides is not measureable. Only the ultimate product, not the rate, is determined by the added reagent.228 Since the effect of the sulfur is too large to be explicable in terms of a carbon sulfur dipole or similar explanation, a cyclic sulfonium ion has been proposed as an... 

Cyclic enone, 12 185 Cyclic ethers, 10 567, 569 12 663 polymerization, 14 271 Cyclic fatigue, in ceramics, 5 633-634 Cyclic gas generators, 6 786-787, 789, 827 Cyclic halides, 19 56 Cyclic hexakis(thio-l,4-phenylene), melt polymerization of, 23 705 Cyclic hydrocarbons, 13 687 Cyclic hydroxyalkyl alkyl peroxide, 18 454 Cyclic ion exchange operation, 14 408-413 Cyclic ketones, 12 176, 177 14 590-592. See also Cyclic 1,2-diketones physical properties of, 14 591t hydroxyalkyl hydroperoxides from, 18 450... 

Monocarbamoylation of diols is generally accomplished only with great difficulty. Reaction of the diol with an alkyl isocyanate is a possibility, but trimerization of the isocyanate frequently occurs [73]. The monocarbamic esters, which have PAF receptor antagonist activity, can be obtained however in acceptable yields via the phase-transfer catalysed in situ formation of the alkyl isocyanate from potassium isocyanate and an alkyl halide, and its subsequent reaction with the diol (see Scheme 3.8 for typical examples) [74], The diols tend to react more rapidly than do simple alcohols and m-diols are more effectively esterified that are /ra/rs-diols. Additionally, the longer the chain length between the hydroxyl centres, the less effective is the reaction. This has led to the reasonable hypothesis that a cyclic H-bonded intermediate between the two hydroxyl groups and the alkyl isocyanate are critical for the preferential and rapid formation of the carbamate. 

Figure 4.2. Dissociative electron transfer rates from aromatic anion-radicals to alkyl halides detetmined by cyclic votommeiry or by pulse-radiolysis (a) iodobutane (b) 1 -iodo-I -methylpropanc. Solvent N-methylpyrroHdone or dimethylformamidc. Data from refs, [3,5].

Reduction of azobenzenes in an aprotic solvent generates nucleophilic nitrogen species, which can react with an added alkyl halide. In this way, cyclic hydrazo compounds can be generated from a,o>-dibromoalkanes [t07]. 

The perfluorohalogenomethylraercapto compound is formed in about 50% yield, the by-products being aryl halides from the Grignard reagent in 5-15% yield. It is assumed that the reaction follows an Sn2 mechanism with a cyclic intermediate state in analogy with the reaction of Grignard reagents with alkyl halides 98, 155), e.g.,... 

Each desired enantiomer of 3-substituted dihydro-2(3.//)-furanones and 3-substituted tetrahydro-2//-pyran-2-ones was prepared starting either from 4,5-dihydro-2-(m-trimethylsilyloxy)oxazoles and alkylating with the corresponding alkyl halide, or by reversing the order of alkyl group introduction. Upon hydrolysis with dilute hydrochloric or sulfuric acid, 2-substituted cyclic lactones were obtained in 40-75% overall yield and 60-86% enantiomeric excess20. 

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