Introduction to Alkyl Halides

Alkyl halides are organic molecules containing a halogen atom X bonded to an sp hybridized carbon atom. Alkyl halides are classified as primary (1°), secondary (2°), or tertiary (3°) depending on the number of carbons bonded to the carbon with the halogen. 

Alkyl halides have the general molecular formula CnHgn+iX, and are formally derived from an alkane by replacing a hydrogen atom with a halogen. 

Allylic halides and benzylic halides have halogen atoms bonded to sp hybridized carbon atoms and do undergo the reactions described in Chapter 7. Allylic halides have X bonded to the carbon atom adjacent to a carbon-carbon double bond, and benzylic halides have X bonded to the carbon atom adjacent to a benzene ring. The synthesis of allylic and benzylic halides is discussed in Sections 15.10 and 18.13, respectively. 

Four types of organic halides (RX) having X near a jt bond 

These organic halides are unreactive in the reactions discussed in Chapter 7. 

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The first mechanism the stndents enconnter (Chapter 4) describes the conversion of alcohols to alkyl halides. Not only is this a nsefnl fnnctional-gronp transformation, bnt its first step proceeds by the simplest mechanism of all— proton transfer. The overall mechanism provides for an early reinforcement of acid-base chemistry and an early introduction to carbocations and nucleophilic substitution. 

In practice this reaction is difficult to carry out with simple aldehydes and ketones because aldol condensation competes with alkylation Furthermore it is not always possi ble to limit the reaction to the introduction of a single alkyl group The most successful alkylation procedures use p diketones as starting materials Because they are relatively acidic p diketones can be converted quantitatively to their enolate ions by weak bases and do not self condense Ideally the alkyl halide should be a methyl or primary alkyl halide... 

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. 

Introduction of an alkyl group to the C-13 position of protoberberine was simply accomplished by the reaction of dihydroprotoberberines (230-232) or their 8-acetonyl derivatives (233,234) with alkyl halides, though yields are not always satisfactory. In some cases, oxidized products, protoberberines, and/or Af-alkyl quaternary bases were concomitantly produced. 

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

The first synthesis of optically pure N-methylated derivatives of Ala, Leu, Phe, and Tyr was published by Fischer and Lipschitz in 1915 73 using the sulfonamide method. Two main developments have ensured that this method remains useful for the preparation of TV-alkyl amino acids both in solution and solid phase (1) the introduction of the Mitsunobu reaction for the alkylation step and (2) the introduction of replacements for Tos (such as the Fukuyama Nbs) that allow easy removal of the sulfonamide protecting group after the alkylation step. Sulfonamide-protected amino acid derivatives can be alkylated in two different ways. Because of the acidity of the sulfonamide hydrogen it is possible to introduce the N-substituent either by direct alkylation (e.g., alkyl halides) or by the Mitsunobu reaction 74 (Scheme 4). 

If the principles, so far outlined, are valid then it is to be expected that n-type doping of polyacetylene would lead to a decrease in stability towards oxidation, and this is indeed so 578). However, the introduction of electrons into the chain can also give a new instability in that the oxidation potential can fall to the point where the polymer is able to reduce water and it becomes hydrolytically unstable. Thus n-type doped polyacetylene reacts rapidly with water and with alcohols, with partial hydrogenation of the chain and a rapid decrease in conductivity 579,580,581). Whitney and Wnek 582) have used the reaction of n-doped polyacetylene with alkyl halides and other reagents to prepare functionalized poly acetylene films. 

Thus reaction with alkyl halides such as allyl bromide or pro-pargyl bromide allow for the introduction of oleflnlc2. . or acetylenic side groups onto the phosphazene ring VI, while alcohol leads to the formation of hydrido-phosphazene complexes VII. The hydrogen in these compounds can be replaced with halogen to yield the first series of iodor-phosphazene compounds VIII. 

Introduction to Derivatization For many years derivatization by alkylation -especially as ethylation, but also as propylation - has been applied to transform Hg species into volatile Hg species before measurement with hyphenated techniques [2, 50, 52]. Sodium tetraphenylborate (NaBPh4) was also used for derivatization prior to measurement with GC-MIP-AED [53], Studies of possible species transformation, for example, during the analytical procedure, have been carried out with isotope-specific determination methods. The results showed that a direct ethylation of Me-Hg in an atmospheric precipitation sample by NaBEt4 produced no significant amount of artifactual Me-Hg [54]. Others investigated the species transformation processes in synthetic solutions to simulate environmental matrices. From the experiments it could be concluded that the species conversion, for example, of Me-Hg into zerovalent Hg, depends on the concentration levels of the halide [2]. Furthermore, the procedural order is of great importance, for example, ethylation should be done after addition of the organic phase to avoid species transformation [55]. 

Introduction their functional groups. In this chapter, we consider the properties and reactions of alkyl halides. We use alkyl halides to introduce substitution and elimination, two of the most important types of reactions in organic chemistry. Stereochemistry (Chapter 5) will play a major role in our study of these reactions. Many other reactions show similarities to substitution and elimination, and the techniques introduced in this chapter will be used throughout our study of organic reactions. 

The 2-cyano-cycloalkanones are easy to prepare but only in moderate yields [18]. The introductions of nitro- [6] and sulfone- [5] [116] [117] groups are simpler than the cyano group, and the yields are better. Sulfone and cyano compounds are most suitable for the introduction of the side chain. Beside the Michael reaction [16] [97], and the Pd(O) catalyzed addition [15], and the reactions with alkyl halides [16] [17] proceed in good yields. In contrast to other compounds, 2-nitroketones generally do not undergo nucleophilic substitution with non-activated alkyl halides. However, Michael addition products [2], as well as products synthesized by Pd(O) catalyzed alkylation [118], are well known derivatives of 2-nitrocycloalkanones. 

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