Aikyl Halides

Conditions (i) NaH/DMF/aikyl halide, (ii) Ac20 or NaH/DMF acid chloride... 

Presented below are some of the most frequently used methods of preparing aikyl halides. It is. important to note that some of the reactions permit the incorporation of one halogen into a moiecuJe, while other reactions allow polyhalogenation of a molecule. 

What procedures are available for the preparation of b Answer Since D is an olefin, we must refer to Chapter II. Keeping in mind that the prescribed starting material is an aikyl halide, procedure II-I would be the method of choice. This would require an alkyl halide with the structure of C or D. CU3... 

Reduction of aikyl halides. Allylic and benzylic chlorides and bromides are reduced by the reagent almost instantaneously at 25° (S 2 displacement). Simple primary halides are completely reduced in 2 min. Even neopentyl bromide is reduced to neopentane (96% yield) in 3 hr. under reflux. Secondary cycloalkyl bromides are reduced at 25° in 24 hr. Even CAro-2-bromonorbomane (I) can be reduced quantitatively. The... 

B6. ComparistHi of Alkylaluminiim-AIkyl Halide Initiator Systems in Mefliyl Halide Solvents... 

Coupling between C(s/ )-Organometallics and Primary Aikyl Halides... 

Thus far. no evidence has been presented lor carbanion intermediates in (irignard reactions ol ulkvl halides. It is not known whether or not (irignard reactions ol aikyl halides have the same... 

The starting naateriais for the Grignard alcohol synthesis are aikyl halides and aldehydes or ketones. These starting materials are themselves made from alcohols by substitution or oxidation. It is possible therefore to build up large molecules by iteration (repetition). A simple example is alcohol (36) needed as part of a project to synthesise authentic samples of all branched octanols for... 

Alkylation of Aldehydes. Aldehydes react with alkyldihalo-boranes in the presence of O2 to produce the corresponding 2 °-aIkyl halides in moderate to good yields. The initial coordination of RBCI2 to the carbonyl is followed by the migration of alkyl group to the carbonyl carbon and the chlorination of the borinate intermediate to produce the halide products (eq 17). ... 

Although pyrrolyl halides are well-known compounds, their instability to acid, alkali, and heat precludes their commercial availability. Since pyrrole is a very reactive, Jt-excessive heterocycle, it undergoes halogenation extremely readily [6, 7], For example, the labile 2-bromopyrrole, which decomposes above room temperature, is a well-known compound, as are A-aIkyl-2-halopyrroles, readily prepared by direct halogenation, usually with NBS for the synthesis of bromopyrroles [8, 9], The 2-halopyrrole is usually the kinetic product but the 3-halopyrrole is often the thermodynamic product, and this property of halopyrroles can be exploited in synthesis. For example, A-benzylpyrrole (1) can be dibrominated to give 2 as the kinetic product, which rearranges to 3 upon treatment with acid [10, 11]. Other A-alkyl-2,5-dibromopyrroles are available in this fashion. 

Oximes can be alkylated by alkyl halides or sulfates. N-AIkylation is a side reaction, yielding a nitrone.739 The relative yield of oxime ether and nitrone depends on the nature of the... 

Boron Hydride Derivatives. Alkyl boranes can be prepd by alkylation of key intermediates, of diborane or of higher boranes. Alkyiation of a borane will proceed more readily if a functional group, such as a halogen or an active merai arom, is attached to the borane. For example, a halo-borane may react with a metal aikyl to produce an alkyl borane, or a metal polyhydropolyborate may react with an alkyl halide to produce an alkyl borane(Ref 35). Boranes may be alkylated or ary-iated with an unsaturated hydrocarbon(Ref 13). Alkoxy derivs of boranes can be prepd by allowing a borane to react with an appropriate alccho (Ref... 

Aikyl hnlicies are compounds containing halogen bonded to a saturated. sy -h,vl>ndiz< fl carbon atom. The C-X bond is polar, and alkyl halides can therefore behave as electrophiles. 

Methods of (V-AIkylation. In analogy with acylation techniques, metalated oxazolidinones add to alkyl halides to afford the A-alkylated products in high yields. 

The anionic intermediates generated by the cathodic reduction of CHT and some of its derivatives such as 1-MeO- and 3-MeO-CHTs are regioselectively alkylated with alkyl halides to give 6-aIkyl-l,3-cycloheptadiene and l-MeO-6-alkyl-l,3-cycloheptadiene as the main products, respectively ... 

Olah and Kuhn S found that fluorochloro-, fluorobromo- and fluoroiodo-alkanes are effective chloro-, bromo- and iodo-aikylating agents, respectively, in Friedel-Crafts alkylations of arenes in the presence of boron halide catalysts (equation 86). Boron trihalides catalyzq reactions of only the C—F bonds, but not of the C—Cl, C—Br or C—I bonds. The order of reactivity of the catalysts was found to be BI3 > BBr3 > BCI3 > BF3, and that of the carbon-halogen bonds C—F > C—Cl > C—Br > C—I. 

AIkylation of a lactam thiocarbonyl by a phenacyl halide is followed by cyciization with the neighbouring aldehyde group. The intermediate quaternary salt is converted into the free base by heating it above its melting point and at reduced pressure. 

Thieno[3,2-d]pyrimidine-2(l//)-thiones 217-219 and -4(3//-thiones 245 were S-methylated smoothly with methyl iodide in base to the corresponding 2-methylthio (82EUP43054 89CPB1197) and 4-methylthio (86JHC 1757) compounds. 5-AIkylation of thieno[3,2-d]pyrimidin-4(3H)-one-2(l//)-thione 223 with alkyl halides in dilute sodium hydroxide solution afforded 2-alkylthio derivatives 284. Nucleophilic displacement of the alkyl-thio group in compound 284 by primary amines has also been reported (90EUP404356). 

No Name Boiling point, C n > "D Df S-AIkyl thiuronium picrate 1 Naphthyl amide Antlide Alkyl mer- curic halide Picrate of 2-naph- (hyl 2.4-Di- ntlro- phenyl ihio- 2.4-Di- nilro- phenyl sulfone Miscellaneous... 

Aikyl fluorides by exchange from alkyl halides or methanesulfonates. The resin used for the reaction is the F form of Amberlyst-A26 (Rohm and Haas), a macroreticular anion-exchange resin containing ammonium groups. When this material and primary alkyl halides or sulfonates are refluxed in a solvent (pentane, hexane, ether), alkyl fluorides are formed, usually in satisfactory yields. Alkenes accompany fluorides in the reaction of secondary substrates. This reaction has been conducted previously under phase-transfer catalysis (5, 322). ... 

Calix[n]arenes 1-3 were used as inverse PT catalysts in the alkylation of active methylene compounds with alkyl halides in aqueous NaOH solutions,and in aldol-type eondensation and Michael addition reactions. In the aikylation of phenylacetone with octyl bromide, the IPTC procedure enhanced the alkylation versus hydrolysis and C versus O alkylation selectivities with respect to those observed xmder classical PTC reactions in the presence of tetrabutylammonium bromide (TBAB) or hexadecyltributylammonium bromide (HTPB). Moreover, the aqueous catalyst solution was easily separated from the organic phase eontaining the products, and no organic solvent was required. In the case of the aldol-type condensation of benzaldehyde with indene or acetophenone in aqueous NaOH (Fig. 9), IPTC reaetions eatalyzed by I were compared with those conducted in aqueous micelles in the presence of cetyltrimethylammonium bromide (CTAB) as the sufactant. Although selectivities and yields were similar, the IPTC proeedure avoided the formation of emulsions, thus faciUtating product separation and catalyst recovery. In the light of the results obtained, water-soluble calix[ ]arenes 1-3 were proposed... 

A selenium linker has been used in the preparation of various nitrogen-containing heterocycles. Cycloaddition of nitrile oxides to resin-bound alkynes gave resin-bound isoxazoles (Scheme 11.41). a-AIkylation of the resin-bound cycloadducts with halides under basic conditions gave additional diversity for the products. Traceless oxidative cleavage of the isoxazoles was achieved via the elimination of the resin with hydrogen peroxide. The diversity of the products was still expanded with a second cascade of 1,3-dipolar cycloadditions to alkenes attached to the resin. 

---