Alkyl halide synthesis

PROPARGYLATION OF ALKYL HALIDES SYNTHESIS OF (E)-6,10-DIMETHYL-5,9-UNDECADIEN-1-YNE AND (E)-7,11-DIMETHYL-6,10-DODECADIEN-2-YN-1-OL... 

PROPARGYLATION OF ALKYL HALIDES SYNTHESIS OF (E)-6,10-DIMETHYL-5,9-UNDECADIEN-1-YNE AND (E)-7,11-DIM ETHYL-6,10-DODECADIEN-2-YN-1-OL (5,9-Undecadien-1-yne, 6,10-dimethyl-, (E)-) and (6,10-Dodecadien-2-yn-i-ol, 7,11-dimethyl-, (E)-)... 

Another method o-f alkyl halide synthesis is the reaction of an alkane with Cist or Bf2 by a radical chain reaction pathway 5.31. Although... 

Another method of alkyl halide synthesis is the reaction of an alkane with CI2 or Br2 by a radical chain-reaction pathway (Section 5.3). Although inert to most reagents, alkanes react readily with Clj or Br2 in the presence of light to give haloalkane substitution products. The reaction occurs by the radical mechanism shown in Figure 10.1 (p. 360) for chlorination. 

Alkane halogenation is a poor method of alkyl halide synthesis because mixtures of products invariably result. Por example, chlorination of methane does not stop cleanly at the monochlorinated stage. Rather, the reaction continues on to give a mixture of dichloro, trichloro, and even tetrachloi products ... 

Williamson ether synthesis Alkyl halides react with sodium or potassium alkoxides or phenox-ides to give ethers. 

Wuftz synthesis Alkyl halides react with sodium in dry ethereal solution to give hydrocarbons. If equimolecular amounts of two different halides are used, then a mixture of three hydrocarbons of the types R — R, R — R and R —R, where R and R represent the original radicals, will be formed. The yields are often poor owing to subsidiary reactions taking place. 

Mixed ethers may be prepared by the interaction of an. alkyl halide and a sodium alkoxide (Williamson s synthesis), for example ... 

The monosubstituted malonic ester still possesses an activated hydrogen atom in its CH group it can be converted into a sodio derivative (the anion is likewise mesomeric) and this caused to react with an alkyl halide to give a C-disubstituted malonic ester. The procedure may accordingly be employed for the synthesis of dialkyImalonic and dialkylacetic acids ... 

Alkylation of Enolates (condensation of enolates with alkyl halides and epoxides) Comprehensive Organic Synthesis 1991, vol. 3, 1. 

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. 

Dehydrogenation of alkanes is not a practical laboratory synthesis for the vast majority of alkenes The principal methods by which alkenes are prepared m the labo ratory are two other (3 eliminations the dehydration of alcohols and the dehydrohalo genation of alkyl halides A discussion of these two methods makes up the remainder of this chapter... 

Section 8 13 When nucleophilic substitution is used for synthesis the competition between substitution and elimination must be favorable However the normal reaction of a secondary alkyl halide with a base as strong or stronger than hydroxide is elimination (E2) Substitution by the Sn2 mechanism predominates only when the base is weaker than hydroxide or the alkyl halide is primary Elimination predominates when tertiary alkyl halides react with any anion... 

Before we describe the applications of organometallic reagents to organic synthesis let us examine their preparation Organolithium compounds and other Group I organometal he compounds are prepared by the reaction of an alkyl halide with the appropriate metal... 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

A reaction useful only with sub strates that do not undergo E2 elimi nation readily It is rarely used for the synthesis of alcohols since alkyl halides are normally prepared from alcohols... 

A long standing method for the preparation of ethers is the Williamson ether synthesis Nucleophilic substitution of an alkyl halide by an alkoxide gives the carbon-oxygen bond of an ether... 

Preparation of ethers by the Williamson ether synthesis is most successful with methyl and primary alkyl halides... 

Both reactants m the Williamson ether synthesis usually originate m alcohol pre cursors Sodium and potassium alkoxides are prepared by reaction of an alcohol with the appropriate metal and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4 7) thionyl chloride (Section 4 13) or phosphorus tri bromide (Section 4 13) Alternatively alkyl p toluenesulfonates may be used m place of alkyl halides alkyl p toluenesulfonates are also prepared from alcohols as their imme diate precursors (Section 8 14)... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

The acetoacetic ester synthesis brings about the overall transformation of an alkyl halide to an alkyl derivative of acetone... 

We see that a secondary alkyl halide is needed as the alkylating agent The anion of diethyl malonate is a weaker base than ethoxide ion and reacts with secondary alkyl halides by substitution rather than elimination Thus the synthesis of 3 methylpentanoic acid begins with the alkylation of the anion of diethyl mal onate by 2 bromobutane... 

Section 21 6 The acetoacetic ester synthesis is a procedure in which ethyl acetoac etate is alkylated with an alkyl halide as the first step in the preparation... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

Although this reaction is useful for preparing a ammo acids (Table 22 3 fifth entry) it IS not a general method for the synthesis of amines Its major limitation is that the expected primary amine product is itself a nucleophile and competes with ammonia for the alkyl halide... 

A method that achieves the same end result as that desired by alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis Alkyl halides are converted to primary alkylamines without contam mation by secondary or tertiary amines The key reagent is the potassium salt of phthal imide prepared by the reaction... 

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