Primary alkyl

Although the yields are often poor, especially for halides other than primary alkyl halides, it remains a valuable method for synthesizing unsymmetrical ethers. 

Place a mixture of 0-5 g. of finely powdered thiourea, 0-5 g. of the alkyl halide and 5 ml. of alcohol in a test-tube or small flask equipped with a reflux condenser. Reflux the mixture for a j)eriod depending upon the nature of the halide primary alkyl bromides and iodides, 10-20 minutes (according to the molecular weight) secondary alkyl bromides or iodides, 2-3 hours alkyl chlorides, 3-5 hours polymethy lene dibromides or di-iodides, 20-50 minutes. Then add 0 5 g. of picric acid, boil until a clear solution is obtained, and cool. If no precipitate is obtained, add a few drops of water. RecrystaUise the resulting S-alkyl-iso-thiuronium picrate from alcohol. 

Triraethylsilylation of allenyllithium afforded predominantly HCsCCH2SiMe3, while in the cases of the homologues of allene (R = CH3 or primary alkyl) 10-20% contamination by RCsCCHjSiMe3, probably formed by trimethylsilylation of RC(Li )=C=CH2, was present. 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. /i-Hectane for example, has been made by this method in 60%... 

Ethyl (CH3CH2—) heptyl [CH3(CH2)5CH2—] and octadecyl [CH3(CH2)i6CH2—] are examples of primary alkyl groups... 

Those derived from isobutane are the 2 methylpropyl (isobutyl) group and the 1 1 dimethylethyl (tert butyl) group Isobutyl is a primary alkyl group because its poten tial point of attachment is to a primary carbon tert Butyl is a tertiary alkyl group because Its potential point of attachment is to a tertiary carbon... 

Alcohols and alkyl halides are classified as primary secondary or tertiary according to the degree of substitution of the carbon that bears the functional group (Section 2 13) Thus primary alcohols and primary alkyl halides are compounds of the type RCH2G (where G is the functional group) secondary alcohols and secondary alkyl halides are compounds of the type R2CHG and tertiary alcohols and tertiary alkyl halides are com pounds of the type R3CG... 

Primary alkyl halide slowest rate of El elimination... 

Addition of a bromine atom to C 2 gives a primary alkyl radical... 

Compound A (C7Hi5Br) is not a primary alkyl bromide It yields a single alkene (compound B) on being heated with sodium ethoxide in ethanol Hydrogenation of compound B yields 2 4 dimethylpentane Identify compounds A and B... 

Effect of Chain Branching on Reactivity of Primary Alkyl Bromides Toward Substitution Under Sn2 Conditions ... 

As crowding at the carbon that bears the leaving group decreases the rate of nude ophilic attack by the Lewis base increases A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to pre dominate and primary alkyl halides react with alkoxide bases by an 8 2 mechanism m preference to E2... 

As a practical matter elimination can always be made to occur quantitatively Strong bases especially bulky ones such as tert butoxide ion react even with primary alkyl halides by an E2 process at elevated temperatures The more difficult task is to find condifions fhaf promofe subsfifufion In general fhe besf approach is fo choose condi lions lhal favor fhe 8 2 mechanism—an unhindered subslrale a good nucleophile lhal IS nol slrongly basic and fhe lowesl praclical lemperalure consislenl wilh reasonable reaclion rales... 

Rate IS governed by stability of car bocation that is formed in loniza tion step Tertiary alkyl halides can react only by the SnI mechanism they never react by the Sn2 mecha nism (Section 8 9) Rate IS governed by steric effects (crowding in transition state) Methyl and primary alkyl halides can react only by the Sn2 mecha nism they never react by the SnI mechanism (Section 8 6)... 

Anions of acetylene and terminal alkynes are nucleophilic and react with methyl and primary alkyl halides to form carbon-carbon bonds by nucleophilic substitution Some useful applications of this reaction will be discussed m the following section... 

The major limitation to this reaction is that synthetically acceptable yields are obtained only with methyl halides and primary alkyl halides Acetylide anions are very basic much more basic than hydroxide for example and react with secondary and ter tiary alkyl halides by elimination... 

The desired 8 2 substitution pathway is observed only with methyl and primary alkyl halides... 

One drawback to Fnedel-Crafts alkylation is that rearrangements can occur espe cially when primary alkyl halides are used For example Friedel-Crafts alkylation of benzene with isobutyl chloride (a primary alkyl halide) yields only tert butylbenzene... 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Friedel-Crafts acylation followed by Clemmensen or Wolff-Kishner reduction is a standard sequence used to introduce a primary alkyl group onto an aromatic ring... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

Rearrangement is especially prevalent with primary alkyl halides of the type RCH2CH2X and R2CHCH2X Aluminum chloride induces ionization with rearrangement to give a more stable carbocation Benzylic halides and acyl halides do not rearrange... 

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... 

Methyl and primary alkyl halides especially iodides work best Elimination becomes a problem with secondary and tertiary alkyl halides... 

Lithium diarylcuprates are prepared m the same way as lithium dialkylcuprates and undergo comparable reactions with primary alkyl halides... 

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... 

Tertiary alkyl > secondary alkyl > primary alkyl > methyl... 

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... 

Because fhe new carbon-carbon bond is formed by an 8 2 lype reaction fhe alkyl halide musl nol be slerically hindered Melhyl and primary alkyl halides work besl secondary alkyl halides give lower yields Tertiary alkyl halides fail reacting only by elimination nol subslilulion... 

Phthalimide with a of 8 3 can be quantitatively converted to its potassium salt with potassium hydroxide The potassium salt of phthalimide has a negatively charged nitrogen atom which acts as a nucleophile toward primary alkyl halides m a bimolecu lar nucleophilic substitution (Sn2) process... 

Nucleophilic substitution results when primary alkyl halides are treated with amines... 

Infrared The absorptions of interest m the IR spectra of amines are those associated with N—H vibrations Primary alkyl and arylammes exhibit two peaks m the range 3000-3500 cm which are due to symmetric and antisymmetric N—H stretching modes... 

The alkyl halide must be one that reacts readily by an 8 2 mechanism Thus methyl and primary alkyl halides are the most effective alkylating agents Elimination competes with substitution when secondary alkyl halides are used and is the only reac tion observed with tertiary alkyl halides... 

Potential energy diagram (Section 4 8) Plot of potential en ergy versus some arbitrary measure of the degree to which a reaction has proceeded (the reaction coordinate) The point of maximum potential energy is the transition state Primary alkyl group (Section 2 13) Structural unit of the type RCH2— in which the point of attachment is to a pnmary carbon... 

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