Alkyl halides tests

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. 

For details of test, see under Alkyl Halides, Section III,42,(ii). 

One of the fundamental questions about the mechanism is whether the radical is really free in the sense of diffusing from the metal surface.7 For alkyl halides, there is considerable evidence that the radicals behave similarly to alkyl free radicals.8 One test for the involvement of radical intermediates is to determine whether cyclization occurs in the 6-hexenyl system, where radical cyclization is rapid (see Part A, Section 12.2.2). 

Normally the reaction Is useful for the conversion of alkyl halides to primary amines without concomitant formation of secondary amines.29 Treatment of polymer 17 with hexamethylenetetramine in a mixture of ethanol/THF afforded an insoluble resin. Using diazabicyclooctane (DABCO), we demonstrated that the reaction could be limited to attack by a single nitrogen in a multifunctional amine, so we did not anticipate crosslinking via bis-quat salt formation. Hydrolysis of 2 with anhydrous HC1 in ethanol generated free amino groups as evidenced by a positive ninhydrin test, but quantitative hydrolysis could not be achieved and the product remained insoluble. One would have expected a simple bis-quat to hydrolyse and open the crosslinked structure. 

Further experimental studies involved the determination of the rate constant of the reaction of several alkyl halides with a series of electrochemically generated anion radicals so as to construct activation driving force plots.39,40,179 Such plots were later used to test the theory of dissociative electron transfer (Section 2),22,49 assuming, in view of the stereochemical data,178 that the Sn2 pathway may be neglected before the ET pathway in their competition for controlling the kinetics of the reaction. 

Alkyl halides, alkyl sulfonates and other alkylating agents have also been subject to scmtiny in spheres other than pharmaceuticals, such as in environmental analysis. Various approaches have included two-step SPE, derivatisation with trifluoroacetic anhydride followed by GC/MS (for cyclophosphamide and its analogues in sewage water) SPE on surface water to isolate the antineoplastic agents carmustine, chlorambucil, cyclophosphamide and melphalan for LC-UV and LC-fluorescence measurements and derivatisation of alkyl halides and epoxides with 4-nitrothiophenol followed by HPLC-UV detection (claimed to be better than NBP derivatisation). A patent exists for a field test kit for mustard gases in military use based on NBP derivatisation. 

Alkylation of Alkali Metal Cyanides by Alkyl Halides Activated in the a-Posi-tion by a Double Bond. When a mixture consisting of 4 to 8 moles of an alkyl halide activated in the apposition by a double bond is heated with 1 mole of alkali metal ferrocyanide, several alkylation products of the ferrocyanide anion can be isolated from the reaction mixture (12). The relative proportions of the tetra-, penta-, and hexaalkylated complexes can be varied by varying the alkyl halide to ferrocyanide ratio and the time of reaction. When potassium ferrocyanide is alkylated with benzyl bromide at a ratio of 4 alkyl halides to ferrocyanide anion, short reaction times favor the tetraalkylated complex an 8 to 1 ratio and long reaction times favor the hexaalkylated complex of the alkylating agents tested benzyl bromide provided the fastest alkylation ... 

Alkyl halides are often used as substrates instead of alcohols. In such cases the salt of the inorganic acid is usually used and the mechanism is nucleophilic substitution at the carbon atom. An important example is the treatment of alkyl halides with silver nitrate to form alkyl nitrates. This is used as a test for alkyl halides. In some cases there is competition from the central atom. Thus nitrite ion is an ambident nucleophile that can give nitrites or nitro compounds (see 0-60).731 Dialkyl or aryl alkyl ethers can be cleaved with anhydrous sulfonic acids.732... 

Heavy-metal salts, particularly those of silver, mercury, and copper, catalyze SX1 reactions of alkyl halides in much the same way that acids catalyze the SN reactions of alcohols. A heavy-metal ion functions by com-plexing with the unshared electrons of the halide, thereby making the leaving group a metal halide rather than a halide ion. This acceleration of the rates of halide reactions is the basis for a qualitative test for alkyl halides with silver nitrate in ethanol solution ... 

Reaction with ethanolic potassium hydroxide. Boil 0.5 ml of the compound with 4 ml of 0.5 m ethanolic potassium hydroxide under reflux for 15 minutes. Most alkyl halides and benzyl halides give a crystalline precipitate of the potassium halide. Dilute with 5 ml of water, acidify with dilute nitric acid and test with silver nitrate solution. 

A characteristic feature of this solid-phase amino acid synthesis is the use of the phosphazene bases 53 and 54 for the PTC alkylation reaction [64, 65]. Because these compounds, which are soluble in organic media, do not react with alkyl halides, both alkyl halide and phosphazene bases can be added together at the start of the reaction, which is useful practically [65], Cinchonine and cinchonidine-derived salts, e.g. 25, were found to be very efficient catalysts. Under optimum conditions the alkylation proceeds with enantioselectivity in the range 51-99% ee, depending on the alkyl halide component [65], Seventeen different alkyl halides were tested. After subsequent hydrolysis with trifluoroacetic acid the corresponding free amino acids were obtained in high yield (often >90%). 

Silver nitrate test The compound to be tested is treated with a few drops of 1% alcoholic silver nitrate. A white precipitate indicates a positive reaction. This could be due to either silver chloride (reaction with a reactive alkyl halide), silver alkynide (reaction with a terminal alkyne), or the silver salt of a carboxylic acid (reaction with a carboxylic acid). 

Other C-electrophiles besides iminium salts and carbonyl compounds have not yet extensively been tested for C-C-forming cyclopropane ring cleavage. However, whereas acyl or tertiary alkyl halides do not give addition products, benzaldimine at least provides the expected secondary amine 194 with good yield and diasteroselectivity 61). 

The reaction of a compound with silver nitrate in ethanol is used as a chemical test to determine if the compound is an alkyl halide. The formation of a precipitate of the silver halide constitutes a positive test. 

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