Alkyl halides—continued

Representative Functional Group Transformations by Nucleophilic Substitution Reactions of Alkyl Halides (Continued)... 

The lUPAC rules permit alkyl halides to be named m two different ways called func twnal class nomenclature and substitutive nomenclature In functional class nomencla ture the alkyl group and the halide (fluoride chloride bromide or iodide) are desig nated as separate words The alkyl group is named on the basis of its longest continuous chain beginning at the carbon to which the halogen is attached... 

Recall from Section 5.3 that radical substitution reactions require three kinds of steps initiation, propagation, and termination. Once an initiation step has started the process by producing radicals, the reaction continues in a self-sustaining cycle. The cycle requires two repeating propagation steps in which a radical, the halogen, and the alkane yield alkyl halide product plus more radical to carry on the chain. The chain is occasionally terminated by the combination of two radicals. 

Although interesting from a mechanistic point of view, alkane halogenation is a poor synthetic method for preparing alkyl halides because mixtures of products invariably result. For example, chlorination of methane does not stop cleanly at the monochlorinated stage but continues to give a mixture of dichloro, trichloro, and even tetrachloro products. 

Methyl-l//-l,5-benzodiazepin-2(3//)-one (17.4g, 0.1 mol) and an alkyl halide (0.1 mol) in benzene (70 mL) was stirred at 50 C and treated with 50% aq NaOII (30 mL, 0.15 mol) and a catalytic amount of TBAB. Stirring at 50CC was continued for 1 h and the mixture was cooled and separated. The organic phase was washed with H20, dried (MgS04) and evaporated under reduced pressure, leaving the product. 

To a solution of the silylated glycinate (50 mmol) in ether (50 ml), cooled to —10 to 0°C, was added a solution of sodium hexamethyldisilazide (55 mmol) in ether (100ml) with stirring. Stirring was continued at ambient temperature for a short time, and then the alkyl halide (50 mmol) was added dropwise. The mixture was heated under reflux for 10-15 h, cooled, filtered, and the product was distilled directly (52-70%). 

B. From Cyano-compounds and Phosphorus(v) Halides.—Continued reports of the reactions of alkyl cyanides with phosphorus pentachloride appear. With dicyanides the formation of phosphazenes occurs via a series of intermediates whose stability varies with the nature of X ... 

Rhodium catalyzed carbonylations of olefins and methanol can be operated in the absence of an alkyl iodide or hydrogen iodide if the carbonylation is operated in the presence of iodide-based ionic liquids. In this chapter, we will describe the historical development of these non-alkyl halide containing processes beginning with the carbonylation of ethylene to propionic acid in which the omission of alkyl hahde led to an improvement in the selectivity. We will further describe extension of the nonalkyl halide based carbonylation to the carbonylation of MeOH (producing acetic acid) in both a batch and continuous mode of operation. In the continuous mode, the best ionic liquids for carbonylation of MeOH were based on pyridinium and polyalkylated pyridinium iodide derivatives. Removing the highly toxic alkyl halide represents safer, potentially lower cost, process with less complex product purification. 

Reactions of 2 with alkyl halides were generally more successful for C-C bond formation. For example, bibenzyl was formed in good yield from the reaction of 2 with benzyl bromide. Dichlorodiphenylmethane and 1 reacted to give tetraphenylethylene in 63% yield. Similarly, diiodomethane reacted with 1 to give ethylene. This area of study is continuing. 

A continuous procedure for the alkylation of mesitylene and anisole with supercritical propene, or propan-2-ol in supercritical carbon dioxide, with a heterogeneous polysiloxane-supported solid acid Deloxan catalyst has been reported giving 100% selectivity for monoalkylation of mesitylene with 50% conversion at 250 °C and 150 bar by propan-2-ol in supercritical carbon dioxide. p-Toluenesulfonic acid monohydrate has been demonstrated as an efficient catalyst for the clean alkylation of aromatics using activated alkyl halides, alkenes or tosylates under mild conditions. Cyclohexene, for example, reacts with toluene to give 100% cyclohexyltoluenes (o m p-29 18 53) under these circumstances. 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

Concurrent with acetic anhydride formation is the reduction of the metal-acyl species selectively to acetaldehyde. Unlike many other soluble metal catalysts (e.g. Co, Ru), no further reduction of the aldehyde to ethanol occurs. The mechanism of acetaldehyde formation in this process is likely identical to the conversion of alkyl halides to aldehydes with one additional carbon catalyzed by palladium (equation 14) (18). This reaction occurs with CO/H2 utilizing Pd(PPh )2Cl2 as a catalyst precursor. The suggested catalytic species is (PPh3)2 Pd(CO) (18). This reaction is likely occurring in the reductive carbonylation of methyl acetate, with methyl iodide (i.e. RX) being continuously generated. 

The distillation is continued till the greater part of the liquid has distilled over, and no oily drops are to be seen in the condenser. The residue consisting of a concentrated solution of phosphorus and phosphoric acids in addition to excess of red phosphorus is discarded. The distillate is shaken up with water to remove alcohol, and then with dilute caustic soda to remove free iodine. Enough alkali must be used to render the lower layer of alkyl halide colourless. The latter is then separated ofl, dried over granular calcium chloride (6 gms.) and distilled. The preparation should be kept in the dark in a well-stoppered bottle. If exposed to light, iodine slowly separates, but may be prevented from so doing by adding a small quantity of colloidal silver to the liquid. 

No reaction of unmilled aluminum powder with alkyl halides was observed during 10 hours of contact. When aluminum was milled with stainless steel balls in a stainless steel pot under helium at room temperature in the presence of butyl iodide for 8 min, an exothermic reaction was initiated and no more activation was required for the continuation of the reaction. 

As already mentioned, once the reaction was initiated by mechanical activation, it continued without additional activation. This phenomenon suggests that the reaction is au-tocatalytic. As known, activators such as iodine and alkylaluminum halide initiate the conventional thermal reaction of aluminum with alkyl halides. In the case discussed, the reaction was initiated by mechanical working without any activator. 

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