Haloalkane 1,3-dihaloalkane

Janssen DB, D Jager, B Witholt (1987) Degradation of -haloalkanes and a,co-dihaloalkanes by wild-type and mutants of Acinetobacter sp. strain GJ70. Appl Environ Microbiol 53 561-566. 

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

The dihaloalkane (10 mmol) is added to thiourea (20 mmol) in EtOH (25 ml) over 10 min and then stirred under reflux for ca. 3 h. The EtOH is removed under reduced pressure and aqueous NaOH (20%, 30 ml), TEBA-CI (0. II g, 0.5 mmol), and the haloalkane (20 mmol) is added. The mixture is heated at 60°C for ca. 1.5 h and then cooled, filtered, and acidified to pH 2.0 with aqueous HC1 (6M) to yield the bis-sulphide. 

Method A. (liquid liquid conditions) The haloalkane (0.1 mol), or dihaloalkane... 

Method B. (solid.-liquid conditions) Finely ground KCN (1.95 g, 30 mmol) is shaken with H20 (0.54 g), the haloalkane (20 mmol), or dihaloalkane (10 mmol), and Aliquat (0.22 g, 0.4 mmol) for 5 min at room temperature. The mixture is stirred for a further period (Table 6.1) and Et20 (50 ml) is then added. The mixture is filtered through Florosil and evaporated to yield the nitrile (>90%). 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

Janssen, D.B., Jager, D., and Wilholt, B. Degradation of u-haloalkanes and a,(o-dihaloalkanes by wild type and mutants of Aclnetobactersp. sttain GJ70, Appl. Environ. Microbiol, 53(3) 561-566, 1987. 

An alternative approach to the reaction conditions described above employs microwave irradiation for the quaternization reaction of 1-methylimidazole with various haloalkanes and l,reaction times (minutes instead of hours) and scaling up this technology to an industrial scale can easily be achieved. 

Except for the dihaloalkanes (see above), 3-heterosubstituted 1-haloalkanes yield the corresponding organomagnesium-halide reagents in a normal fashion ... 

Alkylation of arylacetonitriles proceeds efficiently with a variety of substituted haloalkanes such as haloethers, esters, and nitriles of haloalkanoic acids, haloamines, etc. The reaction with dihaloalkanes can give cyclic and chain products ... 

There are practically no limitations concerning haloalkane structure mono-and dihaloalkanes, esters of haloacetic acids, halonitriles, haloalkylamines, a-chloroethers, etc., can be used. 

Gandelman and co-workers have reported the synthesis of secondary alkyl fluorides using a Suzuki-Miyaura cross-coupling of 1-halo-l-fluoroal-kanes (Scheme 13.19). Geminal dihaloalkanes were used as starting materials and the report demonstrated that these simple 1-fluoro-l-haloalkanes... 

As discussed in Section 11-6, alkenes can be prepared by E2 reactions of haloalkanes. Application of this principle to alkyne synthesis suggests that treatment of vicinal dihaloalkanes with two equivalents of strong base should result in double elimination to furnish a triple bond. 

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