1,2-Dihaloalkanes

Just as It IS possible to prepare alkenes by dehydrohalogenation of alkyl halides so may alkynes be prepared by a double dehydrohalogenation of dihaloalkanes The dihalide may be a geminal dihalide, one m which both halogens are on the same carbon or it may be a vicinal dihalide, one m which the halogens are on adjacent carbons... 

The malonic ester synthesis has been adapted to the preparation of cyclo alkanecarboxyhc acids from dihaloalkanes... 

Each of the following dihaloalkanes gives an N (haloalkyl)phthahmide on reaction with one equivalent of the potassium salt of phthalimide Write the structure of the phthahmide denvative formed m each case and explain the basis for your answer... 

In view of the ready availabiUty of optically pure lactic acid derivatives this reaction offers an attractive general method for the preparation of optically pure aromatic ester derivatives (41). Stereoselective alkylation (15—60% inversion) of ben2ene with optically active 1,2- 1,3- and 1,5-dihaloalkanes was also reported (42). 

Pyrrohdines also can be obtained by reaction of 1,4-dihydroxyaLkanes with amines in the presence of dehydrating agents at elevated temperatures or by reaction of primary amines with 1,4-dihaloaLkanes. The dry distillation of 1,4-butanediamine dihydrochloride also generates pyrrohdine. Pyrroles can also be catalyticahy hydrogenated to pyrrohdines. 

This reaction gives fair-to-good yields of monoorganotin tribromides and trichlorides when quaternary ammonium or phosphonium catalysts are used (149). Better yields are obtained with organic bromides and staimous bromide than with the chlorides. This reaction is also catalyzed by tri alkyl antimony compounds at 100—160°C, bromides are more reactive than chlorides in this preparation (150,151). a,C0-Dihaloalkanes also react in good yield giving CO-haloalkyltin trihaHdes when catalyzed by organoantimony compounds (152). 

PERKIN Carboxylic Acid (Ester) Synthesis Synthesis of cycloalkane cartxixylic acids Irom o,ci>-dihaloalkanes and diethyl sodiummalonate. 

The second approach is the synthesis of a suitable functionalized thiazitidine followed by constructing the quinoline ring. Thus, cyclization of 44 with a dihaloalkane gave 45 which upon cyclization afforded 26 and 27 (92JMC4727) (Scheme 8). 

The common route for the synthesis of medium-size ring sulfoxides and sulfones is oxidation of the corresponding cyclic sulfides70, which are obtained from the interaction of a, w-dihaloalkanes with sulfide ion in fair to good yields243 (equation 110). 

This reaction is illustrative of a general procedure for the alkylation of active methylene functions in the presence of concentrated aqueous alkali catalyzed by tetraalkylammonium salts. This catalytic method has been used to alkylate arylacetonitriles with monohaloalkanes,2 dihaloalkanes,3 a-chloroethers,4 chloronitriles,.5 haloacetic acid esters,6 and halonitro aromatic compounds.7 It has also been used to alkylate ketones,8 lf/ indene,9 9i/-fluorene,ll) and the Reissert compound.11 The reaction is inhibited by alcohols and by iodide ion.2... 

Reaction between Alkali Metal Carboxylates and Dihaloalkanes... 

The first reported electroorganic synthesis of a sizeable amount of material at a modified electrode, in 1982, was the reduction of 1,2-dihaloalkanes at p-nitrostyrene coated platinum electrodes to give alkenes. The preparation of stilbene was conducted on a 20 pmol scale with reported turnover numbers approaching 1 x 10. The idea of mediated electrochemistry has more frequently been pursued for inorganic electrode reactions, notably the reduction of oxygen which is of eminent importance for fuel cell cathodes Almost 20 contributions on oxygen reduction at modified... 

Thermolysis of the dicarbamic acid silyl ester (CH2 N[SiMe3]C02SiMe3)2) gives the 1,3-diazetane derivative 26 <96JOM93>. Alkylation of the 1,3-dithietane tetraoxide 27 with a,co-dihaloalkanes yields the dispiro compounds 28 (n = 1-4) <95ZOR589>. The first 1,2-dithiete S-oxide 29 is reported <95TL8583>. 

Attempts to exploit the reaction of the dianion with alkyl halides to produce a c/.v-dialkyl complex by using 1,2- or 1,3-dihaloalkanes did not indeed give this result. The reaction of Ru(Por) " with 1,2-dibromoethane was sucessful, but the resulting metallacyclopropane product is better formulated as a /r-complex of ethene, and will be discussed below in the section on alkenc and alkyne complexes. The corresponding reaction of the diiinion with 1,3-dichloropropane gave no evidence for a metallacyclobutane. but instead free cyclopropane was detected by GC analysis and the porphyrin product was Ru(TTP)(THF)2. ... 

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. 

Guengerich FP, Hogy LL, Inskeep PB, et al. 1986. Metabolism and covalent binding of vic-dihaloalkanes, vinyl halides and acrylonitrile. IARC Sci Publ 70 255-260. 

Insertion of germanium into the a, oj-dihaloalkanes and chloromethyl-silanes provides useful germanium halogen derivatives254 ... 

On the other hand, SnX2 easily reacts with a, >-dihaloalkanes affording oj-haloalkyltin trichlorides, provided R3Sb is used as a catalyst322 ... 

Gusarova, N.K., Shaikhudinova, S.I., Dmitriev, V.I., Malysheva, S.F., Arbuzova, S.N., and Trofimov, B.A., Reaction of red phosphorus with electrophiles in superbasic systems. VII. Phospholanes and phosphorinanes from red phosphorus and a,co-dihaloalkanes in a single preparative step, Zhur. Obshch. Khim., 65, 1096, 1995. 

Several syntheses of l,3-dioxoperhydropyrrolo[l,2-c]imidazoles have been developed using different strategies. a-Substituted bicyclic proline hydantoins were prepared by alkylation of aldimines 135 of resin-bound amino acids with a,tu-dihaloalkanes and intramolecular displacement of the halide to generate cr-substituted prolines 136 and homologs (Scheme 18). After formation of resin-bound ureas 137 by reaction of these sterically hindered secondary amines with isocyanates, base-catalyzed cyclization/cleavage yielded the desired hydantoin products <2005TL3131>. 

H202 (30%, 6 ml) is added with stirring to the alkene (50 mmol) and TEBA-Cl (0.1 g, 0.44 mmol) in CC14 (10 ml) and CaCl2 or CaBr2 (50 mmol) in cone. HC1 or HBr (10 ml) at 0°C. The mixture js allowed to come to room temperature and is stirred for a further 20 min. Petroleum ether (50 ml) is added and the mixture is washed well with H20. The dried (Na2S04) organic phase is evaporated to yield the dihaloalkane. 

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... 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

Method A The gem-dihaloalkane (0.02 mol) and the thiol (0.04 mol) in PhMe (25 ml) containing Aliquat (20 mg, 0.05 mmol) are added to dry K2CO, (10 g). The mixture is stirred for 8 h at room temperature and then filtered. The filtrate is fractionally distilled under reduced pressure to yield the thioacetal. 

The conversion of S-alkyl isothiouronium salts into thioethers is aided by the addition of a phase-transfer catalyst (4.1.4.E) [30]. Similarly, a,co-dihaloalkanes are converted in a one-pot reaction into bis-sulphides (> 90%) via the isothiouronium salts (Scheme 4.3) [31]. 

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. 

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