Sulphides disconnection

Retrosynthetic C—S disconnection reveals two possible routes to dialkyl sulphides. 

Chloroacetone is also a recognisable reagent equivalent following disconnection of 2,4-dimethylthiazole (60) the reagent equivalent of the other synthon is thioacetamide, which is formed in situ from acetamide and phosphorus penta-sulphide (Expt 8.20). 

Preparation of Sodium Sulphide. Assemble an apparatus as shown in Fig. 67. Put 0.2 g of finely triturated highly pure sulphur into test tube 1 with a ground-glass joint, and lower the tube into a beaker with a mixture of dry ice and acetone. Connect a source of dry ammonia (see Fig. 62a) to cock 3 of the apparatus, open cock 4, and fill the apparatus with ammonia. Put 2 g of metallic sodium thoroughly purified of oxide films and washed with benzene and diethyl ether onto filter 2. Pass ammonia through the apparatus until test tube 1 is filled with liquid ammonia up to one-third of its volume, after which disconnect the apparatus for preparing ammonia. 

We started with aromatic compounds because the position of disconnection needed no decision. We continue with ethers, amides, and sulphides because the position of disconnection is again easily decided we disconnect a bond joining carbon to the heteroatom (X). This approach is fundamental to synthetic design and is a one-group disconnection since we need to recognise only one functional group to know that we can make the disconnection. The label C-X or C-N etc. can be used. 

The synthesis of amines warrants a separate chapter because the C-X disconnection (la) used for ethers, sulphides, and the like is not satisfactory. The problem is that the product (1) of the reaction is at least as reactive as the starting material (2) (if not more so because of the inductive effect of the methyl group) and reacts further to give (3) and even (4). 

Tactics for the synthesis of five-membered heterocycles are to disconnect both C-X bonds and to identify the electrophilic carbon fragment needed to add to the nucleophilic heteroatom. Cyclic sulphide (20) requires m-dihalide... 

This same disconnection of a carbon atom is also helpful for epoxides (11) without carbonyl substituents. The reagent should be a nucleophilic carbene equivalent and a sulphur ylid (12) is the answer.These can be made from the sulphide (13) by a similar process to phosphorus ylid synthesis (Chapter 15), though the reactions of the two ylids with carbonyl compounds are significantly different (there is a third type of reaction with the ylid CH2N2 in Chapter 31). 

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