Crystalline derivatives preparation esters

Compounds I and II have been obtained in discrete crystalline form but azadirachtin has thus far been obtained only as a white amorphous powder melting at 154-1 58°C., despite several attempts to prepare crystalline derivatives (mainly esters). This is probably due to the presence of different stereoisomers, as Rembold et al. 

B. Boil 2 g of the ester with 30 ml of 10 per cent sodium or potassium hydroxide solution under reflux for at least 1 hour. If the alcohol formed is water (or alkali) soluble, the completion of the hydrolysis will be indicated by the disappearance of the ester layer. Distil off the liquid through the same condenser and collect the first 3-5 ml of distillate. If a distinct layer separates on standing (or upon saturation of half the distillate with potassium carbonate), remove this layer with a capillary dropper, dry it with a little anhydrous potassium carbonate or anhydrous calcium sulphate and determine the b.p. by the Siwoloboff method (Section 2.34). Whether an insoluble alcohol separates out or not, prepare a crystalline derivative (e.g. the 3,5-dinitrobenzoate, Section 9.6.4, p. 1241) and determine its m.p. 

Reliable information relating to a ketose of formula I came first from the research of Ohle and Just.8 They prepared the first crystalline derivatives of D-psicose, namely l,2-isopropylidene-3,4-anhydro-D-psicose (V), and some of its esters by means of a Walden inversion in the detosyla-tion of 3-tosyl-l,2-isopropylidene- a -D-fructose (IV).12 Attempts to... 

G) Identification of Monohydroxy Compounds. The evolution of hydrogen chloride, when acetyl chloride or phosphorus trichloride is added to a compound, indicates the possible presence of a hydroxy group. For identification purposes a derivative should be prepared. 3, 5-Dinitrobenzoic acid forms crystalline derivatives with hydroxy compounds. The melting points of the esters are utilized for identification. 

The p-phenylbenzoate ester was prepared to protect the hydroxyl group of a prostaglandin intermediate by reaction with the benzoyl chloride (Pyr, 25°, 1 h, 97% yield). It was a more crystalline, more readily separated derivative than 15 other esters that were investigated. It can be cleaved with K2CO3 in MeOH in the presence of a lactone. ... 

In addition to these physical studies at the Bureau, Tipson was able to return to his synthetic interests, both alone and in collaboration with other staff members. He was especially pleased to prepare D-talose in crystalline form, an accomplishment that had eluded Emil Fischer. Pursuing his longstanding interest in the reaction of sulfonic esters with iodide and following an earlier observation that the tetratosyl ester of erythritol is converted into butadiene by the action of sodium iodide and zinc, he demonstrated (with A. Cohen) that nonterminal unsaturation may be conveniently introduced into alditol derivatives by reaction of contiguous secondary sulfonates with sodium iodide and zinc dust in boiling A.A-dimethylformamide. This Tipson-Cohen reaction subsequently proved of great utility in other hands for the conversion of more complex carbohydrate structures into vicinal dideoxy derivatives. 

A potential way to avoid the formation of undesired side products, like in 7.2., is the use of such boron compounds that have only one transferable group. In most cases boronic acids are the compounds of choice, as they are easy to prepare, insensitive to moisture and air, and usually form crystalline solids. In certain cases, however the transmetalation of the heteroaryl group might be hindered by the formation of stable hydrogen bonded complexes. In such cases the use of a boronate ester, such as in equation 7.4., provides better yields. For example pyridine-2-boronic acid dimethylester coupled readily with a bromoquinoline derivative under conditions similar to 7.3. (potassium hydroxide was used as base and tetrabutylammonium bromide as phase transfer catalyst).6... 

The ester models, as stated above, were all LC, but two of the ether model compounds, the methoxy- and ethoxy-substituted derivatives, were not, despite the fact that each of these mesogens yielded some liquid-crystallinity in the poly(ether) form. Therefore it seems that the polymers in this system tend to be "more liquid crystalline" than the related small molecules. This hypothesis is supported by the fact that Memeger(H) found liquid crystallinity in allhydrocarbon polymers incorporating the distyrylbenzene mesogen, even in cases where the cis/trans ratio of the unsaturations was as large as 0.3, while Campbell and McDonald (10) noted that iodine isomerization to the all-trans form was essential for the observation of an LC phase in the small-molecule derivatives which they prepared. 

The Pasteur method can also be applied to the resolution of neutral racemates, if these can be first converted into an acidic or basic derivative from which eventually a mixture of crystalline diastereoisomeric salts may be prepared by appropriate neutralisation. Thus, a racemic alcohol (e.g. ( )-octan-2-ol, Expt 5.220) may be converted into the corresponding racemic hydrogen phthalate ester by heating with phthalic anhydride, and the ester is then resolved by the Pasteur procedure using an optically active base. The resulting optically active hydrogen phthalate ester is then carefully hydrolysed with aqueous sodium hydroxide to regenerate one of the optically active forms of the alcohol. 

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