Preparation of intermediates

The two intermediates of commercial furan resins are furfural and fiirfuryl alcohol. Furfural occurs in the free state in many plants but is obtained commercially by degradation of hemicellulose constituents present in these plants. There are a number of cheap sources of furfural, and theoretical yields of over 20% (on a dry basis) may be obtained from both com cobs and oat husks. In practice yields of slightly more than half these theoretical figures may be obtained. In the USA furfural is produced in large quantities by digestion of com cobs with steam and sulphuric acid. The furfural is removed by steam distillation. 

Furfural is a colourless liquid which darkens in air and has a boiling point of 161.7°C at atmospheric pressure. Its principal uses are as a selective solvent used in such operations as the purification of wood resin and in the extraction of butadiene from other refinery gases. It is also used in the manufacture of phenol-furfural resins and as a raw material for the nylons. The material will resinify in the presence of acids but the product has little commercial value. 

---

Preparation of Intermediate Compound N-Acetyl-5-Chloro-2-Methylaniline To a well-stirred mixture of 1,270 g (9 mols) of 5-chloro-2-methylaniline in 7.5 liters of water at 34°C was added all at once 1,710 ml (18 mols) of acetic anhydride. A solution was obtained and then almost immediately the product started to crystallize. The temperature rose to 60°C. The mixture was stirred until the temperature dropped to 30°C. The product was filtered and washed well with water. Yield 97% (1,640 g), MP 134° to 138°C. Product was air dried and then in vacuum over PjOs. 

Preparation of Intermediate Compound 4-Chloro-5-Sulfamyl-N-Acetylanthranilic Acid To a hot solution (80°C) of 366 g (1.482 mols) of magnesium sulfate (Epsom salts) in 2.8 liters of water was added 130 g (0.495 mol) of powdered 5-chloro-2-methyl-4-sulfamyl-acetanilide. With stirring and maintaining the temperature at 83°C, 234 g (1.482 mols) of potassium permanganate was added portionwise over a period of 2 hours. The mixture was then kept at 85°C with stirring for an additional 3 hours. By this time the pink color of the permanganate had been discharged. 

Preparation of Intermediate Compound 2-Methyl-3-o-Tolyl-6-Sulfamyl-7-Chloro-4(3H)-Quinazoiinone Set up a 5-liter 3-necked flask fitted with a stirrer, condenser and a drying tube. To a stirred mixture of 100 g (0.342 mol) of powdered 4-chloro-5-sulfamyl-N-acetylanthranilic acid, 40.2 g (0.376 mol) of o-toluidine and 2.0 liters of dry toluene was added dropwise, over a period of 15 minutes, 21.7 ml (34.1 g) (0.248 mol) of phosphorus trichloride. The mixture was then refluxed for 10 hours. The solid turned somewhat gummy towards the latter part of the first hour. The mixture then became more free flowing as heating was continued. Let stand overnight. The yellow solid was filtered, washed with toluene and dried. The toluene filtrate was discarded. The dried solid was triturated with 1.5 liters of 10% sodium bicarbonate, filtered and the cake washed with water. The filtrate on acidification yielded 11.5 g of the starting acid. The damp product was dissolved in 4,5 liters of 95% ethanol and the solution treated with charcoal and filtered. On cooling filtrate yielded 69.5 g (55.5%) of the title compound, MP 271.5° to 274°C. 

The synthetic challenge is now reduced to the preparation of intermediates 2-4. Although intermediates 3 and 4 could potentially be derived in short order from very simple precursors (see Scheme 4), intermediate 2 is rather complex, particularly with respect to stereochemistry. Through a short sequence of conventional functional group manipulations, it is conceivable that aldehyde 2 could be derived from intermediate 9. Hydrolysis and keta-lization reactions could then permit the formation of 9 from intermediate 11, the cyclic hemiaminal of the highly stereo-defined acyclic molecule, intermediate 12. 

Preparation of intermediate 5 was low yielding, required harsh reaction conditions and the carcinogenic reagent MOM-C1. 

The preparation of intermediate dialkylaminophosphines from the controlled reactions of dialkylaminochlorophosphines with organometallic reagents, and the subsequent reaction of these intermediates with hydrogen chloride, continues to be used as a route to less accessible halogenophosphines. Among compounds recently prepared by this route are (94) 52 and (95). 153 A series of new silylaminohalogenophosphines, e,g. (96), has been prepared... 

Thermal stability of the rotanes has been mentioned in most if not all of the above papers 25 30). But note that none of them mention acid-catalyzed rearrangements of rotanes. The preparation of intermediates for such a process is first mentioned for the eventual possibility of obtaining the compound called [6.4] coronane 8733 . 

Economic and safety considerations encourage minimal stockpiling of chemicals and avoiding transportation of hazardous substances. These increasing demands offer many opportunities for microwave chemistry in the development of environmentally benign methods for the preparation of intermediates, specialty chemicals and pharmaceuticals [6[. It appears likely that within the next few years, individual chemical reactors will be required for diverse tasks and will need to be easily relocated... 

When large rings are constructed by RCM, 2JE- somer c mixtures can result. Hence RCM-based macrocyclizations are best suited for the preparation of intermediates in which the C-C double bond formed by metathesis can be removed (by, e.g., hydrogenation or oxidation) at a later stage of the synthesis. 

Scheme 6. Preparation of intermediate in Stork et al. stereoselective synthesis of quinine. Conditions (i) (a) Et2NH, AlMe3, (b) TBS-Cl, Imidazole, DMF (ii) LDA, -78°C, ICH2CH2OTBDPS (iii) PPTS (0.3 eqiv.), EtOH, 12 h, then xylenes, reflux 8-10 h. (iv) (a) DIBAL-H, -78°C, (b) PhjP = CHOMe (v) PhjP, DEAD, (PhOtjPlOlNj (vi) 5N HCl, THE, CH2CI2...

In the synthesis of the alkaloid gephyrotoxin, L-pyroglutamic acid was used as a starting material for the preparation of intermediate 85 (81TL4197). A related pyrrolooxazine 86 was also obtained from pyroglu-tamic acid after A-substitution and ring closure in the presence of silica... 

References in parentheses refer to the preparation of intermediates or to older methods. Assuming that the acetamido compound is prepared via Beckmann rearrangement from 2-acetyldibenzothiophene. s... 

Figure 9. Preparation of intermediate 22 containing the B ring of the sesbanimides.

The preparation of intermediate petrochemical streams requires different processing alternatives depending on the feedstock quality. In our classification of petrochemical feedstocks we closely follow that of Gary and Handwerk (1994) consisting of aromatics, olefins, and parafftn/cyclo-parafftn compounds. The classification of petrochemical feedstocks into these clusters helps to identify the different sources in the refinery that provide suitable feedstock and, therefore, to better recognize areas of synergy between the refinery and petrochemical systems. 

Problem 18.51 Use o- or p-nitroethylbenzene and any inorganic reagents to synthesize the six isomeric dichloroethylbenzenes. Do not repeat preparations of intermediate products. <... 

In addition to its uses in the preparation of intermediates for a large variety of petrochemical reactions, elhylene is used as an anesthetic, as a fuel with oxygen for high-temperature flames, and as a coloring... 

These zeolites are active and selective catalysts for the preparation of intermediates in the manufacturing of dihydropyridines. 

---