Synthesis example

Synthesis of lrJr3-trimcthylspiro[indolinc-2r5 -[3// naphth[2,l l ][l,4 oxazinc (compound 1) 

Compound 1 was prepared by reacting l-nitroso-2-naphthol (18 g) in MeOH (200 ml) under reflux with solution of l,3,3-trimethyl-2-methyleneindoline (17 g) in 

MeOH (50 ml) which was added over a period of 10 min. After refluxing for 1 h, the reaction mixture was cooled. A brown solid precipitated, which was filtered and washed with plenty of methanol and which yielded 15 g of product. The product was purified by repeated charcoal treatment and recrystallization from acetone, mp 124- 125°C. 

Method A. A solution of 86.5 g (0.5 mol) of l-nitroso-2- naphthol in 650 ml of methanol was heated to reflux and treated in one portion with a solution of 173 g (1.0 mol) of l,3,3-trimethyl-2-methyleneindoline in 100 ml of methanol. The resulting solution was heated under reflux for 10 min and then treated over the course of 1 min with a solution of 86.5 g (0.50 mol) of l-nitroso-2-naphthol in 250 ml of methanol. The resulting dark solution was refluxed for another hour, concentrated, and the residue washed with acetone to obtain compound 7 as a yellow solid mp 253-255°C yield 9%. 

Method B. A solution of 5.80 g (0.020 mol) of 4-indolino-l-nitroso-2-naphthol and 3.46 g (0.020 mol) of 1,3,3-trimethy 1-2-methylene indoline in 100 ml of 1,4-dioxane was heated under reflux for 21 h. The resulting purple solution was evaporated to dryness and the residue purified by flash chromatography over silica with diethyl ether-hexane (1 7 = v v) to give 5.56 g as a green gum or solid, which was further treated by washing with acetone to give compound 7 as a yellow solid mp 255-257°C yield 58%. 

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The first are competitors of PABA (p-aminobenzoic acid) and thus intermpt host de novo formation of the tetrahydrofoUc acid required for nucleic acid synthesis. Examples of dmgs that fall into this group are the sulfones and sulfonamides. The most weU-known of the sulfones is dapsone (70, 4,4 -diaminodiphenyl sulfone, DDS), whose toxicity has discouraged its use. Production of foHc acid, which consists of PABA, a pteridine unit, and glutamate, is disturbed by the substitution of a sulfonamide (stmcturally similar to PABA). The antimalarial sulfonamides include sulfadoxine (71, Fanasd [2447-57-6]) sulfadiazine (25), and sulfalene (72, sulfamethoxypyrazine [152-47-6] Kelfizina). Compounds of this group are rapidly absorbed but are cleared slowly. 

The pyrrole ring in numerous natural products has been constructed using a PK synthesis. Examples include lamellarin L, funebrine, magnolamide, and... 

Arylmetallic compounds have various, but not very widely used, applications in organic synthesis. Examples are acyl-de-metallation reactions using either dicobalt octacarbonyl in tetrahydrofuran (Seyferth and Spohn, 1969 Scheme 10-92), or carbon monoxide and a rhodium catalyst (Larock and Hershberger, 1980). 

Consider again the ammonia synthesis example from Examples 6.1 and 6.2... 

Axial Chirality. For a system with four groups arranged out of the plane in pairs about an axis, the system is asymmetric when the groups on each side of the axis are different. Such a system is referred to as an axial chiral system. This structure can be considered a variant of central chirality. Some axial chiral molecules are allenes, alkylidene cyclohexanes, spiranes, and biaryls (along with their respective isomorphs). For example, compound 7a (binaphthol), which belongs to the class of biaryl-type axial chiral compounds, is extensively used in asymmetric synthesis. Examples of axial chiral compounds are given in Figure 1-5. 

New applications continue to demonstrate the enormous versatility of RCM for organic synthesis. Examples include triple ring closing (Eq. 48) and alkyne metathesis, an example being that of cross-metathesis that provides an efficient synthetic strategy for prostaglandin E2 (Eq. 49). Amines and alcohols deactivate metathesis catalysts, but their protection as ethers, esters, and amides allows them to be incorporated into the designated transformation. 

The most frequently observed 2 + 2 additions are photochemical. The excited-state additions, allowed by the pericyclic selection rules, occur readily and have proved extremely useful in synthesis. Examples will be considered in Section 13.4.47... 

Phthalimide 930 has also been used for phthalocyanine synthesis (Example 25). In case of Mg [2], only the metal itself can be utilized. The process requires a much more careful control of temperature than that utilizing o-cyanobenzamide and gave only 20% of PcMg under optimum conditions. 

With regard to the use of protease in the synthetic mode, the reaction can be carried out using a kinetic or thermodynamic approach. The kinetic approach requires a serine or cysteine protease that forms an acyl-enzyme intermediate, such as trypsin (E.C. 3.4.21.4), a-chymotrypsin (E.C. 3.4.21.1), subtilisin (E.C. 3.4.21.62), or papain (E.C. 3.4.22.2), and the amino donor substrate must be activated as the ester (Scheme 19.27) or amide (not shown). Here the nucleophile R3-NH2 competes with water to form the peptide bond. Besides amines, other nucleophiles such as alcohols or thiols can be used to compete with water to form new esters or thioesters. Reaction conditions such as pH, temperature, and organic solvent modifiers are manipulated to maximize synthesis. Examples of this approach using carboxypeptidase Y (E.C. 3.4.16.5) from baker s yeast have been described.219... 

This chapter also provides a number of more complicated Verilog HDL synthesis examples. These models illustrate the usage of Verilog HDL constructs collectively to model a design that can be synthesized. 

In addition to DCC and EDC many other aliphatic carbodiimides are used in peptide synthesis. Examples include N-t-butyl-N -methylcarbodiimide (BMC), N-t-butyl-N -ethylcarbodiimide (BEC), N,N -dicyclopentylcarbodiimide andN-cyclohexyl-N -isopropylcarbodiimide (CIC). DCC, diisopropylcarbodiimide, BMC and BEC perform similarly in peptide synthesis. " N-cyclohexyl-N -isopropylcarbodiimide (CIC) is comparable or even better than DCC for mediation of peptide bond formation in sohd phase synthesis. Also, the solubility of the derived urea in dichloromethane is useful in the standard procedure. " ... 

Puchot, C. SamueL O. Dunach, E. Zhao, S. Agami, C. Kagan, H. B. Nonlinear effects in asymmetric synthesis. Examples in asymmetric oxidations and aldolization reactions, J. Am. Chem. Soc. 1986,108, 2353-2357. 

The oxidative coupling of enolates, reported for the first time in 1935, represents an interesting application of enolates in organic synthesis. Examples of these reactions. 

LiAlH4 is a versatile reducing agent for many organic compounds, such as ketones, aldehydes, nitriles, and nitro compounds. This ion also has many applications in inorganic synthesis. Examples of the inorganic conversions effected by LiAlH4 include... 

The applications of microwave chemistry to organic chemistry are too numerous to mention. A few representative examples will be given to illustrate the scope and utility. Microwave chemistry is widely used in synthesis. Examples include the Heck reaction (reaction 13-10)," the Suzuki reaction (reaction 13-12)," the Sonogashira reaction (reaction 13-13)," Ullman type couplings (reaction... 

Double-bond isomerization has been exploited as a desired reaction in organic synthesis examples include the synthesis of steroids. It is also an undesired side reaction of industrially relevant reactions such as hydroformylation (cf. Section 2.1.1), hydrogenation (cf. Section 2.2), and hydrosilyation (cf. Section 2.6), it is a subject of current interest [34—36]. Two promising developments are worth mentioning here because they yielded highly selective catalysts which are, at the same time, easy to handle. 

The kinetics of many the reactions of radicals with tin hydrides have been studied because of their importance in organic synthesis. Examples are given in Table 15-5, and a more extensive list is given in a recent review by Chatgilialoglu and Newcomb.111 The solvents are not quoted in the table, but in general they are non-polar (e.g. octane or benzene) and the rates are not sensitive to the nature of the solvent. 

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