Polysubstituted

The Gabriel s synthesis is also applicable when a polysubstituted thiazole is required (381, 550). Thus 2,4,5-trisubstituted thiazoles are obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at 100°C (550) or at higher temperature for heavier substituents (381). (Table 11-31). 

For example, ia the iadustriaHy important alkylation of benzene with ethylene to ethylbenzene, polyethylbenzenes are also produced. The overall formation of polysubstituted products is minimized by recycling the higher ethylation products for the ethylation of fresh benzene (14). By adding the calculated equiUbrium amount of polyethylbenzene to the benzene feed, a high conversion of ethylene to monoethylbenzene can be achieved (15) (see also... 

HydroxyethyUiydrazine (11) is a plant growth regulator. It is also used to make a coccidiostat, furazoHdone, and has been proposed, as has (14), as a stabilizer in the polymerization of acrylonitrile (72,73). With excess epoxide, polysubstitution occurs and polyol chains can form to give poly(hydroxyaLkyl) hydrazines which have been patented for the preparation of cellular polyurethanes (74) and as corrosion inhibitors for hydrauHc fluids (qv) (75). DialkyUiydrazines, R2NNH2, and alkylene oxides form the very reactive amineimines (15) which react further with esters to yield aminimides (16) ... 

Halogenation reactions usually involve pyrroles with electronegative substituents. Mixtures are usually obtained and polysubstitution products, ie, tetrahalopyrroles, predominate. The monohalopyrroles are difficult to prepare and are not very stable in air or light. 

Reaction of olefin oxides (epoxides) to produce poly(oxyalkylene) ether derivatives is the etherification of polyols of greatest commercial importance. Epoxides used include ethylene oxide, propylene oxide, and epichl orohydrin. The products of oxyalkylation have the same number of hydroxyl groups per mole as the starting polyol. Examples include the poly(oxypropylene) ethers of sorbitol (130) and lactitol (131), usually formed in the presence of an alkaline catalyst such as potassium hydroxide. Reaction of epichl orohydrin and isosorbide leads to the bisglycidyl ether (132). A polysubstituted carboxyethyl ether of mannitol has been obtained by the interaction of mannitol with acrylonitrile followed by hydrolysis of the intermediate cyanoethyl ether (133). 

IV-Methylation of polysubstituted pyridazinones is frequently accompanied by some side reactions, mainly substitutions. For example, methylation of 4-nitro-5,6-diphenyl-pyridazin-3(2//)-one with methyl iodide in the presence of sodium methoxide affords... 

Phosphorus pentasulfide in pyridine can be used also for simultaneous substitution of oxygen and chlorine in polysubstituted pyridazinones. For example, 4,5-dichloro- and... 

MO calculations, 7, 364 Oxetene, 2-isopropylidene-polysubstituted rearrangement, 7, 377 Oxetene, tetramethyl-structure, 7, 366 Oxetenes, 7, 363-402 decomposition, 7, 375 metabolism, 1, 243 molecular dimensions, 7, 366 thermal stability, 7, 370 Oxetenyl anions aromaticity, 7, 371 Oxetenyl cations aromaticity, 7, 371 Oxichlororaphine occurrence, 3, 196 Oxichromic developers in colour photography, 1, 378-379 Oxidation... 

Fluorobenzene is readily alkylated with alkenes in the presence of protic acids, however, the isomenc purity of the product is poor, and polysubstitution can result Thus, propene and sulfuric acid alkylate fluorobenzene at 20 C to yield a 45 55 ortho/para ratio of the inonoalkyl product m addition to di- and triiso propylfluorobenzene [i5] The reaction of benzene and trifluoropropene at 25 °C in HF-BF3 gives a mixture of mono-, bis-, and tns(3,3,3-trifluoropropyl)ben zene [72, 75] (equation 12)... 

Another important component of Table 18 is substituent chemical shift (SCS) datadenvedforeachoftheSlentnes The SCS is simply thedifferencein F-NMR chemical shifts of the substituted compounds and that of unsubstituted fluoroben zene (-113 5 ppm in CDCI3) These values numerically represent the mfluence a substituent has on the shieldmg or deshieldmg of the fluorine nucleus and depend upon substituent position o, m, orp) Fluonne chemical shifts can be predicted for polysubstituted fluorobenzene systems simply by addmg the SCS value of each substituent to a base value of -113 5 ppm... 

The Patemo-Buchi reaction " is the photo-eatalyzed eJeetrocyeJization of a carbonyl 1 with an alkene 2 to form polysubstituted oxetane ring systems 3. 

Melles and Backer " found, from a study of the oxidation of substituted thiophenes with perbenzoic or peracetic acid, that sulfones could be obtained from polysubstituted methyl- and phenyl-thiophenes and that the presence of electron-attracting groups, such as nitro, hindered the oxidation. Oxidation of thiophene - led to a product which was formed through a Diels-Alder reaction between the intermediate thiophene sulfoxide (211) and thiophene sulfone (212) and for which two alternative structures, (213) or (214), were suggested. Similar sesquioxides were also obtained from 2- and 3-methylthiophene and 3-phenylthiophene. The structures were not proved. Bailey and Cummins synthesized thiophene-1,1-dioxide... 

Various nucleophilic reactions of polysubstituted 5-halopyri-midines are described in Section II,E,2,e with postulates to explain the degree of reactivity. For pyrimidine derivatives, the effect of the following on nucleophilic substitution is included in earlier sections hydrogen bonding and cationization in Section II, C, the leaving group in Section II, D, and the nucleophile in Sections II,E,2,e and II, F. 

Polysubstituted imidazo[4,5-/]quinolines were prepared and evaluated by Spencer and Alaimo, but also by other authors for possible antihelmintic activity... 

Consuming hydrogen is mainly a function of the number of benzene substituents. Dealkylation of polysubstituted benzene increases hydrogen consumption and gas production (methane). For example, dealkylating one mole xylene mixture produces two methane moles and one mole of benzene it consumes two moles of hydrogen. 

Toluene (methylbenzene) is similar to benzene as a mononuclear aromatic, but it is more active due to presence of tbe electron-donating metbyl group. However, toluene is much less useful than benzene because it produces more polysubstituted products. Most of tbe toluene extracted for cbemical use is converted to benzene via dealkylation or disproportionation. Tbe rest is used to produce a limited number of petro-cbemicals. Tbe main reactions related to tbe cbemical use of toluene (other than conversion to benzene) are the oxidation of the methyl substituent and the hydrogenation of the phenyl group. Electrophilic substitution is limited to the nitration of toluene for producing mono-nitrotoluene and dinitrotoluenes. These compounds are important synthetic intermediates. 

Problem 16.11 Use Figure 16.11 to explain why Friedel-Crafts alkylations often give polysubstitution but Friedel-Crafts acylations do not. 

In another synthetic application, first reported by Smith and Stirling142, the bis-2,3-(phenylsulfinyl)-l, 3-butadiene 94 has been prepared in low yield by two spontaneous sequential [2,3]-sigmatropic rearrangements of the Ws-sulfenate ester (93). More recently, the yield of this reaction (equation 42) has been improved159, and a related dienyl sulfoxide 95 has been reported (equation 43)160. This type of sulfoxide is of considerable interest in view of recent studies on Diels-Alder reactions of polysubstituted butadienes161-164. 

Table 7 Reaction of alkoxycarbenes with polysubstituted alkenes...

Synthesis of polysubstituted anilines using the Diels-Alder reaction of methyl-5-aminofuroate [143]... 

Wong HNC Regiospecific Synthesis of Polysubstituted Furans and Their Application in Organic Synthesis Pure Appl. Chem. 1996 68 335 344... 

Fig. 21 Microwave-promoted multicomponent synthesis of polysubstituted thiophenes on solid-phase. Reagents and conditions a RCOCH2R (R = H, Me, Et, Bn R = Me, i-Bu, i-Pn, Ph, Bn, cyclohexyl), Ss, DBU, toluene, MW 120 °C, 20 min, closed vessel, 100% b R"COCl (R" = Me, Pr, Ph or COOMe), diisopropylethylamine, toluene, MW 100 °C, 10 min, closed vessel c TEA, H2O, CH2CI2, rt, 2h...

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