Indenes 1- alkylation

The original synthesis of indenes alkylated on the benzene ring required multistep sequences, often with low regioselectivity and low overall yield. More efficiently, 4,7-alkyl-substituted indenes can be prepared in a one-step synthesis by cyclocondensation of alkanediones with cyclopentadienes (eq. (1)) [13, 14]. 

Wood, J.L., Pujanauski, B.G., and Sarpong, R. (2009) Synthesis of the tetracyclic core of the neomangicols using a late-stage indene alkylation. Org. Lett., 11, 3128-3131. 

The first resins to be produced on a commercial scale were the coumarone—indene or coal-tar resins (1) production in the United States was started before 1920. These resins were dominant until the development of petroleum resins, which were estabHshed as important raw materials by the mid-1940s. Continued development of petroleum-based resins has led to a wide variety of aHphatic, cyclodiene, and aromatic hydrocarbon-based resins. The principal components of petroleum resins are based on piperylenes, dicyclopentadiene (DCPD), styrene, indene, and their respective alkylated derivatives. 

Coumarone—indene or coal-tar resins, as the name denotes, are by-products of the coal carbonization process (coking). Although named after two particular components of these resins, coumarone (1) and indene (2), these resins are actually produced by the cationic polymerization of predominantly aromatic feedstreams. These feedstreams are typically composed of compounds such as indene, styrene, and their alkylated analogues. In actuaUty, there is very tittle coumarone in this type of feedstock. The fractions used for resin synthesis typically boil in the range of 150—250°C and are characterized by gas chromatography. 

Such copolymers of oxygen have been prepared from styrene, a-methylstyrene, indene, ketenes, butadiene, isoprene, l,l-diphen5iethylene, methyl methacrjiate, methyl acrylate, acrylonitrile, and vinyl chloride (44,66,109). 1,3-Dienes, such as butadiene, yield randomly distributed 1,2- and 1,4-copolymers. Oxygen pressure and olefin stmcture are important factors in these reactions for example, other products, eg, carbonyl compounds, epoxides, etc, can form at low oxygen pressures. Polymers possessing dialkyl peroxide moieties in the polymer backbone have also been prepared by base-catalyzed condensations of di(hydroxy-/ f2 -alkyl) peroxides with dibasic acid chlorides or bis(chloroformates) (110). 

AlClj Alkylation Process. The first step in the AIQ. process is the chlorination of / -paraffins to form primary monochloroparaffin. Then in the second step, the monochloroparaffin is alkylated with benzene in the presence of AIQ. catalyst (75,76). Considerable amounts of indane (2,3-dihydro-lH-indene [496-11-7]) and tetralin (1,2,3,4-tetrahydronaphthalene [119-64-2]) derivatives are formed as by-products because of the dichlorination of paraffins in the first step (77). Only a few industrial plants built during the early 1960s use this technology to produce LAB from linear paraffins. The C q—CC olefins also can be alkylated with benzene using this catalyst system. 

Ethyltoluene is manufactured by aluminum chloride-cataly2ed alkylation similar to that used for ethylbenzene production. All three isomers are formed. A typical analysis of the reactor effluent is shown in Table 9. After the unconverted toluene and light by-products are removed, the mixture of ethyltoluene isomers and polyethyltoluenes is fractionated to recover the meta and para isomers (bp 161.3 and 162.0°C, respectively) as the overhead product, which typically contains 0.2% or less ortho isomer (bp 165.1°C). This isomer separation is difficult but essential because (9-ethyltoluene undergoes ring closure to form indan and indene in the subsequent dehydrogenation process. These compounds are even more difficult to remove from vinyltoluene, and their presence in the monomer results in inferior polymers. The o-ethyltoluene and polyethyltoluenes are recovered and recycled to the reactor for isomerization and transalkylation to produce more ethyltoluenes. Fina uses a zeoHte-catalyzed vapor-phase alkylation process to produce ethyltoluenes. 

All lation of Garbanions. Concentrated N a OH—hen syl triethyl amm onium chloride is the base/catalyst system normally used for this type of process (20). Classes of compounds alkylated in this way include phenylacetonitriles, ben2ylketones, simple aUphatic ketones, certain aldehydes, aryl sulfones, P-ketosulfones, P-ketoesters, malonic esters and nitriles, phenylacetic esters, indene, and fluorene (see Alkylation). 

Tackifiers. Phenolic resins are added to increase strength, oils resistance and resiliency of NBR adhesives. On the other hand, tack and adhesive properties can be improved by adding chlorinated alkyl carbonates. To impart tack, hydrogenated rosin resins and coumarone-indene resins can be added. 

This reaction is illustrative of a general procedure for the alkylation of active methylene functions in the presence of concentrated aqueous alkali catalyzed by tetraalkylammonium salts. This catalytic method has been used to alkylate arylacetonitriles with monohaloalkanes,2 dihaloalkanes,3 a-chloroethers,4 chloronitriles,.5 haloacetic acid esters,6 and halonitro aromatic compounds.7 It has also been used to alkylate ketones,8 lf/ indene,9 9i/-fluorene,ll) and the Reissert compound.11 The reaction is inhibited by alcohols and by iodide ion.2... 

Substituted indenes provide other examples of substituent directive effects. Over Pd-alumina, the indenols 6a-c show both cis stereoselectivity and a syn directive effect. The directive effect is reinforced by steric effects as the alkyl group becomes larger.7... 

The highly aromatic resins are often used as coumarone/indene resin substitutes. A range of soft aromatic resins is available, produced from the alkylation of xylene and other aromatic hydrocarbons with dicyclopentadiene. These are excellent softeners for a wide range of rubbers. In common with other aromatic materials derived from petroleum sources, some of the resins used within the rubber industry are deemed to be carcinogenic. 

Styrene and indene derivatives (Scheme 2, Y = Ph) are dimerized to l,4-dimethoxy-l,4-diphenylbutanes or 1,4-diphenylbutadienes (Table 7, numbers 1 and 2) [52]. The product distribution is in some cases strongly dependent on the anode potential and the supporting electrolyte. Dimerization is promoted by a-substituents that stabilize the intermediate radical cation, for example, phenyl, vinyl, alkoxy, dialkylamino groups. IJ-Alkyl substituents strongly decrease the yield of dimers and favor formation of dimethoxy-lated monomers. 

Catalytic asymmetric methylation of 6,7-dichloro-5-methoxy-2-phenyl-l-indanone with methyl chloride in 50% sodium hydroxide/toluene using M-(p-trifluoro-methylbenzyDcinchoninium bromide as chiral phase transfer catalyst produces (S)-(+)-6,7-dichloro-5-methoxy-2-methyl-2--phenyl-l-indanone in 94% ee and 95% yield. Under similar conditions, via an asymmetric modification of the Robinson annulation enqploying 1,3-dichloro-2-butene (Wichterle reagent) as a methyl vinyl ketone surrogate, 6,7 dichloro-5-methoxy 2-propyl-l-indanone is alkylated to (S)-(+)-6,7-dichloro-2-(3-chloro-2-butenyl)-2,3 dihydroxy-5-methoxy-2-propyl-l-inden-l-one in 92% ee and 99% yield. Kinetic and mechanistic studies provide evidence for an intermediate dimeric catalyst species and subsequent formation of a tight ion pair between catalyst and substrate. 

The intermediate vinylketene complexes can undergo several other types or reaction, depending primarily on the substitution pattern, the metal and the solvent used (Figure 2.27). More than 15 different types of product have been obtained from the reaction of aryl(alkoxy)carbene chromium complexes with alkynes [333,334]. In addition to the formation of indenes [337], some arylcarbene complexes yield cyclobutenones [338], lactones, or furans [91] (e.g. Entry 4, Table 2.19) upon reaction with alkynes. Cyclobutenones can also be obtained by reaction of alkoxy(alkyl)carbene complexes with alkynes [339]. 

The general feature of alkylation reactions at a carbon atom is that they can be achieved under sonication using solid bases even in apolar solvents. The advantage is that side reactions are generally minimised. Deprotonation occurs readily on a benzylic position in the presence of aqueous sodium hydroxide, as shown with indene (Eq. 3.21) [117]. A quantitative yield of the alkylated product can be obtained using sonication in the presence of a PTC. It was suggested that alkylation of cyclopentadiene or indene by secondary or tertiary alkyl halides in the presence of potassium hydroxide and Ali-quat occurred via a SET process [118]. 

Bromine-atom atomic resonance absorption spectrometry (ARAS) has been applied to measure the thermal decomposition rate constants of CF3Br in Kr over the temperature range 1222-1624 K. The results were found to be consistent with recently published theory. The formation of cyclopent[a]indene and acenaphthylene from alkyl esters of biphenyl-mono- and -di-carboxylic acids has been observed in flash vacuum pyrolyses at 1000-1100 °C. The kinetics and mechanisms of free-radical generation in the ternary system containing styrene epoxide, / -TsOH, and i-PrOH have been examined in both the presence and absence of O2. ... 

When l-[o-(phenylethynyl)phenyl]cyclopropanol-Co2(CO)6 complex (36) is heated at 50 °C in 2-propanol under argon in the presence of DABCO, a completely different product, 3a,4-dihydro-3ff-cyclopenta[a]inden-2-one derivative 40, is produced as a 95 5 diastereomeric mixture in 72% yield. As shown in Scheme 18, not only aryl-substituted alkynyl derivatives, but also alkyl-substituted alkynyl derivatives, give the corresponding cyclopenta[a]inden-2-one derivatives 40 in moderate to good yields. 

From a mechanistic point of view, it can be envisaged that this reaction proceeds via the desired benzylated pentanedione intermediate 14f. The subsequent intramolecular Friedel-Crafts alkylation of the electron-rich arene results in the quaternary benzyl alcohol II, which readily eliminates water to give the highly substituted indene 16 (Scheme 14). 

A bismuth-catalyzed alkylation of warfarins has not been described, although a bismuth-mediated synthesis of the coumarin core structure 21 starting from phenols 19 and ethyl acetoacetate 20 is known (Scheme 17) [51]. The synthesis of coumarins proceeds in the same way as the above-described indene synthesis. The initial reaction of phenol 19 and ethyl acetoacetate 20 leads to the ester. 

The ansa metallocene initiators are synthesized in a relatively straightforward manner (Eq. 8-53). Cyclopentadiene or a substituted analog such as an alkyl-substituted cyclopenta-diene, indene, 4,5,6,7-tetrahydroindene, or fluorene (CpH2) is reacted with butyllithium to... 

Recently, a general catalytic method forthe conversionof 2-alkyl-l -ethynylbenzenes to indenes was disclosed by the group of Liu [41]. Their proposed mechanism involves the stepwise insertion of a ruthenium vinylidene into a benzylic C— H bond (Scheme 9.21). 

The ozonides of indenes substituted with bulky alkyl groups in the aUylic position (e.g. 261) nndergo acid-catalyzed dimerization to a 10-membered endoperoxide (262), as shown in eqnation 90. Similarly to equation 89, the process involves hydroperoxide... 

Another method of seeking evidence of the EIcBirr mechanism is to exam heavy-atom isotope effects in the leaving group. Of course, these should be much more significant in an E2 process because the bond is breaking in the transition state. For example, Thibblin and co-workersfound that in the base-induced elimination of an alkyl halide in which the p-carbon is unusually acidic (indene derivative, 12), moderately strong bases (triethylamine and methoxide) lead to a significant Cl/ Cl isotope effect = 1.010 1.009, where a maximum effect of... 

A number of gem-dibromocyclopropane derivatives has been reacted with aromatic compounds in the presence of aluminum chloride or ferric chloride providing indenes in yields up to 80%. To rationalize this interesting anellation process it has been proposed that the cyclopropyl cation formed under the influence of the Lewis acid collapses to an allylic ion, which then functions as the alkylating agent [179],... 

The thermal isomerization of dihalocyclopropanes is facilitated by the presence of aryl, alkyl and alkoxy substituents in the three-membered ring. Phenyl substituted systems may give rise to indenes, and in the alkyl series the dehydro-halogenation of 2,3-dihalocyclopropane derivatives may lead to dienes. 

Sodium toluene dispersion of, 55, 65 Sodium p-toluenesulfinate, 57, 103 Spiro[4 n] alkenones, 58, 62 Spiro[cyclopentane-l,l -indene] 55, 94 Squalene, 56, 116 Squalene, 2,3-epoxy, 56, 116 Stannic chloride, 56, 97 Steroids synthesis, 58, 85 E Stilbene, 55, 115,58, 73 z-Stilbene, 58, 133 Styrene, 56, 35,58, 43 Styrene glycol, 55, 116 Styrene glycol dimesylate, 55, 116 Succinic acid, 58, 85 Succinic anhydride, 58, 85 Sucunimide, 56, 50, 58, 126 Succimmide, Vbromo, 55, 28, 56, 49 SULFIDE CONTRACTION, 55, 127 Sulfide, dimethyl-, 56, 37 SULFIDE SYNTHESIS, 58, 143,58, 138 SULFIDE SYNTHESIS ALKYL ARYL SULFIDES, 58, 143 SULFIDE SYNTHFSIS DIALKYL SULFIDES, 58, 143 SULFIDE SYNTHESIS UNSYMMETRI-CAL DIALKYL DISULFIDES, 58, 147 SULFONYL CYANIDES, 57, 88 Sulfur tetrafluoride, 57, 51... 

Consumption of the DSBPD results from further oxidation of the >NO radical (Reaction 12) but may also occur by hydrogen abstraction from the alkyl group leading to imine formation (5) or by disproportionation reactions yielding quinonoid structures (9). The existence of this reaction system may therefore be transitory. However, the main chain is long, and the effect of 7.5 X 10"3M DSBPD lasts almost throughout the oxidation of 0.15M indene-thiophenol (see Figure 3). 

Those olefins having double bonds sufficiently electron rich to react significantly with these salts include the common monomers, alkyl vinyl ethers (28,79-81), N-vinylcarbazole (82-84) p-methoxystyrene (21,67), indene (34,74,85), cyclopen tadiene (85,86), and vinylnaphthalenes (87). Styrene itself (60,76,77,88-91), cr-divinylbenzene (92), a-methylstyrene (88), linear conjugated dienes (93) and a-olefins are much less reactive (i.e. formation of their corresponding carbocations is energetically unfavourable), and undo- normal conditions give at best slow reactions and low yields of polymer. 

Probably the most rewarding experiments involving stable carbocation salts have been those using the monomers alkyl vinyl ethers (79-81X N-vinylcarbazole (82), p-methoxystyrene (21,67), cyclopentadiene (86), o-divinylbenzene (92), and to a lesser extent indene (34). 

About half of the 1-methylnaphthalene formed from n-pentylbenzene and 2-phenylpentane isomerizes to 2-methylnaphthalene over platinum on silica-alumina (while over platinum on silica less than 3% of the methylnaphthalene isomerizes to 2-methylnaphthalene). Alkylindan (and alkyl-indene) isomerization is also considerable over platinum on silica-alumina (13, 14). 

---