1- Phenyl-l-butanol

Butylbenzene n. a. 1-Butylphenols n. a. 1-Phenyl-l-butanol, 1-phenyl-3-butanol, 1-phenyl-l-butanone, 1-phenyl-3-butanone 30... 

Like the silyl ethers, the stability of the silyl esters parallels the steric bulk of the substituents on the silicon atom. Tris(2,6-diphenylbenzyl)siiy1 esters confer extraordinary steric protection upon the carboxyl group.234 For example, the tris(2,6-diphenylbenzyl)silyl ester of 4-phenylbutanoic acid 104.1 [Scheme 6.104] does not react with butyllithium (2.5 equiv) after 5 h at -78 °C or methylmag-nesium bromide (2,5 equiv) at room temperature. Nor did it react with lithium aluminium hydride after 30 min at 0 °C l M HC1 in THF at 40 °C, or aqueous sodium hydroxide at 50 °C after 5 h. Ester 104.1 was reduced with diisobutyl-aluminium hydride in 99% yield to give the 4-phenyl-l-butanol (99%) and HF pyridine in THF (1 2) at 50 aC cleaved it back to the acid after 5 h. Unfortunately, the penalty for such unusual stability is high the tris(2 6-diphenyl-... 

Indane and tetralin derivatives can be obtained by cyclodehydration of 3-aryl-1-alkanols and 4-aryl-l-alkanols, respectively.665 Isomerization does not occur in such reactions thus 4-phenyl-l-butanol gives tetralin and not 1-methylindane, and only 1,1-dialkylindanes are formed from the corresponding tertiary alcohols, e.g. ... 

Friedel-Crafts alkylation can also occur intramolecularly, in which case a new ring is formed. It is somewhat easier to form six-membered rings than five-membered rings in such reactions. Thus, while 4-phenyl-l-butanol gives a 50% yield of cyclized product in phosphoric acid, 3-phenyl-1-propanol gives mainly dehydration to alkene. If a potential carbonium-ion intermediate can undergo a hydride or... 

To a stirred solution of 3-methylbuta-1,2-diene (19.1 mg, 0.28 mmol) and 4-phenyl-l-butanol (0.43 mL, 2.8 mmol) in anhydrous DMF (0.28 mL) at 0 °C was added IPrAuCl (17.4 mg, 0.028 mmol) and AgOTf (7.2 mg, 0.028 mmol). This was left to stir under N2 atmosphere at 0 °C for 20 h. The reaction mixture was then flushed through two plugs of silica (Et20), washed with water and brine, and then dried over anhydrous MgS04. The product, (4-(2-methylbut-3-en-2-yloxy)butyl)benzene, was obtained by flash column chromatography (eluent 98 2 n-pentane Et20) as a clear colorless liquid (49.9 mg, 0.23 mmol, 82%). ... 

Typical procedure. O-A-PhenylbutYl-O -butyl carbonate 989 [711] To 4-phenyl-l-buta-nol 985 (100 mg, 0.67 mmol) in anhydrous DMF (1.6 mL, 0.4 m) were added cesium carbonate (625 mg, 2.10 mmol, 3 equiv.) and tetrabutylammonium iodide (208 mg, 0.67 mmol, 1 equiv.). CO2 gas (flow rate 25-30 mL min ) was bubbled into the reaction mixture for 2-3 min, and then 1-bromobutane 988 (274 mg, 0.22 mL, 2.0 mmol) was added to the suspension. The reaction proceeded at ambient temperature with CO2 gas bubbling for 3.5 h, after which time the starting material (4-phenyl-l-butanol) had been consumed. The reaction mixture was then poured into water (30 mL) and extracted with hexanes/EtOAc (3 1 v/v, 60 mL). The organic layer was washed with water (2 x 30 mL) and brine (30 mL), and dried over anhydrous sodium sulfate. Evaporation of the solvent followed by flash column chromatography (hexanes/EtOAc, 9 1 v/v) afforded 0-4-phenylbutyl-0 -butyl carbonate 989 (157 mg, 94%) as a colorless oil. 

This straightforward system effectively oxidises a broad range of secondary alcohols to give the corresponding ketones in high yields at room temperature e.g. 1-phenyl-l-ethanol to acetophenone in 30 min with 92% yield and cyclohexanol into cyclohexanone in 15 min with 96% yields). Interestingly, primary alcohols did not react under the experimental condition [e.g. 1-butanol, benzyl alcohol) showing the potential of this system in selective oxidation of secondary alcohols. 

Give efficient syntheses of the following compounds, beginning with benzene, (a) 1-Phenyl-l-heptanol (b) 2-phenyl-2-butanol (c) 1-phenyloctane. (Hint Use a method from Section 15-14. Why will Friedel-Crafts alkylation not work )... 

The additional four carbon atoms required to synthesize 1-phenyl-1-butanol and 1-phenylbutane can be provided by a Friedel—Crafts reaction of benzene and a four-carbon acid chloride. This product, 1-phenyl-l-butanone, has a carbonyl group that can be reduced to provide products (a) and (b). Reduction of 1-phenyl-l-butanone with a metal hydride such as NaBH4 gives 1-phenyl-1-butanol. Reduction of 1-phenyl-l-butanone using either Clemmensen or Wolff—Kishner conditions gives 1-phenylbutane. 

A 1.5 M soln. of 3-bromo-l-(l,l-dimethylpropoxy)propane dropped onto the equivalent amount of Mg-turnings, the resulting Grignard reagent ice-cooled, stirred, and treated under N2 with 0.8 mole of benzaldehyde in ether, refluxed 30 min. 4-(l,l-dimethylpropoxy)-l-phenyl-l-butanol (Y ca. 90%) heated with a little p-toluenesulfonic acid at 150-165° in an oil bath with distillation of the resulting isoamylene and the product at ca. 25 mm pressure 2-phenyl-tetrahydrofuran (Y 70-90%). F. e. s. W. B. Renfrew et al., J. Org. Ghem. 26, 935 (1961). 

An example of an alcohol that can undergo rapid skeletal rearrangement is 3,3-dimethyl-2-phenyl-2-butanol (Eq. 29). Attempts to reduce this alcohol in dichloromethane solution with l-naphthyl(phenyl)methylsilane yield only a mixture of the rearranged elimination products 3,3-dimethyl-2-phenyl-l-butene and 2,3-dimethy 1-3-phenyl-1 -butene when trifluoroacetic acid or methanesulfonic acid is used. Use of a 1 1 triflic acid/triflic anhydride mixture with a 50 mol% excess of the silane gives good yields of the unrearranged reduction product 3,3-dimethyl-2-phenylbutane, but also causes extensive decomposition of the silane.126 In contrast, introduction of boron trifluoride gas into a dichloromethane solution of the alcohol and a 10 mol% excess of the silane... 

Asymmetric reduction of acetophenone led to (/ )-( + )-1 -phenyl-1 -ethanol with 65 to 69, and with 72, whereas the (S)-( - )-alcohol was formed with 70 and 71. Again the optical yields were relatively low, with the highest 48%, obtained with 65. Asymmetric reductions in very low optical yields were observed with the simple alcohols (-)-l-phenyl-1-ethanol (73) and (-)-3,3-di-methyl-2-butanol (74) as chiral auxiliary reagents. 

In gleicher cheraischer Ausbeute, jedoch mit einer optischen Ausbeute von 76%, laBt sich Acetophenon-(O-methyl-oxim) mit Lithium-alanat in Gegenwart eines aus Diboran und (S)-2-Amino-3-methyl-l,l-diphenyl-butanol gebildeten Boran-Adduktes zu (S)-l-Amino-1-phenyl-ethan reduzieren2. 

The Friedel-Crafts alkylation of aromatic compounds by oxetanes in the presence of aluminum chloride is mechanistically similar to the solvolyses above, since the first step is electrophilic attack on the ring oxygen by aluminum chloride, followed by a nucleophilic attack on an a-carbon atom by the aromatic compound present. The reaction of 2-methyloxetane and 2-phenyloxetane with benzene, toluene and mesitylene gave 3-aryl-3 -methyl-1-propanols and 3-aryl-3-phenyl-l-propanols as the main products and in good yields (equation 27). Minor amounts of 3-chloro-l-butanol and 4-chloro-2-butanol are formed as by-products from 2-methyloxetane, and of 3-phenyl-l-propanol from 2-phenyloxetane (73ACS3944). 

When the ethylene oxide contains an aromatic substituent, as in styrene oxide, there is a significant tendency for preliminary isomerization to oocur. Thus, treatment of styrene oxide with methyl-magnesium bromide or ethylmagnesium bromide yields 1 -phenyl-2-propauol and l-phemyJ-2-butanol respectively1 83 (Eq. 841). 

A portion of the olefin (3.5 grams) dissolved in pentane (10 ml) was treated with ozone at —178°C for 8 hrs. The product was treated with excess LiAlH4 in ether at 0°C and refluxed. After usual work up, benzyl alcohol (1.7 grams) and (—)(S)-2-methyl-l-butanol [1.1 grams [< ]D25 —5.50, op 94.5% (16, 17)] were recovered. An optical purity of 94.5% is attributed to ( + )(S)-l-phenyl-3-methyl-l-pentene having D25 +44.95°. 

Cumene does not undergo oxidation at a measurable rate. 1-Butylbenzene undergoes oxidation mainly in the side chain, with traces of aromatic ring oxidation, producing 1-phenyl-1-butanol, l-phenyI-3-butanol, and the corresponding ketones (Clerici, 1991). 

To a stirred solution of 2,4-dihydro-4- 4-[4-(4-hydroxyphenyl)-l-piperazinyl] phenyl -2-(l-methylpropyl)-3H-l,2,4-triazol-3-one in 100 parts of dimethyl sulfoxide are added 0.3 parts of sodium hydride dispersion 78% and the whole is stirred at 50°C till foaming has ceased. Then there are added 3.7 parts of cis-[2-(2,4-dichlorophenyl)-2-(lH-l,2,4-triazol-l-ylmethyl)-l,3-dioxolan-4-ylmethyl]methanesulfonate and stirring is continued for 3 hours at 100°C. The reaction mixture is cooled and poured onto water. The product is extracted with dichloromethane. The extracts are washed with a diluted sodium hydroxide solution and filtered. The residue is crystallized from 1-butanol. The product yield 4.3 parts (75%) of cis-4- 4-[4- 4-[2-(2,4-dichlorophenyl)-2-(lH-l,2,4-triazol-l-ylmethyl)-l,3-dioxolan-4-ylmethoxy] phenyl -l-piperazinyl]phenyl -2,4-dihydro-2-(methylpropyl)-3H-l,2,4-triazol-3-one. 

The best results can be obtained considering the energy of the triplet biradical intermediates (Fig. 3.19). Calculations on these biradical intermediates showed that the first (the precursor of the observed product) was more stable than the other by 0.73 kcal mol-1. Furthermore, the first and the second possible biradical intermediate in the reaction of the ester of (S)-2-methyl-l-butanol and differed by only 0.02 kcal mol-1, in agreement with the observed no stereoselectivity of the reaction. Finally, the first biradical intermediate in the reaction of 8-phenyl-menthol ester proved to be more stable than the other one by 21.9 kcal mol-1. This result is also in agreement with the observed high diastereoisomeric excess. 

In an approach to direct C-functionalization of triazolo[4,5-c]pyridines, shown in Scheme 3, 1-methyl (or phenyl)[l,2,3]triazolo[4,5-c]pyridines (26,33) are alkylated exclusively at C-4 by radicals generated by decarboxylation of carboxylic acids (ammonium persulfate-sulfuric acid-silver nitrate) <90ZOB683>. However, with /-butanol various products are obtained depending on the catalyst employed. For example, with ammonium persulfate-sulfuric acid-silver nitrate, exclusive C(4)-methylation (34) was observed, while ammonium persulfate-sulfuric acid gave exclusively C(4)-/ -hydroxy-/ ,/ -dimethylethylation (cf. (36)). The /-butyl analogue (35) was obtained by decarboxylation of pivalic acid. 

Figure 6.5 Variation in the RH measured during the esterification reaction of butyric acid with different alcohols cinnamyl alcohol ( ), 1-phenyl-1-butanol ( ), and Z-L-Ser-OBzl (A). Experimental conditions 2 ml of toluene, 20 mg of lyophilized mycelia, and 50mM equimolar substrates in a 6ml sealed vial.

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