2-propanol addition reaction

Condensation of vinyl chloride with formaldehyde and HCl (Prins reaction) yields 3,3-dichloro-l-propanol [83682-72-8] and 2,3-dichloro-l-propanol [616-23-9]. The 1,1-addition of chloroform [67-66-3] as well as the addition of other polyhalogen compounds to vinyl chloride are cataly2ed by transition-metal complexes (58). In the presence of iron pentacarbonyl [13463-40-6] both bromoform [75-25-2] CHBr, and iodoform [75-47-8] CHl, add to vinyl chloride (59,60). Other useful products of vinyl chloride addition reactions include 2,2-di luoro-4-chloro-l,3-dioxolane [162970-83-4] (61), 2-chloro-l-propanol [78-89-7] (62), 2-chloropropionaldehyde [683-50-1] (63), 4-nitrophenyl-p,p-dichloroethyl ketone [31689-13-1] (64), and p,p-dichloroethyl phenyl sulfone [3123-10-2] (65). 

The relative proportions of unsaturated carbohydrate, sensitizer (usually acetone), and solvent may have a decided effect upon a photochemical addition reaction, as at least three competing processes (cycloaddition, radical addition, and energy transfer) are possible. The irradiation of 1 in the presence of 2-propanol and acetone provides an illustration (see Scheme 4). When a small proportion of sensitizer... 

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

Tetrakis(triphenylphosphine)-palladium(O), 289 Conjugate addition reactions (IS, 2S)-2-Amino-3-methoxy-1 -phenyl-1-propanol, 17 Camphor, 61... 

The addition of chiral amines to a,/(-unsaturated sulfoximines has been employed for the resolution of racemic sulfoximines 3 utilizing 0.5 equivalents of a chiral amine in chloroform 117. After completion of the reaction, the unreacted starting material is isolated by column chromatography and its optical purity determined by comparison with the reported optical rotation, or by HNMR using a chiral shift reagent. While (—)-(l/f,2.S,)-2-mcthylamino-1-phenyl-l-propanol [(l/ ,2S)-ephedrine] affords material of moderate optical purity, racemic products are isolated from addition reactions with (—)-l-phenyl-2-propanamine [(—)-am-phetamine] or ( + )-( )-l-phenylethylamine. 

Apart from these SET reactions, solvent effects in reactions of organomagnesium reagents with carbonyl compounds have been studied rather extensively. The reaction of ethylmagnesium bromide with benzophenone (Scheme 15) in diethyl ether yields 94% of the expected addition reaction product, 1,1-diphenyl-1-propanol, and 6% benzhydrol, resulting from a reduction reaction of the Grignard reagent [36]. In tetrahydrofuran this reaction yields 21 and 77%. respectively, of both products. 

For case study B.4, a bulk lot sample of drug substance contained an unknown Impurity A present at 0.82% and an unknown Impurity B present at 1.12%. Identification of both impurities was requested within a 1-month time frame. It was confirmed that the impurities did not match any known standards. LC/MS data indicated that Impurity A had a molecular weight of M+60, suggesting propanol addition, and Impurity B had a molecular weight of M+32, suggesting methanol addition. The next step was to look into the synthesis to find possible propanol and methanol addition reactions. In this investigative step, it was found that the reagent 2-propanol was utilized in step 11 of the process synthetic route. 

With bulkier alkoxides, e. g. potassium ter/-butoxide in fcrr-butyl alcohol or potassium (4-chlorophenyl)dimethylcarbinolate, a-bromo ketone 16 is converted into rra x-2,3-di-/cr/-butyl-cyclopropanone (17). Addition of methanol or 2-propanol to cyclopropanone 17 at 25 °C gives a fast addition reaction resulting in hemiacetal 21, which slowly undergoes ring opening at 80 °C in methanol to give a-methoxy ketone 22 (R = Me). ... 

The conversion of 1-propanol over H-ZSM-5 or H-Y was not found to yield any C3 oxygenated products for a range of reaction conditions and the products are mainly propene and butenes. This confirms that the introduction of the carbon-carbon double bond into the reactant molecule significantly affects the reactivity. Conversion of 2-propanol over H-ZSM-5 was found to give significant selectivity to acetone at low flow rates and this indicates that this could be a possible reaction intermediate. In addition, reaction of propene oxide over H-ZSM-5, under comparable conditions to those utilised for allyl alcohol, produced significant selectivities of both acetone and allyl alcohol. 

To understand why the hydroboration-oxidation of propene forms 1-propanol, we must look at the mechanism of the reaction. The boron atom of borane is electron deficient, so borane is the electrophile that reacts with the nucleophilic alkene. As boron accepts the rr electrons and forms a bond with one carbon, it donates a hydride ion to the other carbon. In all the addition reactions that we have seen up to this point, the electrophile adds to the alkene in the first step and the nucleophile adds to the positively charged intermediate in the second step. In contrast, the addition of the electrophilic boron and the nucleophilic hydride ion to the alkene take place in one step. Therefore, an intermediate is not formed. 

Firstly, we have the acetone aldol self-condensation reaction over basic sites to give diacetone alcohol (DAA). Dehydration of this alcohol yeilds mesityl oxide (MSO) winch, in turn, can be selectively hydrogenated over reduced metal sites to finally give methyl isobutyl ketone (MIBK). In addition to the aldol condensation route, the acetone carbonyl functional group can also be directly hydrogenated over reduced metal sites yielding 2-propanol. Other reaction by-products such as methane, propane, diisopropyl ether and diisobutyl ketone have been detected in some experiments, but in very low amounts, lower than 2% of the total reaction products. 

Maleimide. Maleimide and maleic anhydride are simple olefins and very useful molecules in organic syntheses for introducing various substituents. Addition reactions, cyclodimerization, Diels-Alder reactions and polymerization reactions are as well-known as their photochemical reactions. They are also known as electron acceptors in photoinduced electron-transfer reactions. The photosensitized reaction of maleimide with xanthone in 2-propanol has been investigated by TR EPR. The emissive CIDEP spectrum observed in 2-propanol is predominantly assigned to two kinds of maleimide alkyl-type radicals. On the other hand, the absorptive spectrum of the maleimide radical-anion was observed in 2-propanol in the presence of hydrochloric acid. The hydrochloric acid addition effect on the CIDEP patterns indicates the existence of two mechanisms for the photosensitization of maleimide by xanthone. One is a T-T energy transfer to maleimide followed by hydrogen abstraction by maleimide... 

The importance of the dipolar resonance forms is reflected in the stabihties of isomeric carbonyl compounds. Propanal is approximately 27 kj mole" less stable than propanone. For addition reactions, two isomeric products with different stabihties also form. Therefore, we also have to consider the relative stabihties of the products. Hydrogenation of propanal and propanone gives isomeric alcohols. 1-Propanol is approximately 16 kJ mole" less stable than 2-propanol. Since the difference in the stabihties of the reactants is greater than the difference in the stabilities of the products, the equihbrium constants for the addition reactions of carbonyl compounds depend on more differences in the structure of the carbonyl compound than on the differences in the structure of the addition product. Thus, because ketones are more stable than aldehydes, the addition reactions of ketones are less favorable (have smaller equihbrium constants) than addition reactions of aldehydes. 

Classical MPV reduction (Al(Oi-Pr)3 and i-PrOH system) has several disadvantages. That is, stoichiometric amount of Al(Oi-Pr)3 and excess amount of 2-propanol as hydride donor are needed for smooth reaction. In addition, reaction rate is relatively slow. Since these reasons, development of effective catalysts for MPV reduction and/or Oppenauer oxidation is an important task in synthetic organic chemistry. Recently, to solve these problems highly active aluminum catalysts were reported. Maruoka and coworkers reported that bidentate Lewis acids (75a) and (75b) derived from bis-aluminated phenoxide (17) and various secondary alcohols effectively catalyze MPV reductions (Scheme 6.58). In these catalysts, bis-aluminated structure, which is coordinated by one carbonyl oxygen in a double coordination manner, is crucial for high catalytic activity [76]. 

First, the countercation of 4.5 and the other anionic species is the hydronium ion, i.e., protonated water. If a ligand such as PPhj is added, it gets converted to HPPhj which acts as the countercation. Second, 4.5 to 4.6 is an oxidative addition reaction, 4.6 to 4.7 is an insertion reaction, and 4.8 to 4.5 is a reductive elimination reaction. Third, although the main product-forming reaction is the reductive elimination step, hydrolysis of 4.8 to 4.9 also gives acetic acid. The complex 4.9 plays an important role in the carbonylation of propanol and other higher alcohols (see Section 4.3). 

Kobayashi has reported a remarkable series of chiral Zr(IV) complexes as catalysts for enantioselective aldol addition reactions [136, 137]. These are readily prepared from 3,3 -dihalo-BINOL derivatives and Zr(OtBu)4. The putative zirconium complex 266 is reported to mediate the formation of anti aldol adducts with excellent diastereo- and enantioselectivity (Scheme 4.33). It is noteworthy that under optimal conditions, the reactions are carried out in aqueous propanol/toluene solvent mixtures. As such, the process is tolerant of and indeed thrives in, the presence of water. A demonstration of its use was reported in the synthesis of khafrefungin (269), an inhibitor of fungal sphingolipid synthesis [137]. 

Now let s draw the forward scheme. Upon treatment with PCC, 1-propanol is oxidized to give propanal. Treating propanal with sodium hydroxide then gives a P-hydroxyaldehyde (via an aldol addition reaction between two molecules of propanal). Reduction with LAH, followed by water work-up, gives the product. 

Suitable catalysts include the hydroxides of sodium (119), potassium (76,120), calcium (121—125), and barium (126—130). Many of these catalysts are susceptible to alkali dissolution by both acetone and DAA and yield a cmde product that contains acetone, DAA, and traces of catalyst. To stabilize DAA the solution is first neutralized with phosphoric acid (131) or dibasic acid (132). Recycled acetone can then be stripped overhead under vacuum conditions, and DAA further purified by vacuum topping and tailing. Commercial catalysts generally have a life of about one year and can be reactivated by washing with hot water and acetone (133). It is reported (134) that the addition of 0.2—2 wt % methanol, ethanol, or 2-propanol to a calcium hydroxide catalyst helps prevent catalyst aging. Research has reported the use of more mechanically stable anion-exchange resins as catalysts (135—137). The addition of trace methanol to the acetone feed is beneficial for the reaction over anion-exchange resins (138). 

Hydrogen hahdes normally add to form 1,2-dihaLides, though an abnormal addition of hydrogen bromide is known, leading to 3-bromo-l-chloropropane [109-70-6], the reaction is beUeved to proceed by a free-radical mechanism. Water can be added by treatment with sulfuric acid at ambient or lower temperatures, followed by dilution with water. The product is l-chloro-2-propanol [127-00-4]. 

Reactions with NaBH4 go smoothly in water, ethanol or 2-propanol water reacts with NaBH4 but the system can be stabilized by the addition of alkali ethanol also reacts slowly with the hydride and 2-propanol not at all ... 

One of the drawbacks of the Skraup/Doebner-von Miller reaction is the isolation of the desired product from the starting aniline and co-formed alkyl anilines and 1,2,3,4-tetrahydroquinaldine. Isolation can be simplified greatly by addition of one equivalent of zinc chloride at the end of the reaction all of the basic products were precipitated. Washing the brown solids with 2-propanol removed all impurities and left the desired quinoline as a 2 1 complex with zinc chloride in yields of 42-55%. 

To a suspension of 3.0 g of 7-[D-(-)-a-amino-p-hydroxyphenylacetamido] -3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl] -A3arboxylic acid in 29 ml of water was added 0.95 g of anhydrous potassium carbonate. After the solution was formed, 15 ml of ethyl acetate was added to the solution, and 1.35 g of 4-ethyl-2,3-dioxo-1 -piperazinocarbonyl chloride was added to the resulting solution at 0°C to 5°C over a period of 15 minutes, and then the mixture was reacted at 0°C to 5°C for 30 minutes. After the reaction, an aqueous layer was separated off, 40 ml of ethyl acetate and 10 ml of acetone were added to the aqueous layer, and then the resulting solution was adjusted to a pH of 2.0 by addition of dilute hydrochloric acid. Thereafter, an organic layer was separated off, the organic layer was washed two times with 10 ml of water, dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in 10 mi of acetone, and 60 ml of 2-propanol was added to the solution to deposit crystals. The deposited crystals were collected by filtration, washed with 2-propanol, and then dried to obtain 3.27 g of 7-[D-(-)-a-(4-ethyl-2,3-dioxo)-1 -piperazinocarbonylamino)-p-hydroxyphenylacetamido] -3-[5-(1 -methyl-1,2,3,4-tetrazolyl)thiomethyl]-A product forms crystals, MP 1BB°C to 190°C (with decomposition). 

The reaction mixture is then warmed on the steam bath for an additional two hours (90°C to 95°C). The excess hydrazine hydrate is removed in vacuo. The residue of viscous 1-hy-drazlno-3-morpholinyl-2-propanol Is not distilled, but is mixed with 10.16 g (0.0B6 mol) diethyl carbonate and a solution of 0.3 g sodium metal in 15 ml methyl alcohol. The mixture is refluxed about 2 hours under a 15 cm Widmer column, the alcohol being removed leaving a thick, green liquid residue, which is cooled and the precipitate which forms is removed by filtration and washed well with ether. Yield B2%, MP114°C to 116°C. Recrystallization from isopropanol gives purified 3-amino-5-(N-morpholinyl)-methyl-2-oxazolidone, MP 120°C as the intermediate. 

To a stirred and refluxed suspension of 17 parts of 1,2-dibromoethane, 7.8 parts of sodium hydrogen carbonate and 50 parts of 2-propanol is added a mixture of 3.4 parts of dl-2-thio-1-phenyl-lmidazolidine, 9 parts of a 20% potassium hydroxide solution in 40 parts of 2-propanol over a period of about 1 hour. After the addition is complete, the whole is stirred and refluxed for an additional 3 hours. The reaction mixture is evaporated. To the residue are added 18 parts of a 15% potassium hydroxide solution. The whole is extracted with toluene. The extract is dried and evaporated. The oily residue is dissolved in acetone and gaseous hy-... 

To a stirred suspension of 5 parts of N-(4-chlorophenyl)-N-(4-piperidinyl)benzeneacetamide, 5 parts of sodium carbonate, a few crystals of potassium iodide in 200 parts of butanol is added dropwise 4 parts of 2-bromopropane at room temperature. After the addition is complete, the whole is stirred and refluxed for 20 hours. Then the second portion of 4 parts of 2-bromopropane is added and stirring and refluxing is continued for another 19 hours. The reaction mixture is cooled, filtered and the filtrate is evaporated. From the oily free bese, the hydrochloride salt is prepared in the conventional manner in 1,1 -oxybisethane and 2-propanone. The precipitated solid salt is filtered off and crystallized from a mixture of 2-propanone and 2-propanol, yielding 2 parts of N-(4-chlorophenyl)-N-[1-(1-methylethyl)-4-piperidinyl] benzeneacetamide hydrochloride melting point 263°C. 

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