1 -Bromopropane synthesis

Another alternate pathway for the synthesis of racemate product (6) is shown in Scheme 2 [6]. l-phenoxy-2-bromopropane (8) was obtained in 38% yield by the bromination of 1-phenoxy-2-propanol (7) with PBr3. Compound (8) was refluxed in butanol with l-(4-hydroxyphenyl)-2-amino-1-propanol (9) to yield racemate product (6). 

An early synthesis of A5-palmitoy]-.S -[2,3-bis(palmitoyloxy)propyl]cysteine employed cysteine methyl ester, however, this leads to difficulties in the saponification step of the tri-palmitoylated residue. 96 The optimized procedure, in which the cystine di-fert-butyl ester is used, 90 is outlined in Scheme 6 after N-acylation with palmitoyl chloride, the ester is reduced to the cysteine derivative for S-alkylation with l-bromopropane-2,3-diol to yield chirally defined isomers if optically pure bromo derivatives are used. Esterification of the hydroxy groups is best carried out with a 1.25-fold excess of palmitic acid, DCC, and DMAP. The use of a larger excess of palmitoyl chloride is not recommended due to purification problems. The diastereomeric mixture can be separated by silica gel chromatography using CH2Cl2/EtOAc (20 1) as eluent and the configuration was assigned by comparison with an optically pure sample obtained with 2R)- -bromopropane-2,3-diol. 

SYNTHESIS The Grignard reagent of propyl bromide was made by the dropwise addition of 52 g 1 -bromopropane to a stirred suspension of 14 g magnesium turnings in 50 mL anhydrous Et20. After the addition, stirring was continued for 10 min, and then a solution of 50 g piperonal in 200 mL anhydrous Et20 was added over the course of 30 min. The reaction mixture was heated at reflux for 8 h, then cooled with... 

As described in part (b), we prepare propene from 2-bromopropane by E2 elimination. The correct synthesis is therefore... 

In some cases, further functionalization of the preformed phostones allows their more complex derivatives to be obtained. For example, a-alkylation of six-membered 2-oxo-1,2-oxaphosphinanes 62 opens the way to 3-hydroxymethyl-substituted heterocycle 104 as a mixture of cis- and trans-isomers. It is interesting to note that isomeric compounds possess different stability the ds-isomer was isolated in an individual state while the trans isomer easily underwent intramolecular rearrangement to yield the compound 105 bearing the exocyclic phosphoryl moiety (Scheme 59) [134, 135], Furthermore, synthesis of bicyclic compounds 65 (ds-isomers) is based on alkylation of monocyclic phostone by protected 3-bromopropane-l-ol followed by intramolecular transesterification (Scheme 60) [54],... 

If two sets of reagents are available for the synthesis of an alkene, it is better to use the one that requires the less sterically hindered alkyl halide for synthesis of the ylide. Recall that the more sterically hindered the alkyl halide, the less reactive it is in an Sn2 reaction (Section 10.2). Eor example, it is better to use a three-carbon alkyl halide and a five-carbon carbonyl compound than a five-carbon alkyl halide and a three-carbon carbonyl compound for the synthesis of 3-ethyl-3-hexene because it would be easier to form an ylide from 1-bromopropane than from 3-bromopentane. 

SYNTHESIS The Grignard reagent of propyl bromide was made by the dropwise addition of 52 g 1-bromopropane to a stirred suspension of 14 g magnesium turnings in 50 mL anhydrous Et20. 

BF3-etherate added to 2-bromopropanal dimethyl acetal at ca. 5°, and ketene (generated by the pyrolysis of acetic anhydride) bubbled into the mixture for 30 min intermediate ester (Y 85%), added dropwise to a stirred dispersion of KOH in DMF at 0°, stirring continued for 2 h, treated with further powdered KOH at 1 hourly intervals (for a further 4 h), and acidified with 1 M HCl product (Y 84%). F.e.s. P.B. Rasmussen, S. Bowadt, Synthesis 1989, 114-7. 

The synthesis of 46 therefore begins with a Diels-Alder reaction of 18 and methyl vinyl ketone to give 48 (see Section 24.3.2 for regiochemistry and Section 24.3.3 for stereochemistry). Only one step remains 48 reacts with propylmag-nesium bromide, obtained from 1-bromopropane (see Chapter 15, Section 15.1), and an aqueous acid workup to give the target, 46. 

New patent literature dealing with the production of Fluothane (CFa CHBrCl) via reduction of 1,1-dibromo-l-chlorotrifluoroethane with methanolic potash or with isopropanol-u.v. light, the synthesis of the inhalation anaesthetic CHFa CF=CBrCl via dehydrofluorination (soda-lime) of the bromopropane CHFa CFa CHBrCl, the use of fluorocarbon bromides tCFa (CFa) -CFaBr (jf = 4 or 6), Br(CFa) Br (x = 2 or 4), CFa CFBr CFaBr, CeFsBr, or l,2-Br,C,Fa] as contrast media for radio-graphy, and the synthesis of the fluorosilicone —[SiMe(CHa CHa CFa-CFa CCla) 0] — via free-radical addition of the bromide CCla-CFa CFjBr across the double bond in ethylene is now available. Free-radical addition reactions of dihalides of the type X(CF2) X (X = Br or I) are referred to... 

Following is a retrosynthetic scheme for the synthesis of the tricyclic diene on the left. Show how to accomplish this synthesis from 2-bromopropane, cyclopentadiene, and 2 - cyclohexenone. 

Synthesis of piperitone can be worked out from methyl vinyl ketone, ethyl acetoacetate and 2-bromopropane, where in aU steps alkylation, Michael addition and an aldol condensation medium strong base are needed, e.g., NaOEt/EtOH. For decarboxylation of intermediary TM 4.11b, mildly acidic conditions are convenient. 

If you want to synthesize an alkene, you should choose the most hindered alkyl halide possible in order to maximize the elimination product and minimize the substitution product. For example, 2-bromopropane would be a better starting material than 1-bromopropane for the synthesis of propene because the secondary alkyl halide would give a higher yield of the desired elimination product and a lower yield of the competing substitution product. The percentage of alkene could be further increased by using a sterically hindered base such as f rf-butoxide ion or DBN instead of hydroxide ion (Section 10.10). 

Devise a synthesis of Apetinil, an appetite suppressant, firom each of the following starting materials, (a) l-phenyl-2-bromopropane (b) l-phenyl-2-propanone... 

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