Hydride with benzyl bromide

The glycoside derivatives 11, 13, 17 could be synthesized by benzylation methods. Starting from galactoside 1, the 4,6-0-benzyhdene 24 was produced first, then directly reacted with benzyl bromide in the presence of sodium hydride, producing 4,6-0-benzylidene-2-O-benzyl galactoside 13 in 30% total yield (Scheme 2). Higher yield of 13 could be obtained by a more complex synthesis route, where the hydroxyl group in 3-... 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

Lithium aluminum hydride reduction furnishes racemic 2-alkyl-l-alkanols in good yields13. Thus, from alkylation of 1,3-diacylimidazolidinone 1 with benzyl bromide followed by reduction, a 73% yield of ra< -2-methyl-3-phenyl-l-propanol is obtained. When this sequence is carried out with (R,R)-1 as starting material, (S )-2-methyl-3-phenyl-l-propanol is obtained in 93% ee [a]D -10.2 (c = 1.1, C6H6) 13. 

The 2,3-dihydrobenzo[6]selenophene (113) yields the oxide (114) on treatment with ozone. The oxide may be ring opened by treatment with sodium hydride and the product of the ring opening can be alkylated by reaction with benzyl bromide. Thermal rearrangement of the oxide yields a 15 85 mixture of compounds (115) and (116) (Scheme 15) (76JOC2503). 

Dihydro-2,5,8-trisubstituted pyrimido[4,5-alkyl halides or alkyl sulfates and sodium hydride in DMF (72YZ1316). If this reaction is carried out with benzyl bromide and sodium hydride, the 1,4-bisbenzyl product can be obtained (73YZ1043). Alkylation of (91) with ethylmagnesium bromide gives the dialkylated product (92) (75CPB1488). 

JAP(K)87/209067]. 1 -Benzy l-6-cyanoperhydropyrido[ 1,2-a jpyrimidine 682 was obtained by the alkylation of 6-cyanoperhydropyrido[l,2-a] pyrimidine 268 (R = CN) with benzyl bromide in the presence of sodium hydride in dimethylformamide. The l-benzyl-6-cyanoperhydropyrido[l,2-alpyrimidine 682 was alkylated at position 6 with alkyl iodides in tetrahy-drofuran at -78°C in the presence of lithium diisopropylamide to afford 6-alkyl-l-benzyl-6-cyanopyrido[l, 2- ]pyrimidines 680. 

Methyl 2,3-di-0-benzyl-oc-D-glucopyranoside gives 58% of 2,3,6- and 21% of 2,3,4-tri-0-benzyl ether on reaction with 1.4 equiv. of sodium hydride and benzyl bromide [71]. In a remarkably selective reaction, 62% of methyl 2,4,6-tri-0-benzyl-a-D-glucopyranoside result from the unprotected methyl a-D-glucopyranoside [74]. Benzyl chloride has been used for this transformation, as well as for the efficient synthesis of methyl 2,4-di-0-benzyl-a-D-xylopyranoside [75] 1 As expected, OH-2 in methyl 4,6-0-benzylidene-a-D-glucopyranoside is more reactive [71] than OH-3. 

Imidazole or pyridine mediated silylation of l,2-0-[l-exo-ethoxy )ethylidene]-oc-D-glucopyranose failed to give a high yield of the 6-silyl ether due to some polymerization and side reactions. Activation of hydroxyl groups via a tributylstannyl intermediate followed by the tetrabutylammonium bromide catalyzed reaction with tert-butyl-chlorodiphenylsilane was more successful [231], the 6-0-silyl derivative being isolated in 87 % yield.. The lability of this protecting group under benzylation with benzyl bromide and sodium hydride at 0 °C has been observed [449]. 

Reaction of unsubstituted sucrose with benzyl bromide in the presence of silver oxide or sodium hydride affords 2-O-benzylsucrose, obtained in 80% yield among other monosubstituted products together with small amounts of products etherified at positions V and 3 (Scheme 3).60,61 Mixtures enriched in ethers at the same positions are also obtained in electrochemical etherification (Table I).62... 

The Step 3 product (0.133 mol) was added to a slurry of sodium hydride (0.175 mol) in 350 ml DMF, then stirred 15 minutes, and treated with benzyl bromide (0.176 mol) and stirred an additional 48 hours at ambient temperature. The mixture was dissolved in 300 ml methyl alcohol/ THF, 1 1, then treated with 5M NaOH at 50°C until the precipitate dissolved. The mixture was then treated with 12 M HC1 until a pH 2 was obtained and the precipitate was isolated. The solid was washed with water, then dried 48 hours at 40°C, and the product isolated in 87% yield as a white solid, mp = 248—250°C. 

Treatment of the azido diacetal 256 with benzyl bromide and sodium hydride yielded the ether 257 quantitatively (Scheme 33).106,107 And this was subjected to azide reduction to give amine 258, and subsequent deacetonation gave 259. 

OSilyl migration is usually considered a nuisance. However, Lassaletta and Schmidt1 M exploited the reaction to good effect in a synthesis of glycosphingoli-pid precursor 95.4 which had previously required a 14-step sequence from lactose [Scheme 4.95]. Thus treatment of 95.1 (4 steps from lactose) with sodium hydride and benzyl bromide in DMF caused l,2-0-silyl migration of the thexyl-... 

Many sensitive substrates would not survive the ravages of sodium or potassium hydride and the attendant alkoxide anions. There are gentler methods, An alcohol can be protected with benzyl bromide in the presence of silver I) oxide in... 

Potassium diphenylarsenide-2-dioxane reacts with (—)-menthyl chloride in boiling tetrahydrofuran to give (lS,2S,5i )-( + )-neomenthyldiphenylarsine, (S)-( + )-175 (neo-menars). The arsine was obtained as colourless needles in ca 40% yield after recrystallization from warm methanol (Table 9). The neomenthylarsine, upon reaction with benzyl bromide in benzene, affords the epimeric (li ,2S,5i )-benzylmenthylarsonium bromide, (i H-f-)-176, which, upon reduction with lithium aluminium hydride, affords (l/t,2S,5K)-diphenylmenthylarsine, (J )-( — )-177 (menars) (equation 25). 

The molecular size of an alcohol and the steric bulkiness around a hydroxyl group of the alcohol are expected to influence the rate of the benzylation reaction on zeolite. In this respect, the benzylation of five primary alcohols of different sizes was studied by use of K Y (heterogeneous conditions) in comparison with the results obtained by a conventional, homogeneous method [sodium hydride and benzyl bromide in tetrahydrofuran (THF)], as shown in Table III. The steric hindrance around the hydroxyl groups of the alcohols examined was estimated by use of Corey-Pauling-Koltun (CPK) molecular... 

The hydroxy group of the cyclopenta[alkylated with benzyl bromide in dimethylformamide in the presence of sodium hydride and copper bronze, in boiling xylene in the presence of copper bronze, or in boiling 2-butanone in the presence of potassium bicarbonate. ... 

An improved synthesis of 3,4-dihydro-lH-2,l-benzothiazin-4-one 2,2-dioxide (237) was reported by Lombardino and Treadway.154 N-Methyl-sulfonylanthranilic acid methyl ester (242) with benzyl bromide and sodium hydride gives the N-benzyl derivative (243) which directly cyclizes to l-benzyl-4-oxo-3,4-dihydro-IH-2,1 -benzothiazine 2,2-dioxide (244). Catalytic hydrogenation of 244 then gave 237 (Eq. 49). Lombardino155 prepared... 

As mentioned before structure of 2-2 was proposed by spectral analyses, the position of methylenedioxyl group in isoquinoline of 2-2 is in position C-5—C-6, but it did not exclude its possibility in position C-7—C-8. A total synthesis was accomplished in order to confirm the structure and to derive more samples for pharmacological tests. Piperonal 2-4 was used as starting material. It was oxidized by silver oxide in basic condition to get 2-5, then amidized with dimethyl amine to 2-6 and directed ortho-lithiation with n-butyl-lithium in THF (tetrahydrofuran) to get homogeneous yellow solution, which upon treatment with methyl iodide afforded toluamide 2-7, the yield was 85%. The model synthesis study showed that lithiated toluamide 2-7 could condense with compound 2-14 to achieve the final product 2-2 through several steps (see below). The intermediate compound 2-14 could be synthesized starting from the same piperonal 2-4. It was reacted with cyclohexylamine to get Shiff base 2-8, the latter was reacted with 1.13 equiv. of n-butyllithium at -78°C, the metalated intermediate was carbethoxylated in situ by addition of excess ethyl chloroformate and the aldehyde 2-9 was obtained by extraction with dilute acid. Combination of 2-9 with equimolar of propane-1,3-dithiol a compound 2-10 was obtained, then 2-10 was reduced by lithium aluminum hydride and benzylated with benzyl bromide to 2-12. After treatment with bis(trifluoroacetoxy) iodobenzene, the obtained compound 2-13 was reacted with benzylamine to get the key compound 2-14. 

Benzylating the hydroxyl group of 437 provides access to a wide variety of useful chiral intermediates containing a more robust protecting group capable of withstanding either acidic or basic reaction conditions. The benzylation is typically carried out with benzyl bromide and sodium hydride in THF [110,131,132] under phase-transfer conditions, and it results in formation of the benzyl ether 537 in approximately 95% yield. Cleavage of the acetonide with either PTSA [110,132] or iM sulfuric acid [131] affords diol 538 in 92% or 98% yield respectively. 

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