jo, to je fakt. Já si pořád nějak neuvědomuju, že v tomhle případě se bavíme o průmyslové výrobě :-)

BORAG: ja by som povedal, ze technicky salicylaldehyd pri odbere niekolkych ton bude celkom lacny. :)

http://www.acros.com/DesktopModules/Acros_Search_Results/Acros_Search_Results.aspx?search_type=CatalogSearch&SearchString=salicylaldehyde

1kg za 60 Eur, to jeste jde, ne..

LIBRIUM: teda to mě docela překvapuje. Spíš co se ceny látek týče. Používáš chlornitrobenzen, ten je tedy asi o stovku levnější než mnou použitý nitrofenol (resp. jeho redukovaná forma). Druhým reagentem je v tvém případě salicylaldehyd a ten jsem před nějakou dobou potřeboval a byl docela nepříjemně drahý. Já volil chlorbenzaldehyd, tam bych tak kilo tipoval na 1500.

nie som si uplne isty, ale myslim, ze takto nejak ho vyrabali Briti pre potreby armady a policajnych zloziek.

Mel bych novy navrh pro chemiky. Obrazky stale neumim, takze snad to pujde takto. Je to lakrimator - latka CR. (dibenzo-1,4-oxazepin)

jaj, no...dost casto plati pravidlo, ze ked nieco mozes urobit v jednom kroku s +- podobnym vytazkom a cistotou, tak "rozporcovanie" do viacerych krokov, pokial nedocieli vyrazne vyssiu ucinnost, selektivitu atd je to be omitted.

LIBRIUM: No, uz jsem nenasel vytezek te "druhe" redukce, ale mozna mas pravdu.. 2 stepy i ve vysokem vytezku dost srazi overall vytezek.. a navic proc delat 2 stepy, kdyz to jednim jde jednodusse a ve slusnem vytezku.

zatimco LAH si tak dobre nevede..

20 grams of LAH was added to 200ml THF in a 1000ml two-necked RB flask, equipped with a magnetic stirrer, and it fizzed some, but not much. Now 20 grams of the above nitrostyrene was added dropwise as a solution in 200ml THF through a dropping funnel, which caused the solution to boil, and when all had been added, the solution was allowed to reflux for 24 hours. The reaction mixture was allowed to cool, and 15ml IPA, followed by 15ml 15% NaOH solution, 30 ml THF, and finally 50ml of cold water, as fast as the exothermic reaction allowed. The solution now became a white sludge, which was filtered through a pad of celite, and the filter cake washed with some additional THF. The solvent was removed under vacuum, and the residue dissolved in dilute H2SO4, and washed with 3x25ml CH2Cl2, made basic with 25% NaOH solution, and extracted with 3x30 ml CH2Cl2. The extracts was dried over MgSO4, filtered, and the solvent removed under vacuum. The residue was distilled at 3 mmHg to give 10 grams (57%) of a slightly yellow oil, 2,4-dimethoxy-3-methylphenetylamine.

WILDENBURY_SQ: no a prave, ked si tie dva kroky spocitas, vyjde ti max. 78.7% vytazok, ak su ti bohovia nakloneni a s predpokladom, ze tu zadany substrat pobezi rovnako dobre alkebo lepsie...proste si stale myslim, ze one-pot redukcia rovno na amin by bola lepsia...

LIBRIUM: citacia jen pochybne reference narkomanu z volne pristupnych "chemickych" webu :) Solidni reference ve skole, kde ted nejsem..

1-(2-fluorophenyl)-2-nitropropane

4,15g NaBH4 stirred happily in 50ml EtOAc and 10ml EtOH at 15°C. 5g 1-(2-fluorophenyl)-2-nitropropene was added in small portions. Be careful here! The first 250mg or so caused a violent bubbling, much more than the earlier ones. The temp rose 8°C from that small portion. Wierd! When 1/3 had been added the suspension turned to a thick white paste which had to be diluted with more EtOH. So another 10ml EtOH was added. Kept on adding happily, but kept a close eye on the temp. When 2/3 was added, another 10ml EtOH had to be added. Paste again! The total amount of EtOH added was 30ml. This will cause a problem in the workup since it will carry the ester and some product over to the water phase. This time I destroyed the borohydride with dropwise addition of diluted acetic acid to the rxn vessel. When this was done, 100ml toluene was added together with 50ml brine. The solvent layer washed two times with water, once again with brine, dried and stripped of solvents in a rotovap.

Yield; 4,3g (84,9%) 1-(2-fluorphenyl)-2-nitropropane as a clear yellow oil. Purity; 97% (HPLC)



1-(2,4,5-trimethoxyphenyl)-2-nitropropane

25,3g (100mmol) 1-(2,4,5-trimethoxyphenyl)-2-nitropropene was added portionwise to a suspension of 11,4g (300mmol) NaBH4 in 150ml AcOEt and 43,2ml (1,2mol) EtOH @ 20-25 deg C. An ice-water bath needed to cool the reaction mixture. The addition took 25 minutes. It was the allowed to stir at room temp for an additional 20min. Excess borohydride was destroyed with diluted acetic acid. When gas evolution ceased 100ml toluene and 150ml brine was added. The organic phase was washed twice with water (2x100ml) and once again with 100ml brine. The solvent was dried with MgSO4 and stripped off in a rotovap. The residue solidified to a clear yellow cake. This cake was dissolved in 150ml MeOH which gave a bright yellow solution. To this solution 500ml ice-cold water was added. This gave in 5min a thick slurry of colorless fluffy crystals which were filtered off and dried.

Yield 23,7g (92,9%) 1-(2,4,5-trimethoxyphenyl)-2-nitropropane

WILDENBURY_SQ: citacia? dovolim si zapochybovat, ze AR-CH=CH-NO₂ --> AR-CH₂CH₂-NO₂ --> AR-CH₂CH₂-NH₂ pojde s 90+% vytazkom tymi metodami.
zato beta-nitrostyren pridavany k prebytku LAH v refluxujucom THF, alebo pri hydrogenacii na Adamsovej platine pod MPa vodiku, pojde na primarny amin s dost dobrym vytazkom v kvazi jednom kroku/one pot (redukcia na enamin/imin, s okamzitou dalsou redukciou na amin).

LIBRIUM: ha, ale tohle povazuji za vylozene vyborny napad! :)

Premyslim nad duvodem, proc by to melo bezet s hydroxidem, ale s propargylatem ne.. a nic me nenapada..

WILDENBURY_SQ: nukleofilny atak bromarenu hydroxidom za katalyzy medou pojde asi celkom dobre, ale zase, ked uz propargyrylalkohol, preco si to nezjednodusit a nestiahnut tie dva kroky do jedneho s pouzitim propargylatu ako nukleofilu?

LIBRIUM: no, tahle dvoukrokova redukce se pry dela.. uvadi se vytezky nad 90%, to alanat myslim nedava u prime redukce nitrostyrenu..

WILDENBURY_SQ: tedy ani kys. katalyza pry neni potreba (!)

Jsou 2 veci, ktere budou, obavam se, delat problemy. Jak jsi zminil, ethylbenzen na acetofenon, to bude tricky oxidation. Pak je jeste jeden navod s KMnO4, FeCl3 na alumine pri velmi nizke teplote, ktera se necha pomalu rust na RT.. Ale KMnO4 u relativne citliveho substratu, kde se muze lecos oxidovat... ehm :)

A dalsi vec, co mi povite na tu reakci bromaromat -> fenol? Dle referenci to jde solidne, mechanismem S(N) Ar.. A kupodivu i na substituovanem jadre a selektivne. Verite tomu?

no, neviem. ja by som to urobil s praopargyrylbromidom a ta reduckia nitrostyrenoveho segmentu najskor na nasyteny nitrocykloalkan a az potom na amin mi pride zbytocna, ked by to slo v jednom kroku na amin s dobrym vytazkom napriklad alanatom.

LIBRIUM: ten propargynylalkohol, tomu jsem se take divil. jde to naprosto hladce i s nim. Ten je dostatecne kysely na to, aby protonizoval ten alkohol.. A protoze ten alkohol je vpodstate "allylova poloha" (je tam tedy trojna vazba, ale vznikajici karbokation toho alkoholu furt bude krasne stabilni..), karbokation krasne atakuje vznikly.. deprotonizovany fenol.

To se pouziva v prumyslove synteze robalzotanu, v navode podobnem prumyslove vyrobe, ktery jsme meli k dispozici videt.