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.

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.

WILDENBURY_SQ: prave preto sa pouziva roztok v tetrachlormetane. tam nema co "horiet", ergo sa vybusnina nekona (ak je Tetan dostatocne zriedeny).

LIBRIUM: ad NaBH4 .. Opet, to se pouziva. na tom samym webu jako nize je treba tohle:

http://www.erowid.org/archive/rhodium/chemistry/nitrostyrene.nabh4.reduction.html

WILDENBURY_SQ: nie. alkiny (na rozdiel od alkenov) nie su natolko pristupne katalytickej hydrogenacii (ide to, samozrejme, ale za ostrejsich podmienok, nez reaktivne substraty). suvisi to s sp-hybridizaciou, resp. bi/koplanarne "vyvazenym" dvom pi-vazbam.

LIBRIUM: a AFAIK, tetranitrometan s org. rozpoustedly jsou myslim strasne jedovate a brizantni a citlive vybusniny.. Nevim, jak zrovna tetrachlormetan, ale nekde jsem to cetl.

LIBRIUM: Ta reakce s INO2 bezi a pouziva se. Protoze jsem doma, nemam pristup na placene chemicke weby, ale treba tady vygooglena reakce:
http://www.erowid.org/archive/rhodium/chemistry/nitryliodide.html

LIBRIUM: A v Tvem postupu.. V tech redukcich a hydrogenacich se nevyznam, jako Ty, ale me pripada, ze jakakoli hydrogenace a) da prednost b) bude redukovat take alkyn .. vedle stabilniho alifatickeho hydroxylu. Tu hydrogenaci s tim mravčanem neznam, tak nevim.

tak 1. preco pri tvorbe toho propargyrylfenyleteru vychadzat z propargyrylalkoholu, ked halogenid alebo mesylat, tosylat atd by O-alkylovaly ten fenol rychlo a lahko...
dalej, nakolko "nitroniumjodid" (ci je vobec ten species stabilny, resp. ci uvedena reakcia bezi ponechavam teraz stranou -- ja by som pouzil ten C(NO₂)₄ v tetrachlore skor a suicidalny teda nie som) nebude oxidovat styrenovu dvojnu vazbu, pri redukcii cyklickeho "beta-nitrostyrenu" borhydridom by som cakal, ze SBH pojde po nitroskupine, je predsa len dost reaktivna, co by mohlo viest az (cez imin) k sek. alkoholu (aj ked amin by asi tiez vznikol za ostrejsich podmienok, redukovat rovno ten nitrostyren s LAH, 1 MPa H₂/PtO₂/AcOH/80°C apod.), no a konecne, oxidacia etyloveho retazca s Se(IV+) na tom pyranovom heterocykle moze robit celkom dost bordel (lakton apod.)...

BORAG: Pak bych se bal ochraneneho ketonu a TFA nebo SOCl2, tyhle podminky to nevydrzi, ochraneny keton je stabilni v bazickem prostredi, ne?

BORAG: Jinak ad Tve reseni, my se tam dost bali diazotace, viz. priprava Stoffu (1), misto toho, abych nitroval, redukoval a provedl diazotaci, pouzivam ten uvedeny sileny zpusob.. Acetofenon a diazotace pry nic moc, ale je to spekulace, nezkousel jsem to.

Tak alespon muzete diskutovat, co podle vas nepujde, bude neselektivni atd.. :(

Jé, ja se omlouvam, ja jsem strasne nepozornej a uz nevim, co s tim mam delat. Ja zadal analog robalzotanu, jehoz syntezu jsme navrhovali.