Gabriel Amine Synthesis

00:06:43
https://www.youtube.com/watch?v=wgHx_AFNqF8

摘要

TLDRSelles orgaanilise keemia osas käsitletakse nime reaktsioone, mis on kasulikud sünteesis ja nimetatud avastajate või arendajate järgi. Reaktsioonide tundmine on oluline, et mõista keemiliste uurimuste konteksti. Käsitlemist alustatakse Gabriel'i sünteesist, mis võimaldab saada primaarset amiini, kasutades ftalimidi soola ja alkillatsiooni. Reaktsioon välistab mitmekordse alkillatsiooni, hoides ära mittevajaliku aluse moodustumise. Gabrieli sünteesi kasutatakse peamiselt primaarsete alküülhalogeniididega. Erinevaid reaktsiooni muundamisi kasutatakse sünteesi laiendamiseks.

心得

  • 🔬 Nime reaktsioonid on tähtsad keemiliste uurimuste ja eksamite mõistmiseks.
  • 🧪 Gabriel süntees tegeleb primaarsete amiinide sünteesiga.
  • 🔍 Ammoniaagi reaktsioonide probleemid lahendab Gabriel süntees ftaliimidi abil.
  • 📉 O-alküleerimise produkt on võimalik kõrvalreaktsioon Gabriel sünteesis.
  • ⚛️ Gabrieli sünteesis kasutatakse tavalist SN2 mehhanismi.
  • 🔄 Deprotektsiooniks kasutatakse hüdralasiini tundlike aminide korral.
  • 🧬 Kasutatakse sageli primaarseid alküülhalogeniide.
  • 🔓 Ftaalimidi negatiivne laeng on delokaliseeritud, mis aitab vältida mitmekordset alkillatsiooni.
  • 🧹 Kergelt happelised tingimused on vajalikud tert-butoksükarbonüülgrupi eemaldamiseks.
  • 💡 Gabrieli sünteesi laiendatakse teistele alkiilhapetele muundamiste abil.

时间轴

  • 00:00:00 - 00:06:43

    See keemia videoseeria käsitleb orgaanilise keemia nimega reaktsioone, mis on nimetatud nende avastajate või arendajate järgi ja on kasulikud sünteesis. On oluline neid tunda, kuna need esinevad tihti eksamitel ja teadustöös. Näidetena on käsitletud reaktsioone nagu Williamsoni eetri süntees ja Grignardi reaktsioon. Nüüd vaatleme Gabrieli sünteesi, mis tekitab primaaramiine. Ajalooliselt oli see keeruline, kuna ammoniaak võib reageerida mitme mehhanismiga, andes soovimatuid kõrvalprodukte. Gabrieli süntees kasutab alküülbromiidi ja ftalimiidi potase soola, läbides SN2 mehhanismi, mis väldib mitmekordset alküülimist tänu suurenenud stabiilsusele ja vähendatud aluselisele reaktsioonivõimele.

思维导图

视频问答

  • Mis on Gabriel süntees?

    Gabriel syntéesi on meetod primaarsete amiinide saamiseks.

  • Kuidas lahendab Gabriel süntees ammoniaagi ja alküülhalogeniidide probleemid?

    Gabrieli süntees lahendab ammoniaagi ja alküülhalogeniidide probleemid, kasutades ftaliimidi soola, et vältida mitmekordset alkillatsiooni.

  • Miks on ftaliimid vähem aluselised kui primaarne amiin ja kuidas see aitab reaktsioonis?

    Ftaalimid väldib mitmekordset alkillatsiooni ja mittesobilikku alusseisundit, kuna tema negatiivne laeng on delokaliseeritud süsinik- ja hapnikrühmade vahel.

  • Milliseid alküülhalogeniide Gabriel sünteesis eelistatakse?

    Gabriel sünteesi kasutatakse peamiselt primaarsete alküülhalogeniididega, kuna sekundaarsed alküülhalogeniidid ei ole SN2 reaktsioonides eriti reaktiivsed.

  • Mis on üks Gabrieli sünteesi võimalikest kõrvalreaktsioonidest?

    Gabrieli sünteesi käigus võib tekkida O-alkillatsiooni produkt, mida on isomeerilise N-alkillatsiooniproduktiga raske eristada.

  • Miks ja kuidas viiakse Gabrieli sünteesis läbi deprotektsioon modifitseeritud tingimustes?

    See on oluline kergemreaktsioonidele tundlike aminide puhul, kus kasutatakse hüdralasiini nukleofiilina.

  • Kuidas eemaldatakse tert-butoksükarbonüülgrupp pärast teist alkillatsiooni variatsioonis Gabriel sünteesist?

    Tert-butoksükarbonüülgrupp eemaldatakse kergelt happelistes tingimustes, et lõpuks saada sekundaarset amiini kahe erineva alküülrühmaga.

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  • 00:00:06
    In this organic chemistry series, we’ve learned a handful of name reactions.
  • 00:00:11
    These are reactions with synthetic utility that are named after their discoverers or
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  • 00:00:35
    We’ve already talked about Williamson ether synthesis, Robinson annulation, Claisen condensation,
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  • 00:00:52
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  • 00:00:55
    And now for the next significant portion of this series we are going to investigate many
  • 00:01:00
    more important name reactions.
  • 00:01:03
    First up is the Gabriel synthesis, which is a method of generating primary amines.
  • 00:01:09
    Primary amine synthesis was problematic at one time.
  • 00:01:12
    One could suggest that the SN2 reaction of ammonia with a primary alkyl halide should
  • 00:01:18
    give the corresponding primary amine.
  • 00:01:20
    However, ammonia is not only nucleophilic but also rather basic.
  • 00:01:25
    If the alkyl halide has β-hydrogens, elimination will compete, and large amounts of alkenes
  • 00:01:31
    will be obtained via E2, alongside low yields of the desired amine.
  • 00:01:38
    Even if the alkyl halide has no β-hydrogens, the reaction still works poorly, because the
  • 00:01:43
    primary amine that is produced is also rather nucleophilic, and will engage in sequential
  • 00:01:48
    alkylations, yielding complex mixtures of primary, secondary, and tertiary amines, and
  • 00:01:54
    even some quaternary ammonium salts.
  • 00:01:58
    The first general solution to this problem was discovered by German chemist Siegmund
  • 00:02:03
    Gabriel, and published in Chemische Berichte in 1887.
  • 00:02:08
    The reaction is still of synthetic importance, so let’s get a closer look.
  • 00:02:13
    Gabriel reacted a primary alkyl halide, in particular almost always alkyl bromides, although
  • 00:02:19
    alkyl iodides can also be used, with the potassium salt of phthalimide in a highly dipolar solvent
  • 00:02:26
    like DMSO or DMF.
  • 00:02:28
    This reaction follows a typical SN2 mechanism.
  • 00:02:32
    Phthalimide can be seen as a doubly protected version of ammonia.
  • 00:02:36
    This “protection” avoids multiple alkylations and imparts reduced basicity onto the nucleophile,
  • 00:02:43
    which makes E2 eliminations unlikely.
  • 00:02:46
    The reason this substrate is less basic than a primary amine is because it has its negative
  • 00:02:51
    charge delocalized across two carbonyl groups, which means it is highly stabilized and therefore
  • 00:02:57
    less prone towards acting as a base.
  • 00:03:00
    Once the substitution process has taken place, the phthalimide moiety has to be hydrolyzed
  • 00:03:05
    away.
  • 00:03:06
    This can be done under very strongly acidic or basic conditions.
  • 00:03:10
    However, if the amine has sensitive functionalities, it is best to carry out the deprotection under
  • 00:03:16
    modified conditions, using hydrazine as a nucleophile.
  • 00:03:21
    These nitrogen atoms attack these two carbonyls, which will eventually push this nitrogen out
  • 00:03:26
    of the ring to produce the amine.
  • 00:03:30
    This process is milder and yields a phthalyl hydrazide along with the desired primary amine,
  • 00:03:36
    the latter of which can be extracted into an aqueous acidic phase, whereas the hydrazide,
  • 00:03:42
    being a neutral compound, stays in the organic layer or precipitates out and can be filtered
  • 00:03:47
    off.
  • 00:03:48
    Now this synthesis is generally performed on primary alkyl halides.
  • 00:03:53
    With secondary alkyl halides, other methods must be used, because these substrates are
  • 00:03:58
    much less reactive in SN2 reactions, which is the first step of the synthesis.
  • 00:04:05
    There are very few side reactions, but one problem is the potential formation of the
  • 00:04:09
    O-alkylation product.
  • 00:04:12
    Phthalimide is referred to as an ambident nucleophile, because the negative charge which
  • 00:04:17
    does the attacking is localized on both the nitrogen and the carbonyl oxygen, given the
  • 00:04:23
    resonance.
  • 00:04:24
    Normally, the more stable N-alkylation product is obtained, but it is always wise to look
  • 00:04:30
    out for the isomeric O-alkylation product.
  • 00:04:32
    It is actually very difficult to distinguish between these two isomeric alkylation products,
  • 00:04:38
    because they have similar spectral characteristics.
  • 00:04:41
    The distinction requires complex carbon-13 NMR methods, which we will not discuss.
  • 00:04:47
    However, hydrolysis of the O-alkylated product ultimately yields an alcohol, which is neutral
  • 00:04:53
    and can be readily distinguished from the desired amine.
  • 00:04:58
    Now it is certainly the case that this synthetic concept has been fine-tuned by chemists over
  • 00:05:03
    the many decades since its development.
  • 00:05:06
    One useful variation consists of using differentially protected ammonia surrogates.
  • 00:05:11
    Here we see an example involving the use of this benzyl tert-butyl imidodicarbonate.
  • 00:05:19
    In the presence of strong base this compound can be alkylated just as in the Gabriel synthesis.
  • 00:05:25
    Then the benzyloxy carbonyl group can be removed under mild conditions using palladium-catalyzed
  • 00:05:32
    hydrogenolysis, which involves loss of CO2.
  • 00:05:37
    A second alkylation can be carried out in similar fashion, and then the tert-butoxycarbonyl
  • 00:05:43
    group can be removed under mildly acidic conditions, yielding a secondary amine with two different
  • 00:05:50
    alkyl groups, thus considerably expanding the scope of the Gabriel synthesis.
  • 00:05:56
    While such modifications are excellent tools to be aware of, the original Gabriel primary
  • 00:06:02
    amine synthesis is a classic reaction with great utility in modern synthesis, and every
  • 00:06:07
    organic chemist should be familiar with this important reaction.
标签
  • Gabriel süntees
  • nimi reaktsioonid
  • primaarne amiin
  • ftaliimid
  • alküülhalogeniidid
  • N-alkylation
  • O-alkylation
  • SN2 reaktsioonid
  • hüdrolüüs
  • hüdralasiin