Name: metal-free synthesis of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts
Uploaded: 2015-02-24T14:00:00.000+00:00
Duration: 9 min 58 s
Description: Watch this Scientific Journal Video about Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts at JoVE.com

This work was supported by the UOIT start-up fund. We thank Mr. Matthew Baxter (UOIT) for his assistance in the laboratory.

Ynone 1. sentezi <ol><li> Bir analitik terazi kullanılarak, istenen potasyum alkynyltrifluoroborate tuzu (1.5 eşdeğer), 0.15 mmol tartın ve bir manyetik karıştırma çubuğu ile donatılmış bir temiz bir viale eklenmektedir. </li><li> Trifloroborat bir 0.3 M çözelti elde şişeye susuz DCM ve 0.5 ml ilave bir iğne ile donatılmış cam bir piston şırınga kullanarak. NOT: Bu bir yeni metodoloji olduğundan, tepkiler kavramının kanıtı için yapılmıştır. Israfı azaltmak amacıyla bir küçük ölçekte yapılmıştır. Reaksiyon gerektiği gibi daha büyük bir verim elde etmek için ölçeklenebilir. </li><li> Bir cam şırınga kullanılarak, karıştırma ile, oda sıcaklığında (20 ° C) &#39;de tepkime kabına 1.0 M bor triklorür çözeltisi 0.15 mmol (1.5 eşdeğer, 150 ul) damla damla ilave edin. Kapağı değiştirin. Tutun veya reaksiyon çözeltisi sonikatörde su sınırının altında olacak şekilde kapatılmış bir reaksiyon kabı kelepçe. 20 ° C&#39;de 30 saniye için bir çözüm, bir frekans o sonikasyonf 40 kHz. </li><li> Ilave bir 20 dakika boyunca, oda sıcaklığında (20 ° C), reaksiyon çözeltisi karıştırılır. Alkynyltrifluoroborate başlangıç ​​malzemesinin niteliğine bağlı olarak, bir renk değişimi dikkate alınmalıdır. Tan beyaz veya kahverengi koyu kırmızı veya mor gelen bir renk değişikliği yaygındır. </li><li> Karıştırma ile çevre sıcaklığında, şişe (20 ° C) uygun bir asil klorür (1.0 eşdeğer) içinde 0.1 mmol ekleyin. Seçenek olarak ise, bir manyetik karıştırma çubuğu ile yüklenmiş bir şişeye, reaksiyon kabının içerikleri transferi ve asil klorit, 0.1 mmol. Kapağı değiştirin. 30 dakika boyunca oda sıcaklığında (20 ° C), reaksiyon çözeltisi karıştırılır. Not: Genellikle, çok koyu renkli bir değişiklik tepkimenin meydana göstergesidir. </li><li> Bir ince tabaka kromatografisi (TLC), 34 kullanılması, uygun asil klorid standartla karşılaştırılması ile tepkime seyrini izler. NOT: Başlangıç ​​malzemelerinin doğasına bağlı olarak, reaksiyon tamamlanmaya kadar olabilir. birsilindir klorit başlangıç ​​malzemesi, bu yöntem kullanılarak bugüne kadar hazırlanan ynones tüm nihai üründen daha yüksek bir çalışma noktası olarak tespit edilmiştir. <ol><li> Küçük bir cam şişe içinde etil asetat, 1 ml başlangıç ​​malzemesinin asil klorür, yaklaşık 10 mg seyreltilmesiyle asil klorid standardı hazırlayın. </li><li> TLC gözcü kullanarak, TLC plakası başlangıç ​​hattı üzerinde reaksiyon çözeltisi ve standart nokta. Reaksiyon çözeltisi ve standardı ile bir ko-nokta yine, reaksiyon çözeltisi içinde mevcut başlangıç ​​materyali olup olmadığını belirlemek için yararlı olabilir. </li><li> Deneme ve yanılma ile uygun bir TLC mobil faz belirleyin. Ürün 1a hazırlanması için, bir mobil faz 01:30 etil asetat içeriği: ynone ürün ve benzoil klorür, yaklaşık 0.5 ve 0.8 Rf değerleri hekzan sonuç, sırasıyla, başlangıç ​​malzemesi. </li><li> UV ışığı altında geliştirilen TLC plakası gözünüzde canlandırın. Herhangi bir görünür noktalar işaretlemek için bir kalem kullanın. </li></ol></li></ol> 2. Sulu Çalıştırma <ol><li> Reaksiyon kabına soğuk su (yaklaşık 5 ° C) bir 1 ml ilave etmek suretiyle reaksiyonu söndürün. Pasteur pipeti kullanılarak, temiz bir ayırma hunisine çözeltisi aktarın. Bundan başka 10 ml soğuk su ile ayırıcılı bir huniye seyreltmek ve 15 ml etil asetat içine bir kez ürünü çıkarmak. </li><li> Alt sulu katman atılır ve 10 ml su ve 10 ml tuzlu sadece bir kez organik katman, bir kez yıkayın. Temiz bir Erlenmeyer şişesi içine Organik tabakayı toplayın ve magnezyum sülfat ile kurutulur. Gravite filtrasyonu kullanılarak temiz bir yuvarlak dipli bir şişeye solüsyonu filtre. </li></ol> Ynone 3. saflaştırılması <ol><li> Ince tabaka kromatografisi kullanarak, ürünün flaş kromatografisi ile arıtılmış, uygun bir mobil faz belirler. Yaklaşık 0.5 bir tutma faktörü (Rf) herhangi bir geri kalan başlangıç ​​ürünü ayırmak için genellikle yeterlidirmateryal ve ürünleri yan ing. Not: ürün, bir daha düşük Rf değerine sahip olduğu düşük ayrılması durumunda, daha az polar bir çözücü sistemi gibi kullanılabilmektedir. 1-5: 30 aralığında etil asetat karışımı: başlangıç ​​malzemeleri, bir heksan polaritesine bağlı olarak 1, genel olarak uygundur. </li><li> Uygun mobil faz ile ıslak bir sütun içeren silis hazırlayın. Ürün ve yıkama sıvısı ilavesi üzerine rahatsız edici bir silis önlemek için kolonun üstüne kum tabakası ekleyin. </li><li> 40 ° C&#39;de banyo sıcaklığında ve 120 rpm&#39;ye ayarlanmış rotasyonu ile bir döner buharlaştırıcı kullanılarak muamele çözeltisi buharlaştırın. Mobil faz 2 ml şişenin içeriğini çözülür ve dikkatle kolon üzerine eşit bir şekilde bir çözüm yerleştirin. Silika ıslak ama çözücü hat silis yüksekliğini aşmayacak emin olun. Bu durum bazı çözgen ürün silika üzerinde olacak şekilde elüte izin verin. Mobil faz ve tekrar bir miktar ekleyin. </li><li> Col doldurunAşama 3.1 belirlenen mobil faz ile UMN; Ürün 1a durumda, 30: 1 heksan: etil asetat karışımı uygundur. Saflaştırma işlemi hızlandırmak için flaş kromatografisi kullanılarak test tüplerinde kesirler toplanır. Basitçe bir hava çıkışına tüp ile bir adaptör bağlayın. Yıkama sıvısı, uygun bir oranda bir sütun üzerinden akacak şekilde hava basıncını ayarlar. </li><li> Bir TLC plakası üzerinde kolon fraksiyonları, her spot. İsteğe bağlı olarak, bir referans olarak asil klorid standart nokta. Mobil faz aşamasında 1.8 uygun gördüğü kullanarak TLC geliştirin. Ürün asil klorür standardından daha düşük R f olması bekleniyor belirterek, UV ışık altında görülebilen noktalar işaretleyin. </li><li> Büyük bir yuvarlak tabanlı bir şişe içine görünür lekeler içeren tüm fraksiyonlar toplanır. Başlangıç ​​malzemesi daha düşük Rf birden fazla nokta mevcut ise, ayrı şişeler içerisinde toplamak. Bir döner buharlaştırıcı kullanılarak çözücü buharlaştırılmakta ve unde toplanan malzemenin kuruiki saat boyunca yüksek vakum r. </li><li> Eğer gerekirse, bundan başka, bir elektron zayıf asil klorid başlangıç ​​malzemesinden hazırlanan bir ynone ürünün arıtılması için küçük bir sütun üzerinde pentan yıkama yapar. Küçük bir skala üzerinde bu, kolonu gibi bir Pasteur pipeti kullanılarak gerçekleştirilebilir. <ol><li> Pentan ile ıslak bir silis kolonu üzerine kloroform, DCM veya dietil eter ve yükün bir minimum ürün çözülür. Zehir 1-2 sütun sütun aracılığıyla pentan uzunlukları ve atık beher içine toplamak. </li><li> Dietil eter ya da etil asetat kullanılarak pentan sütun saf ynone ürünü elute edin. Ayrı bir şişe içinde eluent toplamak buharlaşması ve iki saat içinde en az yüksek vakum altında yerleştirin. NMR spektroskopisi ile karakterize ürünün yaklaşık 10 mg elde edilir. </li></ol></li></ol> Ynone 4. karakterizasyonu <ol><li> Karakterize 1 H ve 13C NMR spektroskopisi kullanarak nihai ürünün saflığını değerlendirmek. 34Tipik olarak, karbonil karbon kimyasal kayma 13C NMR spektrum 177 ppm yakın görünür. ynone fonksiyonel grubun her iki SP karbon 87 ve 93 ppm yakınında karakteristik zirveleri ile temsil edilmektedir. </li><li> Ynone ürünün karakteristik karbonil tepe noktasını belirleyebilir, kızılötesi spektroskopi 34 kullanın. Komşu üçlü bağ elektron delokalizasyon genellikle karbonil zirve 1.600 ila 1.650 cm görünmesini -1, bileşiğin elektronik özelliklerine bağlı olarak neden olur. </li><li> Ürünün moleküler kütlesi belirlemek ve daha yüksek çözünürlüklü kütle spektrometrisi kullanılarak kimlik doğrulama. 34 </li></ol>

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W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amide&#8208;Forming+Ligation+of+Acyltrifluoroborates+and+Hydroxylamines+in+Water.">Amide&#8208;Forming Ligation of Acyltrifluoroborates and Hydroxylamines in Water.</a> Angew. Chem. Int. Ed. 51, 5683-5686 (2012).</li><li>Mitchell, T. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Dialkyl+Ethers+from+Organotrifluoroborates+and+Acetals.">Synthesis of Dialkyl Ethers from Organotrifluoroborates and Acetals.</a> J. Am. Chem. Soc. 131, 18057-18059 (2009).</li><li>Vo, C. -. V. T., Mitchell, T. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expanded+substrate+scope+and+improved+reactivity+of+ether-forming+cross-coupling+reactions+of+organotrifluoroborates+and+acetals.">Expanded substrate scope and improved reactivity of ether-forming cross-coupling reactions of organotrifluoroborates and acetals.</a> J. Am. Chem. Soc. 133, 14082-14089 (2011).</li><li>Zeng, J., Vedachalam, S., Xiang, S., Liu, X. -. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+C-Glycosylation+of+Organotrifluoroborates+with+Glycosyl+Fluorides+and+Its+Application+to+the+Total+Synthesis+of+(+)-Varitriol.">Direct C-Glycosylation of Organotrifluoroborates with Glycosyl Fluorides and Its Application to the Total Synthesis of (+)-Varitriol.</a> Org. Lett. 13, 42-45 (2010).</li><li>Lehman, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+student's+lab+companion:+laboratory+techniques+for+organic+chemistry:+standard+scale+and+microscale.">The student's lab companion: laboratory techniques for organic chemistry: standard scale and microscale.</a> Pearson College Div. , (2008).</li><li>Molander, G. A., Cavalcanti, L. N., Canturk, B., Pan, P. -. S., Kennedy, L. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+Hydrolysis+of+Organotrifluoroborates+via+Silica+Gel+and+Water.">Efficient Hydrolysis of Organotrifluoroborates via Silica Gel and Water.</a> 74, 7364-7369 (2009).</li><li>Molander, G. A., Ellis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organotrifluoroborates:+protected+boronic+acids+that+expand+the+versatility+of+the+Suzuki+coupling+reaction.">Organotrifluoroborates: protected boronic acids that expand the versatility of the Suzuki coupling reaction.</a> Acc. Chem. Res. 40, 275-286 (2007).</li><li>Calloway, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+Syntheses.">The Friedel-Crafts Syntheses.</a> Chem. Rev. 17, 327-392 (1935).</li><li>Gore, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+acylation+reaction+and+its+application+to+polycyclic+aromatic+hydrocarbons.">The Friedel-Crafts acylation reaction and its application to polycyclic aromatic hydrocarbons.</a> Chem. Rev. 55, 229-281 (1955).</li><li>Groves, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel&#8211;Crafts+acylation+of+alkenes.">The Friedel&#8211;Crafts acylation of alkenes.</a> Chem. Soc. Rev. 1, 73-97 (1972).</li><li>Kim, B. J., Matteson, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conversion+of+alkyltrifluoroborates+into+alkyldichloroboranes+with+tetrachlorosilane+in+coordinating+solvents.">Conversion of alkyltrifluoroborates into alkyldichloroboranes with tetrachlorosilane in coordinating solvents.</a> Angew. Chem. 116, 3118-3120 (2004).</li><li>Thompson, L., Doraiswamy, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonochemistry:+science+and+engineering.">Sonochemistry: science and engineering.</a> Ind. Eng. Chem. Res. 38, 1215-1249 (1999).</li></ol>

The authors declare that they have no competing financial interests.

Tablo 1, tekabül eden ynone ürünü oluşturmak üzere benzoil klorid ile fenilasetilen trifloroborat reaksiyonu koşulları optimize etmek için alınan adımları göstermektedir. Başlangıçta, organodifluoroboranes için organotrifluoroborates dönüştürmek için bilinen katalizörler test edilir. Ne yazık ki silika jel, 35 silikon tetraklorür, 36 ve bor trifluorür 31,32 istenen ynone oluşumunu (Tablo 1, girişleri 1-3) teşvik etmedi. kanıtladı klorlu Lewis asidi katalizör kullanımı daha başarılı olmak için. İstenen ynone 1a düşük verimli bir demir (III) klorür katalizörün (Tablo 1, giriş 4) mevcudiyetinde elde edildi. Daha sonra, alüminyum (III) klorür, Friedel-Crafts açillemeler olarak oxocarbenium iyonu oluşumunu teşvik etmek için, iyi kurulmuş yeteneğinin bir sonucu olarak incelenmiştir., Bir alüminyum (III) klorür katalizörün zaman 37-39 istenen ürün% 62 verim ile elde edildi employed. Daha fazla optimizasyon hava ve nem tepkimenin veriminde (Tablo 1, girişleri 5-7) üzerinde çok az bir etkiye sahip olduğunu göstermektedir. Bunun bir sonucu olarak, daha sonraki reaksiyonlar hava varlığında olmayan kurutulmuş cam malzemede gerçekleştirildi. Çözücünün optimize etmek için girişimler diklorometan (DCM) reaksiyonu (Tablo 1, girişleri 8-12) için özellikle uygun olduğunu göstermiştir. Alüminyum (III) klorür ile katalize edilen reaksiyonlara sonuçlarında tutarsızlıklar alternatif katalizörlerin araştırılmasını teşvik. Ticari olarak elde edilebilen alüminyum (III) klorür heksahidrat, reaksiyon koşulları altında (Tablo 1, giriş 13) altında tamamen etkisizdi. Bu alüminyum (III) klorür hidrat oluşturma reaksiyonunu inhibe ettiği iyi bir göstergesidir. Bor triklorür daha tutarlı (Tablo 1, giriş 14) benzer verimler elde etmek için bulunmuştur. Potasyum alkynyltriflu etkileşimi üzerinebor triklorürle oroborate, daha reaktif organodichloroborane türleri oluşturulmuştur. 40 Bu ilk aşama devam etmek ynone asil klorür ve oluşumu ile reaksiyon için kritik önem taşır. Organotrifluoroborate edilebilir tuzları, DCM içinde çözünür olmadığı için, reaksiyon, heterojen bir karışım olarak gerçekleşir. Bor triklorür ilave edildikten sonra çözelti, reaksiyon için uygun trifloroborat tuzu, yüzey alanını arttırarak, reaktif dichloroborane türlerinin oluşumunun kolaylaştırılması için ses dalgalarına tabi tutulur. Reaksiyon karışımına ultrason dalgalarının uygulama kavitasyon kabarcıklarının hasıl edilmesi ile mekanik etkilere neden olmaktadır. Sonikasyonun sırasında, kavitasyon çöküşü, yüksek sıcaklık ve basınç yerelleştirilmiş alanlarında sıvı sonuçlar kabarcıkları. 41 Şok dalgaları katı trifloroborat tuzlarının kinetik enerji bir artışa neden mikroskobik türbülans oluşturmak üretilmektedir. Sonication promo sırasında sistemin enerji artıştrifloroborat tuzu TES parçalanma bor triklorür ile etkileşim için uygun olan yüzey alanının arttırılmasını elde. Önce asil klorid başlangıç ​​malzemesi ilavesinden tepkime karışımın sonikasyonu daha zorlayıcı koşullar veya daha uzun reaksiyon süreleri için gerek kalmadan reaktif alkynyldichloroborane türlerin verimli oluşumunu sağlar. Şekil 2, fenilasetilen trifloroborat optimum reaksiyon koşulları altında, asil klorürler, çeşitli ile reaksiyona sokuldu zaman elde edilen sonuçlar gösterilmektedir. Nötr aromatik (1b, 1c) ve alifatik (1 i-l), asil klorürler, sentetik olarak yararlı verimlerle gelen ynones vermek. Elektron çeken gruplar nispeten mütevazı verimleri (1h, 1i, 1m) neden olurken elektron verici gruplar (1d-g) taşıyan bu asil klorürler mükemmel verimi sağlamak. Intereelektron çekici grup orto konumunda (1i,% 59) bulunduğu zaman stingly, önemli bir verim artışı benzer para olan karşılaştırılması görülmektedir asil klorür (1h,% 30) ikame edilebilir. orto konumunda ikame sterik etkileşim böylece bir aromatik halkanın bir elektron çekme karakteri dengelemek, düzleminden dışarı karbonil grubu zorlayabilir. Bu 4-bromobutirilbromid klorür% 39 verimle istenen ürün 1m göze tepki dikkati çekiyor. Bildiğimiz kadarıyla, bu bir alkil bromür fonksiyonel grubu tolere ynones sentezi için, ilk bir protokoldür. Başlangıç ​​malzemesi asil klorür nötr veya elektron eksik olduğunda Bazen, alifatik kirlilikler proton NMR görünür. Bu durum, ürünün arıtılması için bir pentan yıkama gerektirebilir. Mümkün iken, ilk arıtma aşaması s sırasında pentan yıkama gerçekleştirmek için ekonomik değildirince pentan, hekzan ile karşılaştırıldığında maliyetlidir. Böyle bir Pasteur pipeti kolonu gibi daha küçük bir ölçekte ayrı olarak ikinci bir arıtma işleminin tamamlanması önemli ölçüde gerekli pentan miktarını azaltır. Şekil 3, reaksiyonun verimi üzerine alkynyltrifluoroborate tuzu kimlik etkisini göstermektedir. Genel olarak, bir aromatik halka üzerinde bir fenilasetilen trifloroborat tuzu taşıyan bir elektron verici ikame türevleri mükemmel verimler (2a-c, 3a-c) iyi istenen ynones üretilmesi için aromatik ve alifatik asil klorürler ile reaksiyona sokulmuştur. Alifatik alkynyltrifluoroborate tuzlan daha az reaktif substratlar olduğunu kanıtladı. Hexynyl- ve cyclopentylethynyltrifluoroborate tuzlan elektron açısından zengin bir benzoil klorür türevleri (4a, 5a) ile reaksiyona sokuldu zaman mütevazı verimler elde edilmiştir. Sonuç olarak, hazırlama O için yeni bir yöntemle def asil klorür ve potasyum alkynyltrifluoroborate tuzlarından ynones geliştirilmiştir. mütevazı gelen asil klorür doğasına bağlı olarak iyi bu yöntem aralığının ile ynones sentezi için elde edilen sonuçlar ve başlangıç ​​maddeleri trifloroborat. Genel olarak, elektron verici ikame edicilerine sahip olanlar başlangıç ​​malzemeleri, nötr ve elektron çekici fonksiyonel grupları taşıyan başlangıç ​​malzemeleri daha kolay tepkimeye girerler. Bu yaklaşımın değeri yöntemin operasyon kolaylığı ve fonksiyonel grup tolerans yer alır. Bu basit, tek-kaplı bir reaksiyonun hava ve nem hariç tutulmaksızın bor triklorür varlığında, oda sıcaklığında hızlı bir şekilde ilerler. Bu uygun yöntem asil klorürler ve alkynyltrifluoroborate tuzlarının çeşitli mükemmel verimler mütevazı olarak ynones hazırlanmasında kullanılabilir.

The intention of this video is to demonstrate a straightforward approach for the preparation of compounds containing an ynone functional group from convenient starting materials. Ynones are valuable building blocks in organic chemistry that have been shown to have biomedical and material significance. Ynones are precursors to valuable organic functional groups including pyrimidines,1,2 quinolones,3 furans,4 pyrazoles,5,6 flavones,7 oximes,8 and chiral propargylic alcohols.9-11 A more convenient method for the preparation of ynones has been sought as a result of the drawbacks of traditional methods including poor functional group tolerance and tedious synthetic routes.
The reaction of metal12,13 and metalloid14 acetylides with acyl chlorides is one common route for the preparation of ynones. Alternatively, the synthesis of ynones from acyl chloride can be achieved via two-step procedures using Weinreb amides and organolithium or Grignard reagents.15 Another prevalent approach includes the addition of organolithium or Grignard reagents to an aldehyde, which is followed by the oxidation of a secondary alcohol to the corresponding ketone.16-19 Poor functional group tolerance of metal acetylides and the need to purify synthetic intermediates after each step are main deficiencies of the aforementioned methods. Transition-metal-catalyzed carbonylative couplings have recently emerged as an alternative approach for the preparation of ynones.20-22 Unfortunately, in addition to cost and toxicity associated with transition metals, metal-catalyzed carbonylative reactions often require elevated CO pressures and suffer from the presence of an undesired Sonogashira coupling byproduct. Given their utility in organic synthesis as well as the drawbacks associated with traditional synthetic methods, the development of a more straightforward method for the preparation of ynones is appealing.
Potassium organotrifluoroborate salts have recently emerged as versatile reagents in organic synthesis. Advantages including ease of preparation,23 inherent stability, low toxicity, and good functional group tolerance have made organotrifluoroborate salts attractive synthetic reagents.24-27 Organotrifluoroborate salts have been used primarily as a bench-stable equivalent of boronic acids for palladium-catalyzed Suzuki-Miyaura coupling.26 Recently, following a seminal work by Matteson and co-workers,28 Bode, Molander and others have highlighted the utility of organotrifluoroborates as reagents in non-metal catalyzed reactions.29-33 The field of transition-metal-free reactions of trifluoroborates is still in its infancy stage. Given the great potential for use of organotrifluoroborate salts in non-metal catalyzed organic synthesis, we sought to develop a novel method for the preparation of ynones from acyl chlorides and alkynyltrifluoroborate salts.

<table><tbody><tr><td>Sonicator</td><td>VGT</td><td>1860QT</td><td>Ultrasonic cleaner. Similar sonication devices may be used.</td></tr><tr><td>Dichloromethane</td><td>Sigma</td><td>270997</td><td>Anhydrous</td></tr><tr><td>Boron trichloride solution&amp;nbsp;</td><td>Sigma</td><td>178934</td><td>1 M solution in DCM</td></tr><tr><td>Acyl chloride</td><td>Sigma</td><td>Various</td><td>Acyl chlorides from other suppliers such as Alfa Aesar may be used. Caution: refer to MSDS for safety information.</td></tr><tr><td>Potassium alkynyltrifluoroborate salt</td><td>N/A</td><td>N/A</td><td>Synthesized&lt;sup&gt;23 &lt;/sup&gt;from terminal alkyne</td></tr><tr><td>Ethyl acetate</td><td>ACP</td><td>E-2000</td><td>ACS grade</td></tr><tr><td>Hexanes</td><td>ACP</td><td>H-3500</td><td>ACS grade</td></tr><tr><td>Pentane</td><td>Sigma</td><td>236705</td><td>Anhydrous</td></tr><tr><td>Magnesium sulfate</td><td>Sigma</td><td>M7506</td><td></td></tr><tr><td>Filter paper</td><td>Whatman</td><td>1093 126</td><td>Student grade. This speceific variety is not necessary.</td></tr><tr><td>Silica Gel 60</td><td>EMD</td><td>1.11567.9026</td><td>Particle size 0.040-0.063</td></tr></tbody></table>

metal-free synthesis of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride.

Ilk çabalar fenilasetilen trifloroborat S1 ve benzoil klorür (Şekil 1) gelen ynone 1a hazırlanması üzerine odaklanmıştır. Tablo 1 optimizasyon adımları çeşitli Lewis asitleri, çözücüler ve aynı zamanda reaksiyon su etkisinin incelenmesi taranması dahil gerçekleştirilir görüntülemektedir . Daha sonra, tepkime kapsamının asil klorürler çeşitli mevcudiyetinde (Şekil 2) optimize edilmiş koşullar fenilasetilen trifloroborat göndererek incelenmiştir. Mükemmel verimler ile mütevazı asil klorid alt-tabakanın doğasına bağlı olarak elde edilebilir. Reaksiyonun kapsamı daha alkynyltrifluoroborate tuzlarının çeşitli ek örnekleri hazırlanması suretiyle değerlendirilmiştir. 3 gelişmiş koşullar altında ynones hazırlanmasında kullanılabilir diğer alkynyltrifluoroborate tuzların seçilen örnekleri göstermektedir, Şekil. Phen türevlerialkynyltrifluoroborate tuzların alifatik türevleri biraz daha az reaktif verecek mütevazı getirileri olduğunu kanıtladı ise mükemmel verimler iyi karşılık gelen ynone ürünleri tanınan ikame ediciler bağış trifloroborat yatak elektron ylacetylene. <img alt="Şekil 1," src="/files/ftp_upload/52401/52401fig1highres.jpg" /> Şekil 1:. Reaktif ara madde dichloroborane oluşumu da dahil olmak üzere ynone 1a hazırlanması için koşullarını gösteren fenilasetilen trifloroborat S1 ve benzoil klorür Şema gelen Ynone 1a hazırlanması. <img alt="Şekil 2," src="/files/ftp_upload/52401/52401fig2highres.jpg" /> Şekil 2:. Ynone 1a Örnek 1 &#39;H-NMR spektrumu Kimyasal kaymalar ve karakteristik protonların görece entegrasyonlar etiketlenir. Şekil 3:. Ynone 1a Örnek 13C NMR spektrumu karakteristiği karbonlu Kimyasal kaymalar etiketlenir. <img alt="Şekil 4," src="/files/ftp_upload/52401/52401fig4highres.jpg" /> Şekil 4:. Atmosferik basınçta kimyasal iyonizasyon yoluyla elde ynone 1a Örnek HRMS spektrumu [M + H] ölçülen m / z değeri + iyonu bildirilmektedir. <img alt="Şekil 5," src="/files/ftp_upload/52401/52401fig5highres.jpg" /> Şekil 5: kimliği değiştirilerek üretilen ürünler için asil klorürler ile phenylacetylenetrifluoroborate tuzu S1 Reaksiyonları Yapıları ve verimleri.asil klorür başlangıç ​​malzemesinin görüntülenmiştir. Reaksiyonlar asil kloridin 1 eşdeğer, 1.5 eşdeğer potasyum phenylacetylenetrifluoroborate S1 ve 1.5 eşdeğer bor triklorür ile elde edildi. <img alt="Şekil 6," src="/files/ftp_upload/52401/52401fig6highres.jpg" /> Şekil 6:. Asil klorürler Yapılar ve alkynyltrifluoroborate başlangıç ​​malzemesinin kimliği değiştirilerek üretilen ürünlerin verimi çeşitli alkynyltrifluoroborates reaksiyonları tasvir edilmiştir. Reaksiyonlar asil kloridin 1 eşdeğer, 2.5 eşdeğer potasyum organotrifluoroborate tuzu ve 2.5 eşdeğer bor triklorür ile elde edildi. <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> Giriş </td><td> Lewis asidi </td><td> Lewis asidi (eşdeğer) </td><td> Koşullar </td><td> Yol Ver (%) </td></tr><tr><td> 1 b &lt;/ Sup&gt; </td><td> SiO 2 </td><td> 16.5 </td><td> CH2C! 2 </td><td> 0 </td></tr><tr><td> 2 </td><td> SiCl 4 </td><td> 1 </td><td> CH2C! 2 </td><td> iz </td></tr><tr><td> 3 </td><td> BF 3 · OEt&#39;dir 2 </td><td> 1 </td><td> CH2C! 2 </td><td> iz </td></tr><tr><td> 4 b </td><td> FeCl3 </td><td> 1 </td><td> CH2C! 2 </td><td> 24 </td></tr><tr><td> 5 C </td><td> AICI3 </td><td> 1 </td><td> CH2C! 2 </td><td> 62 </td></tr><tr><td> 6 d </td><td> AICI3 </td><td> 1 </td><td> CH2C! 2 </td><td> 66 </td></tr><tr><td> 7 E </td><td> AICI3 </td><td> 1 </td><td> CH2C! 2 </td><td> 60 </td></tr><tr><td> 8 </td><td> AICI3 </sub&gt; </td><td> 1 </td><td> THF </td><td> iz </td></tr><tr><td> 9 </td><td> AICI3 </td><td> 1 </td><td> tolüen </td><td> iz </td></tr><tr><td> 10 </td><td> AICI3 </td><td> 2 </td><td> ClCH 2 CH2Ch </td><td> 33 </td></tr><tr><td> 11 </td><td> AICI3 </td><td> 1 </td><td> DMSO </td><td> iz </td></tr><tr><td> 12 </td><td> AICI3 </td><td> 2 </td><td> asetonitril </td><td> iz </td></tr><tr><td> 13 </td><td> AICI3 · 6H 2 O </td><td> 1 </td><td> CH2C! 2 </td><td> 0 </td></tr><tr><td> 14 b </td><td> BCl 3 </td><td> 1.5 </td><td> CH2C! 2 </td><td> 67 </td></tr><tr><td> 15 </td><td> BBr3 </td><td> 1 </td><td> CH2C! 2 </td><td> 20 </td></tr></tbody></table><strong&gt; Tablo 1:. Ürünün ynone 1a a hazırlanması için koşulların optimum hale getirilmesi Verim Reaksiyon koşulları ve Lewis asidi katalizör değişimi üzerine 1a. Bir Tepkimeler 1 eşdeğer benzoil klorür ve 1 eşdeğer potasyum phenylacetylenetrifluoroborate S1 ile elde edildi. 1.5 eşdeğer S1 b c. Susuz koşullar d. Reaksiyon hava altında olmayan kurutulmuş cam malzemede gerçekleştirildi. E Susuz koşullar + su 1 ul.

Watch this Scientific Journal Video about Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts at JoVE.com

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Asil klorür ve potasyum Alkynyltrifluoroborate Tuzlarından Ynones Metal içermeyen sentezi

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups ...

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11.1K Görüntüleme.  University of Ontario Institute of Technology. The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Video: Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

Yaratma Cyanocarbenes Uygulanması için hipervalent iyodonyum Alkınıl triflatların Sentezi

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

Kimya

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Sentezi İçin Protokol<em&gt; Ortho</em&gt; -trifluoromethoxylated Anilin türevleri

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

Ketonlar ile Enolonium türler Umpolung Functionalization için bir iki adım iletişim kuralı

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the possibility of accessing unique fluorine-containing molecules, which are difficult to obtain by other synthetic pathways. Among various metals, which can undergo C-F activation, lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide metals are strong reducing agents with a redox potential Ln3+/Ln&#160;of approximately -2.3 V, which is comparable to the value of the Mg2+/Mg&#160;redox couple. In addition, lanthanide metals display a promising functional group tolerance and their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic and organometallic transformations. However, due to their oxophilicity, lanthanides react readily with oxygen and water and therefore require special conditions for storage, handling, preparation, and activation. These factors have limited a more widespread use in organic synthesis. We herein present how dysprosium metal - and by analogy all lanthanide metals - can be freshly prepared under anhydrous conditions using glovebox and Schlenk techniques. The freshly filed metal, in combination with aluminum chloride, initiates the selective C-F activation in trifluoromethylated benzofulvenes. The resulting reaction intermediates react with nitroalkenes to obtain a new family of difluoroalkenes.

This protocol describes the preparation of elemental lanthanides under inert atmosphere and their application in a selective C-F activation process involving trifluoromethylated benzofulvenes.

Trifluoromethylated Benzofulvenes için çeşitli Difluoroalkenes erişim sağlayan Seçici C-F aktivasyonu Elemental lantanit uygulanması

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the ...

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

1-Iodoalkynes, 1,2-Diiodoalkenes ve 1,1,2-Triiodoalkenes Terminal Alkynes oksidatif iyodinasyon üzerinde dayalı Chemoselective hazırlanması

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC&#8211;NHC &#8220;Wanzlick&#8221; dimer and the synthesis of the related stable organic &#8220;olefin&#8221; radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick&#8217;s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed &#8220;Wanzlick dimer&#8221; and the reduced stable organic radical.

Ücretsiz Carbenes, karışık dimer ve organik radikaller yalıtma

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

Fonksiyonel Monoorganozinc Bromides Conjugate Ilavesi ile tüm karbon Dörernary merkezlerinin verimli sentezi

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

Acidity of 1-Alkynes

<h4></h4>
The acidic strength of hydrocarbons follows the order: Alkynes &#62; Alkenes &#62; Alkanes. The strength of an acid is commonly expressed in units of pKa &#8212; the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure1left" src="/files/ftp_upload/11833/11833_PT_Figure_1_left.svg" style="text-align: center; height: 75px;" /> 
			Ethane 
			(pKa&#160;= 51)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure1middle" src="/files/ftp_upload/11833/11833_PT_Figure_1_Middle.svg" style="text-align: center; height: 50px;" /> 
			 
			Ethene 
			(pKa&#160;= 44)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;">
			
			<img alt="Figure1right" src="/files/ftp_upload/11833/11833_PT_Figure_1_Right.svg" style="text-align: center; height: 20px;" /> 
			 
			&#160;
			Ethyne 
			(pKa&#160;= 25)
			</td>
		</tr>
	</tbody>
</table>
With a pKa difference of 26 units, acetylene is 1026 times more acidic than ethane. Similarly, a difference of 19 pKa units makes it 1019 times stronger than ethene.
<h4>Hybridization effect</h4>
The pronounced increase in the acidity of terminal alkynes relative to the other hydrocarbons can be explained by considering the stability of the corresponding carbanions formed by deprotonation. Note that, in the nomenclature of organic compounds, the suffix &#34;-ide&#34; indicates that the molecule is a negatively charged ion.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2top" src="/files/ftp_upload/11833/11833_PT_Figure_2_top.svg" style="text-align: center; height: 80px;" /> 
			ethanide&#160;(an alkyl anion) 
			sp3&#160;lone pair, 25% &#8220;s&#8221; character</td>
		</tr>
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2middle" src="/files/ftp_upload/11833/11833_PT_Figure_2_middle.svg" style="text-align: center; height: 60px;" /> 
			ethenide&#160;(a vinylic anion) 
			sp2&#160;lone pair, 33% &#8220;s&#8221; character</td>
		</tr>
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2bottom" src="/files/ftp_upload/11833/11833_PT_Figure_2_bottom.svg" style="text-align: center; height: 40px;" /> 
			acetylide&#160;(an acetylenic anion) 
			sp&#160;lone pair, 50% &#8220;s&#8221; character</td>
		</tr>
	</tbody>
</table>
The stability of the carbanion depends on the nature of the hybridized orbital occupied by the lone pair of electrons. As shown above, in ethane&#160;the lone pair resides in an sp3 orbital, while in ethene&#160;it occupies the sp2 orbital and an sp orbital in the case of acetylene. The sp3, sp2, and sp orbitals have 25%, 33%, and 50% &#34;s&#34; character, respectively. Since &#34;s&#34; orbitals are closer to the positively charged nucleus, a hybrid orbital with a higher &#34;s&#34; character will effectively stabilize the negative charge. Thus, the acetylide ions will be the most stable and readily formed in the presence of a suitable base.
<h4>Choosing a suitable base</h4>
In general, for a base to deprotonate an acid, the pKa of the base&#39;s conjugate acid must be at least 10 pKa units greater than that of the acid.
<img alt="Figure3" src="/files/ftp_upload/11833/11833_Figure_3v2.svg" style="text-align: center; height: 80px;" />
Terminal alkynes have a pKa of 25. Therefore, an appropriate base would be one where the conjugate acid has a pKa that is at least 35. Recall that for an acid-base reaction, the equilibrium favors the formation of weaker acids and bases from stronger acids and bases.
stronger acids + stronger bases <img alt="arrow" src="/files/ftp_upload/11833/arrow.png" style="text-align: center; height: 13px;" />weaker acids + weaker bases
With sodium amide as the base, terminal alkynes form sodium acetylide and ammonia as the conjugate acid. Since the pKa of ammonia is greater than 25, the equilibrium favors the formation of sodium acetylide, making sodium amide a strong enough base for the deprotonation reaction.
<img alt="Figure4" src="/files/ftp_upload/11833/11833_Figure_4.svg" style="text-align: center; height: 100px;" />
Apart from sodium amide, sodium hydride, butyllithium, and lithium diisopropylamide (LDA) are other commonly used bases to form acetylide ions.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;">
			<img alt="Figure5left" src="/files/ftp_upload/11833/11833_PT_Figure_5_left.svg" style="height: 25px;" />
			Sodium hydride
			</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure5middle" src="/files/ftp_upload/11833/11833_PT_Figure_5_middle.svg" style="text-align: center; height: 60px;" /> 
			Butyllithium (n-BuLi)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure5right" src="/files/ftp_upload/11833/11833_PT_Figure_5_right.svg" style="text-align: center; height: 60px;" /> 
			Lithium diisopropylamide (LDA)</td>
		</tr>
	</tbody>
</table>
In the presence of sodium hydroxide as the base, terminal alkynes form sodium acetylide and water as the conjugate acid. However, since the pKa of water is less than 25, the equilibrium favors the reactants. Therefore, sodium hydroxide is not a suitable base to form acetylide ions.
<img alt="Figure6" src="/files/ftp_upload/11833/11833_Figure_6.svg" style="text-align: center; height: 110px;" />
<h4>Synthesis of organometallic reagents </h4>
The relative acidity of terminal alkynes finds application in the synthesis of organometallic compounds when treated with Grignard or organolithium reagents. These are examples of transmetalation reactions involving the transfer of a metal atom from one carbon to another, thereby forming new metal&#8211;carbon bonds. However, they can also be interpreted as acid&#8211;base reactions that favor the formation of weaker acids and bases.
<img alt="Figure7top" src="/files/ftp_upload/11833/11833_Figure_7v3.svg" style="text-align: center; height: 225px;" />
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Acidity of Terminal Alkynes: Formation of Acetylide Anions

1-Alkinlerin Asitliği


The acidic strength of hydrocarbons follows the order: Alkynes &#62; Alkenes &#62; Alkanes. The strength of an acid is commonly expressed in units of pKa ...

Organik Kimya

Alkinler

KEY TERMS AND CONCEPTS

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Alkyne alkylation reaction using NaNH2 and ethyl bromide, chemical equation diagram." src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure1">
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Alkyne ionization reaction equation NaNH2, diagram shows acetylene converting to acetylide ion." src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure2">
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C–C bond.
<img alt="Organic reaction mechanism, Na+ and Br- ion exchange, illustrates chemical synthesis process." src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure3">
<h4>Reaction Mechanism —SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Nucleophilic substitution reaction mechanism diagram with alkynes, NaBr formation, chemical process." src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" data-altupdatedat="1747908711000" data-alt="Figure4">
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Alkyne chain elongation via NaNH₂, CH₃Br; reaction equation diagram for organic synthesis." src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure5">

Alkinlerin Hazırlanması: Alkilasyon Reaksiyonu

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

Preparation of Alkynes: Dehydrohalogenation

<h4>Introduction</h4>
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
<img alt="Chemical reaction diagram, alkyne synthesis, 2NaNH2/NH3, hydrogen elimination, organic chemistry." src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" data-altupdatedat="1747908711000" data-alt="Figure1">
<h4>Reaction Mechanism – E2 pathway</h4>
Vicinal dihalides
In the first elimination step, the strong base abstracts the proton from the dihalide that is oriented anti to the leaving group. Since E2 reactions follow a concerted pathway, the abstraction of a proton and departure of the halide leaving group occur simultaneously to form a haloalkene.
<img alt="Birch reduction mechanism diagram, showing electron flow in organic compound reaction." src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure2">
In the second elimination reaction, another equivalent of the strong base reacts with the haloalkene in a similar fashion to give the desired alkyne.
<img alt="Elimination reaction mechanism diagram, E2 mechanism, showing alkene formation from alkyl halide." src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure3">
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Alkyne formation reaction; sodium amide abstracting proton; chemical equation diagram; synthesis method." src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure4">
<img alt="Chemical reaction mechanism, arrow-pushing diagram, alkyne formation using sodium amide." src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" data-altupdatedat="1747908711000" data-alt="Figure5">
Terminal dihalides 
Dehydrohalogenation of terminal dihalides yields terminal alkynes as the final product. In the presence of a strong base like sodium amide, terminal alkynes get converted to acetylide ions. In such cases, a third equivalent of the base is required to complete the dehydrohalogenation of the remaining haloalkene.
<img alt="Hofmann elimination reaction; chemical equations diagram; synthesis process using NaNH2; alkyne formation." src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" data-altupdatedat="1747908711000" data-alt="Figure6">
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Organic reaction mechanism with sodium acetylide, water; diagram illustrating nucleophilic attack." src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" data-altupdatedat="1747908711000" data-alt="Figure7">
<h4>Application in Organic Synthesis</h4>
Dehydrohalogenation of vicinal dihalides is a useful intermediate step in the conversion of alkenes to alkynes. For example, chlorination of 1-propene gives 1,2-dichloropropane – a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Alkene to alkyne conversion diagram; chemical reaction mechanism, dichlorination, dehydrohalogenation." src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" data-altupdatedat="1747908711000" data-alt="Figure8">
Similarly, alkynes can also be synthesized from ketones via dehydrohalogenation of geminal dihalides. For example, treatment of acetone with phosphorous pentachloride yields 2,2-dichloropropane – a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Organic synthesis mechanism; ketone to alkyne via substitution and elimination; chemical reaction diagram." src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" data-altupdatedat="1747908711000" data-alt="Figure9">

Alkinlerin Hazırlanması: Dehidrohalojenasyon

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ...