Fosforil diazo asetaldehitleri sentez yöntemleri
Synthesis of phosphoryl diazoacetaldehydes
- Tez No: 83073
- Danışmanlar: DOÇ. DR. ÖZKAN SEZER
- Tez Türü: Yüksek Lisans
- Konular: Kimya, Chemistry
- Anahtar Kelimeler: Asetaldehit, Diazo bileşikleri, Sentezleme, Acetaldehyde, Diazo compounds, Synthesizing
- Yıl: 1999
- Dil: Türkçe
- Üniversite: İstanbul Teknik Üniversitesi
- Enstitü: Fen Bilimleri Enstitüsü
- Ana Bilim Dalı: Kimya Ana Bilim Dalı
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: Belirtilmemiş.
Özet
FOSFORIL DIAZOASETALDEHTTLERIN SENTEZİ ÖZET Diazo bileşikleri, karben-karbenoid ara ürünleri üzerinden birçok siklopropanların, heterosikliklerin ve birçok doğal bileşiğin sentezinde kullanılan önemli çıkış bileşikleridir. a-Diazo-P-oksoaldehitler, çok sayıda doğal bileşiğin sentezinde, antibiotiksentezlerinde ve primer amin ile kondenzasyonu vasıtasıyla triazollerin sentezinde çıkış bileşiği olarak kullanılan diazo bileşikleridir. 1994 yılma kadar yalnızca üç örneği bulunan ct-diazo-p-oksoaldehitlerin sayısı, nötral-asidik ortamda piridinyum tuzlanyla diazo transferi ve Vilsmeier- Haack Formilasyonu uygulanmak suretiyle çoğaltılmıştır. Fosforlu diazo bileşiklerinin sentezleri 1970'li yıllarda başlamıştır. Literatürde, fosforu diazo metan, fosforil diazo alkil-aril keton bileşiklerinin sentezi var olmasına rağmen triazol sentezini de mümkün kılabilecek fosforil diazo asetaldehitlerin sentezi mevcut değildir. Bu çalışmada, dietil- ve dimetilfosforil diazo metan bileşiklerine Vilsmeier-Haack-Arnold Formilasyonu uygulanmak suretiyle dietil- ve dimetilfosforil diazo asetaldehit bileşikleri sentezlenmiştir. Fosforil diazo metan bileşikleri, primer aminlerin nitröz asitle diazolanması sonucu elde edilmiştir. Kullanılan primer aminler Gabriel Sentezi ile elde edilmişlerdir.
Özet (Çeviri)
SYNTHESIS OF PHOSPHORYL DIAZOACETALDEHYDES SUMMARY Diazo compounds constitute one of the most important classes of organic chemistry. They can be used to synthesize many cyclopropanes, heterocyclic compounds and natural compounds via carben-carbenoid intermediates generated catalytically, photolycally or thermally (eq 1). R-C-R' ^? »? R-C-R' + N2 (eq.1) 11 catafysist N 2 a-Diazo-P-oxoaldehydes, which can also be used to synthesize some of natural compounds, antibiotics and triazole derivatives, constitute one group of diazo compounds. O R- C- C - cf R = Alkyl, ABcoxy, Aryl II ^H Only three examples of cc-diazo-P-oxoaldehydes were known until 1994 at which time Sezer and Anaç synthesized many of them employing a new and novel diazo transfer reaction using an azidopyridinium salt (eq.2). Vilsmeier- Haack formylation of diazo methyl ketones, the old synthetic method for a-diazo- P-oxoaldehydehydes, was re-investigated by the same group and new compounds were synthesized again (eq.3). VIR. ~~C CH2 C^ O R-A O :-c: N2 (eq.2) O r4 - C- H + II N2 Me2N=CHCl CI O O Oh R-C-C-C* + R-C-CH2C1 (eq. 3) II ti N, Dihydrofurans, dioxalenes, 1-3-oxazoles and triazoles can be synthesized by reaction of enol ethers/esters, carbonyl compounds, nitriles and amines with o> diazo-p-oxoaldehydes (scheme 1). O R- C- c- cr II O SCL N^R“ N-C-R' H2N- R' Rax^« * o- RC *L,N-R' N Scheme 1. Using of acyldiazo acetaldehydes in organic chemistry. The first three products forms via carbene intermediates, whereas the fourth product forms via an ionic mechanism. Studies on phosphsorylated diazo compounds have begun around 1970s. Although many synthetic methods for phosphoryl diazo methanes and phosphoryl diazo alkyl/aryl ketones exist, there is no synthetic routes to phosphoryl diazoacetaldehydes, which can be used to prepare phosphoryl triazoles. Therefore,.in this study, syntheses of phosphoryl diazoacetaldehydes are aimed for both producing starting materials for new bio-active compounds and for contributing to organic chemistry with its new reactions. vu- p-c-c* R,/ N,.0 H R = Akyl,Alkoxy,Aryl Acyl diazoacetaldehydes are synthesized by both transdiazotization of acyl acetaldehydes in neutral-acidic medium by using azido pyridinium salts as the transdiazotization agent, and using Vilsmeier-Haack formylation of acyl diazomethanes by iminium salts, which are equvalent to formyl chloride (eq.2-3). In basic medium, when the acyl acetaldehydes are reacted with sulfonyl azides as diazo donors, deformylating diazo transfer takes place(Scheme2). ? *° oir'OR”R- C- CH,-CV 2 vH O - H“ O II e R- C - CH-CL Tos- N3 triazen O O II, R- C - CH- (X N II _e N- N- Tcs.1 -cf R-C^J N2..e Tcs- tfH ”H O O e R- C- CH=C- H Tos- N3 triazDİin Of « N^-Tos.O OK, OR“ OH, OR”O II R- C - C- H II N2 -e+ <? Tcs- N-C. ~ ^H Scheme 2. Diazo transfer reaction in basic medium. This behavior of acylacetaldehydes could be explained by two mechanisms during transdiazotization in basic medium. The only diazo compound formed in the reaction is the cc-diazo ketone and can result from the cycloadduct of sulfonyl azide and keto-aldehyde tautomer. Alternatively, an a-diazo-P- oxoaldehyde is formed first, probably via a triazene intermediate, then yields the a-diazo ketone by solvolysis in basic conditions. When acylacetaldehydes are reacted with azido pyridinium salts as the diazo donor in neutral-acidic medium, both oc-diazo-P-oxoaldehydes and a-diazo.ketones form. The reaction proceeds via triazoline cyclo intermediates: a-Diazo- P-oxoaldehydes form via the ring cleavage reaction of the triazoline intermediate. This cleavage ability is due to the tautomerization of the triazoline structure. Diazomethyl ketones, on the other hand, result from the competing retro~(3+2) reactivity of the triazoline intermediate. If the acyl-R group has electron- VHlwithdrawing character, the acidity of triazoline proton increases, therefore, a-diazo- P-oxoaldehydes form more than acyl diazomethanes. If the acyl-R group is electron- releasing, it has less acidity, so, acyl diazo methanes form more than a- diazo-(3- oxoaldehydes because the retro-(3+2) reaction dominates (Scheme 3). r - c- CH2-C Py+ = Et O II R- C- CH=C OH ^H BF, ?N3 I“ Ş oh. ROC \| / retro (3 + 2) N^^-Py AcO”OH 9 N- n HT N, OH *. ROC - C - H + N V ROC OH 1ST I H OH RCO ^CH II N=Py N2 RCO^ ^CH=0 ^ Pv N P NH-NH N2 Scheme 3.Diazo transfer reaction in neutral-to-acidic medium. h2n- Py When the phosphorylacetaldehydes and sulfonyl azides are reacted for diazo transfer in basic conditions, as mentioned before, phosphoryl IXdiazomethanes form. Phosphoryl diazomethanes are also the only diazo product in neutral-acidic medium when azido pyridinium salts are used as the transdiazotization agents (Scheme 4). 0 o RO^ * ^H ROnJI e JO RO^ - ^H O * BF4-Pyt-N.,0 RO N - N=Py RO' O <f jrp-CH=cCu RO^ H p-C-H + ( BF4_Pyl-NH- CHO) N, Scheme 4.Diazo transfer reaction in neutral-acidic medium with phosphorylacetaldehydes. This reaction should form via triazoline intermediate. Phosphoryl diazomethane should result from a synchoronous cyclo-elimination (retro-(3+2)) reaction of triazoline. Triazoline intermediate could form by either dipolar cyclo addition of the pyridinium salt to the phosphorylacetaldehydes ((3+2) addition) or via triazene intermediate. As a result, phosphoryl group with less electron-withdrawing character as compared to its carbonyl analogues causes much less acidity in the triazoline CH proton. Therefore, deformylating diazo transfer takes place in the reaction of phosphorylacetaldehydes and azido pyridinium salts in neutral-acidic medium. In this study, a-diazo-P-oxoaldehydes were obtained by Vilsmeier-Haack formylation reaction of phosphoryl diazomethanes. Phosphoryl diazomethanes were synthesized by Michaelis-Arbuzov reaction (Scheme 5). 3 RO-Jp. O O ı-v RO^p,_c_c* R0< II ^ N2 R=Et,Me i : N-(CMororrethyI)phtalimide ii : H2N- NH2 iii:HN02 iv:ClCH=NMe2+cf v: H20 Scheme 5. Planed route of synthesis of phosphoryl diazo acetaldehydes.
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Türkçe
1987
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