Fosforil diazo asetaldehitleri sentez yöntemleri

Abstract

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.

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). VI R. ~~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+