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15AZOTLI GETEROTSIKLLAR SINTEZIDA ALKINLAR INTERNAL VA TERMINAL TUZILISHINING AHAMIYATI
Egamberdiyeva Rohatoy Mamajonovna
Namangan muhandislik-texnologiya instituti Kimyo kafedrasi o'qituvchisi Dadaxanova Gulnoza Axmadjonovna Namangan muhandislik-texnologiya instituti, mustaqil izlanuvchi https://doi.org/10.5281/zenodo.7440999
Annotatsiya: Ushbu maqolada azid-alkin siklobirikish reaksiyasi va uning katalizatorlari, shuningdek, jarayon borishiga alkinlar tuzilishining ahamiyatiga oid tadqiqot ishlari natijalari keltirilgan.
Kalit so'zlar: klik-kimyo, azid-alkin siklobirikish reaksiyasi, katalizator, triazol.
Yangi-yangi samarador biologik faol birikmalarni kashf qilish ko'p sonli molekulyar strukturalarni saralab olish va sintez qilishni talab qiladi. Yuqori unum bilan boradigan bir nechta ishonchli reaksiyalardan foydalanish kerakli moddalarlarning sintezini sezilarli darajada soddalashtiradi va shu bilan yangi birikmalarni yaratish jarayonini tezlashtiradi. Bunday reaksiyalarni amalga oshirishda umumiy nom bilan "klik-kimyo" deb ataluvchi azid-alkin siklobirikish, tio-yenol birikish, Dils-Alder reaksiyasi va boshqa usullardan foydalaniladi.
Ayniqsa, azid-alkin siklobirikish reaksiyalarining "klik-kimyo"dagi o'rni beqiyos bo'lib, bu mavzuda jahonning eng taniqli olimlari tadqiqot ishlarini olib borishgan. Jumladan, amerikalik kimyogarlar - Karolin Rut Bertotssi va Barri Sharples hamda daniyalik kimyogar Morten Meldallar "klik-kimyo va bioortogonal kimyoni rivojlantirganliklari uchun" 2022 yil Nobel mukofotini qo'lga kiritishdi.
Azid-alkin siklobirikish azidlar va alkinlar o'rtasidagi reaksiya bo'lib, bunda
1,2,3-triazollar hosil bo'ladi.
Reaksiya birinchi marta 1893 yilda amerikalik kimyogar A.Maykl tomonidan
tasvirlangan bo'lib, u fenilazid va asetilendikarbon kislota dimetil efirining efirli eritmasini yopiq ampulada (100°C da 8 soat) qizdirish natijasida almashingan triazol hosil bo'lishini aniqlagan [1]. Reaksiyaning katalitik bo'lmagan varianti 1960-
yillarning boshida Xyusgen tomonidan 1,3-dipolyar birikish reaksiyalari tadqiqining bir qismi sifatida o'rganilgan va adabiyotlarda u Xyusgen reaksiyasi deb nom olgan [2, 3].
Odatda reaksiya 1,3-dipolyar birikish mexanizmiga muvofiq boradi hamda 1,4-
va 1,5-dialmashingan 1,2,3-triazollar aralashmasini hosil qiladi:
PhO—v . . . . /—OPh
- © © + N=N-N
5 4
A . P
™ —Ph * H » N ^
2 Ph * Ph
3a 3b
Reaksiya uchun 2002 yilda Meldal [4] va Sharplesslarning [5] laboratoriyalarida mis (I) katalizatorini qo'llash kashf etilgandan so'ng keng miqyosda o'rganila boshlandi va "klik-kimyosi" [6] kontseptsiyasidagi eng muhim reaksiyaga aylandi.
Mis katalizatorligidagi reaksiyaning bosqichli mexanizmida beqaror oraliq birikmalar - mis asetilenidlarning hosil bo'lishi orqali boradi [7]. Shu sababli, bu reaksiyada faqat terminal alkinlar yuqori reaksion faollikni namoyish etadi. Shu bilan birga, mis atomi o'zining koordinatsiyasi orqali azidga faollashtiruvchi ta'sir ko'rsatadi, bu ham reaksiyaning regioselektivligini belgilaydi. Keyin esa, triazolil-mis hosilasi hosil bo'lishi bilan qaytaruvchi eliminatsiyaga uchragan olti a'zoli metall sikli hosil bo'ladi. Uning gidrolizlanishi natijasida 1,4-almashingan 1,2,3-triazol hosil bo'ladi [8, 9, 10].
R1 — H
N''N'R2
H
R1 CuL, f
[Cuy
R1
■C uU
N=N-N—R2
r1Ac^CuLk
nen^^R2
/
■CuU
Mis asetilenid hosil bo'lishining imkoni yo'qligi sababli internal alkinlarning bu usul bilan reaksiyaga kirishishi imkonsizdek sanalsada, siklik alkinlar ishtirokida reaksiyani amalga oshirish mumkin. Reaksiyani tezlatishga faqat katalizator yordamida emas, balki alkinning faolligini oshirish orqali ham erishish mumkin.
Ushbu yondashuv kuchlanish bilan taminlangan azid-alkin siklobirikish (strain-promoted azide-alkyne cycloaddition, SPAAC) usulini yaratishda qo'llangan [11, 12,
13]. Kuchlanish bilan taminlangan siklooktinni azidlar bilan reaksiyaga kiritish reaksiya kinetikasini yaxshilaydi va sitotoksik hisoblanuvchi mis katalizatorini
qo'llamasdan jarayonni amalga oshirishga imkon beradi [14, 15].
Reaksiya elektronlarning asinxron peritsiklik siljishiga muvofiq standart 1,3-dipolyar siklobirikish sifatida davom etadi. 1,3-dipollikning ambivalent tabiati aziddagi elektrofil va nukleofil markazlarni belgilashga imkon bermaydi, shuning uchun elektron o'tish yo'nalishini ko'rsatish ma'nosizdir. Biroq, hisob-kitoblar shuni ko'rsatadiki, ichki azot atomi eng katta manfiy zaryadga ega [16].
Ж
N
Shunday qilib, azid-alkin siklobirikish reaksiyalarida alkin molekulasining tuzilishi muhim o rin tutadi. Ochiq zanjirli terminal alkinlar ishtirokidagi reaksiyalarni turli katalizatorlarni qo'llash bilan tezlatish mumkin. Siklik alkinlar esa katalizator ishtirokisiz azid-alkin siklobirikish reaksiyalariga kirishadi. Internal alkinlarning klik-kimyodagi reaksiyalari va katalizatorlariga oid tadqiqotlarni davom
ettirish zarur.
Foydalanilgan adabiyotlar:
1. Michael A. Ueber die Einwirkung von Diazobenzolimid auf Acetylendicarbonsauremethylester (нем.) // J. Prakt. Chem. — 1893. — Bd. 48. — S. 94-95.
2. Huisgen R. 1,3-Dipolar Cycloadditions. Past and Future (англ.) // Angew. Chem. Int. Ed. — 1963. — Vol. 2, no. 10. — P. 565-598.
3. Huisgen R. Kinetics and Mechanism of 1,3-Dipolar Cycloadditions (англ.) // Angew. Chem. Int. Ed. — 1963. — Vol. 2, no. 11. — P. 633-645.
4. Tornoe C. W., Christensen C., Meldal M. Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides (англ.) // J. Org. Chem. — 2002. — Vol. 67, no. 9. — P. 3057-3064.
5. Rostovtsev V. V., Green L. G., Fokin V. V., Sharpless K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective "Ligation" of
Azides and Terminal Alkynes (англ.) // Angew. Chem. Int. Ed. — 2002. — Vol. 41, no. 14. — P. 2596-2599.
6. Kolb H. C., Finn M. G., Sharpless K. B. Click Chemistry: Diverse Chemical Function from a Few Good Reactions (англ.) // Angew. Chem. Int. Ed. — 2001. — Vol. 40, no. 11. — P. 2004-2021.
7. M. Soliev, O. Abdilalimov. Reactions of Thymol, Menthol, and 3-Hydroxymethyl-Chamazulene in a Superbase Medium // Spanish Journal of Innovation and Integrity. Volume: 05, 2022. P. 625-628. http://sj ii. indexedresearch. org
8. Wu P., Fokin V. V. Catalytic Azide-Alkyne Cycloaddition: Reactivity and Applications (англ.) // Aldrichimica Acta. — 2007. — Vol. 40, no. 1. — P. 7-17.
9. M.I.Soliev, A.K.Okhundadaev. Theoretical calculations of the electronic structure of the menthol and thymol molecules // Journal of Science and Education. No. 8 (20), 2018. Russia. Journal website: https: //scientificpublication.ru.
10. Nurmanov S.E., Soliev M.I., Mirkhamitova D.Kh. Electronic structure of aromatic acetylene alcohols and modeling of their vinylation // Modern scientific research and innovations. 2015. No. 3. Part 1 [Electronic resource]. URL: https://web.snauka.ru/issues/2015/03/43329 (date of access: 09/13/2022).
11. Baskin J. M., Prescher J. A., Laughlin S. T., Agard N. J., Chang P. V., Miller I. A., Lo A., Codelli J. A., Bertozzi C. R. Copper-free click chemistry for dynamic in vivo imaging (англ.) // Proc. Natl. Acad. Sci. USA. — 2007. — Vol. 104, no. 43. — P. 16793-16797.
12. Soliev M.I., Abdilalimov O., Nurmonov S.E. The reaction for obtaining 3-vinyloxymethyl-chamazulene // Universum: chemistry and biology: electron. scientific magazine 2020.1(79). URL: https: //7universum.com/en/nature/ archive/item/11051 (date of access: 09/26/2022).
13. Soliev M.I., Abdilalimov O., Nurmonov S.E. Technology for the production of vinyl esters of menthol and thymol // Universum: technical sciences: electron. scientific magazine 2021.9(90). URL: https://7universum.com/ru/tech/archive/ item/12254 (accessed 26.09.2022).
14. Agard N. J., Prescher J. A., Bertozzi C. R. A Strain-Promoted [3 + 2] Azide-Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems (англ.) // J. Am. Chem. Soc. — 2004. — Vol. 126, no. 46. — P. 15046-15047.
15. Agard N. J., Baskin J. M., Prescher J. A., Lo A., Bertozzi C. R. A Comparative Study of Bioorthogonal Reactions with Azides (англ.) // ACS Chem. Biol. — 2006. — Vol. 1, no. 10. — P. 644-648.
16. Codelli J. A., Baskin J. M., Agard N. J., Bertozzi C. R. Second-Generation Difluorinated Cyclooctynes for Copper-Free Click Chemistry (англ.) // J. Am. Chem. Soc. — 2008. — Vol. 130, no. 34. — P. 11486-11493.
