Anugrah

Before y ou begin:

A brie f c omment: Some of the schemes had russian w ords in the actual scheme imag es. Some of these ha ve been tr anslated in to english, ho wever some ar e s till in russian. If y ou f eel it is necessary t o tr anslate these w ords (I no long er r emember if the un translated w ords w ere necessary), it ma y in terest y ou t o pass a scr eenshot of the russian w ords in ques tion thr ough Yandex imag e tr anslation.

Solutions t o all pr oblems c an be f ound a t http://www.chem.msu.ru/rus/olimp/welcome.html The russian na tional olympiads ar e on the righ t c olumn titled Всероссийские олимпиады школьников по химии ( or All-Russian Chemis try Olympiads in english). Simply g o t o the y ear that y ou’re looking f or and find the solutions link (f or some y ears this migh t t ake some dig ging)

Lastly, I tried t o r ate some of the ques tions with dif ficulty r atings since I find such things amusing. My advice ho wever is t o not pa y t oo much a ttention t o the numeric al r anking and jus t try the pr oblem if it look s in teresting.

Difficulty Ra ting 1: Generic USNC O s tyle e xtremely short scheme 2: Older ICHO/ older UK CHO (lots of in termediates, hin ts e tc.) 3: Legitima te scheme with beginner r eagents (1987 ICHO #4) 4: Some mor e in termediate r eagents (2016 ICHO #6, har der UK CHOs) 5: Adv anced r eagents, but the pr oblem isn’t tha t har d o verall (2014 ICHO #7) 6: Pr oblem solving r equired, but not t oo long (2016 ICHO #7, sec ond half )* 7: V ery non trivial, but doable giv en enough time and trial & err or 8: Ex treme Cle verness r equired, dif ficult-impossible f or 80-90% of c ampers (2015 ICHO #6) 9: Impossible. (T etracycline, Russian Camp)

*5 & 6 ar e r oughly in terchangeable. Har d r eagents ar e in timidating if y ou’ve ne ver seen them before. Pr oblem solving is alw ays dif ficult. I r anked 6 abo ve 5 bec ause adv anced r eagents c an be fix ed b y e xperience, but pr oblem solving is some thing y ou need t o w ork f or.

On some ques tions I’ ve le ft hin ts tha t ar e highligh ted in black in c ase y ou don't w ant t o see them. F or e xample: HINT: This is an e xample hin t If y ou w ant t o vie w the hin t, simply highligh t the t ext and the highligh ting will mak e it vie wable (or y ou c an c opy pas te it without f ormatting in to a w ord doc e tc).

Anugrah

2011 Russia T our 1 Class 11 T ask 4 Abridg ed

Substance Y has f ormula C 5 H 8 . F or a long time, this c ompound w as c onsidered the champion in the leng th of one of the C – C bonds (1.62 Å). It is kno wn tha t Y also does not in teract with a solution of KMnO 4 a t 0 ° C. One of the s yntheses of Y w as c arried out fr om cy clopentadiene and DEAD acc ording t o the scheme

4. W rite the s tructural f ormulas of c ompounds G - K , Y .

5. W rite the f ormulas of the thr ee other C 5 H 8 s tha t do not disc olor the pot assium permanganate solution.

2012 Russia T our 2 Or ganic T ask 1 Abridg ed (p t 1) CL-20 is pr epared as f ollows:

Draw B and C .

2012 Russia T our 2 Or ganic T ask 1 Abridg ed (p t 2) Recently, Americ an scien tists ha ve described a series of high-ener gy sub stances based on nitro-containing he teroaromatic c ompounds:

Draw D - I

Anugrah

2011 Russia T our 2 Or ganic T ask 1 In 2009, a s wine flu pandemic s wamped the w orld, the virus of which w as r esistant t o exposure t o c ommonly used M2 pr otein inhibit ors such as riman tadine and aman tadine in the treatment of c onventional flu. E ffective ag ainst s wine flu ar e only c ompounds which inhibit the enzyme neur aminidase. The mos t popular drug of this type is Oselt amivir (tr ade name T amiflu):

This drug w as de veloped b y Gilead Sciences Inc. Scien tists of this c ompany used na tural (-)-shikimic acid as the s tarting ma terial (a simplified s ynthesis scheme is giv en belo w):

1. W rite the s tructural f ormulas of c ompounds A – D , t aking in to acc ount tha t the opening of the thr ee-membered ring b y nucleophiles c an be c onsidered as an e xample of the SN2 r eaction, that is, the a ttack b y the nucleophile pr oceeds a t the less hinder ed c arbon a tom, leading t o inversion of c onfiguration.

Subsequently, se veral other r outes f or the s ynthesis of oselt amivir w ere pr oposed. One of the most e ffective me thods f or pr oducing r acemic oselt amivir fr om simple s tarting c ompounds w as proposed b y a gr oup of scien tists led b y Nobel laur eate E. J. Cor ey:

In L the br omine a tom is loc ated a t the same c arbon a tom as in J .

2. W rite the s tructural f ormulas of c ompounds F – N . Anugrah

AstraZeneca (a British-S wedish pharmaceutic al c ompany) used a dif ferent appr oach t o pr epare Compound M as described in the f ollowing scheme:

3. W rite the s tructural f ormulas of c ompounds P – R.

Oseltamivir is a pr odrug. In the human body , under the action of the enz yme c arboxyl es terase, it is h ydrolyzed t o an activ e f orm.

4. Dr aw the s tructural f ormula of the h ydrolysis pr oduct.

The enan tiomer of oselt amivir pictur ed in the beginning of the ques tion is bioactiv e (of c ourse the other enan tiomer e xists, but it is pr obably not bioactiv e). Indic ate the ab solute configuration of each chir al cen ter of the enan tiomer sho wn a t the beginning of the ques tion.

Anugrah

2011 Russia T our 1 Or ganic T ask 2

Below is a diagr am describing some me thods f or the s ynthesis of barr elene C 8H 8 ( X ), which has long been of in terest t o theor etical chemis ts. The s ynthesis of X w as fir st c arried out b y Zimmerman and Puf fler in 1960, with Coumalic acid ( A ) being t aken as the s tarting c ompound. In 1997, a gr oup of It alian chemis ts pr oposed a mor e e fficient s ynthesis of X , s tarting fr om .

Hydrocarbon X c ontains tw o types of h ydrogen a toms and tw o types of c arbon a toms. Substances B – F ha ve a sec ond-order a xis of s ymmetry (tha t is, the y c oincide with their imag e when the y r otate 360 ° / 2 = 180 ° ar ound a cert ain a xis). Upon o zonolysis of B f ollowed b y treatment with an alk aline solution of h ydrogen per oxide, c ompound N is f ormed, which has two planes of s ymmetry.

1. W rite the s tructural f ormulas of c ompounds B, C , E – N, and X , t aking in to acc ount tha t in none of the s tages sho wn in this diagr am does the c onfiguration in vert a t r eacting c arbon atoms.

2. Ho w man y chir al cen ters ar e ther e in molecule B ? Ho w man y s tereoisomers ar e ther e f or compound B ?

Upon br omination of X , tw o isomer s with the molecular f ormula C 8 H 8 Br 2 ar e f ormed. One the isomer ( O ) c ontains 6 types of h ydrogen a toms; in the other ( P), all h ydrogens ar e nonequivalent. When k ept in an a tmosphere of h ydrogen in the pr esence of a c atalyst a t a moderately ele vated t emperature and pr essure, both isomer s giv e a mix ture of isomeric hydrocarbons Q and R of c omposition C 8H 1 4. In c ompound Q , ther e ar e only tw o types of hydrogen a toms in a 6: 1 r atio, and in c ompound R ther e ar e 5 types of c arbon a toms.

3. W rite the s tructural f ormulas of c ompounds O – R .

Anugrah

Upon irr adiation, X turns in to an isomeric c ompound Y , in which ther e ar e only CH gr oups, and in the molecule ther e ar e 5 types of c arbon a toms. Hy drogenation of Y a t moder ate elevated t emperature and pr essure leads t o the f ormation of a mix ture of R and isomeric product S c ontaining thr ee types of c arbon a toms.

4. W rite the s tructural f ormulas of c ompound Y and S .

(comment: P art 4 of this ques tion is actually v ery in teresting, and w as the idea behind a v ery long ques tion w e had a t c amp 2020 about the phot oisomerization t o Y which I g ot <50% on because I had not seen a r elevant pr eparatory pr oblem, or ma ybe I’ m jus t bad who kno ws lol)

Anugrah

2011 Russia T our 1 Or ganic T ask 3 The simples t ar omatic h ydrocarbon - benz ene - w as isola ted b y M. F araday in 1825 fr om an oily film tha t deposit ed fr om the g as used f or ligh ting. A f ew y ears earlier , a sharp-smelling whit e substance w as isola ted fr om c oal t ar. In 1821, J . Kidd c alled it naph thalene, and in 1826 F araday established its c omposition as (C 5 H 4 ) x . Ho wever, the s tructure of naph thalene w as fir st pr oposed only in 1866. F ollowing is a pair of s ynthetic schemes in terconverting benz ene t o naph thalene which w ere used t o pr ove the pr oposed s tructure w as c orrect.

My c omment: The O 2 /V 2O 5 reaction is a bash which I usually find tiresome. I recommend you at leas t tr y it, but if you ge t held up figuring it out then you migh t wan t t o jus t use m y hin t f or what that specific s tep does be fore you look at the ans wer k ey. T o vie w the hin t simply highligh t the t ext belo w and you should be able t o read it

Hint: The r eaction of Benz ene with O 2/V 2 O 5 pr oduces Maleic Anh ydride (y ou c an look this up if you don’t kno w wha t it is). The r eaction with naph thalene pr oduces an analog ous pr oduct of maleic anh ydride a ttached t o a benz ene ring.

1. W rite the s tructural f ormulas of c ompounds A – I .

So naph thalene c an be c onverted in to benz ene, and also ob tained fr om tw o benz ene molecules. Using a r eaction sequence similar t o tha t used t o c onvert benz ene t o naph thalene, naphthalene itself c an be c onverted in to a t etracyclic ar omatic h ydrocarbon M :

2. W rite the s tructural f ormulas of c ompounds J- M .

The s ynthesis of c omplex poly aromatic h ydrocarbons has a ttracted the a ttention of chemis ts f or many y ears. In 1956, [6]helicene w as fir st s ynthesized: Anugrah

3. Dr aw the s tructural f ormulas of c ompounds N – W . Not e tha t in the 1 H NMR spectrum of compound Q ther e is a double t in the alipha tic r egion.

By the s ynthetic scheme sho wn abo ve, [6]helicene is ob tained in the f orm of a r acemic mix ture, which c an be divided in to tw o enan tiomers.

4. Explain wh y the [6]helicene molecule is chir al, although it does not c ontain as ymmetric carbon a toms.

Anugrah

2013 Russia T our 2 Or ganic T ask 2 Abridg ed The lo w boiling fr actions of the p yrolysis of pe troleum f eed and c oking of c oal c ontain hydrocarbon I , fr om wher e it is e xtracted b y dis tillation (t b oil=40.8 ° C). When s tanding, I slo wly dimerizes t o f orm the only pr oduct II , which, when hea ted, ag ain turns in to I . Homolog ous t o I , compound III (bp 71.3 ° C), w as fir st ob tained b y Wilc ox in 1960 as a r esult of multis tep synthesis fr om 2-me thylcyclohexanol:

HINT (f or scheme): If y ou ar en't sur e about the r egioselectivity of A →B, y ou c an figur e it out b y continuing in the scheme and making some guesses about B →D.

(Identities of I and II ): Cyclopentadiene and its dimer

1. Dr aw A - K and I -III

An a ttempt t o ob tain J b y one-s tage acid deh ydration of G ins tead of G leads t o the f ormation of product L .

2. Dr aw the s tructural f ormula L.

In a benz ene solution a t 20 ° C , I en ter an e xothermic r eaction with the g eometric isomer s M and N , in the fir st c ase, tw o c ompounds O (85%) and P (15%) ar e f ormed, and in the sec ond, the only pr oduct Q .

3. W rite the s tructural f ormulas M – Q , giv en tha t O , P and Q ha ve the molecular f ormula

C9 H 1 0O 4 .

4. Dr aw a (qualit ative) ener gy diagr am of the r eaction of I with M, giv en tha t O is thermodynamically less s table than P .

Anugrah

2013 Russia T our 2 Or ganic T ask 3 The s ynthesis of polyhedr anes whose c arbon sk eleton has the shape of r egular polyhedr a is a difficult t ask e ven f or modern or ganic chemis try. So , dodec ahedrane has the empiric al f ormula CH and is a molecular analog of the r egular polyhedr on of the dodec ahedron.

The fir st a ttempt t o s ynthesize this c ompound w as made in 1964 b y R . W oodward, who proposed t o use f or this purpose the eleg ant, but un fortunately impossible, dimeriz ation of hydrocarbon X . This h ydrocarbon is in teresting in itself , primarily bec ause of its high s ymmetry. X w as s ynthesized b y W oodward as f ollows:

1. W rite the s tructural f ormulas of c ompounds A – I and h ydrocarbon X , if it is kno wn tha t: ● B and C ar e isomer s, and the y c ontain the same number of cy cles and do not c ontain C=C bonds ● E belongs t o the class of cy clic hemiace tals ● In the 1 H NMR spectrum of c ompound X ther e ar e only thr ee signals (double t, double t of triplets and quadruple t with r elative in tegral in tensities of 6: 3: 1).

(1st half is be fore the Pb(O Ac)4 pr oduct in termediate, 2nd half is a fter) HINT (1s t half ): R emember alpha c arbon chemis try

HINT (2nd half ): G →F is a v ariant of the w olff r earrangement

HINT (2nd half ): X is highly s ymmetric

HINT (2nd half ): X doesn’t c ontain Nitr ogen

The s tarting c ompound w as s ynthesized fr om a vailable h ydrocarbons Y and Z :

HBSia 2

2. W rite the s tructural f ormulas of c ompounds Y , Z , J – L . Not e tha t K and L ar e s tereoisomers. Anugrah

2014 Russia T our 2 Or ganic T ask 1

Tetrabenzoporphyrin X, its deriv atives and their c omplexes with me tals attract the gr eat a ttention of chemis ts in c onnection with their use ful properties. F or e xample, the y ar e used t o cr eate field-e ffect tr ansistors, photoelectric elemen ts, and other electr onic de vices. This use is connected, among other things, with the ability of t etrabenzoporphyrins t o form peculiar s tacks due t o the o verlapping of π -orbitals of neighboring molecules ( π-π s tacking). But the same e ffect c auses the lo w solubility of these c ompounds, which not only c omplicates their s ynthesis, but also complicates the manuf acture of the c orresponding electr onic de vice.

In 2012, K orean scien tists of fered their o wn me thod t o a void these dif ficulties. F or this, the y synthesized sub stance I (see diagr am belo w). Their idea is tha t a r elatively highly soluble substance I c an be e ffectively applied t o the desir ed surf ace, and the sub sequent hea ting will lead t o the f ormation of X as a r esult of the elimina tion of f our molecules of g aseous sub stance Y fr om each molecule I.

Пропаргилбромид = pr opargyl br omide DDQ - мягкий окислитель = DDQ is a mild o xidant.

1. Name one na tural sub stance c ontaining porph yrin cy cle. 2. W rite the s tructural f ormulas of c ompounds A -I and Y . 3. Giv en the giv en yields, de termine ho w much pr opargyl br omide (in g) is r equired t o pr oduce 1 g of c ompound I. 4. Compound D e xists in a solution in the f orm of tw o main c onformations, D1 and D2, with the D1 c onformation pr evailing in polar solv ents, and D2 pr edominating in non-polar solv ents. Dr aw these c onformations.

Anugrah

2014 Russia T our 2 Or ganic T ask 3 Abridg ed The Mannich r eaction w as used, f or e xample, t o ob tain the alk aloid Lasubin II. The s ynthesis scheme (f or the r acemic mix ture) of its epimer a t position 2 is sho wn belo w.

2. W rite the s tructural f ormulas A - G, t aking in to acc ount tha t C , unlik e its isomer D , is c apable of en tering in to the halof orm r eaction, but does not giv e the r eaction of a silv er mirr or, B is a salt, and c ompound F c ontains a non-c onjugated double bond.

The Mannich r eaction is used f or aminoalkyla tion and other types of c ompounds tha t c an act as nucleophiles. F or e xample, the s ynthesis of t olmetin, an an ti-inflammatory ag ent used in the treatment of arthritis, arthr osis and the lik e, includes aminoalkyla tion of N-me thylpyrrole.

3. W rite the s tructural f ormulas of c ompounds N-K.

4. During acyla tion of J , along with K, an isomeric pr oduct of acyla tion of L. is f ormed in a small amount. W rite do wn its s tructure, t aking in to acc ount tha t 4 signals ar e pr esent in the ar omatic region of its 1 H NMR spectrum: tw o double ts and tw o single ts.

Anugrah

2014 Russia T our 2 Biochemis try T ask 1 While this is a biochemis try t ask, the sec ond half of it is a good quality scheme, and I quit e enjoyed the firs t half of it e ven though it isn’t c onventional organic.

One of the big gest pr oblems f or mankind in the XXI cen tury is c ancer. The main ther apy of these diseases is sur gery, which oft en pr olongs a per son’s lif e f or some time. Ther e is such a f orm of cancer as glioblas toma of the human br ain. In sur gery of this tumor , the main pr oblem is the visualization of its bor ders. One of the imaging me thods is in traoperative fluor escent na vigation. 2 hour s be fore sur gery, a pa tient is adminis tered a lar ge dose of 5-aminole vulinic acid (5ALA or 5ALK), which is a pr ecursor of pr otoporphyrin IX c ontaining 4 p yrrole rings and ha ving an intense fluor escence, in travenously. This pr oduct selectiv ely accumula tes in abnormal cells. Thus, the sur geon c an clearly mark the bor der of the tumor and c arry out its mor e c omplete removal.

In the human body , 5ALA is ob tained b y c ondensation of succin yl-SCoA and gly cine with the formation of a C – C bond. The r esulting acid is then c onverted t o pr otoporphyrin IX as f ollows:

Hints: A c ontains a p yrrole ring A => B in volves an isomeriz ation s tep B is t etracyclic and made up of f our fr agments, thr ee of which ar e c onnected “head t o t ail”, and the las t one is “t ail t o t ail” 1. Giv e the s tructural f ormulas of sub stances A- E and 5ALA .

Anugrah

In 2011, a gr oup of scien tists fr om the Unit ed St ates de veloped a me thod f or the s ynthesis of porphyrins fr om 2,4-pen tanedione (F) f or a de tailed s tudy of the mechanisms of some enz ymes of the pr otoporphyrin IX bios ynthesis pa thway.

2. Giv e the s tructural f ormulas of the sub stances F-M. When c onverting G t o H, one es ter gr oup is split of f. The c onversion of I t o J a ffects only one gr oup, and trifluor oacetic acid decarboxylates a single c arboxyl gr oup dir ectly a t the he terocycle. Not e also tha t in the connection L = 0.0583. L in its s tructure r esembles c ompound B. In c ompound M, it is necessar y to specif y sub stituents (iden tical sub stitutes ar e equally mark ed).

Fluorescence - the ability of some c ompounds t o emit a quan tum of ligh t when g oing fr om an excited s tate t o the gr ound s tate. This pr ocess is success ful if the s tructure is rigid (pr actically does not chang e when the molecule is e xcited) and has a s ystem of c onjugated bonds. It is s till not kno wn wh y pr otoporphyrin IX selectiv ely accumula tes in c ancer cells; ho wever, in normal cells, this c ompound is tr ansformed in to heme, a c omplex c ompound, wher e the ir on a tom is coordinated b y f our nitr ogen a toms of the p yrrole rings, and the other tw o fr ee orbit al w ater. .

3. Based on the f oregoing, pr edict whe ther heme will sho w fluor escent activity .

Anugrah

2015 Russia T our 1 Class 11 T ask 3 In 1985, Americ an scien tists described the highly s ymmetric c ompound X ha ving only tw o types of c arbon a toms and thr ee types of h ydrogen a toms. This c ompound w as s ynthesized acc ording to the scheme belo w. The main isomer of the Diels – Alder r eaction pr oduct w as c onverted t o compound G b y r eaction with me thanol in the pr esence of an acid c atalyst. The o zonation of G, according t o the author s, g ave c ompound H a fter tr eatment with sodium bor ohydride, which was further c onverted t o F , and the t arget pr oduct X w as ob tained fr om it. Since no physicochemical char acteristics of F - H and X w ere giv en in this w ork, in 2013 Fr ench scien tists studied this s ynthesis mor e thor oughly and f ound tha t under the described c onditions, ins tead of H, a tricy clic c ompound (I, С 1 7Н 1 8О 5 ) is ob tained, which, ho wever, upon r eduction with LiAlH 4 (and sub sequent neutr alization) giv es the same c ompound F, which under the pr eviously described c onditions turns in to X .

Fr ench scien tists ha ve pr oposed a modified s ynthesis scheme X , acc ording t o which B is fir st reduced with lithium aluminum h ydride t o c ompound C . The f ollowing s teps ar e sho wn in the scheme belo w.

Draw the s tructural f ormulas of c ompounds A – I and X .

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2015 Russia T our 1 Class 11 T ask 4 Abridg ed In 2004, K orean scien tists used the me tathesis r eaction t o f orm a cy cle f or the s tereoselective synthesis of the alk aloid (+)-allosedamine (X).

3. Giv e the s tructural f ormulas of c ompounds A , B1, B2, C1, C2, D – G. Not e tha t B1 / B2 and C1 / C2 ar e pair s of dias tereomers, while in the molecules B1 and C1 one chir al cen ter has an R configuration and the other an S c onfiguration.

Attention! A full sc ore is giv en f or s tructures with c orrectly specified s tereochemistry. If the stereochemistry is ab sent or inc orrect, the s tructure is assessed b y an inc omplete sc ore.

Anugrah

2015 Russia T our 2 Biochem T ask 3 Fingerprints ar e the r esult of secr etions fr om the surf aces of the fing ers. B y themselv es, these precipitates ar e 99% w ater, the r est ar e sodium chloride and or ganic c ompounds, among which are a mix ture of dif ferent amino acids. The f ollowing s ynthetic pa thways f or amino acids ar e proposed:

1. Decipher the s ynthesis schemes. B is a v ery r eactive sub stance, easily f orms me tal deriv atives. Assume which of the s ynthesis pa ths is the mos t c onvenient t o e xecute. Jus tify y our ans wer. Ninhydrin r eacts with amino acids. The s ynthesis of Ninh ydrin and its r eaction with amino acids are depict ed in schemes belo w.

The f orensic chemis t, suspecting some thing w as wr ong, isola ted the r esulting aldeh yde and analyzed it acc ording t o the f ollowing scheme: Anugrah

2015 Russia T our 2 Or ganic T ask 1

Structure of X (C 1 0H 1 7OH) w as fir st es tablished b y the Russian or ganic chemis t E.E. W agner, who used o xidation f or this r eaction. When X is tr eated with an acidified KMnO 4 solution, when heated, a mainly equimolar mix ture of ace tic acid and acid Y is f ormed. The s tructure of the latter w as c onfirmed b y its c ounter s ynthesis:

2. W rite the s tructural f ormulas of c ompounds A – E , Y .

3. Es tablish s tructure X if its c onversion t o Y in volves the f ormation of a k etone, which o xidizes to f orm E. Not e tha t the o xidation of as ymmetric k etones pr oceeds pr edominantly fr om the side of a less h ydrogenated c arbon a tom.

One of the fir st s yntheses of X w as c arried out acc ording t o the f ollowing scheme:

4. W rite the s tructural f ormulas of c ompounds F - L .

In an acidic medium, X isomeriz es in to a bicy clic c ompound Z, the molecule of which c ontains a plane of s ymmetry. In the f orm of a drug c alled "Euc alyptol," this c ompound, which has antimicrobial and an ti-inflammatory pr operties, is used f or t opical use in ENT pr actice.

5. W rite the s tructural f ormula of c ompound Z .

Anugrah

2015 Russia T our 2 Or ganic T ask 2 Potassium channel activat ors

ATP-sensitive pot assium channels ar e pr esent in endocrine cells, smooth muscle cells and skeletal muscle tissue, e tc. These channels ar e in volved in import ant ph ysiological pr ocesses: hormone secr etion, smooth muscle c ontraction, and neur otransmitter secr etion. The w ork of potassium channels c an be r egulated with the help of special sub stances - activ ators. Such substances ar e activ ely used in medicine f or the tr eatment of h ypertension and angina pect oris, as w ell as br onchodilators.

One of the mos t c ommon pot assium channel activ ators is cr omakalim ( X ). This c ompound c an be ob tained as f ollows fr om c ompound A .

[Mn*] = Chir al Mang anese Comple x

1. Giv e the s tructural f ormulas of c ompounds A – B . 2. Wh y is the chir al c omplex used in the fir st s tage of s ynthesis?

In or der t o ob tain a drug tha t lo wers the secr etion of insulin in the β -cells of the pancr eas, but at the same time minimally a ffects smooth muscle cells, in 2006, Belgian scien tists s ynthesized a number of sub stances of similar s tructure, which, lik e cr omakalim, c ontain a chr omane (dihydrobenzopyran) he terocyclic s ystem. Compound Y turned out t o be the mos t e ffective and selective, the s ynthesis scheme of which is giv en belo w.

3. Giv e the s tructural f ormulas of c ompounds C - G and Y , giv en tha t: ● In the ar omatic r egion of the 1 H NMR spectrum of c ompound D c ontains one signal mor e than f or c ompound C . ● In the alipha tic r egion of the 1H NMR spectrum of c ompound E , ther e ar e only tw o signals with an in tensity r atio of 3:1.

In 2004, T aiwanese scien tists s ynthesized sub stance Z , the s tructure of which is also quit e similar t o tha t of cr omakalim, although Z does not c ontain a chr oman s ystem. Not e tha t compound Z contains tw o six -membered rings. Anugrah

4. Giv e the s tructural f ormulas of c ompounds H - N and Z .

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2015 Russia T our 2 Or ganic T ask 3 Inhibitors of the ar omatase enz yme, which pla ys an import ant r ole in the s ynthesis of es trogen, are used t o tr eat a number of diseases, primarily br east c ancer. Ho wever, these c ompounds ma y not be used f or g ood purposes. Dishones t a thletes use them as doping bec ause the y incr ease testosterone le vels. One of the an ti-cancer drugs of this type used b y doping en thusiasts w as Fadrozole (X), tw o s ynthesis me thods of which ar e sho wn in the diagr am.

Dishonest a thletes also t ake fur osemide (Y), which in itself c annot impr ove r esults, but, being a diuretic, help s t o hide the use of doping. The s ynthesis of fur osemide is pr esented belo w.

Decrypt these schemes. W rite the s tructural f ormulas of c ompounds A – P and Y . Not e tha t:

● A is an uns table in termediate tha t dec omposes slo wly a t lo w t emperatures and quickly when hea ted ● in the ar omatic r egion of the 1 H NMR spectrum of c ompound B , t aken on a de vice with a not v ery high r esolution, ther e ar e 6 signals: tw o double ts, tw o br oadened double ts and two multiple ts with a r atio of in tegrated in tensities of 2: 2: 1: 1: 1: 1 ● in the ab sence of c atalysts, per acids ar e not able t o o xidize the ar omatic cy cle ● the da ta of IR spectr oscopy sho w the pr esence in Y of a s trong in tramolecular h ydrogen bond.

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2016 Russia T our 2 Or ganic T ask 1 The alk enes me tathesis r eaction w as disc overed in 1967, and in 1985 the fir st e xample of metathesis with the participa tion of alk enes and alkynes, pr oceeding b y a similar mechanism, appeared. This r eaction w as used, f or e xample, in the s ynthesis of (±) -dif erolide isola ted fr om a culture of Str eptomyces aur antiogriseus actinom ycetes. Compound A slo wly dimeriz es with the formation of (±) -dif ferolide and its s tructural isomer B e ven when s tanding a t r oom temperature, which sug gests tha t the dif ferentiate is not actually pr esent in this cultur e, but is an artif act of e xcretion:

1. W rite the s tructural f ormulas A and B .

It w as la ter f ound tha t other types of c ompounds also en ter in to similar me tathesis r eactions. So, ir on c ompounds c atalyze the me tathesis r eaction with the participa tion of alkynes and aldehydes.

2. W rite the s tructural f ormula of the pr oduct (C) of the in tramolecular me tathesis r eaction of 2 - [(but -2-yn-1-yl) o xy] benz aldehyde.

Despite all the adv antages of the alk enes me tathesis r eaction, it also has a dr awback: in man y cases mix tures of cis and tr ans alk enes ar e f ormed. Ob viously, the me tathesis r eaction of alkynes is de void of this dr awback. The alkynes me tathesis pr oduct c an be further selectiv ely reduced t o either cis or tr ans alk ene. This appr oach w as r ecently used in the s ynthesis of Kukujolid XI, the pher omone of the Surinamese muk oed Or yzaephilus surinamensis.

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2016 Russia T our 2 Or ganic T ask 2

In modern or ganic chemis try, one of the main me thods f or the s ynthesis of t erminal alkynes is the Se yfert – Gilbert r eaction, the scheme and mechanism of which ar e giv en belo w.

A dr awback of the Se yfert – Gilbert r eaction is the use of a s trong pot assium t ert-butoxide base, which oft en leads t o side r eactions.

1. Sug gest the s tructure of a possible b y-product f ormed fr om phen ylacetaldehyde under the conditions of the Se yfert – Gilbert r eaction.

Side pr ocesses c an be a voided if the Se yfert – Hilbert r eaction is c arried out with the Ohir a – Bes tmann modific ation, when the Z anion (in the above figur e) is g enerated in situ fr om the so-c alled Ohir a-Bestmann Reagent (her einafter denot ed as OBR ) upon r eaction with pot assium carbonate in me thanol. This minimiz es side pr ocesses and achie ves high yields of the desir ed alkyne. In addition, under such c onditions, the reaction c an be c arried out a t r oom t emperature, and not a t –78 ° C.

2. Sug gest a mechanism f or the f ormation of anion Z fr om Ohir a Bes tmann's r eagent under reaction c onditions

In 2013, Br azilian scien tists used the Se yfert-Hilbert r eaction in the Ohir a-Bestmann modification t o s ynthesize the sub stance CMI-977, a pr omising drug f or the tr eatment of chronic as thma. The f ollowing is an encr ypted diagr am of this s ynthesis. Anugrah

3. Giv e the s tructural f ormulas of c ompounds A - G. Not e tha t c ompound C is not r educed b y lithium aluminum h ydride. Another e xample of the use of the Se yfert – Gilbert r eaction in the Ohira – Bes tmann modific ation is the s tereoselective s ynthesis of the alk aloid (-) - s temoamide contained in the plan t St emona tuber osa used in tr aditional Chinese medicine.

4. Giv e the s tructural f ormulas of c ompounds H - Q , giv en tha t O is a bicy clic c ompound and P is a tricy clic

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2016 Russia T our 2 Or ganic T ask 3

1. W rite the s tructure of X giv en tha t it c ontains a qua ternary c arbon.

Instead of an enone, y ou c an also use its s ynthetic equiv alent - an salt of the type + R 3N CH2 CH 2 C(O)R’ , which in turn c an be easily ob tained fr om k etone, and f ormaldehyde by the Mannich r eaction. An e xample of the applic ation of R obinson annela tion is the s ynthesis of sesquit erpene v aleranone (Z), an import ant c onstituent of fr agrant v alerian oil, sho wn in the diagram.

2. W rite the s tructural f ormulas A - G and Z, giv en tha t Z has thr ee chir al c arbon a toms.

The diagr am belo w sho ws one of the fir st s yntheses of v aleranone cr eated in 1986.

5. W rite the s tructural f ormulas of c ompounds H - R, t aking in to acc ount tha t c ompound L contains 2 six -membered rings, Q - 3 cy cles, O is the pr oduct of ace toxylation, and J c ontains one sulfur a tom.

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2017 Russia T our 2 Or ganic T ask 1 Steroid hormones r egulate the vit al pr ocesses in animals and humans. A c ommon f eature of all steroids is the pr esence of a s ystem of f our c ondensed cy cles, thr ee of which ar e six -membered, and one fiv e-membered, as sho wn in the figur e. F or e xample, one of the mos t import ant f emale sex hormones is pr ogesterone (Z), which pla ys an import ant r ole in pr egnancy. The fir st complete s ynthesis, which includes 15 s tages, of pr ogesterone w as published b y W . Johnson in 1971. This s ynthesis c an be divided in to tw o parts. The pr oduct of the fir st is (E) -4-methyldec-3-en-8-inal (X), which is further used in the s ynthesis of pr ogesterone.

1. Giv e the s tructural f ormulas of c ompounds A – C , t aking in to acc ount tha t the c onversion of A to B is a s tepwise pr ocess, including the Kleisen r earrangement (the so-c alled Johnson-Kleisen rearrangement).

The sec ond part of the s ynthesis is sho wn in the diagr am belo w:

2. Giv e the s tructural f ormulas of c ompounds D – L , t aking in to acc ount tha t G c ontains tw o double bonds of the tr ans c onfiguration.

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2017 Russia T our 2 Or ganic T ask 2 Artemisinin (Z) w as disc overed in 1971 b y Chinese pharmac ologist T u Y uu during a sear ch f or cures f or malaria during the Vie tnam W ar. Based on the r ecipe described in a book writ ten in 340 AD e., she isola ted Z fr om w ormwood annually . In 1973, she r eceived dih ydroartemisinin (A), which has a higher an timalarial activity than Z, and then other activ e deriv atives. F or these studies, in 2015 she w as a warded the Nobel Priz e in medicine or ph ysiology. Curr ently, artemisinin and its deriv atives (art emether, art esunate) ar e the s tandard f or the tr eatment of malaria w orldwide. The an titumor activity of c ompound Z has been disc overed in the pas t f ew years, and is no w being t ested as a c ancer drug.

The high c ost and limit ed bioa vailability of Z led t o the need t o sear ch f or s ynthetic me thods f or its pr eparation, allo wing t o incr ease the pr oduction v olume of the drug. Belo w is a scheme f or producing Z fr om art emisininic acid, the c ontent of which in w ormwood is an or der of magnitude higher than the amoun t of art emisinin itself .

1. Decipher the tr ansformation scheme and writ e the pr oduct f ormulas B – E.

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Compound B c an also be ob tained fr om a vailable na tural sub stances - isopuleg ol and citr onellal, which ar e f ound in essen tial oils.

2. Decipher the tr ansformation scheme and writ e the pr oduct f ormulas G – S.

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2017 Russia T our 2 Or ganic T ask 3 In Oct ober 2016 w as the 85th anniv ersary of the birth of K enkichi Sonog ashira, who in 1975 discovered the cr oss c oupling r eaction be tween ar yl halides and alkynes under v ery mild conditions in the pr esence of a tr ansition me tal c omplex Y .

Complex Y c an be ob tained fr om a c ommercially a vailable salt of Z and triphen ylphosphine. Salt Z is ob tained b y c o-crystallization fr om an aqueous solution of tw o halides Q and R . It is kno wn that the c ontent of the tr ansition me tal in Q , Z and Y is 60.01%, 36.17% and 15.16%, espectiv ely.

Tasks: 1. De termine the f ormulas of halides Q and R , salt Z and c omplex Y . Also dr aw the s tructural formula of c omplex Y .

The Sonag ashira r eaction has firmly en tered the ar senal of s ynthetic chemis ts as a r eliable and general me thod f or cr eating a c arbon-carbon sp 2 -sp bond. In 2003, chemis ts fr om T exas published a paper describing the pr oduction of NanoPutians, human-lik e or ganic molecules with a gr owth of about 2 nm. In the s ynthesis scheme of the "nanokid" sho wn belo w, the Sonogashira r eaction is used 4 times!

2. Dr aw the s tructural f ormulas of c ompounds A – L and “NanoKid” ( N).

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2017 Russia T our 2 Or ganic T ask 4 In 1992, a number of c ompounds of similar s tructure, c alled dec arestritins, w ere isola ted fr om the fungus P enicillium Simplicissimum. Curr ently, 20 dec arestritins ar e kno wn tha t ha ve different le tter designa tions fr om A t o O (f or e xample, “ decarestritin A1”). Man y of these compounds ar e of c onsiderable in terest due t o their ability t o inhibit choles terol s ynthesis, therefore, in r ecent y ears c onsiderable e fforts ha ve been made t o de velop me thods f or the synthesis of dec arestritins. So , in 2015, acc ording t o the scheme belo w, the fir st s ynthesis of decarestritin G, a macr ocyclic lact one with a t en-membered cy cle, w as c arried out.

1. Giv e the s tructural f ormulas of c ompounds A – E and dec arestritin G (without stereochemistry). Not e tha t: a) the OsO4 / NMO s ystem is used as an e ffective and highly selective r eagent used ins tead of a neutr al aqueous solution of KMnO4; b) N, N’-dicyclohexylcarbodimide (Cy – N = C = N – Cy) f acilitates the c ondensation r eaction b y binding a w ater molecule. W rite the s tructure of the r esulting pr oduct.

Unlike mos t other dec arestritins, dec arestritin L is not a lact one and does not c ontain a ten-membered cy cle. Ho wever, its high biologic al activity led t o gr eat in terest in him fr om synthetic chemis ts. The diagr am sho ws the fir st s ynthesis of dec arestritin L , c arried out in 1993.

2. W rite the s tructural f ormulas of c ompounds F – P and dec arestritin L , if it is kno wn tha t: ● at the fir st s tage, only one epo xy cy cle is a ffected, and the r eaction pr oceeds acc ording to a mechanism similar t o the SN2 mechanism ● compound L c ontains tw o cy cles.

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2018 Russia T our 2 Or ganic T ask 1 As far back as the end of the 19th century, it was believed that pale skin was characteristic of aristocrats, and dark skin testified to a peasant origin. In the XX century, the opinion of tanned skin changed dramatically, and tanning became popular. However, to date, it has been convincingly proven that excess ultraviolet radiation can cause premature aging and even skin cancer. To protect the skin from the effects of the sun, special creams are used - complex mixtures containing inorganic (usually titanium dioxide and zinc oxide, not more than 8%) and organic substances that can absorb either UV-A (315–400 nm) or UV -B (280-315 nm) radiation. Only some of the substances provide simultaneous protection against UV radiation in the range from 280 to 400 nm. One of these substances is zincate I, the synthesis of which is shown in the diagram below.

1. Write the structural formulas of compounds A – F, given that hydrocarbon A contains 91.3% by weight of carbon.

2. What substances X and Y are we talking about in the problem? Suggest their structure if it is known that X from Y is obtained selectively.

In recent years, a combination of different organic substances has replaced cyanoxate, each of which takes part of the radiation, but in total they cover the entire ultraviolet spectrum. One of the most common and stable substances is Avobenzon II , which absorbs the entire spectrum of UV-A radiation. The protective function of the cream can be enhanced by introducing additional substances that protect against UVB rays, for example, by adding homosalate III .

3. Write the structural formulas of substances G , H , J – L and components of the cream of Avobenzene II and homosalate III , if it is known that K has a cyclic structure.

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2017 Russia T our 2 Or ganic T ask 2 Cardiovascular disease is currently the most common cause of death in people around the world. One of the ways to prevent cardiovascular diseases is to lower blood cholesterol, for which so-called statins are actively used - inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme that catalyzes the limiting stage of cholesterol biosynthesis. Some statins can be isolated from natural sources, others are synthetically produced, for example, atorvastatin (X), first obtained in 1985. It went on sale in 1996 and during this time it won first place in the world among all drugs in terms of sales. The diagram below shows the final stages of the synthesis of atorvastatin (in the form of calcium salt used in practice).

1. Give the structural formulas of compounds A– C and X if four aromatic rings are present in the structure of atorvastatin, one of which contains a heteroatom.

In 2003, an atorvastatin analog appeared on the market - pitavastatin (Y ), also used in the form of calcium salt. Below is a diagram of the synthesis of pitavastatin, carried out in 2015 by scientists from Fudan University in Shanghai.

2. Give the structural formulas of compounds D – Q. Anugrah

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2018 Russia T our 2 Or ganic T ask 3 Platonic molecules In Euclidean space, there are only five regular polyhedra, also called Platonic solids - tetrahedron, octahedron, cube (hexahedron), icosahedron and dodecahedron:

1. Which of the Platonic solids can theoretically have organic analogues with the same carbon skeleton?

Below are the synthesis schemes for compounds X , Y , Y′ , and Z , the framework of which contains one of the polyhedra given above.

To obtain X , the product of [2 + 2] cycloaddition A is irradiated at liquid nitrogen temperature. In this case, compound B is formed, which incorporates a five-membered cycle. The bromination product B , substance C, contains three types of hydrogen atoms in a ratio of 1: 1: 1, and D contains two types of hydrogen atoms in a ratio of 1: 1. Upon exposure to D , gas evolution was detected lighter than air.

2. Give the structural formulas of compounds A – D and X .

3. Give the structural formulas of compounds E – K, Y, Y′ , and Z . Note that:

• Substance G is a salt of a highly symmetric cation; • In the 1 3C NMR spectrum of substance J , only two signals are observed at 0.1 and 171.6 ppm, and in the 1 3C NMR spectrum of Y , two signals are observed at 0 and –20.5 ppm. In the 1 H NMR spectrum, both substances give only one signal at 0.1 ppm.

Upon receipt of K , a substance is released that is a generally accepted standard in 1H NMR spectroscopy for measuring chemical shifts. Anugrah

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2019 Russia T our 2 Or ganic T ask 1 For a long time, it was believed that allene (also called cumulated dienes) should be extremely unstable compounds. For example, the first synthesis of cumulated diene by Burton and von Pehmann in 1887 was originally an attempt to prove the impossibility of the existence of this class of compounds. However, it later emerged that the allens are quite stable, and, moreover, allene fragments are present in about 150 natural compounds. Almost all of these compounds are chiral, and many also exhibit biological activity, due to which they are of interest as objects of complete synthesis.

One of the most famous natural allens is the so-called “grasshopper ” (eng. Grasshopper ketone), which was isolated in 1968 from the protective secret of the grasshopper Romalea microptera living in the southern United States. The structural fragment of the "grasshopper ketone" is also found in other natural alleles, such as fucoxanthin, peridinine, neoxanthin, etc. The first enantioselective synthesis of the "grasshopper ketone" was carried out by the Japanese scientist Kenji Mori in 1973 according to the scheme given below.

1. Give the structural formulas of compounds A – C. Note that in the IR spectrum of substance A there is a band at 3500 cm – 1. Substance B gives only two signals in the 1H NMR spectrum with chemical shifts greater than 3 ppm, and in the IR spectrum - a band at 2200 cm – 1. At the stage of preparation of substance C, two diastereomeric products are formed, of which only one is used to produce the “grasshopper ketone”.

Another example of a natural allen is (-) - apliziallen, isolated in 1985 from the red alga Laurencia okamurai Yamada, and later from the mollusk Aplysia kurodai. This substance, in addition to cumulated double bonds, also has a structural fragment of cis-2,6-dioxabicyclo [3.3.0] octane, which makes it a very nontrivial object for complete synthesis. For the first time (-) - apliziallen was synthesized by Van and Pagenkopf in 2007, which also clarified its structure. Below is a scheme for the synthesis of (-) - apliziallen from intermediate product H according to Van and Pagenkopf, as well as an alternative scheme for obtaining H proposed in 2016 by a group of scientists from the Osaka Institute of Technology. Anugrah

2. Give the structural formulas of the compounds D - P. Note that all compounds, except D and E, encrypted in the scheme, contain two non-aromatic cycles in their structure, and in the 1H NMR spectrum of the substance F there are no signals in the range from 5 to 7 ppm .

The substance M obtained during the synthesis was an inseparable mixture of two epimers with a fourfold predominance of the epimer with the S-configuration of the chiral center formed at this stage. The initial purpose of the synthesis of Van and Pagenkopf was compound X - the enantiomer of the previously proposed structure (-) - aplysiallen. To do this, they carried out the following sequence of transformations with substance M, as a result of which compound X was actually obtained along with the minor diastereomeric product Y:

However, after comparing the NMR spectra of compounds X and Y with the spectra of natural (-) - apliziallen, it became clear that in fact the natural (-) - apliziallen has the structure Y. Next, Van and Pagenkopf modified the synthesis scheme, which allowed them to obtain compound Y without admixture diastereomers (this scheme is given in paragraph 2). Selectivity was achieved due to the fact that compound N was able to be separated from its epimer N ′, formed as a by-product, using column chromatography.

3. Give the structural formula that was proposed for (-) - apliziallen before the synthesis of Van and Pagenkopf. Anugrah

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2019 Russia T our 2 Or ganic T ask 2 The Nobel Prize is awarded for some discovery or invention. However, at least once the committee awarded the prize for the totality of achievements of the laureate. Robert Burns Woodward for 30 years spent about 20 complex syntheses of natural compounds, which previously seemed impracticable, and also made a tangible contribution to the definition of the structures of numerous substances. With its wording, the committee emphasized the uniqueness of the laureate, and Woodward, in turn, promptly completed the complete synthesis of β-lactam antibiotic cephalosporin C specifically for the Nobel ceremony.

1. One of the successful syntheses by Woodward was the preparation of marasmic acid in 1976. You are invited to decipher the transformation scheme carried out by the laureate and bring the structures of substances A to N. Additionally, it is known that substance B contains one cycle and L - 3 cycles

Woodward, together with another prominent chemist, Robert Robinson, based on penicillin hydrolysis products, first proposed the structure of this antibiotic, which later served as the starting material in one of the methods for the synthesis of cephalosporin C, which has a related chemical structure with it. One of the most popular semi-synthetic broad-spectrum antibiotics of this class is amoxicillin, which is synthesized by attaching 2-amino-2- (4-hydroxyphenyl) acetyl chloride to the core of 6-APA.

2. The diagram below shows the products of hydrolysis of amoxicillin. Like the great chemists, you are invited on the basis of these data to suggest its structure. Additionally, it is known that 6-APC contains two condensed cycles with the number of atoms in each cycle exceeding three. Consider that in both cases of hydrolysis there are no other organic products other than those indicated in the diagram. Anugrah

3. How can you spell out the abbreviation 6-APK, based on the structure of the compound? Suggest your option.

Note: At the stage of obtaining the substance H, a mixture of two was formed in a 1: 1 ratio, which was further used without separation. Because of this, substance I was also obtained as a mixture of two isomers, which at the next stage gave the same product J. As the correct answer for compounds H and I, either of two possible isomers is counted

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2019 Russia T our 2 Or ganic T ask 3 (-) - α-Zedren - sesquiterpene, a bright representative of the class of terpenes. It is obtained from wood scraps of virgin cedar growing in the northern states of the United States, and it is also found in some species of juniper. The first complete synthesis of the racemic α-zest was performed by Stork and Clark in 1955. In subsequent years, alternative methods for the synthesis of α-zest were proposed by other synthetic chemists, including the future Nobel laureate Elias James Corey. Below is a diagram of one of these syntheses, carried out in 1978 by Canadian scientists (for simplicity, the diagram shows the structure of the natural enantiomer α-cue, although in fact this way the racemic mixture of enantiomers was obtained)

1. Give the structural formulas of compounds A - I. In 1983, Solas and Volinski proposed the stereospecific synthesis of (-) - α-peadin from (+) - pulegon through the intermediate formation of another sesquiterpene - (-) - α-acoradiene (T), whose carbocation cyclization in (-) - α-pead at that time was already known. The scheme of this synthesis is given below.

2. Give the structural formulas of compounds J - T. Note that all substances ciphered on the scheme, except for compound J, contain at least one five-membered cycle in their structure. Compounds L, M and N in the 1H NMR spectrum give the following signals with chemical Anugrah shifts of more than 3 ppm: L - one signal at 11.6 ppm, M - no signal, N - four signals at 9.7, 4.8, 4.75 and 3.9 ppm Compounds L and M are isomers.

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2019 Russia T our 2 Or ganic T ask 4 [m.n] Coronanes are polycyclic hydrocarbons with an interesting structure, containing an m-membered central ring, to the sides of which n-membered rings are adjoined. In 1987, Lutz Fitjer synthesized [6.5] coronane according to the scheme given below.

Compounds B and C have the same empirical formulas and the same number of signals in their NMR spectra (2 signals in the 1 H NMR spectrum and 4 signals in the 1 3C NMR spectrum), but the molar mass C is 1.5 times the molar mass of B . In the IR spectrum of compound F there are two intense bands in the frequency range of 1650-1800 cm– 1, while the G spectrum has only one band in this region. None of the compounds A – J shown in the diagram contains conjugated double bonds or rings with more than 6 carbons. I and J contain six rings, none of which is four-membered. Regroupings of the adjoined rings occurs in exactly two distinct stages of the [6.5] coronane synthesis.

1. Give the structural formulas of compounds A- J . 2. Calculate the percent yield of [6.5] coronane given the percent yields in each step shown above.

Shortly after the synthesis of [6.5] coronane, Fitjer synthesized [4.5] coronane from the same precursor (cyclobutanecarboxylic acid chloride) according to the following scheme:

Note that compound L does not contain a single four-membered cycle.

3. Give the structural formulas of compounds K and L .