Reactions ring-opening

The ring-opening reactions of lithiated derivatives have been reviewed comprehensively. A well-known example of this latter possibility is the ring-opening of 3-lithiobenzo[ ]furan (401) to the lithium salt of 2-ethynylphenol (402) (78CHE353). 

The tendency for the 3-lithio derivatives of furans and thiophenes to undergo ring opening has been exploited for the synthesis of polyunsaturated acyclic compounds. A trimethylsilyl group in the 

Reactivity of Five-membered Rings with One Heteroatom 

3- bromothiophene-2-carbaldehyde (405) also illustrates this point. 

3-Lithio-2,5-dimethylselenophene shows a much greater tendency to undergo ring opening than 

The ring opening reactions of azetidine derivatives have been employed for the synthesis of various acyclic and heterocyclic compounds of biological interest. It would therefore be appropriate to discuss the reactions leading to acyclic and cyclic products separately. 

7(i) Ring opening reactions leading to acyclic products 

The ring opening of 4,4-disubstituted l-tosyl-3-methyleneazetidine-2-carboxylates 53 proceeded smoothly under acidic condition to yield the chiral acyl silane 54 (Equation 12) in quantitative yields and with an enantiomeric excess up to 97% 20030L3691 . 

3-Dichloroazetidines 83 are easily converted into aziridine derivatives 84 in excellent yields by sodium methox-ide in methanol (Equation 22). Conversion to the aziridine ring system has been explained by the intermediacy of a 2-azetine ring system 2002JOC2075 . 

Strained ring systems (epoxides, lactones, etc.) are cleaved by cuprate reagents these reactions have found application in prostaglandin chemistry and in pheromones synthesis. 

Example (see also [13, 14] for other examples) ring opening reaction of lactones [15] synthesis of a pheromone of Danam chrysippys (an African butterfly). 

Moreover, the substitution of allylic acetates affords the product corresponding to a formal Sj 2 substitution reaction [17]. The reaction is therefore remarkably regioselective and stereoselective (in favour of the /rans -isomer) and also chemoselective, since a homoallylic acetate does not react. The stereoselectivity is an indication of the participation of a cyclic transition state involving copper, a transient Tt-allyl copper species can also be formulated but the existence of such Tt-allyl intermediates has never been clearly established (in opposition to metals of Group Vni). 

Details have been published of the base-catalysed ring-opening reactions of a-diketone monothioketals, which give (o-dithianyl carboxylic acids. 

The cycloheptatriene monoepoxide, 8-oxabicyclo[5,l,0]octa-2,4-diene, gave 2,4,6-heptatrienaldehyde as the major primary product on pyrolysis at 2(X) °C. Irradiation of the cycloheptatriene epoxide gave mixtures of 2,4,6-heptatrienealdehyde, cyclo-hepta-3,5-dienone, and 3-oxatricyclo[4,2,0,0 ]oct-7-ene (252). Irradiation of 

2-cyano-2-methylcycloheptanone in methanol gives the unsaturated aldehyde (253). its geometrical isomer, and the methoxyimine (254).  

Sodium periodate oxidations of several cycloalk[h]indoles and their JV-methyl analogues have been reported to give ring-expanded keto-lactams, 

spectrum of cycloheptatriene has been reported. Several studies of mass spectral behaviour of cycloheptatrienes have been described.  

We ve seen a great number of reactions in this chapter and Chapter 10 in which two species combine, resulting in an addition or substitution, or in which a reagent such as acid or base initiates a process. There are some reactions, however, that are inherently unimolecular, not requiring any kind of reagent. Chapter 16 describes unimolecular reactions initiated by the absorption of a photon. Chapter 15 considers unimolecular thermal reactions and rearrangements that involve a cyclic array of orbitals, called pericyclic reactions. 

For the vast majority of organic molecules, however, heating does not lead to an elegant, concerted process involving a cyclic array of orbitals. By far the most common consequence of heating a molecule is simple bond cleavage. For polar molecules in polar solvents, hetero- 

In a reaction of 3H-pyrrolizine (1) with a lithium dicarbenoid species described in Section 8.01.5.4, anion (63) was assumed to be an intermediate which formed the butenyne (64) by ring opening 79HCA540 . A similar ring-opening reaction has been described 82JCR(S)54  

Pyrrolizinones can react with nucleophiles with opening of the carbonyl-containing ring. Pyr-rolizin-3-ones (65) react with alcoholates in alcohol to give ester (66), hydrolysis by dilute sodium 

Bicyclic 5-5 Systems, One Ring Junction N No Extra Heteroatoms 

Dialkylaminopyrrolizin-3-ones (67) were reported to be stable to sodium ethoxide but hydrolyzed by aqueous acid or alkali to give 2-acetylpyrrole presumably via -ketoacids which decarboxylate 

The pyrrolizinimine (68), reacted with methyl iodide or with methylamine in water to give pyrroles (69) and (70) 74LA2ll0 . 

Theory Model without ZPEC with ZPEC 

Influence of substituents upon the reactivity of cyclobutene ring opening 

El -computed with HF/6-31G(d) theory model En - computed with HF/6-31G(d) -f Zero Point Energy Correction (ZPEC) Em - computed with B3LYP/6-3lG(d) Ejv -computed with B3LYP/6-31G(d) + ZPEC Ey - computed with BLYP/6-31G(d) Eyi -computed with BLYP/6-3lG(d) + ZPEC Evil - computed with SVWN/6-31G(d) Eviil - computed with SVWN/6-3 lG(d) + ZPEC Ejx - experimental activation barriers. 

AAEi - Computed with HF/6-3lG(d) theory model AAEn -Computed with B3LYP/6-3lG(d) theory model AAEni - Computed with BLYP/6-3lG(d) theory model DDEiv -Computed with SVWN/6-31G(d) theory model. 

A - difference of atomic charges for carbon atom (C-3) that has substituents and is involved in bond breaking B - The difference of atomic charges for carbon atom (C-4) involved in bond breaking AACj - Computed with HF/6-3lG(d) theory model AACiI - Computed with B3LYP/6-31G(d) theory model AACm - Computed with BLYP/6-31G(d) theory model AACiV - Computed with SVWN/6-3lG(d) theory model. 

Miyadera, E. Ohki, and I. Iwai, Chem. Pharm. Bull. 12, 1344 (1964). 

Acheson et a/.167a found that treatment of quinolizinium 1,2,3,4-tetra-carboxylates with weak aqueous base gave the quinolizones, as shown in Eq. (53), presumably via the monocyclic intermediates. 

When the quinolizinium salt bears a very powerful electron-withdrawing group, ring opening can occur at low temperatures in aqueous acid. Such a group is the diazonium cation, and attempts to diazotize 1-aminoquino-lizinium salts led, via the ring-opened intermediate 196 to triazolo[l,5- ]-pyridines 197-199.133 170-171 jt js noteworthy that the Z double bond is retained in the side chain, and that the deuterium was fully retained when a [2,4-2H2]-l-amino-3-methylquinolizinium salt was treated with nitrous acid, giving compound 200. 

The substituted 4-quinolizones 201 and 202 are hydrolyzed by hot 80% sulfuric acid, giving presumably a pyridone (203) which recyclizes to quino-lones 204 and 205.39 

Diazotization of 1 l-aminobenzo[b]quinolizinium salts 211 and 212 leads to ring opening and formation of pyridotriazoles,77 as reported for bicyclic 

The jS-CD inclusion complexes of aryloxyepoxides with amines afforded amino-alcohols enantioselectively in the solid state. When carried out in water as the reaction medium, nearly racemic aminoalcohols were produced. 

The direct one-pot synthesis of j8-hydroxy selenides was reported. In the presence of j8-CD, highly regioselective ring-opening of oxiranes with benzenesenol was achieved ( 75%). jS-CD could also be recovered and reused. 

The use of CD provides a unique way to study the reactivity of cation radicals of small oligothiophenes and oligopyrroles in water, especially in the case of bithiophene and terthiophene for which the lack of water solubility does not allow such a study. After photochemical oxidation, the cation radical leaves the CD host to undergo coupling with another cation radical, similar to reactions occurring in organic media, with no reaction between cation radicals. 

An oxidative cleavage of cycloalkanones to unsaturated aldehyde-esters has been developed. Thus, for example, cyclononanone was converted into 2,2-dithio-trimethylenecyclononanone, which was cleaved using lead(iv) acetate (66 %), and the product so obtained treated with methanol and sodium periodate to give (208 in = 5). Cyclododecanone was similarly converted into (208 n = 8). 1,2-Bis(trimethyl-silyloxy)cycloalkenes, prepared by acyloin condensations, have been converted into 2-alkyl-2-hydroxycycloalkanones by treatment with methyl-lithium and an alkyl halide, and the oximes of these a-hydroxyketones cleaved to give open-chain co-cyanoketones using mesyl chloride-pyridine.  

The low-temperature [6 + 6]photocleavage of [2,2]cyclophanes has been reported, e.g. [2,2](2,5)furanophane gave 2,5-dimethylene-2,5-dihydrofuran (isolated at — 78°C), [2,2]paracyclophane gave l,4-dimethylenecyclohexa-2,5-diene (detected spectroscopically at — 190°C), and [2,2](l,4)naphthalenophane gave (212).  

9 General Chemistry of Medium- and Large-ring Carbocyclic Compounds 

Unlike heptatrienyl anions, which cyclize to cycloheptadienyl anions even at — 30°C, nonatetraenyl anion is stable at room temperature and cyclization is not observed even at higher temperatures. In fact, (284) reacts with n-butyl-lithium to give (285) which opens to (286 R = Et) even at — 30°C 7-vinyl-cycloheptatriene reacts similarly to give (286 R = Bu ).  

Tsuruta, K. Tomisawa, and T. Mukai, Bull. Chem. Soc. Japan, 1972, 45, 1584. 

Heller, A. Yogev, and A. S. Dreiding, Helv. Chim. Acta, 1972, 55, 1003. 

5-Dimethylcyclo-oct-l-ene isomerizes to 2,6-dimethylocta-1,7-diene at 500°C. Ring-opening polymerization of 5-substituted cyclo-octenes and ozonolysis of (-f-)-5-methoxycyclo-octene are discussed. 

The reaction of cyclo-octatetraene dianion with a variety of esters and anhydrides is reported with ethyl oxalate at — 60°C the tetraene (287) is obtained, via 7,8-disubstituted cyclo-octa-l,3,5-triene, whereas with ethyl acetate the product is (288).  

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Evidence of 3, 4, 8, and 9 was reported by Todesco and coworkers (51, 87, 88), while 2 and 8 were found by Illuminati and coworkers (96). The ring-opening reaction is a slow process in methanol and can be made faster using a solvent such as DMSO. 

Angle strain is the main source of strain in epoxides but torsional strain that re suits from the eclipsing of bonds on adjacent carbons is also present Both kinds of strain are relieved when a ring opening reaction occurs... 

There is an important difference in the regiochemistry of ring opening reactions of epoxides depending on the reaction conditions Unsymmetncally substituted epoxides tend to react with anionic nucleophiles at the less hindered carbon of the ring Under conditions of acid catalysis however the more highly substituted carbon is attacked... 

Lactam polymerization represented by reaction 5 in Table 5.4 is another example of a ring-opening reaction, the reverse of which is a possible competitor with polymer for reactants. We shall discuss this situation in Sec. 5.10. 

Several qualitative predictions can be made concerning the ring-opening reaction described by (5. EE) ... 

The formation of polymers by the ring-opening reaction (5. FF) requires an initiator to get the reaction started, and perhaps a catalyst to assure a suitable rate, but otherwise is quite feasible for 1 < 4 and 1 > 7. 

Frequendy unique and synthetically usehil are a series of ring-opening reactions. Butyrolactone and anhydrous hydrogen haUdes give high yields of 4-halobutyric acids (164). In the presence of alcohols, esters are formed. 

TFEO is by fai the most reactive epoxide of the series. However, ail the reported perfluoroepoxides undergo similar ring-opening reactions. The most important reactions of these epoxides ate those with the fluoride ion or perfluoroalkoxides. The reaction of PIBO and the fluoride ion is an example (27). It also illustrates the general scheme of oligomerization of perfluoroepoxides (eq 5). 

The reaction is very slow in neutral solution, but the equiUbrium shifts toward the lactam rather than glutamic acid. Under strongly acidic or alkaline conditions, the ring-opening reaction requires a very short time (10). Therefore, neutralization of L-glutamic acid should be performed cautiously because intramolecular dehydration is noticeable even below 190°C. 

From Multiring Systems Containing Pyrazoles. The pyrazolopyrimidine (65) on treatment with diazomethane forms the cyclopropane (66), which undergoes a ring-opening reaction with potassium hydroxide to yield the pyrazole (67) (eq. 16) (44). 

The oxirane ring-opening reaction requires the presence of a basic catalyst. An acidic catalyst also works, but the polymerization of the oxirane limits its usehilness. In the case of 2-mercaptoethanol (eq. 8), the product has been found to be autocatalytic, ie, the product is a catalyst for the reaction. 

Ring-Opening Polymerization. Examples of the formation of copolymers by ring-opening reactions are shown in equations 33 and 34... 

Polymerization. The polymer chain is formed by a ring-opening reaction caused by the action of alkaUes on the monomer, a cycHc siloxane ... 

Fig. 5. Enzymatic resolution of amino acids by ring-opening reaction.

Ring-opening reactions are best known in the pyridazine ring. For example, the N-aryl cyclic hydrazides (321) undergo ring opening with alkali to give the N-aminoimides (322),... 

Removal of AT-oxide groups by PCI3 follows normal behaviour (63JCS6073), but with acetic anhydride the AAoxides (332) underwent a complex ring-opening reaction leading to (333), and an isomeric 8-alkoxy-6-oxide behaved similarly (75H(3)38l). 

The chemical consequences of /3-protonation are illustrated further by the ring-opening reactions of furans with methanolic hydrogen chloride and of (V-substituted pyrroles with hydroxylamine hydrochloride (Scheme 11) (82CC800). 

Some examples of ring opening reactions with carbanions leading to five-membered heterocyclic ring formation are shown in Scheme 85. Pyrrole syntheses from functionally substituted oxiranes and amines are often described and typical examples are shown in Scheme 86. 

For ring-opening reactions of C-metallated azoles, see Section 4.02.3.8. 

Small Rings as Substrates for Ring-opening Reactions... 

Small Rings As Substrates for Ring-opening Reactions 4.03.7.3.1 Three-membered rings... 

The pyrazole ring is particularly difficult to cleave and, amongst the azoles, pyrazoles together with the 1,2,4-triazoles are the most stable and easiest to work with. This qualitative description of pyrazole stability covers the neutral, anionic and cationic aromatic species. On the other hand, the saturated or partially saturated derivatives can be considered as hydrazine derivatives their ring opening reactions usually involve cleavage of the N—C bond and seldom cleavage of the N—N bond. It should be noted, however, that upon irradiation or electron impact the N—N bond of pyrazoles can be broken. 

Grandberg Ring opening reactions of pyrazolines 66RCR9... 

Pyrazoles can be prepared by ring opening reactions of fused systems already containing the pyrazole nucleus. Thus several [5.5], [5.6] and [5.7] fused heterocycles have been opened to substituted pyrazoles, usually in basic medium. In general, the method has little preparative interest since another pyrazole derivative has usually been used to build the ring-fused system. However, due to the unexpected structures obtained, two publications are worthy of notice. 6//-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine (638) was readily obtained from the corresponding pyrazolopyrimidine by the action of diazomethane at room temperature (Scheme 59) (81H(15)265). When (638) was treated with potassium hydroxide, the pyrazole (640) was formed, probably via the diazepine (639). 

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