5-7-membered cyclic

Phenylhydroperoxides 307a-h are converted into the corresponding 5-7-membered cyclic peroxides 308a-h, in variable yields, upon treatment with lead tetraacetate (Scheme 76)239 240. The best yields were observed for the endoperoxides 308d (76%) and 308e (66%)239. A plausible mechanism that may conform with the yield distribution of products 308 involves the transitory intermediates 309-311 (Scheme 76). Singlet... 

Derived from an aldehyde or ketone and an alcohol using an acid catalyst. Ethylene glycol or 1,3-dihydroxypropane are frequently used to give 5-or 6-member cyclic products. 

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

A standard synthetic sequence for building a six membered cyclic ketone onto an existing aromatic ring is shown in outline as follows Specify the reagents necessary for each step... 

Conversion to dialkyl ethers (Sec tion 15 7) On being heated in the presence of an acid catalyst two molecules of a primary alcohol combine to form an ether and wa ter Diols can undergo an intramo lecular condensation if a five membered or six membered cyclic ether results... 

Diols that bear two hydroxyl groups m a 1 2 or 1 3 relationship to each other yield cyclic acetals on reaction with either aldehydes or ketones The five membered cyclic acetals derived from ethylene glycol (12 ethanediol) are the most commonly encoun tered examples Often the position of equilibrium is made more favorable by removing the water formed m the reaction by azeotropic distillation with benzene or toluene... 

Hydroxy acids compounds that contain both a hydroxyl and a carboxylic acid function have the capacity to form cyclic esters called lactones This intramolecular esterification takes place spontaneously when the ring that is formed is five or six membered Lac tones that contain a five membered cyclic ester are referred to as 7 lactones, their six membered analogs are known as 8 lactones... 

Aldoses incorporate two functional groups C=0 and OH which are capable of react mg with each other We saw m Section 17 8 that nucleophilic addition of an alcohol function to a carbonyl group gives a hemiacetal When the hydroxyl and carbonyl groups are part of the same molecule a cyclic hemiacetal results as illustrated m Figure 25 3 Cyclic hemiacetal formation is most common when the ring that results is five or SIX membered Five membered cyclic hemiacetals of carbohydrates are called furanose forms SIX membered ones are called pyranose forms The nng carbon that is derived... 

Notice that the eclipsed conformation of d ribose derived directly from the Fischer pro jection does not have its C 4 hydroxyl group properly oriented for furanose ring forma tion We must redraw it m a conformation that permits the five membered cyclic hemi acetal to form This is accomplished by rotation about the C(3)—C(4) bond taking care that the configuration at C 4 is not changed... 

During the discussion of hemiacetal formation in d ribose in the preceding section you may have noticed that aldopentoses have the potential of forming a six membered cyclic hemiacetal via addition of the C 5 hydroxyl to the carbonyl group This mode of ring closure leads to a and p pyranose forms... 

When fragmentation is accompanied by the formation of a new bond as well as by the breaking of an existing bond, a rearrangement process is involved. These will be even mass peaks when only C, H, and O are involved. The migrating atom is almost exclusively hydrogen six-membered cyclic transition states are most important. 

Dicyano-l,2,3-trithiole 2-oxide (143) has been prepared from the silver salt of 2,3-dimercaptomaleonitrile (142) and thionyl chloride (66HC(2l-i)67). Similarly, the reaction of ethylene glycol (144) with thionyl chloride gave 1,3,2-dioxathiolane 2-oxide (145), the parent compound of saturated five-membered cyclic sulfites (see Chapter 4.33). 

The proton affinities (gas phase) of thiirane and other three-membered heterocycles have been determined azirane (902.5), thiirane (819.2), phosphirane (815.0), oxirane (793.3 kJ moF ) (80JA5151). Increasing s character in the lone electron pairs decreases proton affinities. Data derived from NMR chemical shifts in chloroform indicate the order of decreasing basicity is azirane > oxirane > thiirane (73CR(B)(276)335). The base strengths of four-, five- and six-membered cyclic sulfides are greater than that of thiirane. 

Derive the tc-MO patterns for these three molecules by treating them as derivatives of the three-, five-, and seven-membered cyclic conjugated systems. Explain the relationship between the derived MO pattern and the observed properties and stabilities of the molecules. 

Substitution, addition, and group transfer reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic applications, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. ° The preference for a six-membered cyclic transition state in the hydrogen abstraction step imparts position selectivity to the process ... 

Preferential formation of a 5-membered cyclic acetal is not a general rule in the steroid series e.g., the 1,3-dioxolane (23) is obtained directly from the parent triol (22) and acetone. 17,21-Acetals are obtained only by acetal exchange. ... 

A mechanism of the 1,2-addition of Grignard reagents to ketones has been suggested by Swain involving a six-membered cyclic transition state. Ashby proposed a detailed mechanism as shown in (l)-(2). 

It has been proposed that oxygen adds to the excited keto group [- (112)]. The rearrangement of the resulting hydroxyhydroperoxy diradical (112) could then proceed by intramolecular hydrogen abstraction involving a six-membered cyclic transition state, followed by fission of the former C —CO bond to form the unsaturated peracid (113) as the precursor of the final product. Such a reaction sequence demands a hydrogen atom in the J -position sterically accessible to the intermediate hydroperoxy radical. 

In the field of nucleosides, an interesting example of a cleavage of a nonfluor-inated six-membered cyclic ether containing oxygen and nitrogen atoms to give a fluoro nucleoside has been reported [5] (equation 5)... 

An illustration of the tendency of alkane 1,2- and alkane-1,3-dicarboxylie acids to a ring closure during the reaction with sulfur tetrafluoride is the reaction of propane-1,2,3-tricarboxylie acid The corresponding six- and five-membered cyclic ethers are formed in a 1 4 ratio [211] (equation 106)... 

On treatment with sulfur tetrafluoride followed by hydrolysis, D- and L-hy droxysuccimc acids and D-tartanc acid give complex mixtures of products in which the predominant components are five-membered cyclic ethers, derivatives of 2,2,5,5-tetrafluorotetrahydrofuran [209, 272] (equation 108)... 

In cases where information about atomic arrangements cannot be obtained by X-ray crystallography owing to the insolubility or instability of a compound, vibrational spectroscopy may provide valuable insights. For example, the explosive and insoluble black solid SesNaCla was shown to contain the five-membered cyclic cation [SesNaCl]" by comparing the calculated fundamental vibrations with the experimental IR spectrum. ... 

The bicyclic compound 8.17 also serves as a source of the five-membered ring 8.20 upon reduction with SbPhs. In contrast to the related S or Se systems, 8.11a and 8.11b, both Cl substituents are attached covalently to Te in 8.20. Reaction of 8.20 with an excess of AsFs in SO2 produces the eight-membered cyclic [Tc2S2N4] dication, which exhibits a Te-Te bond length of 2.88 A (cf. 2.70 A for a Te-Te single bond) and no transannular S S bonding J... 

Alkyl sulfonyl chlorides, having an a-hydrogen atom, react with enamines derived from aldehydes and cyclic ketones in the presence of triethylamine to give cyclic sulfones. Thus the enamine (22) gave the four-membered cyclic aminosulfone (143) on reaction with methanesulfonyl chloride (95). 

Amination of the deactivated carbanion of 4-benzylpyridine formed with excess sodamide presumably proceeds because the strong indirect deactivation is overcome by electrophilic attack by Na+ at the partially anionic azine-nitrogen and by concerted nucleophilic attack by H2N at the 2-position via a 6-membered cyclic transition state (75). However, in simple nucleophilic displacement a carbanion will be more deactivating than the corresponding alkyl group, as is true in general for anionic substituents and their non-ionic counterparts. 

Dipolar cycloadditions of five-member cyclic nitrones to a,(3-unsaturated acid derivatives 99H(50)1213. 

To verify the generality of the cyclization of iodopyrazolecarboxylic acids, copper p-phenylbenzoylacetylide was used in the reaction with 3-iodo-l-methylpyra-zole-4-carboxylic acid. The assumed intermediate, alkynylpyrazolylcarboxylic acid, has a distribution of the electron density which is the most favorable for closure of the five-membered cyclic ether. However, the reaction leads only to the 5-lactone (Scheme 120). 

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