Tetrahydro Compounds

Cationic rings are readily reduced by complex hydrides under relatively mild conditions. Thus isoxazolium salts with sodium borohydride give the 2,5-dihydro derivatives (217) in ethanol, but yield the 2,3-dihydro compound (218) in MeCN/H20 (74CPB70). Pyrazolyl anions are reduced by borohydride to pyrazolines and pyrazolidines. Thiazolyl ions are reduced to 1,2-dihydrothiazoles by lithium aluminum hydride and to tetrahydrothiazoles by sodium borohydride. The tetrahydro compound is probably formed via (219), which results from proton addition to the dihydro derivative (220) containing an enamine function. 1,3-Dithiolylium salts easily add hydride ion from sodium borohydride (Scheme 20) (80AHC(27)151). 

Compounds of types (313 R = H) and (314 R = H) are in equilibrium with open-chain forms (315) such tetrahydro compounds are readily hydrolyzed by dilute acid (R H). 

Following the classification of Chapter 4.01, three classes will be considered, (a) Compounds isomeric with aromatic compounds (6), (7) and (8). The quaternary, non-aromatic salts (Scheme 7, Chapter 4.01) will be discussed only in connection with protonation studies which lead to the conclusion of their non-existence. The carbonyl derivatives (9), (10), (13) and (14) will also be included here because it is possible to write an aromatic tautomer for each one, (9 )-(14 ), even if it is energetically unfavoured, (b) Dihydro compounds. In this class not only pyrazolines (15), (16) and (17) but also pyrazolidinones (18) and pyrazolinediones like (1) are included, (c) Tetrahydro compounds. Besides the pyrazolidines (19), the pyrazolidinetriones (2) are included here. 

Dihydro and tetrahydro compounds have been little studied. Too few reactions are known to merit full classification. They have therefore been placed in two classes only. 

Erythroidine behaves as a lactone and when one of its salts with an alkali or alkaline earth metal is catalytically hydrogenated under pressure, a mixture of dihydro-j3-erythroidines, with two tetrahydro- compounds is produced, from which dihydro- -erythroidine can be isolated as the hydrobromide. The dihydro- base has m.p. 85-6° (dec.), + 102-5° and... 

The discovery of junipal focused the attention of Sorensen, who had been investigating the occurrence of polyacetylenes in Com-positae, on the possibility that these acetylenes were accompanied by thiophenes. From Coreopsis grandiflora Hogg ex sweet, 2-phenyl 5-(1-propynyl) thiophene (240) was isolated and its structure confirmed by synthesis of the tetrahydro compound, 2-phenyl-5-n-propyl-thiophene. From the root of tansy, the cis and trans isomers of methyl 5-(l-propynyl)-2-thienylacrylate (241) have been isolated. The total synthesis of trans (241) was achieved by reacting junipal with methylcarbethoxy triphenylphosphonium bromide (Wittig reaction) Several monosubstituted thiophenes, (242), (243), and... 

A similar sequence of reactions on l,2-dihydroindeno[l,2-tautomeric mixture of the oxo 11a and hydroxy 12a forms.57 Prolonged treatment of the tetrahydro compound 10 with NBS in refluxing dibro-momethane results in bromination of the indene ring and formation of the 10-bromo derivative... 

The tricyclic benzothiazepinone 1 is reduced by ethanolic sodium borohydride to a tetrahydro compound, which is isolated as the sulfoxide 2, formed by air oxidation. Reaction of 1 with dichloroketene or various nitrile oxides results in cycloadducts.426... 

Jenny and Reiner 107> obtained the di- and tetrahydro compounds 153 and 154 by Birch reduction of [2.2]paracyclophane. On the basis of spectroscopic findings, the authors postulate the configuration 153 a A, for the dihydro compound, where the benzene rings are slightly distorted in a tublike fashion. 

In the case of 8-methylquinoline, the intermediate dihydro derivative yields nearly equal amounts of the two disproportionation products, while with quinoline itself only a trace of the tetrahydro compound was formed. ° In the latter case some other oxidizing agent, perhaps traces of oxygen, must have been involved. 

The biologically active relatives of folic acid and biopterin are the tetrahydro compounds with a reduced pyrazine ring. Reduction to this level occurs rapidly in vivo. The corresponding electrochemical process is well illustrated by reduction of the N-methylated analogue 28 [95], Reduction to the 5,8-dihydro stage is a reversible two-electron and two-proton process. The product rapidly tautomerises to the... 

Photodehydrogenation of salts 148 gave the pentacycles 149, but this type of reaction is not restricted to iminium structures as shown by photocycliza-tion of the tetrahydro compounds 150, which yield the pyrido[3,2,l-yfc]-carbazole derivatives 151 (78T363) (Scheme 25). 

One of the earliest authentic eight-membered heterocyclic compounds to be described was 6,7-diphenyldibenzo[e,g][l,4]diazocine (212) prepared by Tauber in 1892 by condensation of 2,2 -diaminobiphenyl and benzil. The diazocine ring is opened hydrolytically under vigorous conditions and is reduced to the 5,6,7,8-tetrahydro compound with sodium amal-... 

A number of reduction products of 2,8-dichloro-6,12-diphenyldibenzo[f>,/][l,5]diazocine (283) have been obtained (66JOC3356). LAH in ether gives mainly the frans-diphenyl-tetrahydro compound (282), whereas reduction in pyridine stops at the dihydro stage (284) (78%). Catalytic hydrogenation or zinc-acid reduction gives the tetracyclic indolo[3,2-6]indole system (286) which is readily oxidized back to the diazocine. Transannular cycliz-ation to (286) occurs on treatment of the dihydrodiazocine with NaH. Troeger s base derivatives, e.g. (287), were formed from the tetrahydro derivatives with formaldehyde. 

The pyridine ring in l,3-dimethylimidazo[l,2-a]pyridinium salts (196) is reduced in two two-electron steps in aqueous media to a dihydro- and then to a tetrahydro compound 197 [Eq. (116)],... 

Three types of dihydropyrrole (11-13) and two types of dihydro-furan and -thiophene exist (12-13), but only a single class of tetrahydro compounds (14). 

Reduced thiophenes and furans are named systematically as 2,3-dihydro (12), 2,5-dihydro (13) and 2,3,4,5-tetrahydro compounds (14). Alternatively, delta (A) can be used to indicate the position of the remaining double bond. Thus, (12) and (13) are named as A2- and A3-dihydro compounds, respectively tetrahydrothiophene is also called thiophane. 

Cationic rings are readily reduced under relatively mild conditions. 1-Methylpyridinium ion with sodium borohydride (in H20, 15°C) gives the 1,2-dihydro derivative (330) at pH > 7 and the 1,2,3,6-tetrahydro derivative (331) at pH 2-5. The tetrahydro compound is probably formed via (332) which results from proton addition to (330). Pyridine cations are also reduced to 1,2-dihydropyridines by dissolving metals, e.g. Na/Hg. 

Tetrahydro compounds still contain one ring double bond and thus can exist in several tautomeric forms (cf. Section 2.2.5.2). Little systematic work is available regarding the position of such equilibria, but 1-methyl-A2-piperideine is more stable than the A3-isomer by 16 kJ mol 1 (Equation 12). 

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