3,5-Unsubstituted-4/7-pyrans

Isoxazoles 88 can serve as a convenient masked form of aldehydes and ketones (84H(22)1, 85JCS(P1)2581). They can be cleaved by EtONa in the presence of aldehydes. The 3-oxonitriles, generated in situ, react as aldehydes with UCC 26 formation, followed by reaction with MN 27a to give pyrans 89. The yields are usually low, rarely reaching 60-76%, but the access to 6-unsubstituted pyrans should be regarded as the advantage of this method (Scheme 25). 

Naphthalene-1,8-dicarboxylic add, its nitro-substituted derivatives, and naphthalene-1,4,5,8 tetracarboxylic acid, on treatment with sulfur tetrafluoride at 0 C, undergo dehydration to form quantitatively the corresponding anhydrides [218, 221] Unsubstituted and mononitrated monoanhydndes react further at 200-250 °C to give derivatives of 1,1,3,3-tetrafluoro-l// naphtho[I,8 c,d]pyran Dinitronaphthalene-l,8-di-carboxyhc acid anhydndes and naphthalene 1,4,5,8 tetracarboxylic acid dianhydnde give the respective tetra- and octafluoroethers only in the presence of an excess of anhydrous hydrogen fluoride [221] (equabons 113 and 114)... 

Thiopyrans formed on irradiation of the corresponding 4H derivatives are less prone to ring opening than 2//-pyrans. This led to the study of the photochemistry of variously substituted 4//-thiopyrans. Irradiation of 3,5-unsubstituted... 

Substituent effects on the Vax of the colored form in these series are interesting and are dependent on the pyran component. For compound 20, substitutions at position 3, 6, or 8 (or 3, 6, 8 ) affects the X substantially, i.e., the absorption band lies in a wide range 475-609nm. The 7,7 -, 8,8 -, or 10,10 -dinitro-substituted compounds 21 reveal a somewhat hypso-chromic shift, relative to unsubstituted derivative, whereas the bathochromic shift (1(M0 nm) is observed with dinitro substitution at the same position in compound 22. For compound 23, the pronounced shift is also observed with 8-nitro substitution. Many other spectral data are collected in Ref. 1. 

There are early reviews discussing the chemistry and properties of pseudoazulenes.311312 Unsubstituted pseudoazulenes are rather unstable, but benzocon-densation and substituents stabilize the molecule, for the latter in agreement with the electronegativities of the heteroatoms. No Diels—Alder reactions occur between pseudoazulenes and dienes, a fact which is consistent with a certain degree of aromaticity. A pseudoazulene with a pyranic ring was formed from benzyl and cyclopentadiene with sodium methox-ide.313... 

The best approach to unsubstituted 4//-pyran (5) is from glutaric dialdehyde and hydrogen chloride, which gives up to a 40% yield of 5. Intermediate 23 is not isolated.9,19,57 This procedure was successfully extended to the preparation of 4-methyl-4//-pyran.7... 

The amount of a given isomer in reaction mixtures is affected by substitution patterns of the starting pyrylium ions and by the structure of a reagent, in accordance with quantum chemical interpretations using various LCAO-MO methods.201-2028 Almost all additions to 2,6-disubstituted pyrylium ions occur at position 4 to give 4//-pyrans. Unsubstituted or 2,4,6-trisubstituted substrates may be attacked, on the other hand, at a or y positions providing 2H- and/or 4//-pyrans. Limited information on tetrasubstituted and penta-substituted pyrylium ions leads to the conclusion that the former afford AH-pyrans, whereas the latter tend to be attacked by nucleophiles only at positions 2 or 6. 

The elimination of methanol, ethanol, or acetic acid is useful for the preparation of 4f/-pyrans, provided that the products exhibit sufficient stability. Thus the thermolyses of 2-ethoxy- and 2-acetoxy-2, 3-dihydro-4//-pyrans 265 undoubtedly led to unsubstituted 4//-pyran (5),18,293 but only when R = Ac was it possible to separate the unstable product 5 from reaction mixtures by GLC in 15 to 30% yields.18 Analogously, 25% of air-sensitive 2-methoxy-2//-pyran (267) was obtained on heating 266 with aluminum tri-butoxide under a nitrogen atmosphere at 155°C.33 A general technique for the preparation of condensed 4//-pyrans from their 2-ethoxy-2,3-dihydro derivatives is based on the elimination of ethanol in the presence of p-toluenesulfonic acid or polyphosphoric acid at decreased pressures293 to give... 

Dehydration procedures have led to 2//-thiopyrans. Thus unsubstituted parent heterocycle 6 was prepared by the dehydration of hydroxy derivative 287 with potassium hydrogen sulfate.20 The same procedure applied to a mixture of isomeric hydroxy 2-methyl-5,6-dihydro-2//-thiopyrans and 3,5-dihydroxy-2,4,5,6-tetrahydrothiopyran gives all the corresponding thio-pyrans.91 3-Phenylthiopyran dioxide 289 was obtained after the dehydration of hydroxy derivative 288a with phosphoric acid at elevated temperatures.300,301 The same approach was explored for the preparation of furano-2//-thiopyran 14.42... 

Unsubstituted 4//-pyran (5) as well as its 4-methyl derivative react with trityl perchlorate or with PC15 to give pyrylium salts of the 157a type.7,90 The reaction of 5 with hydrogen sulfide in the presence of hydrogen chloride gave... 

If both thermodynamic and kinetic factors operate simultaneously in favor of open-chain forms like 460 and 463, then 2//-pyran 459 may not be identifiable. This may be the reason why attempts to prepare unsubstituted 2//-pyran (4) from cis-2,4-pentadienal (466) have failed (for other attempts to prepare 4, see reference 386). Thus even if 466 had been generated by thermolysis of epoxycyclopentene 465, no traces of 4 were detected.28 Moreover, 466 seems to be thermodynamically more stable than cyclic form 4 according to ab initio MO calculations.56... 

Unsubstituted 4//-pyran (5) and 4//-thiopyran (7) with 2,4-dinitrophenyl-hydrazine afford identical bishydrazones 503.18,19 Analogous product 504 was obtained from 4//-pyran derivative 68 (X = EtO, Y = Me), whereas a slightly modified precursor possessing Y = Ph provided monohydrazone 505.86... 

Unsubstituted 2//-pyran (6) was converted to dienyl sulfide 510a along with a small amount of the methyl homolog 510b by treating with sodium in HMPTA or naphthylsodium in THF followed by alkylation with methyl iodide. The conversion probably proceeded via a short-lived anion.419... 

V-Unsubstituted dihydropyridines can exist in at least five tautomeric forms (Section 2.2.5.2). At least for /V-substituted compounds 1,4-dihydropyridines (cf. 453) are generally more stable, by ca. 9 kJ mol than the 3,4-dihydro and the 1,2-dihydro isomers (cf 454). By contrast 2/f-pyrans appear to be thermodynamically more stable than 4//-pyrans. All three types of 1,3-oxazine are known. 

The unsubstituted pentanedial yields the parent 4/f-pyran on successive treatment with hydrogen chloride and A AT-diethylaniline (62AG465). This two-step approach involving elimination of hydrogen chloride from the initially formed tetrahydropyran has been extended to the synthesis of substituted 4/f-pyrans (Scheme 15) (67MI22400). 

It has been found (72BSF707) that in general the reaction of methylmagnesium iodide with 2,4,6-trisubstituted pyrylium salts leads to 2//-pyrans. However, as the bulk of the 2-and 6-substituents increases, minor amounts of 4//-pyrans are formed. When the pyrylium salt is unsubstituted at C-4, significant quantities of the 4//-pyran are produced, along with the corresponding 2//-pyran and unsaturated ketones. It appears that substituents in the 3- and 5-positions of the pyrylium salts have little effect on the course of the reaction. 

The reaction of substituted pyrylium salts with sodium borohydride yields pyrans, but again attack at C-2 and subsequent ring opening of the resulting 2//-pyran are observed (62T257). Yields of the 4//-pyran are highest when C-4 is unsubstituted. 

Because of the high electron densities at these positions protonation of unsubstituted pseudoazulenes should take place at a 1- and/or 3-position of the five-membered ring. As was investigated in more detail for the cyclopen ta[/ ]pyran series (e.g., 27 and 40) by NMR protonation takes place... 

In this sequence29,30 a (substituted or unsubstituted) benzophenone (15) is reacted witb sodium acetylide (16) in an etber solvent at room temperature to yield a 1,1-diaiyl-2- propyn-l-ol (17). This intermediate can be condensed with a P-naphthol in the presence of an acid catalyst at 30 to 50°C to yield the pyran. 

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