HETEROCYCLES

Review | Regular issue | Vol. 87, No. 3, 2013, pp. 493-526
Received, 5th October, 2012, Accepted, 30th November, 2012, Published online, 7th December, 2012.
DOI: 10.3987/REV-12-755

■ Direct Routes to 2H-Tetrazoles by Cyclization and Ring Transformation

Dietrich Moderhack*

Institute of Medicinal and Pharmaceutical Chemistry, Technical University, Braunschweig, Beethovenstrasse 55, Germany

Abstract

This review summarizes the known routes to the title compounds that were formed from cyclization of open-chain precursors and ring transformation of non-tetrazolic heterocycles, i.e. procedures that are not based on ring substitution of the corresponding N-unsubstituted tetrazoles.

INTRODUCTION
It is well known and has been confirmed by a recent review1 that the major way of making 2H-tetrazoles consists in substitution of the N-unsubstituted parents2 – a reaction that, in most cases, does not proceed regioselectively and therefore requires separation of isomers. However, a considerable number of title compounds can (or even have to) be prepared directly, i.e. (1) by cyclization of open-chain substrates and (2) ring transformation of non-tetrazolic heterocycles (Scheme 1).

A specific review of these strategies has not been produced till now. Only in a wider context – in general reports on synthesis and properties of 2-aryl­tetrazoles3 and ring transformations in tetrazole chemistry4 – the field has received attention and been treated briefly. The present overview is intended to be more detailed, with the material being organized as outlined in Scheme 2. To provide an integral picture, the historical routes compiled in refs.3,4 will be dealt with too.

GENERAL
For practical purposes, Scheme 2 shows starting materials rather than intermediates prone to ring closure. Apart from the routes (G), (J), (K), (N), and (O), all approaches are one-pot reactions. Since emphasis is placed on methods, resultant tetrazoles will be signed after the actual procedure; identical products arising from different routes will not be marked as such.

1) CYCLIZATION REACTIONS
A) Amidrazone + Nitrous Acid
Nitrosation of amidrazones of the type (1) has led to the very first tetrazole to be reported, viz. the cyano functionalized representative (Aa) (Scheme 3).5a Since the precursor (1a), which had been obtained from cyanogen and phenylhydrazine, was originally assumed to be phenylated at the adjacent nitrogen, the cyclization product was assigned the isomeric 1H structure,5a but this error could be corrected soon.5b Later, the preparative procedure (1a → Aa) was modified: the solid that precipitated on addition of nitrite ion to the acidic solution of 1a was immediately taken up with an organic solvent like dichloromethane; this also enhanced the yield.5c

While the preparation of Ab constitutes another early case6 of application of this synthesis, more recent examples pertain to tetrazoles like Ac7 and Ad-f.8 Regarding the latter, the products are susceptible to hydrolysis; hence, the process was utilized as a convenient route to the N-unsub¬stituted tetrazoles (2), and their yields testify to a smooth ring closure.8 Finally, also the amidrazonic moiety in compound (1g) could be transformed into a tetrazole (Ag), but the product was not stable: it expelled hydrogen cyanide to give the azide (3).9

B) Hydrazone (Anion) + Azide
Not unlike the preceding process, the reaction of the title compounds (4) with (5) giving tetrazoles (B) has already been described in the early literature.10a,b The transformation requires a strong base and has been interpreted as proceeding via a linear adduct, but later a [3+2] cycloadduct was postulated as intermediate (Scheme 4).11 While the older and most of the newer examples for this reaction

have been collected in a previous review,3 the list may be complemented by Ba12,13 and its di-p-tolyl analogue,13 Bb,12 Bc,13 Bd,14 Bh,15a,b Bi,15a,b Bj (X = Cl),15b Bj (X = Me, MeO),16 Bk (X = Cl),15b Bk (X = Me, MeO),16 and Bl,m.17 Regarding preparation of the carboxylic acid (Be),3 two further protocols using the azides (5b)18 and (5c)19 have appeared. Moreover, reactions of 5c with respective hydrazones were claimed to afford also tetrazoles such as Be-g [including derivatives having (i) R' = R = Ph and (ii) R' = 2-furyl or (1-R'')-indol-3-yl, R = Ar; all isolated as salts of hydrochloric acid !].19,20 However, for this and other inconsistencies – e.g., authentic Bg (Het: X = Br)21 melts distinctly lower (ca. 130 °C) – the work needs to be revisited.

C) Diazoalkane + Diazoalkane (same or different)
It is known that diazoketones such as (6a-c) readily dimerize in the presence of a strong base, and the participation of the anion (6') as an active species is suggested (Scheme 5). The nature of the products depends on the conditions: applying potassium t-butoxide–t-butyl alcohol, tetrazoles like Ca-c were obtained,22a whilst with concentrated methanolic sodium methoxide or potassium hydroxide–DMSO the dihydro-s-tetrazines (7a,b) resulted.22b However, studies with 6a performed in dilute methanolic sodium methoxide gave

rise to complex mixtures that were devoid of Ca and contained only traces of 7a.22c A very interesting process was found to occur when the N-isocyanide (8) was treated with an excess of triphenylphosphine–hexachloroethane. Attack at the isocy­anide carbon and concomitant loss of the silyl groups led to a diazo compound like 9; dimerization of this putative intermediate gave rise to another transient species (10), which took up unconsumed reagent to furnish the final product (Cd) in 85% yield. The remarkable struct­ure was established by X-ray diffraction performed with the congener (Ce).23
It should be added that two diazomethyl groups residing at appropriate positions in the same molecule are also capable of 'dimerizing.' This has been encountered with the intermediary biphenyl derivative (12) [generated by Bamford-Stevens reaction of the bishydrazone (11)], but here such process, evidently, can only lead to a 1H-tetrazole (→ 13).24

Regarding interaction of two different diazoalkanes, the first example on record pertains to the synthesis of the conspicuously substituted tetrazoles (Cf-j), which were obtained in moderate yield (Scheme 6).25 The formation of these compounds requires the presence of a tertiary amine. For making Cf-h, the second reactant (15) was simply generated in situ by treatment of the respective diazophosphoryl compound (14) with 0.5 eq. of the bis(tetramethylamidinio) ether (16). Identification of this series of 2H-tetrazoles was, inter alia, achieved by an X-ray diffraction study of the representative (Ch).
A useful preparative method for 2H-tetrazoles bearing acylmethyl groups at ring nitrogen (Ck-m) has turned out treatment of diazo(trimethylsilyl)methane (17) with LDA or butyllithium and a carboxylic ester (ca. 0.5 eq.); also phthalide proved reactive, giving the hemiketal (Cn) that could be acetolyzed to the ketone (Co) (Scheme 7).26,27 The formation of Ck-m was understood as follows: after metallation of 17 to 17' half of the latter species was acylated to 18 (FG(1)), which cycloadded across unconsumed 17' to yield a transient tetrazole (19; FG(1)) that led to the final product. Later, this principle served to prepare tetrazoles having dicarbamoylmethyl groups at N(2) like Cp,q; of the latter product, X-ray diffraction data exist.28 Yet, the straightforward entry was accompanied by a side reaction: part of 17' was functionalized at the terminal nitrogen, forming a nitrile imine (20) that cyclized to the respective 1,3,4-oxadiazole (21a,b) [isolated as the silicon-free derivatives (22a,b)]. Comparing the yields of Cp and 22a with those of Cq and 22b, it is apparent that carbamoylating agents having bulkier groups favour this unwanted reaction.

D) Nitrile + Azide
As a rule, cycloadditions of organic azides across nitriles do not yield 2H-tetrazoles, but lead to the 1H-isomers.29 However, an inverse regioselectivity is observed with silyl and stannyl azides. The first known example constitutes the process (23a + 24a → DSia) (Scheme 8).30 Further, heating trimethylsilyl iodide and sodium azide (1:1) in acetonitrile as a solvent gave the tetrazole (DSib) (small quantity), whilst the same procedure using the silyl iodide (24b; I instead of N3) led to the compound (DSic), the structure of which was determined by X-ray diffraction.31 However, the formation of regioisomers, e.g. 5-phenyl-32 and 5-(trihalomethyl)-1-(trimethylsilyl)tetrazoles,33 has been communicated too – findings that, in part, appear questionable and should be re-examined. A recent theoretical study (DFT) has revealed fairly similar energy barriers for the formation of DSib and its 1H-isomer (50.2 and 45.3 kcal/mol, respectively).34

Cycloaddition reactions using stannyl azides have been carried out in much larger numbers (Scheme 9). The earliest reports pertain to the preparation of the 2H-tetrazoles (DSna-c).35a,b Later, cycloadducts such as DSnd-i arose in a like manner.36–42 Interestingly, on prolonged heating the products (DSnf) extruded tributyl(phenyl)stannane to afford the bicyclic systems (25; n = 2, 3).40a,b

On extending this cycloaddition to substrates having more than one nitrile functions, poly(tetrazoles) were obtained (Scheme 10). Representatives containing two heterocyclic moieties include the phenylene- and alkylene-bridged species (DSnj-l)43 and (DSnm-q).44 An additional, quite remarkable example constitutes the product (DSnr).42 Tris(tetrazole) derivatives of the type (DSns) also arose in reasonable yield; the same procedure can be applied to benzene-1,3,5-tricarbonitrile.45 Similarly, tetrakis(tetrazole) derivatives such

as DSnt were prepared from propane-1,1,3,3-tetracarbonitrile and the corresponding ones were obtained in 30–70% yields from pentane-1,3,3,5-tetracarbo­nitrile and benzene-1,2,4,5-tetracarbo­nitrile.46
A number of the (triorganostannyl)tetrazoles (DSn) have been studied by X-ray crystallography, such as DSnc (Ar = 2-MeC6H4),37 DSni (Het = 4-pyridyl, [Sn] = SnEt3),42 DSnka,43 DSnq,44 DSns (R = Bu),45 and, in addition, the tetrakis(tetrazole) obtained from benzene-1,2,4,5-tetracarbonitrile and 24e.46 A prominent feature of these compounds is the propensity to oligomerize – via coordination of N(4) of the tetrazole unit(s) – to afford supramolecular structures with a trans-trigonal-bipyramidal geometry around tin (cf. also refs.35b,40b).
Finally, it should be mentioned that besides the processes shown in Schemes 8–10 further applications of that mode exist. However, in such cases the N-unsubstituted tetrazoles are the proper targets; therefore the respective cycloadducts of the type (DSi) or (DSn) were demetallated in situ and never isolated.47
In contrast to the DSi-yielding processes shown in Scheme 8, this kind of reaction which was performed in the presence of an allyl acetate and a palladium catalyst gave rise to products that are carbon-substituted at N(2) (Scheme 11).48 Treatment of the alkylidenemalononitriles (26) with the azide (24a), the respective alkene (27), and a certain amount of tetrakis(triphenylphosphine)-palladium(0) afforded the tetrazoles (Da-e). Their structure was confirmed by an X-ray study of the derivative (Da; R1 = Ph). Expectedly, isomers were encountered on reacting (E)-but-2-enyl acetate (27b): besides the tetrazole (Db; E or Z) the 1-methylprop-2-enyl congener (Dc) was formed; however, a parallel run with (E)-cinnamyl acetate (27d) gave a single tetrazole (De), and in place of the

phenyl analogue of Dc some cinnamyl azide was isolated. This important regiospecific route to 2-allyltetrazoles was in turn applied to make other representatives (Scheme 12).49 Using an allyl methyl carbonate (29) and a modified palladium catalyst together with a special phosphine, a wider range of cyano substrates (28, 30) could be converted to tetrazoles like Df-k and Dl-s, respectively. Mechanistically, a π-allylpalladium azide complex (31) was proposed as the key intermediate; its cycloaddition across the nitrile would generate the species (32), which on demetallation would yield the final product. It may be noted that 32 differs by type from the traditional metallotetrazoles obtained from nitriles and metal-coordinated azides (see process in brackets). Work on this field – a subject considered to fall outside the scope of the present review – has been commenced around 197050 and is in rapid progress:51 It calls for a specialized account.52

E) Diazonium Ion + Hydrazone
Interaction of the title reagents in the presence of a base constitutes a standard route to formazans. However, treatment of sulfonylhydrazones (33) with diazonium salts (34) does not afford the expected open-chain compounds (35), but leads directly to 2H-tetrazoles (E) (Scheme 13). The process has been discovered in the early 1970s.53a In the ensuing decades it proved successful to such an extent as to gradually displace the classical entry via route (B) (Scheme 2). Actually, it is the most frequently used method. Of the plethora of examples reported in the literature, only selected ones such as Ea-f, which show the wide scope of the reaction and were obtained in reasonable (often excellent) yields, can be presented here. Since no intermediates could be isolated, it has been speculated whether the product (E) arises by a concerted elimination of arenesulfinate ion from the formazanide ion (35') or from the

preformed diazo derivative (36). Considering the electronic structure of the species (35') and its potential for cyclization and, in particular, the slower rate of the Bamford-Stevens reaction of α-ylidenesulfonylhydrazones to give pyrazoles,53b,54 the first mentioned pathway appeared to be the most probable one. Ring closure of 35' prior to release of the sulfinate ion, i.e. the transient formation of a dihydro tetrazolide ion like 35'', was deemed unlikely, too.54

F) Hydrazine + Hydrazonoyl Chloride
With respect to the starting materials, this approach can be regarded a counterpart to the preceding route: here N-phenylsulfonyl-arenehydrazonoyl chlorides (38a) were reacted with arylhydrazines (37) to afford tetrazoles like Fa in 16–70% yield (Scheme 14).63 Although again no intermediates could be isolated, the overall conversion was understood to proceed as follows: Nucleophilic attack of

37 onto 38a afforded the hydrazidine (40) which, susceptible to air oxidation, was in turn converted into the respective formazan; deprotonation of the latter and ring closure of the resulting 40' (cf. above 35' → E) led to 2H-tetrazole (F). Later, experiments using phenylhydrazine (37: R = Ph) and the 2-naphthylsulfonyl congeners of 38a gave Fb (with R' = R = Ph: 50% yield).64 An interesting deviation was found on replacing 37 with benzohydrazide (39: R = Ph):65 In contrast to 40, isolation of the hydrazidine (41a) was possible (92% yield); treatment of this compound with mercury(II) oxide and potassium carbonate led to the 2-benzoyltetrazole (Fc) which in turn was hydrolyzed to 2a (56%). When the oxidant was absent, 41a cyclized to a 4-sulfonamido-4,5-dihydro-1H-1,2,4-triazole and then was aromatized to 42a – a process accompanied by the formation of side products, inter alia 2,5-diphenyl-1,3,4-oxadiazole and hydrazine derivatives. Without citing that result, the authors of the above tetrazoles (Fb) also reported on triazoles (42), viz. the derivatives (42b); the materials were obtained from the respective substrates (38b) and (39) in 70–90% yield.64

G) Hydrazine + Thiohydrazonate (Quaternary Salt)
Another route involving a transient hydrazidine starts from thiohydrazonate salts like 43. Treatment with phenylhydrazine led to the species (44) which underwent spontaneous cyclodehydrogenation to afford the 2H-tetrazolium salts (45) in 64 and 83% yield, respectively (Scheme 15). These products proved rather labile, especially 45 with Alk = CH2Ph: they were dealkylated on heating to give the target (Ga).66

H) α-Nitrohydrazone + Hydrazine
The third approach via a labile hydrazidine stage is given by the reaction of α-nitrohydrazones (46a,b) with hydrazine hydrate (Scheme 16). The latter component acts in a twofold manner: as a nucleophile it displaces the nitro group at the hydrazonic carbon, and as a reductant it converts the nitro group in the R-substituent into an amino group (→ 47a,b).67 The final step (→ Ha,b) has been compared with the ring closure of the linear adduct originally assumed to have formed from a hydrazone and an aryl azide (cf. Section B).10

I) N-Acyl-, N-Carbamoyl- or N-Amidinoformazan + Oxidant
Formazans are well established substances for constructing diverse classes of heterocycles – a topic that has recently been highlighted.68 Suitable precursors to 2H-tetrazoles are formazans having a functional group at one of the terminal nitrogens which can readily be split off, viz. either during the course of ring closure or from the tetrazolium species formed. The starting formazans of both the present and the following section belong to this category.
First experiments in the field date back to the 1890s when treatment of the formazans (48a,b) with nitrous and/or nitric acid led directly to the tetrazoles (Ia,b) (Scheme 17).69 Later, analogous findings resulted from oxidation of 48c (→ Ic); the reagent is crucial, as the use of bromine produced 3-aryl-6-bromo-s-tetrazines.70 Also bis(formazans) like 49a,b underwent this kind of conversion to give Ia (100%) and e, respectively.71 Formation of I from 48 having Y = O was first encountered during oxidation studies with the carbamoyl

derivatives (48d-f); again, the products (Ia,d) were obtained directly and the expected tetrazoliums not observed.72 Regarding N-acyl formazans, transformation into I could be achieved in hot acetic acid – obviously an air-assisted process – , but for success the presence of an electron-withdrawing substituent at the other terminal nitrogen in the substrate is necessary.73 Thus, while 48g,h were cyclized to the oxadiazoles (51a,b),74 the species having R = 4-NO2C6H4 gave rise to If. This divergent behaviour was realized by considering the tautomeric form (48'). In a complementary study, If was also made by treating 48'b,c with yellow mercury(II) oxide, but these experiments were not extended to 48g,h.73

As an excursion to the foregoing, oxidation of a substrate viewed as compound (50) should be mentioned here. This material, which resulted from the action of phenylmagnesium bromide on diazodeoxybenzoin, furnished the tetrazole (Ia) when treated with aqueous iron(III) chloride.75 This scattered result appears worthwile to be duplicated.

J) N-Hetarylformazan + Oxidant
As a source of 2H-tetrazoles, the title reaction is lavishly documented in the literature. As apparent from Scheme 18, formazans bearing ten different heterocyclic moieties (including three dihydro systems) have been studied. Isolation of a tetrazole originating from this kind of substrate was first reported in the 1950s and at that time caused surprise: When the product from 52a and N-bromosuccinimde [i.e. the tetrazolium salt (53a)] was dried in vacuo at 100 °C, it decomposed to the tetrazole (Ja) and 4-hydroxypyridinium bromide (almost quantitatively within 12 hours).76 Later, the high proclivity of 53 to undergo N–Het bond fission became notorious. Thus, the pyrimidine congener generated from 52b eluded isolation and was directly converted into Jb; the same behaviour applies to the analogue having Het = 4-methoxy-6-methylpyrimidin-2-yl.77 Oxidation of the quinoxalylformazan (52c) with lead tetraacetate gave rise to the tetrazolium salt (53b) which was not isolated in pure state but directly treated with ca. 6 M hydrochloric acid to afford a 1:1 mixture of Jb and quinoxalin-2(1H)-one.78 This conversion has been extended to the phthalazine series, as exemplified by the process (52d → 53d → Jb).79
Regarding benzazolyl-substituted formazans, derivatives bearing a benzoxazolyl moiety like 52e,f were directly converted into the tetrazoles (Jb,c) when oxidized with N-bromosuccinimide.80a,b By contrast, the benzothiazolyl analogues (52g,h) gave isolable tetrazolium salts (53d,e), but on being treated with boiling hydrobromic acid they were dequaternized to the tetrazoles (Jb,c).80b This two-step procedure applies also to the benzimidazolyl and tetrazolyl substrates, as illustrated by the sequences (52i → 53f → Jd)81 and (52j → 53g → Jb),82 respectively. The latter process, however, could be abridged by treatment of 52j with an alkaline solution of potassium hexacyanoferrate(III) to furnish Jb quantitatively as well; another direct approach to this tetrazole consists in oxidation of the

ylideneformazan (52k) with lead(IV) oxide in acetic acid.82 Concerning the transformation of ylidenehydrazidines (54), these materials gave tetrazoles accompanied by the respective formazans as side products; thus, treatment with nitric acid produced the mixtures (Jb/52l) and (Je/52m).83
Finally, two loosely related processes are added: (i) the oxidative degradation of 3-(4-hydroxyphenyl)-2,5-diphenyl-2H-tetrazolium chloride to Jb;84 and (ii) the rapid decomposition of the tetrazolinyl radical (55) to Jf and the formazan (52n) on exposure to methanol; species (55) – the first tetrazolinyl to be isolated in crystalline state – was obtained from 52n almost quantitatively (Scheme 19).85

K) Ylidenetetrazene + Oxidant
Direct precursors to 2H-tetrazoles are not only tetrazolium salts of the series (53), but the 4-substituted congeners having an appropriate leaving group at this position should also possess this potential. Indeed, when the substrate (58) – obtained from the tetrazene (57) – was heated with concentrated hydrochloric acid, the unit at N(4) was split off as 1H-tetrazol-5(4H)-one to leave 2,5-diphenyltetrazole (Ka) in high yield (Scheme 20).86 While the sequence (57 → 58 → Ka) seemed reasonable, the formation of 57 from 56 was not self-evident, as the reaction of a 1,3-diaryltetrazene with an aromatic aldehyde was known to give a formazan (via rearrangement).87 Thus, the condensation with benzaldehyde might have produced a derivative (52: R' = R = Ph, Het = tetrazol-5-yl), but this possibility could easily be excluded, because an authentic sample of that formazan had earlier been shown to give an oxidation product of the type (53).88

L) (α-Aminoalkylidene)triazene + Oxidant
A new kind of oxidative cyclization leading to a 2H-tetrazole was reported in conjunction with studies on the behaviour of the (α-cyanobenzylidene)triazene (59) towards nucleophiles (Scheme 21). When this compound was treated with ammonia, the product (60) (or a tautomer) resulted. To prove above conversion, this material (60) was exposed to potassium permanganate in hot aqueous alkali to form the corresponding tetrazole (La) (crude yield: 8%).89

2) RING TRANSFORMATIONS
M) 3-Triazeno-isoxazole and -1,2,5-oxadiazole
Azoles having an =N–O– unit are widely used as a source for other heterocycles with functional groups originating in the substrates.90 According to this principle isoxazole derivatives (61a-c) smoothly gave 5-acetonyltetrazoles like Ma-c on treatment with a base (Scheme 22).91,92 While the condtions for causing this rearrangement proved effective to all of the triazenes (61), their synthesis

required different preparative modes, depending on the R ligand. Thus, the nitrophenyl derivatives (61a) were accessible via coupling of the isoxazolamine with the respective arenediazonium ion [mode (A)],91 but application of this mode for making 61b gave 1,3-diphenyltriazene instead; here, only the inverse protocol (B) was successful.92 Regarding 61c, this derivative resulted directly on diazotization of the starting amine.91
Efforts to achieve the analogous transformation with the triazeno-1,2,5-oxadiazole (61d) were reported to be fruitless.93 Since the substrate (61d) bears the same side chain as occurring in 61a-c, the failure to form Md illustrates the lower reactivity of the starting ring with respect to the isoxazole – a gradation that has been generalized some time later.90b Yet, in contrast to the foregoing trial, the derivatives (61e) having an oxadiazolyltriazeno side chain could be caused to undergo the ring transformation very readily (→ Me).94

N) 5-Triazeno-1H-pyrazole and -1H-tetrazole
Substrates in which the =N–O– moiety of 61a-c is replaced with an =N–NH– unit can yield azapentalenes on treatment with an oxidant. Thus, from the pyrazoles (62a) the fused tetrazoles (63a) resulted (Scheme 23).95 When these materials were irradiated in dichloromethane, the original pyrazole underwent N–N bond scission to produce the 5-(2H-azirin-2-yl)tetrazoles (Na).96

In view of the above step (62a → 63a) one has speculated that oxidation of the tetrazole analogue (62b) should generate the system (63b) and, since such an azapentalene is higher in energy than its open-chain isomer, expected that the bicycle once formed should ring-open to the azidotetrazole (Nb).97,98 However, the related experiments showed that the process (62b → 63b → Nb) did not occur, nor could the conceivable alternative, i.e. the linear coupling of two molecules of 62b giving a hexazene, be observed. Rather, the oxidant produced the tetra-azafulvene (64) which after elimination of molecular nitrogen gave the diazocyanide (65) as the final product.97 This species might have formed via a transient N-isocyanide99 or by combination of an arene­diazonium ion and cyanide ion as additional fragments of 64.97
O) 2-/3-Triazeno-pyridine, -quinoline, and -isoquinoline
An important entry to 2H-tetrazoles bearing a diene functionality at C(5) has turned out the two-step procedure consisting of (i) oxidative ring closure of 2-triazenopyridines (or appropriate benzologues) to tetrazoloaziniums and (ii) cleavage of the latter with a nucleophile. While step (i) became known already in the mid 1960s,100 the crucial ring opening was first described in the early 1970s101 and then studied consecutively over three decades.102–110 The access to the tetrazoloaziniums is illustrated by Scheme 24. Oxidation of the triazenes (66a-f) with 2,4,4,6-tetrabromocyclohexa-2,5-dienone gave the salts (67a-f) in good yield.111 In a like manner the benzologues (69),105 (71),102 and (73)102 were were prepared from 68, 70, and 72, respectively. In the case of 70, ring closure was accompanied by bromination of the isoquinoline moiety. The salts (69; Br in place of BF4), (71), and (73) were obtained in 61, 72, and 79% yield.

In principle, nucleophilic attack to the tetrazolopyridiniums (67) can occur at C(5) or C(8a); both modes were observed, with 2H-tetrazoles (O) arising by the former, i.e. via intermediates like 74 or 75. Whilst the stereochemistry and mechanism of this ring cleavage

were studied in detail,106,107 the employment of a wide variety of nucleophiles demonstrated the versatility of the reaction (Scheme 25). Tetrazoles with an unsubtituted or alkyl substituted dienic chain were obtained from the reaction with sodium tetrahydroborate (→ Oaa-ae),101 and Oae (≡ Oh) also with methylmagnesium iodide.107 Of course, especially useful are ring openings that gave side chains bearing a functionality like an alkoxy or a cyano group (→ Ob-e,106,107 Of,107 Og106,107), an N-linked heterocycle (→ Oj,k,107 Ol,m,106

On104,106) or an amino group (→ Oo,101,106,107 Op,107,108 Oq-s108). As expected, the formation of a deuterated dienic chain could be achieved too (→ Oi).107
Ring opening of 67 with tetramethylammonium hydroxide should provide alkenals, but clean results were obtained only with a single member of this class (see Scheme 26: 67e → 76 → Ot; 73% yield); most substrates (67) rapidly decomposed on exposure to that reagent.102
Sodium methoxide102 as well as 2,2,2-trifluoroethoxide107 attacked 67b (X = Cl) at both C(5) and C(8a) to give as a side product the aminopyridone (79). However, phenolate and thiophenolate ions affected the bicycle at C(8a) only. The resultant species (78a,b) expelled nitrogen and, depending on the nucleophile used, in turn stabilized to either 79 (via hydrolysis) or to the pyridinium-N-aminide (80).109
Regarding the behaviour of benzologues towards nucleophiles (i.e. the hydroxide ion), only in the case of linear anellation (69) the ring opening to a 2H-tetrazole could be observed (→ Ou; 40%); nevertheless, the respective intermediate (81) underwent a competing reaction to afford the indazoloisoquinoline (82; 35%).105 In analogy to the reaction of the salt (67e), the angularly anellated congener (71) should also be capable of giving a tetrazole, but here the bridgehead carbon was attacked to form the isoquinolin-1(2H)-one (83; 74%). Similarly, the salt (73) was transformed into the quinolin-2(1H)-one (84; 78%) rather than the corresponding 2-aryl-5-[2-(o-hydroxyphenyl)vinyl]tetrazole.102 These regioselectivities, changing with the site of benzoanellation of the bicyclic substrate (67), were rationalized in terms of the FMO theory.105
Finally, it is evident that tetrazoles of the type (O), in particular those having dienol ether and dienamine groupings, are desired starting materials for specifically functionalized derivatives (cf. refs.104,108,112,113). Considering the reaction of v-triazolodiazinium salts with nucleophiles,114 further series of elaborately substituted 2H-tetrazoles may arise from ring opening of the tetrazolo congeners. However, such bicycles have not been prepared till now.

P) 4-(Acyloxyimino)-1,2,3-triazol-5(4H)-one
Of ring transformations starting from the v-triazole system, the present example stands out for its peculiar course (Scheme 27): When the process (85 → Pa) was discovered a century ago,115 the authors imagined a new type of Beckmann rearrangement and realized that none of the two classical modes were operative, as in those cases the isomeric tetrazole (86) [via bond scission (A)] or the nitrile (87) [via bond scission (B)] would have formed.116 Whilst the product (Pa) was shown to arise almost quantitatively (even under mild conditions), the mechanism [via bond scission (C)] remained open. Possibly it is the attack of hydroxide ion onto C(5) in 85 to give an intermediate which is capable of undergoing this particular conversion, since the molecule did not change in the absence of alkali. The behaviour of 85 towards acidic agents has not been investigated, while an attempt to rearrange the corresponding oxime-type compound with benzenesulfonyl chloride/pyridine met with failure.115

Q) 4-Arylazo-1,2,3-triazole
Allowing for the capacity of ring opening of certain 1H-1,2,3-triazoles to α-diazoimines, the special type of substrates (88) can be viewed as sources of 2H-tetrazoles (Q), because the diazo group of the open-chain form (88') invites the arylazo unit to cyclization (Scheme 28). Indeed, this conversion, though not recognized, was encountered already in 1904: When the azo compound (88c) was prepared, a colourless side product occurred,117 and a related observation was made by others who recrystallized the derivative

(88e) from acetic acid.118 The break-through came in the 1950s, when it was shown that the triazoles (88a-d), on heating in acetic acid, rapidly rearrange to the tetrazolecarboxanilides (Qa-d).119 In view of this finding the unknown materials of refs.117,118 were looked upon as the tetrazoles (Qc) and (Qe).

R) 2H-1,2,3-Triazolo[4,5-e][1,2,3,4]tetrazine
An unexpected entry to a 2H-tetrazole was encountered when the bicyclic system (90) – the first molecule showing a 1,2,3,4-tetrazine moiety [generated from the aminotriazole half-ring of 89] – was allowed to decompose in dichloromethane (Scheme 29). The extrusion of molecular nitrogen from the labile substrate (90) led to the intermediary species (91) and (92), which then rearranged to the cyanotetrazole (Ra) and, after additional loss of nitrogen, to the 1,2,3-triazole (93), respectively.120a These products were isolated in a ratio 3:1, whereas an NMR study showed 50% each, but when the decomposition was performed in CDCl3, the yield of the (deuterated) triazole was distinctly lower than that of Ra due to the isotope effect which originated from the hydrogen-abstraction step.120b While the interesting degradation pathway of 90 was studied theoretically by AM1 calculations,121 the structure of the tetrazole (Ra) was investigated by X-ray crystallography.122

CONCLUSION
The foregoing inspection of direct routes (A) – (R) to 2H-tetrazoles demonstrates that this kind of entry is specially suited for making two major types of derivatives (cf. also Table 1 overleaf): (i) representatives having aryl substituents at N(2),123 and (ii) tetrazoles bearing particular functionalities at N(2) and/or C(5), the insertion of which is difficult or impossible by other methods. Beyond that, quite a number of processes reviewed here attract interest because of their mechanism. Unfortunately, no direct access to tetrazoles having simple alkyl groups at N(2) is available until now, evidently owing to the lack of appropriate precursors; to overcome this long-standing deficiency remains a challenge.

References

1. G. I. Koldobskii and R. B. Kharbash, Zh. Org. Khim., 2003, 39, 489; Russ. J. Org. Chem., 2003, 39, 453. – A report on 2H-tetrazole chemistry essentially covering the 1990s. CrossRef
2. For a general survey of this kind of reaction, cf.: V. A. Ostrovskii and A. O. Koren, Heterocycles, 2000, 53, 1421. CrossRef
3. E. Lippmann and A. Könnecke, Z. Chem., 1976, 16, 90.
4. D. Moderhack, J. Prakt. Chem./Chem.-Ztg., 1998, 340, 687. CrossRef
5. a) J. A. Bladin, Ber. Dtsch. Chem. Ges., 1885, 18, 1544; CrossRef J. A. Bladin, Nova Acta Regiae Soc. Sci. Ups. C, 1893, 16, 1; b) E. Bamberger and P. de Gruyter, Ber. Dtsch. Chem. Ges., 1893, 26, 2385; CrossRef O. Widman, Ber. Dtsch. Chem. Ges., 1893, 26, 2617; CrossRef c) K.-H. Goos, 'Synthese und Eigenschaften 1- und 2-substituierter 5-(Diazomethyl)tetrazole,' Dissertation, Tech¬nical University of Braunschweig (Germany), 1985 (see p. 83).
6. F. D. Chattaway and G. D. Parkes, J. Chem. Soc., 1926, 113. CrossRef
7. J. T. Witkowski, L. F. Christensen, and R. K. Robins, J. Carbohydrates, Nucleosides, Nucleotides, 1978, 5, 363.
8. J. Boivin, S. Husinec, and S. M. Zard, Tetrahedron, 1995, 51, 11737. CrossRef
9. J. Faganeli, S. Polanc, B. Stanovnik, and M. Tišler, Croat. Chem. Acta, 1976, 48, 161.
10. a) O. Dimroth and S. Merzbacher, Ber. Dtsch. Chem. Ges., 1907, 40, 2402; CrossRef b) O. Dimroth and S. Merzbacher, Ber. Dtsch. Chem. Ges., 1910, 43, 2899. CrossRef
11. J. E. Baldwin and S. Y. Hong, J. Heterocycl. Chem., 1968, 5, 565. CrossRef
12. J. K. Stille and A. T. Chen, Macromolecules, 1972, 5, 377. CrossRef
13. C. Wentrup, A. Damerius, and W. Reichen, J. Org. Chem., 1978, 43, 2037. CrossRef
14. D. Moderhack, J. Heterocycl. Chem., 1977, 14, 757. CrossRef
15. a) J. K. Stille and L. D. Gotter, J. Polym. Sci. A-1, 1969, 7, 2493; b) N. V. Schwartz, J. Appl. Polym. Sci., 1972, 16, 2715. CrossRef
16. P. Weinberg, C. Csongár, M. Gessner, and G. Tomaschewski, J. Prakt. Chem., 1988, 330, 879. CrossRef
17. P. Weinberg, C. Csongár, and G. Tomaschewski, Z. Chem., 1987, 27, 407.
18. K. Bhattacharyya, D. Ramaiah, P. K. Das, and M. V. George, J. Photochem., 1987, 36, 63. CrossRef
19. N. D. Trieu, H. T. Diep, L. T. Huong, and L. T. T. Vinh, Tap Chi Hoa Hoc, 1980, 18 (2), 22 (Chem. Abstr., 1981, 94, 121415).
20. This work has been reviewed erroneously, showing loss of NHR (instead of NAr) and formation of a 1H-tetrazole: W. Lwowski, '1,3-Dipolar Cycloaddition Chemistry: Azides and Nitrous Oxide,' ed. by A. Padwa, Wiley, New York, 1984, Vol. 1, pp. 559–651 (see p. 636).
21. L. Janda, Z. Votický, J. Jacubcová, J. Světlík, J. Grimová, and E. Maturová, Collect. Czech. Chem. Commun., 1984, 49, 1699. CrossRef
22. a) P. Yates, R. G. F. Giles, and D. G. Farnum, Can. J. Chem., 1969, 47, 3997; CrossRef cf. also P. Yates and D. G. Farnum, Tetrahedron Lett., 1960 (17), 22 [note: structure (Ca) misprinted]; CrossRef b) P. Yates, O. Meresz, and H. Morrison, Tetrahedron Lett., 1967, 77 [note: structures (Ca-c) misprinted]; CrossRef for addition of third author, see correction on p. 1576; c) P. Yates and R. J. Mayfield, Can. J. Chem., 1977, 55, 145. CrossRef
23. G. Zinner, G. Beck, W. P. Fehlhammer, and N. Wiberg, J. Organomet. Chem., 1989, 368, 23. CrossRef
24. M. D. Banciu, A. Banciu, C. Drăghici, A. Petride, and F. Chiraleu, Rev. Roum. Chim., 1995, 40, 1165.
25. G. Maas, H. Gümbel, G. Weise, and M. Regitz, Chem. Ber., 1985, 118, 2105. CrossRef
26. T. Aoyama and T. Shioiri, Chem. Pharm. Bull., 1982, 30, 3450; CrossRef cf. also: T. Aoyama, K. Sudo, and T. Shioiri, Heterocycles, 1983, 20, 163. CrossRef
27. Chisso Corp., Jpn. Kokai Tokkyo Koho, 1983, 58-140083 (Chem. Abstr., 1984, 100, 34546).
28. D. Bourissou, C. Dupuch, F. Dahan, and G. Bertrand, Bull. Soc. Chem. Belg., 1997, 106, 533.
29. F. Himo, Z. P. Demko, L. Noodleman, and K. B. Sharpless, J. Am. Chem. Soc., 2002, 124, 12210, and refs. cited therein. CrossRef
30. E. Ettenhuber and K. Rühlmann, Chem. Ber., 1968, 101, 743. CrossRef
31. A. Alvanipour, N. H. Buttrus, C. Eaborn, P. B. Hitchcock, A. I. Mansour, and A. K. Saxena, J. Organomet. Chem., 1988, 349, 29. CrossRef
32. A. D. Sinitsa, N. A. Parkhomenko, and L. N. Markovskii, Zh. Obshch. Khim., 1977, 47, 232; J. Gen. Chem. USSR, 1977, 47, 216.
33. L. A. Lazukina and V. P. Kukhar', Zh. Org. Khim., 1979, 15, 2216; J. Org. Chem. USSR, 1979, 15, 2009.
34. D. Cantillo, B. Gutmann, and C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465. CrossRef
35. a) K. Sisido, K. Nabika, T. Isida, and S. Kozima, J. Organomet. Chem., 1971, 33, 337; CrossRef b) S. Kozima, T. Hitomi, T. Akiyama, and T. Isida, J. Organomet. Chem., 1975, 92, 303. CrossRef
36. B. B. Semenov and Yu. I. Smushkevich, Izv. Akad. Nauk, Ser. Khim., 2002, 334; Russ. Chem. Bull., 2002, 51, 357. – The cycloadducts are erroneously shown as 1H-isomers. CrossRef
37. M. S. Hill, P. B. Hitchcock, and N. Smith, Polyhedron, 2004, 23, 801. CrossRef
38. J. V. Duncia, M. E. Pierce, and J. B. Santella III, J. Org. Chem., 1991, 56, 2395. CrossRef
39. P. A. Bethel, M. S. Hill, M. F. Mahon, and K. C. Molloy, J. Chem. Soc., Perkin Trans. 1, 1999, 3507. CrossRef
40. a) M. F. Mahon, K. C. Molloy, and P. C. Waterfield, J. Organomet. Chem., 1989, 361, C5; CrossRef b) S. J. Blunden, M. F. Mahon, K. C. Molloy, and P. C. Waterfield, J. Chem. Soc., Dalton Trans., 1994, 2135. CrossRef
41. C. A. K. Diop and K. C. Molloy, Main Group Met. Chem., 2002, 25, 267.
42. S. Bhandari, C. G. Frost, C. E. Hague, M. F. Mahon, and K. C. Molloy, J. Chem. Soc., Dalton Trans., 2000, 663. CrossRef
43. M. Hill, M. F. Mahon, J. McGinley, and K. C. Molloy, J. Chem. Soc., Dalton Trans., 1996, 835. CrossRef
44. A. Goodger, M. Hill, M. F. Mahon, J. McGinley, and K. C. Molloy, J. Chem. Soc., Dalton Trans., 1996, 847. CrossRef
45. M. Hill, M. F. Mahon, and K. C. Molloy, J. Chem. Soc., Dalton Trans., 1996, 1857. CrossRef
46. S. Bhandari, M. F. Mahon, and K. C. Molloy, J. Chem. Soc., Dalton Trans., 1999, 1951. CrossRef
47. See, for example: S. S. Washburne and W. R. Peterson, Jr., J. Organomet. Chem., 1970, 21, 427; CrossRef S. J. Wittenberger and B. G. Donner, J. Org. Chem., 1993, 58, 4139; CrossRef D. P. Curran, S. Hadida, and S.-Y. Kim, Tetrahedron, 1999, 55, 8997; CrossRef D. Amantini; R. Beleggia, F. Fringuelli, F. Pizzo, and L. Vaccaro, J. Org. Chem., 2004, 69, 2896. CrossRef
48. Y. S. Gyoung, J.-G. Shim, and Y. Yamamoto, Tetrahedron Lett., 2000, 41, 4193. CrossRef
49. S. Kamijo, T. Jin, and Y. Yamamoto, J. Org. Chem., 2002, 67, 7413; CrossRef cf. also S. Kamijo, T. Jin, Z. Huo, Y. S. Gyoung, J.-G. Shim, and Y. Yamamoto, Mol. Divers., 2003, 6, 181. CrossRef
50. a) W. Beck and W. P. Fehlhammer, Angew. Chem., 1967, 79, 146; CrossRef Angew. Chem. Int. Ed., 1967, 6, 169; CrossRef W. Beck, W. P. Fehlhammer, H. Bock, and M. Bauder, Chem. Ber., 1969, 102, 3637 (structure of isomers open, but established in refs.50b,c); CrossRef b) W. Beck, K. Burger, and W. P. Fehlhammer, Chem. Ber., 1971, 104, 1816 (viz. p. 1820); CrossRef c) P. Kreutzer, C. Weis, H. Boehme, T. Kemmerich, W. Beck, C. Spencer, and R. Mason, Z. Naturforsch., 1972, 27b, 745.
51. See, for example: J. Lasri, M. J. Fernández Rodríguez, M. F. C. Guedes da Silva, P. Smoleński, M. N. Kopylovich, J. J. R. Fraústo da Silva, and A. J. L. Pombeiro, J. Organomet. Chem., 2011, 696, 3513, and refs. cited therein. CrossRef
52. In reviews on organometallic tetrazoles this area has not been treated52a or covered only briefly:52b,c a) S. V. Voitekhovich, P. N. Gaponik, and G. I. Koldobskii, Zh. Org. Khim., 2005, 41, 1599; Russ. J. Org. Chem., 2005, 41, 1565; CrossRef b) P. N. Gaponik, S. V. Voitekhovich, and O. A. Ivashkevich, Usp. Khim., 2006, 75, 569; Russ. Chem. Rev., 2006, 75, 507 (passim); CrossRef c) E. A. Popova, R. E. Trifonov, and V. A. Ostrovskii, ARKIVOC, 2011 (i), 552 (passim).
53. a) S. Ito, Y. Tanaka, A. Kakehi, and K. Kondo, Chem. Lett., 1973, 1071; CrossRef b) S. Ito, Y. Tanaka, A. Kakehi, and K. Kondo, Bull. Chem. Soc. Jpn., 1976, 49, 1920. CrossRef
54. A. S. Shawali, A. A. Fahmi, and N. F. Eweiss, J. Heterocycl. Chem., 1979, 16, 123. CrossRef
55. H. Meier and H. Heimgartner, Helv. Chim. Acta, 1985, 68, 1283. CrossRef
56. C. Csongár, P. Weinberg, H. Slezak, and G. Tomaschewski, J. Prakt. Chem., 1988, 330, 629. CrossRef
57. D. Vlaović, G. Ćetković, I. Juranić, J. Balaž, S. Lajšić, and D. Djoković, Monatsh. Chem., 1990, 121, 931. CrossRef
58. G. L’abbé, S. Emmers, W. Dehaen, and L. K. Dyall, J. Chem. Soc., Perkin Trans. 1, 1994, 2553. CrossRef
59. M. J. Genin, D. A. Allwine, D. J. Anderson, M. R. Barbachyn, D. E. Emmert, S. A. Garmon, D. R. Graber, K. C. Grega, J. B. Hester, D. K. Hutchinson, J. Morris, R. J. Reischer, C. W. Ford, G. E. Zurenko, J. C. Hamel, R. D. Schaadt, D. Stapert, and B. H. Yagi, J. Med. Chem., 2000, 43, 953. CrossRef
60. a) J. Roppe, N. D. Smith, D. Huang, L. Tehrani, B. Wang, J. Anderson, J. Brodkin, J. Chung, X. Jiang, C. King, B. Munoz, M. A. Varney, P. Prasit, and N. D. P. Cosford, J. Med. Chem., 2004, 47, 4645; CrossRef b) D. Huang, S. F. Poon, D. F. Chapman, J. Chung, M. Cramer, T. S. Reger, J. R. Roppe, L. Tehrani, N. D. P. Cosford, and N. D. Smith, Bioorg. Med. Chem. Lett., 2004, 14, 5473; CrossRef c) N. D. Smith, S. F. Poon, D. Huang, M. Green, C. King, L. Tehrani, J. R. Roppe, J. Chung, D. P. Chapman, M. Cramer, and N. D. P. Cosford, Bioorg. Med. Chem. Lett., 2004, 14, 5481. CrossRef
61. Y. Wang and Q. Lin, Org. Lett., 2009, 11, 3570. CrossRef
62. Z. Yu, L. Y. Ho, Z. Wang, and Q. Lin, Bioorg. Med. Chem. Lett., 2011, 21, 5033. CrossRef
63. S. Ito, Y. Tanaka, and A. Kakehi, Bull. Chem. Soc. Jpn., 1976, 49, 762. CrossRef
64. H. M. Hassaneen, A. A. Fahmi, H. Abdelhamid, A. A. Yassin, and A. S. Shawali, J. Heterocycl. Chem., 1984, 21, 797. CrossRef
65. S. Ito, Y. Tanaka, A. Kakehi, and M. Kawahata, Bull. Chem. Soc. Jpn., 1978, 51, 953. CrossRef
66. R. Grashey, M. Baumann, and H. Bauer, Chem.-Ztg., 1972, 96, 225.
67. G. Ponzio and C. Macciotta, Gazz. Chim. Ital., 1914, 44 (II), 63.
68. a) For azoles, see: B. I. Buzykin, Khim. Geterotsikl. Soedin., 2010, 483; Chem. Heterocycl. Compd., 2010, 46, 379; CrossRef b) for azines, see: B. I. Buzykin, Khim. Geterotsikl. Soedin, 2010, 1295; Chem. Heterocycl. Compd., 2010, 46, 1043. CrossRef
69. a) E. Wedekind, Ber. Dtsch. Chem. Ges., 1897, 30, 449; CrossRef b) E. Wedekind, Ber. Dtsch. Chem. Ges., 1898, 31, 473. CrossRef
70. V. A. Grakauskas, A. J. Tomasewski, and J. P. Horwitz, J. Am. Chem. Soc., 1958, 80, 3155. CrossRef
71. a) F. L. Scott, D. A. O’Sullivan, and J. Reilly, J. Chem. Soc., 1951, 3508; CrossRef b) F. L. Scott, D. A. O’Sullivan, and J. Reilly, J. Am. Chem. Soc., 1953, 75, 5309. CrossRef
72. W. Ried and H. Hillenbrand, Liebigs Ann. Chem., 1954, 590, 128. CrossRef
73. B. I. Buzykin, L. P. Sysoeva, and Yu. P. Kitaev, Zh. Org. Khim., 1974, 10, 2200; J. Org. Chem. USSR, 1974, 10, 2211.
74. The leaving moiety (benzenediazonium ion) was trapped with naphthalene-2-amine.
75. M. O. Forster and D. Cardwell, J. Chem. Soc., 1913, 103, 861; CrossRef M. O. Forster and D. Cardwell, Proc. Chem. Soc., 1913, 29, 150.
76. D. Jerchel und H. Fischer, Chem. Ber., 1956, 89, 563. CrossRef
77. E. S. Karavaeva, N. P. Bednyagina, T. A. Sharkova, and I. I. Mudretsova, Khim. Geterotsikl. Soedin, 1975, 1420; Chem. Heterocycl. Compd. (USSR), 1975, 11, 1208. CrossRef
78. Yu. A. Sedov, A. I. Zabolotskaya, and N. V. Koba, Khim. Geterotsikl. Soedin, 1973, 1705; Chem. Heterocycl. Compd. (USSR), 1973, 9, 1542. CrossRef
79. Yu. A. Sedov and M. A. Chernova, Khim. Geterotsikl. Soedin, 1978, 545; Chem. Heterocycl. Compd. (USSR), 1978, 14, 450. CrossRef
80. a) N. P. Bednyagina and G. N. Lipunova, Khim. Geterotsikl. Soedin, 1968, 902; Chem. Heterocycl. Compd. (USSR), 1968, 4, 652 [at that time the product, i.e. compound (Jb), was not recognized yet]; b) G. N. Lipunova, E. P. Motyleva, and N. P. Bednyagina, Khim. Geterotsikl. Soedin, 1971, 831; Chem. Heterocycl. Compd. (USSR), 1971, 7, 776. CrossRef
81. Yu. A. Sedov and I. Ya. Postovskii, Zh. Org. Khim., 1969, 5, 781; J. Org. Chem. USSR, 1969, 5, 765. – The leaving benzazole moiety was isolated as 2-chloro-1-methylbenzimidazole (94%).
82. V. P. Shchipanov, S. A. Nagovskaya, and L. S. Podenko, Khim. Geterotsikl. Soedin, 1977, 266; Chem. Heterocycl. Compd. (USSR), 1977, 13, 213. CrossRef
83. B. I. Buzykin and N. N. Bystrykh, Zh. Org. Khim., 1983, 19, 1069; J. Org. Chem. USSR, 1983, 19, 953. – The leaving benzodiazine moiety was isolated as 4-chloro-2-methylphthalazin-1(2H)-one.
84. E. Wedekind, Ber. Dtsch. Chem. Ges., 1896, 29, 1846. CrossRef
85. F. A. Neugebauer, Tetrahedron, 1970, 26, 4843; CrossRef see also: F. A. Neugebauer, Angew. Chem., 1973, 85, 485; CrossRef Angew. Chem. Int. Ed., 1973, 12, 455. CrossRef
86. a) J. P. Horwitz and V. A. Grakauskas, J. Am. Chem. Soc., 1955, 77, 6711; structure of benzylidene¬tetrazene (II) misprinted; CrossRef b) J. P. Horwitz and V. A. Grakauskas, J. Am. Chem. Soc., 1958, 80, 926; structure of tetrazolium betaine (Xa) misprinted. CrossRef
87. M. Busch and H. Pfeiffer, Ber. Dtsch. Chem. Ges., 1926, 59, 1162. CrossRef
88. R. Kuhn and H. Kainer, Angew. Chem., 1953, 65, 442. CrossRef
89. P. A. S. Smith and G. D. Mendenhall, J. Org. Chem., 1990, 55, 3362. CrossRef
90. a) M. Ruccia, N. Vivona, and D. Spinelli, 'Advances in Heterocyclic Chemistry: Mononuclear Heterocyclic Rearrangements,' Vol. 29, ed. by A. R. Katritzky and A. J. Boulton, Academic Press, London, 1981; pp. 141–169; b) G. L'abbé, J. Heterocycl. Chem., 1984, 21, 627; CrossRef c) N. Vivona, S. Buscemi, V. Frenna, and S. Cusmano, 'Advances in Heterocyclic Chemistry: Ring Transformations of Five-Membered Heterocycles,' Vol. 56, ed. by A. R. Katritzky, Academic Press, London, 1993; pp. 49–154.
91. H. Kano and E. Yamazaki, Chem. Pharm. Bull., 1962, 10, 993; CrossRef H. Kano and E. Yamazaki, Tetrahedron, 1964, 20, 461. CrossRef
92. D. Moderhack, D. Decker, and B. Holtmann, J. Chem. Soc., Perkin Trans. 1, 2001, 720. CrossRef
93. A. J. Boulton, Lect. Heterocycl. Chem., 1974, 2, S-45.
94. S. D. Shaposhnikov, S. F. Mel'nikova, and I. V. Tselinsky, Izv. Akad. Nauk, Ser. Khim., 2004, 1077; Russ. Chem. Bull., 2004, 53, 1121. CrossRef
95. a) G. Ege, K. Gilbert, and R. Heck, Angew. Chem., 1982, 94, 715; CrossRef Angew. Chem. Suppl., 1982, 1508; CrossRef Angew. Chem. Int. Ed., 1982, 21, 698; b) G. Ege, R. Heck, K. Gilbert, H. Irngartinger, U. Huber-Patz, and H. Rodewald, J. Heterocycl. Chem., 1983, 20, 1629. CrossRef
96. A. Ding, G. Ege, and R. Heck, '100 Jahre HN3 – Das Erbe von Theodor Curtius,' International Sym¬posium under the auspices of Chemische Gesellschaft zu Heidelberg and Gesellschaft Deutscher Chemiker (GDCh), Heidelberg, Germany, 1990; Abstracts of Papers, poster 32.
97. R. N. Butler and D. P. Shelly, J. Chem. Soc., Perkin Trans. 1, 1986, 1101. CrossRef
98. Density Functional Theory calculations (B3LYP/6-311+G**) performed with the methyl analogues of 63b and Nb (ap conformer) showed the bicyclic system to be higher in energy than the isomeric azide by 34.78 kcal/mol (D. Moderhack, unpublished result); for this kind of relationship, cf. also: D. Moderhack, Heterocycles, 2008, 75, 1 (p. 13); CrossRef I. Alkorta, F. Blanco, and J. Elguero, Tetrahedron, 2010, 66, 5071. CrossRef
99. For this class of compound, cf. D. Moderhack, Tetrahedron, 2012, 68, 5949. CrossRef
100. A. Messmer and A. Gelléri, Angew. Chem., 1965, 77, 171; CrossRef Angew. Chem. Int. Ed., 1965, 4, 154. CrossRef
101. A. Gelléri and A. Messmer, Tetrahedron Lett., 1973, 4295. CrossRef
102. A. Messmer, A. Gelléri, and G. Hajós, Tetrahedron, 1986, 42, 4827. CrossRef
103. I. Nagy, Z. Riedl, G. Hajós, A. Messmer, N. Gyémánt, and J. Molnár, ARKIVOC, 2004 (vii), 177.
104. I. Nagy, D. Kónya, Z. Riedl, A. Kotschy, G. Tímári, A. Messmer, and G. Hajós, Tetrahedron, 2003, 59, 7485. CrossRef
105. A. Messmer, G. Hajós, A. Gelléri, and L. Radics, Tetrahedron, 1986, 42, 5415. CrossRef
106. A. Gelléri, A. Messmer, S. Nagy, and L. Radics, Tetrahedron Lett., 1980, 21, 663. CrossRef
107. A. Messmer, G. Hájos, and G. Tímári, Tetrahedron, 1992, 48, 8451. CrossRef
108. A. Messmer, G. Hájos, and G. Tímári, Monatsh. Chem., 1988, 119, 1113. CrossRef
109. A. Messmer, P. Kövér, Z. Riedl, Á. Gömöry, and G. Hajós, Tetrahedron, 2002, 58, 3613. – In the introduction to this paper the authors briefly mention that compounds of the type (79) also form on treatment of 67 with hydroxide ion; however, in both the present and preceding studies, e.g. ref.102, they do not verify this. CrossRef
110. For short extracts, see also: a) G. Hajós, 'Comprehensive Heterocyclic Chemistry II: Bicyclic 5-6 Systems with One Ring Junction Nitrogen Atom: Three Extra Heteroatoms 3:0,' Vol. 8, ed. by G. Jones (Series ed. by A. R. Katritzky, C. W. Rees, and E. F. Scriven), Pergamon, Oxford, 1996, pp. 405–416 (passim); b) G. Hajós and Z. Riedl, 'Comprehensive Heterocyclic Chemistry III: Bicyclic 5-6 Systems with One Bridgehead (Ring Junction) Nitrogen Atom: Three Extra Heteroatoms 3:0,' Vol. 11, ed. by J. Cossy (Series ed. by A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven, and R. J. K. Taylor), Pergamon, Oxford, 2008, pp. 645–670 (passim).
111. All bromide salts were also characterized as tetrafluoroborate salts; for an X-ray crystallographic study of 67a (X = H, Z = BF4), see: K. Sasvári, M. Czugler, A. Gelléri, G. Náray-Szabó, H. Hess, and W. Schwarz, Acta Cryst. B, 1979, 35, 2145. CrossRef
112. A. Messmer, Gy. Hajós, G. Timári, and A. Gelléri, Monatsh. Chem., 1988, 119, 1121. CrossRef
113. I. Nagy, G. Hajós, and Z. Riedl, Heterocycles, 2004, 63, 2287. CrossRef
114. S. Bátori, E. Gácz-Baitz, S. Bokotey, and A. Messmer, Tetrahedron, 2003, 59, 4297. CrossRef
115. O. Dimroth and O. Dienstbach, Ber. Dtsch. Chem. Ges., 1908, 41, 4055. CrossRef
116. Because of spontaneous decarboxylation, both materials would have eluded isolation as such: For compound (86), see: C. R. Jacobson, A. B. Kerr, Jr., and E. D. Amstutz, J. Org. Chem., 1954, 19, 1909; CrossRef regarding 87, cf.: A. Bertho, J. Prakt. Chem., 1927, 116, 101. CrossRef
117. O. Dimroth, Liebigs Ann. Chem., 1904, 335, 1. CrossRef
118. T. Curtius and J. Thomsen, Ber. Dtsch. Chem. Ges., 1906, 39, 4140. CrossRef
119. C. Pedersen, Acta Chem. Scand., 1958, 12, 1236. CrossRef
120. (a) T. Kaihoh, T. Itoh, K. Yamaguchi, and A. Ohsawa, J. Chem. Soc., Chem. Commun., 1988, 1608; CrossRef (b) T. Kaihoh, T. Itoh, K. Yamaguchi, and A. Ohsawa, J. Chem. Soc., Perkin Trans. 1, 1991, 2045. CrossRef
121. T. Kaihoh, T. Itoh, K. Yamaguchi, and A. Ohsawa, Chem. Pharm. Bull., 1990, 38, 3191. CrossRef
122. K. Yamaguchi, A. Ohsawa, T. Kaihoh, and T. Itoh, Acta Cryst. C, 1990, 46, 1161. CrossRef
123. Selective N(2)-arylation – described, for example, in refs.124a,b – cannot compete with the approach via ring synthesis.
124. a) V. Yu. Zubarev, S. M. Putis, and V. A. Ostrovskii, Khim. Geterotsikl. Soedin, 2001, 400; Chem. Heterocycl. Compd., 2001, 37, 372; CrossRef (b) I. P. Beletskaya, D. V. Davydov, and M. S. Gorovoy, Tetrahedon Lett., 2002, 43, 6221. CrossRef