Reaction with ortho esters

Biphenyl-2,2 -diamine and ring-substituted biphenyl-2,2 -diamines are transformed into dibenzo[rf,/][l JJdiazepines 1 in various ways by reaction with ortho esters (Method A),169 with hydrochlorides of imido acid esters (Method B)170 or with the benzenesulfonates of pro-tonated nitriles (Method C).171 Selected examples are given. 

For a review of the reaction with ortho esters, see DeWolfe, R.H. Carboxylic Ortho Acid Derivatives, Academic Press, NY, 1970, pp. 44-45, 224-230. 

Reaction with ortho esters. Trialkyl(triaryl) ortho esters react with sulfur dioxide to produce esters and dialkyl sulfites (equation 1). 

The dehydration of oximes by such reagents as phosphorus pentoxide, thionyl chloride, acetic anhydride, acyl chlorides, and phosphorus pentachloride is well known [26]. In effect, this dehydration procedure permits the conversion of aldehydes to nitriles with the same number of carbon atoms. A modification applicable only to the aromatic series makes use of boiling acetic acid as a dehydrating agent [27]. With other dehydrating agents, aliphatic aldehydes also may be converted to nitriles. Oximes may be converted readily to nitriles by an acid-catalyzed reaction with ortho esters [28]. 

The reaction of 2-aminobenzoic acid hydrazidcs with ortho esters gives 4-methyl-3//-1,3,4-benzotriazepin-5(4//)-ones 17 or 4-methyl-l//-l, 3,4-benzotriazepin-5(4//)-ones 18, depending on the structure of the hydrazide. Selected examples are given.359 11 360 361... 

Furo[2, 3 4,5]pyrrolo[l,2-d][l,2,4]triazolo[3,4-/][l,2,4]triazines 667 were prepared by reaction of 664 with phosphorus pentasulfide to give 665 followed by conversion to the hydrazino derivative 666 and subsequent cyclization with ortho-esters (84CCC65, 84M13). Similarly, the indolo analogue 670 was prepared from 668 by sulfurization and hydrazinolysis to give 669, which cyclized with ortho-esters (84CCC1529). 

Cyclization of 776 with ortho-esters gave (83JOC1628) [l,2,4]triazolo-[4,3-fc]pyrimido[5,4-< ][ 1,2,4]triazines 777, whereas reaction with sodium nitrite afforded the corresponding tetrazolopyrimidotriazine 778.3-Azido-pyrimido[4,5-e][l, 2,4]triazine 779 exists in a cyclic form as tetrazolo derivative 780, as shown by X-ray analysis (86KGS114). In solution the position of the 779 780 equilibrium depended on temperature and solvent. Higher temperatures favored 779. Azido compound 779 predominated in water, and tetrazolo compound 780 predominated in pyridine. Addition of sodium azide to the aqueous solution shifted the equilibrium toward 780. The... 

These X -phosphorins 720 a-c also fail to react with carbonyl compounds. However, they are attacked by electrophiles (H or alkyl cations) at the C—2 position. In this manner new 1,1-diphenyl-2,3-benzo-X-phosphorins which are sustituted at positions C—2 (and C-4) can be prepared. Diazonium ions attack at C—4 to form azocompounds if an excess is used, C—2 is also substituted Hydrolysis with hot water affords 747. The reaction with ortho-formic acid ester forms a cyanine dye having a bridge at the C—4 positions 142 The experimen-... 

Enol Ethers and Esters 0-15 O-Alkylation of carbonyl compounds with diazo alkanes 0-17 Transetherification 0-20 Reaction between acyl halides and active hydrogen compounds 0-23 Transesterification 0-24 Acylation of vinylic halides 0-94 Alkylation with ortho esters 0-107 O-Acylation of 1,3-dicarbonyl compounds... 

Epoxidation. Reaction of ortho esters with 90% H,0, generates a species that can epoxidize alkenes. Of several ortho esters tested, triethyl orthoacetate was most satisfactory. An example is shown in equation (l).1... 

Eliel, E. L. Nader, F. W. Conformational analysis. XX. The stereochemistry of reaction of Grignard reagents with ortho esters. Synthesis of 1,3-dioxanes with axial substituents at C-2.]. Am. Chem. Soc. 1970, 92, 584-590. 

Another important synthesis involves the reductive cyclization of 4-ethoxyalkylidinehydrazino-5-nitropyrimidines of type (372), which are obtained readily by reaction of 4-hydrazino-5-nitro-pyrimidines (371) with ortho esters. Catalytic reduction of the nitro group in (372) affords the 5-aminopyrimidine intermediate (373), which cyclizes in situ to the dihydro product (374). This may be oxidized without isolation to give the fully aromatic product (375). These reactions are shown in... 

An alternative to the imidazolium salts as starting materials is the elimination of an alcohol from 2-alkoxy-l,2-dihydro-l f-imidazoles that are accessible by reaction of vicinal diamines with ortho-esters of formic acid [59-61] (see Figure 1.9). 

Cyclization of 2-aminobenzamides or 2-aminothiobenzamides 3 with ortho esters to form 2-substituted quinazolin-4(3f/)-ones or quinazoline-4(3//)-thiones 5 is a general although little studied cyclization process which can be applied also to hetarenic 2-aminocarboxamides. The isolation of intermediate 4 (R = H = Me X = CH = CH Y = O) from the reaction of 2-aminobenzamide with triethyl orthoacetate and the demonstration of its facile cyclization to 2-methylquinazolin-4(3//)-one on heating in ethanolic solution strongly supports the intermediacy of compounds of type 4 in the formation of 5. ° ... 

The reaction of aminomalonodiimidamide dihydrochloride with ortho esters in dimethyl-formamide gives 2,8-disubstituted adenines 7. ... 

Regiochemical synthesis of 1-substituted imidazole-4-carboxylates can be achieved by treatment of a (Z)-)3-dimethylamino-of-isocyanoacrylate with an alkyl or acyl halide (see Section 2.1.1 and Scheme 2.1.8), by cyclization of 3-alkylamino-2-aminopropanoic acids with triethyl orthoformate followed by dehydrogenation of the initially formed imidazoline (see Section 3.1.1 and Scheme 3.1.2), by condensation of 3-arylamino-2-nitro-2-enones with ortho esters in the presence of reducing agents (see Section 3.1.1 and Scheme 3.1.4), by reaction of an alkyl A -cyanoalkylimidate with a primary amine (see Section 3.2 and Scheme 3.2.1), the poor-yielding acid-catalysed cyclization of a 2-azabutadiene with a primary amine (see Section 3.2 and Scheme 3.2.3), the cyclocondensation of an isothiourea with the enolate form of ethyl isocyanoacetate (see Section 4.2 and Scheme 4.2.5), and from the interaction of of-aminonitrile, primary tunine and triethyl orthoformate (see Chapter 5, Scheme 5.1.5, and Tables 5.1.1 and 5.1.2). 

Dietsche, W., Reaction of trivalent phosphorus chlorides with ortho esters and their thio analogs. Preparation of C-phosphorylated formaldehyde acetals, Liebigs Ann. Chem., 712, 21, 1968. 

Moskva, V.V., Maikova, A.L, and Razumov, A.L, Phosphinic and phosphinous acid derivatives. Part 58. Reaction of ortho esters of carboxylic acids and acetals with phosphorus(in) acid chlorides, Zh. Obshch. Khim., 39, 595, 1969 Chem. Abstr, 71, 50076r, 1969. 

The condensation of 4-hydraziopyrimidie 52 with ortho esters led to the formation of l,2,4-triazolo[4,3-c]- and [l,5-c]pyrimidines, where the reaction was found to be dependent on the structure of the ortho ester (78AJC2505 86TL3127 89JHC687).Thus, the ortho acetate gave the unre-... 

A special type of modification of substituents bound to the 1,2,4-triazine nucleus is the formation of condensed 1,2,4-triazines, such as formation of imidazo[4,5-c]-l,2,4-triazines 21 by reaction of 1,2,4-triazine-5,6-diamines with ortho esters 103-189 with glyoxal or substituted glyoxals dihydro- and tetrahydropyrazino[2,3-e]-l, 2,4-triazines 22 are obtained. Pyrazino[2,3-e]-1,2,4-triazine 23 is synthesized by dehydration of the tetrahydropyrazino[2,3-< ]-l,2,4-tri-azine.293-297-301... 

The mechanism of cyclization with ortho esters differs from that of simple acylating agents, such as acetic anhydride, in that the aromatic rather than the aliphatic primary amino group is the first site of attack. The extended conjugation that arises in this way, as in 65 for example, promotes the reaction. Ring closure is aided by the loss of the —OEt group and by its... 

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