Ralf Kreß

Orthoamide, LXIII [1]. Tris(dichlormethyl)amin, ein neues breit anwendbares Formylierungsmittel für Aromaten / Orthoamides, LXIII [1]. Tris(dichloromethyl)amine, a New Formylating Reagent for Aromatic Compounds of Wide Scope

The reagent system formed from tris(dichloromethyl)amine (5) and aluminium chloride allows the formylation of aromatic compounds. The scope of the method is comparable with that of the Olah formylation and the Groß-Rieche procedure, since benzene and even chlorobenzene can be formylated. One formyl group is transferred from 5 to the aromatic nucleus. In order to find optimal reaction conditions, the molar amounts of aromatic compounds, 5 and aluminum chloride were varied as well as reaction temperatures and solvents. The activation of 5 with other Lewis acids is also described

Orthoamide und Iminiumsalze, XCII. Synthese und Reaktionen von Orthoamiden aus ethinylierten Terpenderivatena

Abstract β-Ionone and camphor were ethynylated to give the alkynols 14, 16, 17 which can be transformed to the alkynolethers 5b, 5i, 5j, 5k, 5l, 5m by treatment with dimethylsulfate and chlorotrimethylsilane, respectively. From the alkynolethers 5h, 5i, 5j/5k, 5l/5m the orthoamide derivatives 4h, 4i, 4j/4k, 4l/4m can be prepared by treatment with N,N,N′,N′,N″,N″-hexamethylguanidinium chloride (8) in the presence of sodium hydride. The orthoamides 4h, 4i react with the sulfonamide 30 under condensation yielding the N-sulfonylated acrylamidines 31, 32. From the orthoamide 4h and p-nitroaniline the propiolamidine 29 could be obtained. The orthoamides 4j/4k and 4l/4m, react with benzamidine to give the pyrimidines 33, 34, respectively. In the reaction of malonodinitrile (9a) with the orthoamides 4i and 4j/4k, mixtures of 1,1-diamino-1,3-butadienes 36, 38 and 1,3-diamino-1,3-butadienes 37 and 39 are produced, respectively. From CH2-acidic compounds as ethylcyanacetate (9b), diethyl-malonate (9c) and nitromethane (9d) and the orthoamide 4i the 1,1-diamino-1,3-butadienes 36b–d were produced. The pyridone derivative 40 can be prepared from cyanoacetamide (9e) and the orthoamide 4i. The condensation of the orthoamides 4j/4k with cyanoacetamide (9e) affords a mixture of the pyrimidone 41 and the nicotinonitrile 42.

Orthoamide und Iminiumsalze, LXXXVIII. Synthese N,N,N′,N′,N″,N″-persubstituierter Guanidiniumsalze aus N,N′-persubstituierten Harnstoff/Säurechlorid-Addukten**

Abstract N,N,N′,N′,N″,N″-Hexamethylguanidinium chloride 9c was prepared by treating the reaction mixture formed from N,N,N′,N′-tetramethylurea (1a) and phthaloyl chloride (16) with dimethyltrimethylsilylamine 15. N,N,N′,N′-Tetramethyl-chloroformamidinium chloride (2a) is an intermediate in this synthesis. The chloroformamidinium chloride 2a can also be prepared by treating the urea 1a with thionyl chloride or phosphorus pentachloride, respectively. The guanidinium salt 9c can be obtained from the crude 2a thus prepared and the silylamine 15. From urea/phosphoryl chloride adducts and primary aromatic amines have been prepared guanidines 38, which are converted to N,N′-diaryl-N,N′,N″,N″-tetramethyl-guanidinium iodides 39 on treatment with methyl iodide. The N,N′,N″-trimethyl-N,N′,N″-triphenylguanidinium salt 44a was prepared from the chloroformamidinium salt 43 and N-methylaniline. The guanidinium salt 9c is the reaction product when the urea 1a/POCl3 adduct is treated with the silylamine 15.

Orthoamide und Iminiumsalze, LXXXIII [1]. Die Synthese von starken Formylierungsmitteln im präparativen Großmaßstab: Triformamid (Triformylamin) / Orthoamides and Iminium Salts LXXXIII [1]. The Synthesis of Strong Formylating Reagents on Large Preparative Scale: Triformamide (Triformylamine)

The preparation of sodium diformamide (7) from formamide and sodium methanolate under azeotropic removal of methanol with cyclohexane, or from formamide and sodium ethanolate in ethanol, is described. Diformamide (8) can be prepared by treatment of sodium diformamide (7) with formic acid. Triformamide (triformylamine) (1) is formed in the reaction of sodium diformamide with inorganic acid halides such as SOCl2, SO2Cl2 or PCl3 in acetonitrile at low temperatures. Triformamide (1) can be prepared on a large scale by the action of methanesulfonyl chloride on finely powdered sodium diformamide (7) in acetonitrile. Tris(diformylamino)methane (4) can be formed as a side product. A procedure was developed for the large-scale preparation of N;N-diformylacetamide (6) from sodium diformamide and acetyl chloride. Triformamide (1) can be prepared from N;Ndiformylacetamide (6) and diformamide with good yields Graphical Abstract Orthoamide und Iminiumsalze, LXXXIII [1]. Die Synthese von starken Formylierungsmitteln im präparativen Großmaßstab: Triformamid (Triformylamin) / Orthoamides and Iminium Salts LXXXIII [1]. The Synthesis of Strong Formylating Reagents on Large Preparative Scale: Triformamide (Triformylamine)

Orthoamide, LXIX [1]. Beiträge zur Synthese N,N,N´,N´,N´´-peralkylierter Guanidine und N,N,N´,N´,N´´䞲,N´´-persubstituierter Guanidiniumsalze / Orthoamides, LXIX [1]. Contributions to the Synthesis of N, N, N´, N´, N´-peralkylated Guanidines and N, N, N´, N´, N´´, N´´-persubstituted Guanidinium Salts

N, N, N´, N´-Tetraalkyl-chloroformamidinium chlorides 6 are prepared from N, N, N´, N´-tetraalkylureas 5 and phosgene in acetonitrile. The iminium salts 6 react with primary and secondary amines in the presence of triethylamine to give N, N, N´, N´, N´´-pentasubstituted and N, N, N´, N´, N´´, N´´- hexasubstituted guanidinium salts 7 and 8, respectively, Treatment of the guanidinium salts 7 with sodium hydroxide in excess affords the N, N, N´N´, N´´-pentasubstituted guanidines 9a - 9aa. Additionally, the N, N, N´, N´, N´´-pentasubstituted and N, N, N´, N´, N´´, N´´-hexasubstituted guanidinium salts 7l´, 7p´ and 8a - c can be obtained from the reaction mixtures by addition of stoichiometric amounts of sodium hydroxide. A modified method is described for the preparation of guanidinium salts possessing dialkylamino substituents consisting of two long-chain alkyl groups (>C14). Some guanidines 9 were alkylated with allyl chloride and bromide, ethyl bromide, butyl bromide, benzyl bromide and chloride, dimethyl sulfate, diethyl sulfate, and methyl methansulfonate to give the corresponding guanidinium salts 11 - 15. By alkylation of the N, N, N´, N´, N´´-pentasubstituted guanidine 9v with triethyloxonium tetrafluoroborate the guandinium tetrafluoroborate 16a is accessible. N-Functionalized guanidinium salts 17 - 18a - c result from the reaction of N, N, N´, N´, N´´-pentasubstituted guanidines with ethyl bromoacetate and bromoacetonitrile, respectively, and subsequent anion exchange with sodium tetraphenylborate. N, N, N´, N´-Tetramethylguanidine (21) adds to ethyl acrylate to give the labile guanidine 22, which forms the guanidinium salt 23a on treatment with methyl iodide. Zwitterionic guanidinium salts 25 result, when N, N, N´, N´, N´´-pentasubstituted guanidines are treated with sultones 24. Graphical Abstract Orthoamide, LXIX [1]. Beiträge zur Synthese N,N,N´,N´,N´´-peralkylierter Guanidine und N,N,N´,N´,N´´䞲,N´´-persubstituierter Guanidiniumsalze / Orthoamides, LXIX [1]. Contributions to the Synthesis of N, N, N´, N´, N´-peralkylated Guanidines and N, N, N´, N´, N´´, N´´-persubstituted Guanidinium Salts

Orthoamide, LXVII [1]. Bis(diformylamino)methan – ein neues leistungsfähiges Formylierungsmittel für aromatische Verbindungen / Orthoamides, LXVII [1]. Bis(diformylamino)methane – a New Efficient Formylating Reagent for Aromatic Compounds

Abstract Formaldehyde reacts with diformamide (10) to give N-(hydroxymethyl)diformamide (11), which upon treatment with thionylchloride yields N-(chlormethyl)diformamide (12) together with small amounts of oxydimethylenebis(diformamide) (13). Various diformylamine derivatives, such as diformylaminomethyl formiate (14), diformylaminomethylisothiocyanate (15) and the N-diformylaminomethylated guanidinium salt 16, can be prepared from 12. Bis(diformylamino) methane (7) can be obtained by the reaction of sodium diformamide (8) with either 1-(chloromethyl)pyridinium chloride (9) or N-(chloromethyl)diformamide (12) in acetonitrile. The action of tris(chloromethyl) amine (18) on sodium diformamide (8) affords tris(diformylaminomethyl)amine (19). The constitution of the compounds 7, 11 and 19 was confirmed by crystal structure determination. The nature of the products from the reactions of aromatic compounds with 12 depends on the Lewis acid which is used as activator. Thus the N-benzylformamides 20a, b can be obtained from toluene and mesitylene and 12/BF3-ether, whereas 1,2,4-trimethoxybenzene is formylated by 12/AlCl3 to give the aldehyde 22. Interestingly enough, a novel and efficient formylating reagent resulted from these investigations: bis(diformylamino)methane (7), which can be activated by Lewis acids, e. g. AlCl3. The scope of this procedure is comparable with that of the Olah-formylation method (formylfluoride/BF3).

Orthoamide, LXIV [1]. Aromatenformylierungen mit Tris(dichlormethyl)amin und Oligoformylamin-Derivaten in Gegenwart von Supersäuren / Orthoamides, LXIV [1]. Formylation of Aromatic Compounds by Tris(dichloromethyl)amine and Oligoformylamine Derivatives in the Presence of Superacids

Tris(dichloromethyl)amine (4), triformamide (1) and tris(diformylamino)methane (“formylaalen”) (2) can be activated by addition of trifluoromethanesulfonic acid. The formylating systems thus formed transform activated aromatic compounds, such as toluene, anisole or 2,4- dimethoxybenzene to the corresponding aldehydes. The formylating ability of systems from 4 and superacids, such as FSO3H, FSO3H/SbF5, C4F9SO3H, and mixtures of aluminum chloride with C4F9SO3H and chlorosulfonic acid, respectively, is compared. In general, low reaction temperatures (−20 to −10 °C) are necessary to obtain aldehydes with acceptable to good yields. Remarkably, at higher temperatures (~ 100 °C) compound 4 can also act as a formylating agent in the presence of suitable zeolites, as e. g. zeolite HBEA. Reaction mechanisms of the new formylation reactions are proposed.

Orthoamide, LXV [1]. Kondensationsreaktionen von Amidinen, Guanidinen, Hydrazin und Hydrazin-Derivaten mit Orthoamiden von Alkincarbonsäuren / Orthoamides,LXV [1]. Condensation Reactions of Amidines, Guanidines, Hydrazine and Hydrazine Derivatives with Orthoamides of Alkyne Carboxylic Acids

The orthoamide derivatives 4 react with amidines 10 and guanidines 11 to give 4-dimethylaminopyrimidines 12. The 3-dimethylamino-pyrazoles 13a - c can be prepared from orthoamides 4 and hydrazine. The hydrazine derivative 14, whose constitution was established by crystal structure analysis, is obtained in low yield when hydrazine is added dropwise to a boiling solution of 4d in THF. Methyl- and phenylhydrazine, undergo reaction with the orthoamides 4a, c yielding mixtures of the isomeric pyrazoles 19 and 20. The reaction of 4c with acylhydrazines 21a - e affords the pyrazole 13b. The pyrazole 26 is produced in the reaction of 4a and acet-hydrazide according to this scheme, whereas 4a reacts with aromatic acid hydrazides 21c - e to give condensation products, which are presumably amidrazones 28. The 4,5-diaza-octatetraene derivative 30 results from the reaction of 4c with p-toluenesulfonylhydrazide. Ketene aminals 34a - c are the products of the reaction of the orthoamides 4b - d with 4,4-dimethylthiosemicarbazide 34, which cyclize on heating to give highmelting pyrazolethiones 35a - c. According to the crystal structure analysis of 35c the compounds have zwitterionic character and are associated via hydrogen bridges in the solid state.

Orthoamide, LXI [1]. Ein neues leistungsfähiges Verfahren zur Synthese von Orthoamid- Derivaten von Alkincarbonsäuren / Orthoamide, LXI [1]. A New, Efficient Procedure for the Synthesis of Orthoamide Derivatives of Alkyne Carboxylic Acids

Tris(dimethylamino)ethoxy-methane (3) reacts with 1-alkynes 7a - h to give orthoamides of alkyne carboxylic acids 4a - h.

Orthoamide, LXII [1]. – Mikrowellen-unterst ¨ utzte Formylierung schwach CH2-acider Verbindungen mit dem Bredereck-Simchen Reagenz – Umwandlung der Kondensationsprodukte in Heteroaromaten / Orthoamides, LXII [1]. – Microwave Assisted Formylation of Weak CH2-Acidic Compounds with the Bredereck-Simchen Reagent – Preparation of Heteroaromatic Compounds from the Condensation Products

The diformylation of the dinitriles 4 and diesters 7 with the Bredereck-Simchen reagent HC[N(CH3)2]2[OC(CH3)3] (1) under microwave irradiation give the bis-enamines 6 and 8 with dramatically reduced reaction times and improved yields compared to conventional heating. The condensation products formed can be easily converted to bis-pyrazole and bis-isoxazole derivatives 13 and 20, respectively. Methyl anthranilate reacts on prolonged heating with the orthoamide 21 to give ketene aminal 23 in low yield (8 %). Under microwave irradiation the same reagents lead to a mixture of 23 (14 %) and dihydropyrane 24 (28 %).