Synthesis and study of N,N-disubstituted 4-aminophenylazobenzaldehydes

A series of ^N , ^N -disubstituted 4-aminophenylazobenzaldehydes (azo dyes) were synthesized by the reaction of phenylpiperazine derivatives with 4-formylbenzenediazonium tetrafluoroborate. The salt was easily prepared by reacting poly(aminobenzaldehyde) with sodium nitrite in the presence of tetrafluoroboric acid. A representative sample was studied by crystallography, and the charge distribution of the molecule was calculated with the aim of understanding the form of molecular stacking on the basis of crystal data. The mesogenic behaviour of the azo dyes was also studied.     

Synthesis of N,N-disubstituted aminoacetophenones

Conclusions Reaction of p-bromoacetophenone with secondary amines affords mixtures of N,N-disubstituted p- and m-aminoacetophenones, with a predominance of the m-isomers.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 665–666, March, 1976.     

Synthesis and study of N,N-disubstituted 4-[(4-aminophenyl)diazenyl]benzylidene-4'-alkylanilines

A series of N,N-disubstituted-4-[(4-aminophenyl)diazenyl]benzylidene-4'-alkylanilines (azo dyes) were synthesized from the reaction of the corresponding benzaldehyde with alkylanilines. These azo dyes exhibit nematic and SmC phases on heating. Their order parameter, photo-stability and miscibility were studied by investigation of a representative sample.     

Synthesis and Structural Characterization of N,N-disubstituted Acylguanidines

A series of five N,N-disubstituted acylguanidines R~1C(O)N=C[N(H)R~2]NR_2~3(R~1=Mes or Ph; R~2=Ar??or Ar?; R~3=Cy, Bn, iPr, or Et)(Mes=2,4,6-Me_3C_6H_2, Ar??=2,6-iPr_2C_6H_3, Ar?=2,6-Me_2C_6H_3) was synthesized from the reactions of parent acylthioureas with respective secondary amines. According to structutral characterization by single-crystal X-ray diffraction, the rough reduction of the steric hindrance of R substitutents of R~1 C(O)N=C[N(H)R~2]NR_2~3(also abbreviated as R~1-R~2-R~3 for comparison purposes) led to the slight enlongation of N(1)–C(1) bond lengthes and small decrease of N(1)–C(1)–N(3) bond angles from Mes–Ar??–Cy(1) to Ph–Ar??–Bn(2), Ph–Ar??–iPr(3) and Ph–Ar?–Cy(4). At the same time, the N(1)–H(1)···O(1) intramolecular hydrogen bonds were observed in these cases. When R~3=Et, an interesting compound Ph-Ar?-Et(5) was obtained with the formation of intermolecular hydrogen bonds instead. 1 belongs to the monoclinic system, space group P2_(1/n) with a=9.6488(3), b=28.5318(8), c=11.9155(3) ?, b=91.439(2)o, V=3279.27(16) ?~3, and Z=4. 2 belongs to the triclinic system, space group P1 with a=9.6759(7), b=10.8613(8), c=15.7642(12) ?, a=70.429(3), b=79.257(4), g=69.052(4)o, V=1453.63(19) ?~3 and Z=2. 3 belongs to the monoclinic system, space group P2_(1/c) with a=11.1393(4), b=13.0643(4), c=17.6600(6) ?, b=101.866(2)o, V=2515.09(15) ?~3 and Z=4. 4 belongs to the monoclinic system, space group C2/c with a=17.8466(3), b=13.6126(2), c=21.6710(4) ?, b=90.7310(10)o, V=4992.72(14) ?~3 and Z=8. 5 is of orthorhombic system, space group P2_12_12_1 with a=10.5555(2), b=11.8913(2), c=14.9558(4) ?, V=1877.23(5) ?~3 and Z=4.     

Synthesis and CH-acidity of N,N-disubstituted aminotriphenylphosphonium salts

Several substituted methylaminotriphenylphosphonium salts (APS) of general formula have been synthesized. The CH-acidities of some of the prepared APS have been measured by the indicator method in DMSO, with K⁺ counterion and 9-phenylfluorene (pK 18.5) as standard, showing a pK range of 14.7–24.8. The acidification effect of and groups has been evaluated. The results obtained suggest that there is an effective charge on the nitrogen atom in the APS studied and an increased multiplicity of the N-P bond.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1598–1604, July, 1991.     

N,N-二取代甘氨酸酯的合成及其经皮促渗活性

合成了4个新的N,N-二取代甘氨酸酯,其结构经^1HNMR谱、IR谱、MS-ESI谱和元素分析确证。在改良的Franz扩散池上,用离体裸鼠皮作生物膜,扑热息痛或消炎痛作药物模型进行经皮促渗活性对比试验。结果显示：N,N-二甲基甘氨酸-（E）-3,7-二甲基-2,6-辛二烯酯（2a）具有出色的促透活性,含2．5％的2a促进扑热息痛、消炎痛经皮渗透的效果分别是Azone的2．1和2．6倍,且时滞缩短,超过DDAA的经皮促渗活性;而N,N-二甲基甘氨酸-6-戊氧基-1-己酯（2b）的经皮促渗活性接近Azone,且时滞更短。     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XVI. Synthesis of N,N-disubstituted 4-amino-5,6-tetramethylene-3-phenyl-2-pyranones

1,4-Cycloaddition of phenylchloroketene (prepared in situ from α-chlorophenylacetyl chloride and triethyl-amine) to a number of N,N-disubstituted (E)-2-aminomethylenecyclohexanones gave the corresponding adducts, namely N,N-disubstituted 4-amino-3-chloro-3,4,5,6,7,8-hexahydro-2H-1-benzopyran-2-ones III in the case of aliphatic N,N-disubstitution or aromatic N-monosubstitution. Purification of III was possible only in the case of IIIh (NR₂ = NMePh), therefore they were dehydrochlorinated in situ with DBN to give the title compounds in moderate overall yields.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones VIII. Synthesis of N,N-disubstituted 4-amino-3-chloro-6-phenyl-2H-pyran-2-ones

The dipolar 1,4-cycloaddition of dichloroketene to N,N-disubstituted 3-amino-1-phenyl-2-propene-1-onesled directly to N,N-disubstituted 4-amino-3-chloro-6-phenyl-2H-pyran-2-ones only in the case of an usual aliphatic N,N-disubstitution. In the case of partial or full aromatic N-substitution, N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-6-phenyl-2H-pyran-2-ones were instead obtained, which were dehydrochlorinated with DBN to the corresponding 4-amino-3-chloro-6-phenyl-2H-pyran-2-ones.     

Synthesis of N,N-disubstituted phosphoramidates via a Lewis acid-catalyzed phosphorimidate rearrangement

A Lewis acid-catalyzed rearrangement of phosphorimidates allows a direct, high-yielding transformation of azides with commercially available phosphites into secondary phosphoramidates.     

Reaction of substituted sulfenes with N,N-disubstituted α-amino-methyleneketones. I. Synthesis of N,N-disubstituted cis- and trans-4-amino-3,4,5,6,7,8-hexahydro-3-phenyl-1,2-benzoxathiin 2,2-dioxides

The polar 1, 4-cycloaddition of phenylsulfene (generated in situ from phenylmethanesulfony] chloride and triethylamine) to N, N-disubstituted (E)-2-aminomethylenecyclohexanones I gave in general a mixture of N, N-disubstituted cis- and trans-4-amino-3, 4, 5, 6, 7, 8-hexahydro-3-phenyl-1, 2-benzoxathiin 2, 2-dioxides III and IV, which were separated by column chromatography and whose structural and conformational features were determined from uv, ir and nmr spectral data. In the case of N, N-diisopropylamino enaminone 1c, the cyclo-addition took place with elimination of an alkyl group as propene to give the adduct III?.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XVIII. Synthesis of N,N-disubstituted 4-amino-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones

1,4-Cycloaddition of phenylchloroketene to N,N-disubstituted 2-aminomethylene-3,4-dihydro-1(2H)naphthalenones gave the corresponding adducts, namely N,N-disubstituted 4-amino-3-chloro-3,4,5,6-tetrahydro-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones II, in the case of aliphatic N,N-disubstitution or aromatic N-monosubstitution. Apart from IIf (NR₂ = NMePh), adducts II were unstable and were dehydrochlorinated in situ with DBN to give N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones III in fair overall yields. Compounds III were dehydrogenated with Pd/C in boiling p-cymene to afford the title compounds generally in high yields.     

Chemical shift assignments in N,N-disubstituted trifluoroacetamides

Due to hindered rotation about the central C? N bond in N,N-disubstituted trifluoroacetamides, CF₃CONR₁R₂, two resonance peaks are usually observed for each proton in R₁ and R₂. Chemical shift assignments are made for the following amides: 1 , R₁ = R₂ = Me; 2 , R₁ = R₂ = Et; 3 , R₁ = Me, R₂ = 2-Propyl; 4 , R₁ = Me, R₂ = 1-Butyl; 5 , R₁ = Me, R₂ = Cyclohexyl; 6 , R₁ = R₂ = 2-Propyl; 7 , R₁ = 2-Propyl, R₂ = Cyclohexyl. Amides 6 and 7 show an inversion of the relative chemical shift for both the methine and methyl protons of the 2-propyl group as compared with 3 . For non-fluorinated amides, aromatic solvents shift the trans alkyl peaks to higher field faster than those cis (to the carbonyl oxygen atom); however, this generalization does not apply to all trifluoroacetamide proton peaks.     

Reaction of substituted sulfenes with N,N-disubstituted α-amino-methyleneketones. II. Synthesis of N,N-disubstituted cis and trans 4-amino-3-chloro-3,4,5,6,7,8-hexahydro-1,2-benzoxathiin 2,2-dioxides,and 4-amino-5,6,7,8-tetrahydro-1,2-benzoxathiin 2,2-dioxides

The polar 1,4-cycloaddition of chlorosulfene (generated in situ from chloromethanesulfonyl chloride and triethylamine) to N,N-disubstituted (E)-2-aminomethylenecyclohexanones I gave mixtures of N,N-disubstituted cis and trans 4-amino-3-chloro-3,4,5,6,7,8-hexahydro-1,2-benzoxathiin 2,2-dioxides III and IV, except for N,N-diphenyl enaminone which did not react. Only compounds IV could be separated from these mixtures by silica gel chromatography, with the exception of the piperidino adducts (III + IV)d, from which also IIId could be obtained pure. Compounds IV or mixtures III + IV were dehydrochlorinated with DBN in refluxing benzene to afford N,N-disubstituted 4-amino-5,6,7,8-tetrahydro-1,2-benzoxathiin 2,2-dioxides V in satisfactory yields. Structural and conformational features of compounds III, IV and V were determined from uv, ir and nmr spectral data.     

H-Bonded complexes of N, N-disubstituted aminophenylazo-(4)-pyridine and benzoic acid derivatives: preparation, mesogenic study and molecular modelling

N, N-Disubstituted aminophenylazo-(4)-pyridine forms complexes with a series of m-alkoxy benzoic acids by intermolecular hydrogen bonding; liquid crystalline phases of the resulting complexes are thus induced.     

H-Bonded complexes of N,N-disubstituted aminophenylazo-(4)-pyridine and benzoic acid derivatives: preparation,mesogenic study and molecular modelling

N, N-Disubstituted aminophenylazo-(4)-pyridine forms complexes with a series of m-alkoxy benzoic acids by intermolecular hydrogen bonding; liquid crystalline phases of the resulting complexes are thus induced.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. X. Synthesis of N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones and of 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones

Cycloaddition of dichloroketene to N,N-disubstituted 1-amino-4-methyl-1-penten-3-ones and 1-amino-4,4-dimethyl-1-penten-3-ones occurred in moderate to fair yield only in the case of aromatic N-substitution to give N,N-disubstituted 6-alkyl-4-amino-3,3-dichloro-3,4-dihydro-2H-pyran-2-ones, which were dehydrochlorinated with DBN to afford in good yield N,N-disubstituted 6-alkyl-4-amino-3-chloro-2H-pyran-2-ones. In the case of aliphatic N,N-disubstitution, cyclo-addition led directly to 6-alkyl-4-dialkylamino-3-chloro-2H-pyran-2-ones only for N,N-disubstituted 1-amino-4,4-dimethyl-1-penten-3-ones. The reaction between 1-dimethylamino-4-methyl-1-penten-3-one and dichloroketene gave 3-chloro-4-dimethylamino-3,6-dihydro-6-isopropylidene-2H-pyran-2-one in low yield.     

The extraordinary reactions of phenyldimethylsilyllithium with N,N-disubstituted amides

Phenyldimethylsilyllithium reacts with N,N-dimethylamides in a variety of ways, depending upon the stoichiometry, the temperature and, most subtly, on the structure of the amide, with quite small-seeming changes in structure leading to profound changes in the nature of the products. When equimolar amounts of the silyllithium reagent and N,N-dimethylamides 6 are combined in THF at -78 degrees C, and the mixture quenched at -78 degrees C, the product is the corresponding acylsilane . If the same mixture is warmed to -20 degrees C before quenching, the product is a cis enediamine 11. The enediamines are easily isomerised from cis to trans, easily oxidised to dienediamines , and, with more difficulty, hydrolysed to alpha-aminoketones 13. If two equivalents of the silyllithium reagent are used, the product is an alpha-silylamine 20. The mechanism of formation of the enediamines appears to be by way of a Brook rearrangement of the tetrahedral intermediate 17 followed by loss of a silanoxide ion to give a carbene or carbene-like species. The 'carbene' combines with the Brook-rearranging nucleophile to give an intermediate 28, which loses another silanoxide ion to give the enediamine. The same carbene can be attacked by a second equivalent of the silyllithium reagent to give the alpha-silylamine 20. Other nucleophiles, like alkyllithiums, phenyllithium, and tributylstannyllithium also trap the carbene to give products 48-52. The intermediate anions in these reactions, when benzylic, can be further trapped with alkylating agents to give the products 33, 34 and 53-55. In special cases, the anion formed by attack on the carbene can be trapped by intramolecular reactions displacing internal leaving groups, as in the formation of the enamine 37 and the cyclopentane 41, or attacking a carbonyl group, as in the formation of the indanone 61, or attacking a double or triple bond, as in the formation of the cyclopentanes 71 and 75. In another special case, the carbene reacts with vinyllithium to give an allyllithium intermediate 56, which selectively attacks another molecule of carbene to give eventually the gamma-aminoketone 58. Small changes in the structure of the amide lead to a variety of other pathways each of which is discussed in the text. Notably, each member of the homologous series of amides Ph(CH2)nCONMe2 gives rise to a substantially different product: when n= 0, the reaction is normal, and the yield of the alph]-silylamine 20e is high; when n=1, proton transfer in the intermediate anion 64 and displacement of the phenyl group leads to the silaindane 66; when n=2, fragmentation of the intermediate anion 80, and capture of the carbene by benzyllithium leads to the 1,4-diphenylbut-2-ylamine 83; and when n=3, proton transfer in the intermediate anion 67 and displacement of the phenyl group leads to the silacyclopentane 69.     

Transformations of N,N-disubstituted 2-aminocyclopentanones on Pd catalyst

Conclusions It was shown that N,N-disubstituted 2-aminocyclopentanones can be selectively converted on 5% Pd/C catalyst at 350–370 to N,N-disubstituted 2-aminocyclopenten-2-ones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, p. 1905, August, 1982.