Julolidine

Submitted by D. B. Glass and A. Weissbeeger. Checked by Cliff S. Hamilton and Carol K. Ikeda. 

A mixture of 66.5 g. (0.5 mole) of tetrahydroquinoline and 400 g. of trimethylene chlorobromide (Note 1) is placed in a 1-1. round-bottomed flask attached to a reflux condenser, and heated in an oil bath held at 150-160° for 20 hours (Note 2). The reaction mixture is cooled, a solution of 50 ml. of concentrated hydrochloric acid in 500 ml. of water is added, and the excess trimethylene chlorobromide is removed by distillation with steam (Note 3). The acid residue from the steam distillation is made alkaline with a 40% solution of sodium hydroxide (about 75 ml.), and the julolidine is extracted with two 150-ml. portions of ether. The ethereal solution is washed with ISO ml. of water and dried over sodium hydroxide pellets. The ether is evaporated and the residue distilled under reduced pressure. The portion that boils at 105-110°/ mm. is collected (Notes 4 and 5). The yield is 67-70 g. (77-81%). 

The tetrahydroquinoline and trimethylene chlorobromide were Eastman grade materials of the Eastman Kodak Company. 

The trimethylene chlorobromide recovered may be dried over calcium chloride and used in a subsequent run. 

Julolidine has been prepared by the reaction of trimethylene chlorobromide with formanilide, aniline, methylaniline, and tetrahydroquinoline by the reduction of 8,10-diketojuloli- 

---

The lithium- -propylamine reducing system has been found capable of reducing julolidine (113) to /d -tetrahydrojulolidine (114, 66% yield) and 1-methyl-1,2,3,4-tctrahydroquinoline to a mixture of enamines (87% yield), l-methyl-J -octahydroquinoline (115) and 1-methyl-al -octahydro-quinoline (116) 102). This route to enamines of bicyclic and tricyclic systems avoids hydroxylation, which occurs during mercuric acetate oxidation of certain bicyclic and tricyclic tertiary amines 62,85 see Section III.A). 

When the immonium form of the enamine is precluded sterically, enamines are alkylated solely on the nitrogen atom. Methylation of neostrychnine with methyliodide proceeds in this manner as well as that of zl -tetrahydro-julolidine (117) (202), which affords only the N-methylated product (118). 

Bohlmann (207) reported the reaction of /I -dehydroquinolizidine with methyl vinyl ketone and with propargyl aldehyde forming a partially saturated derivative of julolidine 135 and julolidine (136), respectively. Compound 135 can be prepared also by mercuric acetate dehydrogenation of ketone 137, which is formed by condensation of 1-bromoethylquinolizi-dine with ethyl acetoacetate (Scheme 11). 

Fig. 4 Ground-state and excited-state energies of the TICT complexes thioflavin T (a) and 9-(dicyanovinyl)-julolidine (DCVJ) (b) as a function of the intramolecular rotation angle (data from Stsiapura et al. [13] and Allen et al. [14]). In both cases, energy levels were determined by quantum mechanical simulations. For thioflavin T, the energy difference between Si and S0 corresponds to approximately 400 nm in the planar state and 470 nm in the twisted state. In the case of DCVJ, the energy differences correspond to 310 and 960 nm, respectively. The DCVJ energy levels reflect a rotation around the vinyl double bond...

Fluorescence-based bulk viscosity measurement is one application that advertises itself almost immediately, particularly with julolidine-derived molecular rotors where the quantum yield is widely independent from solvent polarity. Solving (5) for r] and assuming proportionality of quantum yield and emission intensity leads to (13),... 

Fig. 6.7. Viscosity sensitive fluorophores molecular rotors. DCVJ = 9-(dicyanovinyl)-julolidine, CCVJ = 9-(carboxy-2-cyano)vinyl julolidine, CMAM = 2-cyano-3-(p-dimethyl-aminophenyl)acrylic acid, methyl ester.

Various xanthene derivatives, including fluorescein, are also used as laser dyes to cover the spectral region from 500 to 700 nm. A modern example is the julolidine-based dye Rhodamine 101 (6.201), which absorbs at 576 nm and lases at 648 nm [79]. 

Reaction of 3-(9-julolidinyl)prop-2-en-l-al with N-( -adamantyl)-4-methyl-pyr-idinium chloride and a-CD in aqueous sodium hydroxide yielded styryl dye rotaxanes 6a and 7a as well as the free dye 8a (Fig. 5) [4, 27]. Analogously, the two rotaxane isomers 6b and 7b, and the free dye 8b were obtained from julolidine aldehyde and 4-methyl-2,6-diphenylpyridinium chloride. As compared to the hydrophobic dyes 8a, 8b, the rotaxanes 6a, 6b and 7a, 7b are highly soluble in water. The absorption/emission maxima of the rotaxanes 6a (525/710 nm) and 7a (535/718 nm) in DMSO are red-shifted compared to free styryl dye 8a... 

Julolidine (3) and benzoquinuclidine (4) can be considered as aniline derivatives with parallel and perpendicular electron lone-pairs, respectively. Relative to N,N-dimethylaniline (5), the simplest tertiary aromatic amine, the n orbital of julolidine is destabilized by 0.20 eV, while that of benzoquinuclidine is destabilized by 0.80 eV42. In the latter compound there is no n/jt conjugation while in the former it has a maximum value and, accordingly, the splitting of the first and the third IP is much smaller (0.70 eV) than in the former (2.55 eV) compound. 

Dispersion polymerizations of methyl methacrylate ntUizing poly(l,l,-dihydroper-fluorooctyl acrylate) as a steric stabilizer in snpercritical CO2 were carried out in the presence of helium. Particle size and particle size distribution were found to be dependent on the amonnt of inert helium present. Particle sizes ranging from 1.64 to 2.66 pm were obtained with varions amounts of helium. Solvatochromic investigations using 9-(a-perflnoroheptyl-p,p-dicyanovinyl)julolidine indicated that the solvent strength of CO2 decreases with increasing helium concentration. This effect was confirmed by calcnlations of Hildebrand solubility parameters (Hsiao and DeSimone, 1997). 

The bathochromic shifts of the tetrahydroquinoline or julolidine couplers, such as in dye (114), are associated with the donor portion of the molecule, and in this case the bathochromic shifts arise due to increased interaction of the nitrogen p-orbital with the ring 7r-orbitals, thereby increasing the electron density associated with the acceptor in the azo dyes (71JCS(B)793). The similar azo dyes derived from lilolidine (115) (74MI11205) absorb at shorter wavelengths and with lower intensities than the analogous julolidine azo dyes (114). 

The julolidine (43) is an active developer and gives dyes which are deeper than those from simpler p-phenylenediamines (55USP2707681). The pyrimidine (44) is a developer of low activity (56JCS3232). 

For example, the julolidine-substituted dithiolene (9) can be obtained18 in low yield by standard procedures the synthesis of the red, crystalline dithione and its conversion to (9) under reducing conditions proceeds in high yield.24 Dithiones are only stable if they are substituted by strongly electron-donating or -withdrawing substituents, and their use is limited to these cases. 

The bis(julolidinylethylenedithiolato) complexes (9) of Ni and Pt absorb in the 1.3 jan region and are thus suited to Q-switch the technically important iodine laser. This laser is one candidate of several thought to be able to initiate nuclear fusion reactions. At present, the julolidine-substituted Ni dithiolene is the best available Q-switch for the iodine laser. In appropriate solvents, the dialkylamino-substituted complexes can be shifted into the 1.3 fun region and also be used for this purpose.202,203... 

Jacobson-Hugershoff synthesis benzothiazoles, 5, 135 Japp-KJingemann reaction N-arylhydrazones from, 4, 337 1,2,4-triazole synthesis by, 5, 768 Jasmine lactone synthesis, 3, 847 Jasminine occurrence, 2, 626 y-Jasmolactone synthesis, 4, 674 cis-Jasmone synthesis, 1, 422, 427 Jatropham synthesis, 1, 426 Josephson junctions, 1, 359 Juliprospine occurrence, 4, 477 Julolidine... 

Bohlmann, F. Arndt, C. Konfiguration, Synfh-ese und Reaktionen der isomeren Hexahydro-julolidine. Chem. Ber. 1958, 91, 2167—2175. 

Further anodic oxidation of the monomethoxylated compound in methanol gives N,N-bis(methoxymethyl)aniline 24, which yields a julolidine derivative 25 upon reaction with two molecules of ethyl vinyl ether. 

---