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Posted on 01/24/2015 2:28:12 PM PST by SoConPubbie
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But just talking is how you get the consultants and the moneybags on your side, isn’t it?
Pssst...hey, Ted...the water’s fine. You know what I mean?
It is gonna take the most ornery, gutsy, ruthless, hard -ass*ed, classy, sharp, smart, real Teflon conservative EVER to lead us out of the current mess this country is in.
I pray Cruz and or someone else is up for the job .... But I’m not so sure anyone can right this ship.
It’s going to take some cracked skulls to shut down the Nazis. Just sayin’, we all know this.
Taking Ted Cruz at his words of ‘show us’, your question is answered by someone who has.
Look to Wisconsin to see how it’s done.
Come on, don’t be disingenuous, you know why that happened.
Before I spend any time on it, is there any explanation which will satisfy you?
If so, give me an example of one such explanation.
As a former Midwesterner myself, his reason was, and still is, solid and benefits the citizens of WI greatly.
It’s telling of his character, he was willing to subject himself to the swords and arrows of his detractors, including the likes of you, in order to do what is best for the populace of WI.
You yourself could take another, different, lesson from Governor Walker, a lesson you very recently mocked.
Here is an example:
By reacting N-benzoyl-3-(B-carboxyethyl)-dihydroindole (see JCS, 3158 (1931) for the preparation of this compound) with thionyl chloride, followed by aluminum chloride gives 1-benzoyl-5-keto-1,2,2a,3,4,5-hexahydrobenzindole. This is then brominated to give the 4-bromo-derivative, which is converted to the ketol-ketone by reacting with methylamine acetone ethylene ketol. This is then hydrolized by acid to yield the diketone and treated with sodium methoxide to convert it to the tetracyclic ketone. Acetylate and reduce this ketone with sodium borohydride to get the alcohol, which is converted to the hydrochloride form, as usual. The above hydrochloride is treated with thionyl chloride in liquid sulfur dioxide, to produce an amorphous chloride hydro chloride, which is converted to the nitrile with sodium cyanide in liquid hydrogen cyanide. Methanolysis then gives the ester of the nitrile. Alkaline hydrolysis of this last compound, followed by catalytic dehydrogenation in water using a deactivated Raney Nickle catalyst (see JOC. 13, 455 1948) gives dl-phentol acid. JACS, 78, 3087 (1956). 3-Indolepropionic acid, 94.5 g (0.5 mole) is dissolved in 600 ml of water containing 20 g of NaOH. The solution is mixed with 100 g of Raney Nickle catalyst and hydrogenated at room temp in a steel bomb at about 3,500 psi until the uptake of hydrogen stops (about 20-30 hours). Filter off the catalyst and wash it with a little water to remove the product that is clinging to it. Add 85 ml of concd HCl acid to the filtrate, and cool. If your reduction is incomplete, you will now have unreacted starting material separate, and this must be removed by filtration. Benzoylate the filtrate (the Schotten and Baumann method is preferable), using 210 ml of 12 N NaOH 180 ml of benzoyl chloride. Keep the solution alkaline throughout the benzoylation, and keep the temp below 40°C by cooling. When the benzoyl chloride is fully reacted, the reaction mixture is cooled and acidified with 300 ml of HCl acid. Filter the crude product by filtration, wash with water, and extract with four 1 liter portions of hot water. Separate, and crystallize the resulting syrupy product from a few volumes of methanol. Filter and wash with a little cold methanol to get a little over 100 g that melts at 151-153°. This is l-Benzoyl-3-beta-carboxyethyl-2,3-dihydroindole. This can be purchased to eliminate this step. 1-Benzoyl-5-keto-1,2,2a,3,4,5,-hexahydrobenzindole. 118 g of the above product (1-benzoyl-3-B-carboxyethyl-2,3-dihydroindole) is mixed with 200 ml of pure thionyl chloride. This solution is allowed to stand for 30 min, then it is warmed gently for 15-21 min on a steam bath. Excess thionyl chloride is completely evaporated with the temp maintained between 22-26°C in vacuo. The crude acid chloride is dissolved in dry carbon disulfate. This solution is added, in a thin stream, to a well stirred suspension of 240 g of aluminum chloride in 1750 ml of carbon disulfate in a 5,000 cc flask. Note: this must be done under a fume hood. A complex will separate and bog down the stirring device. Heat this mixture under reflux with stirring for 1 hour. Decompose this mixture by adding 500 g of ice, 250 ml of concd HCl acid, and 500 ml of water, all while good stirring is continued. Cooling of this operation is affected by periodic distillation of the carbon disulfate in vacuo. After the decomposition is complete, any remaining carbon disulfate is removed completely in vacuo, and the product is extracted with 2 liters of benzene. The extract is washed well with 500 ml of 2 N NaOH in three portions, and then with water. Dry (with the usual magnesium sulfate), and evaporate to a small volume in vacuo. Add this small volume to several portions of ether to get the ketone to crystallize (add slowly), and filter, then wash with ether to get 85 g of pure title product, mp: 146-147°C.
1-Benzoyl-4-bromo-5-keto-1,2,2a,3,4,5-hexahydrobenzindole. A solution of the above indole (305 g) in 2,200 ml of glacial acetic acid is warmed to 40°C. While the reaction is illuminated with a 250 watt bulb, 352 g of pyridine hydrobromide perbromide is added in portions, over 5 min with shaking. The solution is then heated to 60° and is held between there and 55°C for 30 min. Treat the mixture with carbon, and evaporate to a small volume in vacuo. The residue is taken up with 2,200 ml of chloroform, and wash this solution with several portions of water, dry as above, and concentrate in vacuo. Crystallize the residue from 2,200 ml of 50% acetic acid and 50% ether to get 270 g of title product that melts at 180.5-181.5°C. Another crop can be obtained from concentrating the fltrates. Yield: 30 g of less pure product.
1-Benzoyl-2,2a,3,4-tetrahydro-4-methyl-2-methyl-1,3-dioxolan-2-yl-methyl-aminobenzindol-5-(1H)one. A solution of the last indole product above (270 g) and 307 g of methylaminoacetone ethylene ketol in 4,500 ml of dry benzene is refluxed for 21 hours under a slow stream of nitrogen. The mixture is cooled and 151 g of methylaminoacetone ethylene ketol hydrobromide is filtered off. The filtrate is washed with ice water, then extracted with 2.5 liters of cold dilute HCl acid containing 150 ml of the concd acid. The acid extracts are immediately added to an excess of ice cold dilute NaOH. Extract with 1 1iter of chloroform, dry over magnesium sulfate, treat with carbon and concentrate by evaporation in vacuo. The residual ketol-ketone is crystallized from acetone to yield 220 g, mp: 135-136°C.
5-Keto-4-N-methyl-N-acetonylamino-1,2,2a,3,4,5-hexahydrobenzindole. 20 g of the above product is dissolved in a mixture of 250 ml of concd HCl acid and 250 ml of water, and the solution is kept under nitrogen for 5 days at 37°. Cool the mixture, treat with carbon, filter, and concentrate the filtrate in vacuo to a small volume. Treat the residue with an excess of sodium bicarbonate, extract with cold chloroform, and remove the chloroform by evaporation in vacuo at room temp. The crude diketone is powdered, slurried with 75 ml of benzene-ether, and filtered. Yield: 9.8 g, mp: 105-107°C.
9-keto-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3)isoquinoline. 25 g of the above product is mixed with 550 ml of absolute ethanol. Stir this mixture under nitrogen and cool to -15° with an external freezing mixture. Sodium methoxide is added (17 g) and the mixture is stirred for 10 min at -10 to -12°. Cool to -25°, and the product is filtered and washed (while still in the funnel) with cold ethanol and ether. Without exposure to air the crude ketone is immediately slurried with a little ice water and filtered. Wash with ice water, ethanol, then ether (all cold) to yield 16 g of product melting at 145-147°.
4-Acetyl-9-keto-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-4,3-quinoline. 24 g of the last product is added to 80 ml of cold acetic anhydride. The mixture is held at 25° for about 5 min, then thoroughly cooled, filtered, and the product (a solid) washed with ether to yield 20.5 g, mp: 169-170°. A second crop is obtained by concentrating the mother liquor by evaporation.
A mixture of the last product (1.0 g) and 10 g of palladium carbon (5%), in 35 ml of xylene, is heated under reflux for 4 hours. The catalyst is filtered and extracted with hot methanol and chloroform. The combined extract filtrates and the initial filtrate are combined and evaporated in vacuo. The residue is recrystallized from water to give 0.6 g of a monohydrate product that melts at 255-256°. This product is called 4-acetyl-4,5,5a,6-tetrahydro-9-hydroxy-7-methylindolo-(4,3fg)-quinolinium hydroxide betaine.
4-Acetyl-9-hydroxy-7-methyl-4,5,5a,6,7,8,9,10-octahydroindolo-(4,3fg)-quinoline. 1 g of the above betaine in a mixture of 20 ml of ethanol and 5 ml of water, is treated with 0.08 g of sodium borohydride, and this solution is refluxed for 10 min and kept at 25° for 1 hour after the reflux is finished. The solvent is distilled off, and the residue is taken up in a mixture of chloroform and water. The chloroform solution is separated, dried as above, and then the solvent is distilled off. The residue is recrystallized from a nitromethane-ethyl acetate mixture to yield 0.2 g (21%), mp 193-196°. Not only is this a small scale, but it is a poor yield, requiring you to perform it several times to get enough product to perform the next step. When you have more than enough, convert the product into its hydrochloride form by dissolving in dry methanol and precipitating with dry hydrogen chloride.
4-acetyl-9-chloro-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3fg)-quinoline hydrochloride. 3.1 g of the above product in its hydrochloride form is dissolved in 75 ml of liquid sulfur dioxide contained in a glass lined, high pressure bomb, or autoclave. Thionyl chloride (1.2 ml) is added and the vessel is sealed and kept at 25° for 6 hours. Vent the vessel carefully and remove the mixture. Evaporate the sulfur dioxide while keeping the volume of the solution constant by the slow addition of dry ether. The amorphous chloro hydrochloride is filtered, washed with ether (dry) and dried by evaporating in vacuo to give 3.5 g of product, mp:130-135°.
4-Acetyl-9-cyano-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3fg)-quinoline. 40 g of dry, powdered sodium cyanide, is added to ice cold liquid hydrogen cyanide and stirred gently with ice bath cooling. Speed up the stirring, continue the cooling, and add 7.5 g of the amorphous product directly above. Continue stirring for 30 min, then the hydrogen cyanide is distilled under enough reduced pressure to keep it coming over the condenser at a temp below 10-12°. The residue is mixed with chloroform and ice water, and the resulting mixture is filtered. The organic layer of the filtrate is separated and the aqueous layer is extracted with two separate portions of chloroform. The combined extracts (this would include the separated chloroform, as usual) are dried over magnesium sulfate, decolorized, and the solvent removed by distillation in vacuo. Crystallize the product in ethyl acetate. Yield: 3.3 g, mp: 173-174°. Recrystallize again for extra purity.
9-Carbomethoxy-7-methyl-4,5,5a,6,6a,7,8,9-octahydroindolo-(4,3fg)-quinoline. 1 g of the last product is mixed with 15 ml of methanol and 0.25 ml of water. With external (ice bath) cooling add 2 ml of concd sulfuric acid slowly. Seal this solution in a high pressure bomb with a glass liner (or in a glass tube taking safety precautions in case of explosion) with a nitrogen atmosphere, and heat at 100° for 23-24 hours. Note: I have seen a big pressure cooker (like gramma cans peas with) work for some of these bomb procedures. I do not recommend it, but here is how to do it right, if you feel you must. Use only the great big heavy duty models, in excellent condition, set the pop off (relief valve) for near maximum position; never, ever tamper or modify this valve to get more pressure. Put the product in a glass beaker, put it in the cooker, flush with nitrogen, heat and stay in a different house during the reaction. Carefully turn off heat, notice or record pressure gauge after time has elapsed. Wait until pressure drops noticeably, bleed off remaining pressure and get product.
Treat the mixture with decolorizing carbon and then evaporate in vacuo to 10 ml. Pour onto a mixture of 30 ml of chloroform, ice, and 10 g of sodium bicarbonate. Separate the chloroform layer, and extract the aqueous phase with three 10 ml portions of chloroform. The combined chloroforms are dried, evaporated to dryness in vacuo, and the product is crystallized from benzene to give 1/2 g of product that melts at 159-160°. You may purify more by recrystallizing from ethyl acetate. This is not very much product. As with the procedure 4 steps back, you will have to perform this step over and over. If you try to double or triple the amounts given, you may get more product, but you will hurt the yield.
LOL!
Oh that, OK I off doing the research.
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