Acknowledgement is made to the Donors of the American Chemical Society Petroleum Research Fund for support of this research. We acknowledge the Lafayette College Chemistry Department and the Lafayette College EXCEL Scholars program for financial support.

1. Synthesis of tricarbonyl(tropone)iron (1)19
<ol>
	<li>In an argon-atmosphere glovebox, weigh out 4.1 g of diiron nonacarbonyl into an oven-dried 20 mL vial. Cap the vial and remove it from the glovebox. 
	CAUTION: Prolonged storage of diiron nonacarbonyl leads to some deterioration to give triiron dodecacarbonyl and finely divided metallic iron20. This deterioration is evidenced by the presence of a black solid within the shiny orange diiron nonacarbonyl. The iron impurity is pyrophoric and can ignite upon exposure to air. Storing the diiron nonacarbonyl under argon at 2-8 &#176;C in a bottle sealed with electrical tape appears to minimize this deterioration. The pyrophoric iron impurities can be destroyed via addition of dilute hydrochloric acid.</li>
	<li>Add an oven-dried PTFE stir bar, 0.5 mL of tropone, and 10 mL of dry benzene to an oven-dried 50 mL round bottom flask. 
	NOTE: A round bottom flask with a 24/40 ground glass joint is preferred so that the solid diiron nonacarbonyl may be added rapidly with minimal spilling (see Step 1.5).</li>
	<li>Degas the contents of the round bottom flask via three freeze-pump-thaw cycles as follows.
	<ol>
		<li>Submerge the flask in a dry ice-acetone bath until the contents solidify completely. Then, with the flask still submerged in the cold bath, evacuate the flask under vacuum for 2-3 min.</li>
		<li>Allow the contents to thaw under static vacuum.</li>
		<li>Repeat steps 1.3.1 and 1.3.2 twice.</li>
		<li>After the final thaw, backfill the flask with argon and cover the flask with a rubber septum. Keep the flask under a positive pressure of argon.</li>
	</ol>
	</li>
	<li>Cover the flask with aluminum foil and commence vigorous magnetic stirring.</li>
	<li>Briefly remove the rubber septum and add the previously weighed diiron nonacarbonyl in a single portion and replace the septum.</li>
	<li>Immerse the flask in an oil bath at 55-60 &#176;C and stir for 30 min.</li>
	<li>After 30 min, remove the flask from the oil bath and allow to cool to room temperature.</li>
	<li>Isolate the tropone complex via alumina column chromatography as follows.
	<ol>
		<li>Pack a chromatography column (~30 mm diameter) with 12 cm of alumina (Activity II/III) and hexanes.</li>
		<li>Pipette the crude reaction mixture directly onto the alumina. Rinse the flask with a small amount (1-3 mL) of hexanes and add to the top of the column.</li>
		<li>Drain the column until the solvent is level with the top of the alumina and add ~2 cm of sand.</li>
		<li>Elute with hexanes until the blue-green band (triiron dodecacarbonyl) comes off the column.</li>
		<li>Elute with 1:1 hexanes:methylene chloride until the red-orange tropone iron complex elutes completely.</li>
		<li>Remove the solvent from the red-orange solution via rotary evaporation to obtain the tropone complex as a dark red oil that solidifies on standing. 
		NOTE: The tropone complex isolated in this fashion is occasionally contaminated with paramagnetic, iron-based impurities, as evidenced by severely broadened peaks in the 1H NMR spectrum. These impurities can be removed by redissolving the complex in methylene chloride&#160;and passing through a short plug of alumina, eluting with 1:1 hexanes:methylene chloride.</li>
	</ol>
	</li>
</ol>
2. Synthesis of tricarbonyl(5-ketocycloheptadienyl)iron tetrafluoroborate (2)21
<ol>
	<li>Add a PTFE magnetic stir bar, 432 mg of tricarbonyl(tropone)iron, and 10 mL of methylene chloride to a 50 mL round bottom flask.</li>
	<li>Cool the flask in an ice bath and commence vigorous magnetic stirring.</li>
	<li>Add 3.2 mL of concentrated sulfuric acid dropwise.</li>
	<li>Vigorously stir the mixture at 0 &#176;C for 30 min.</li>
	<li>To a separate 100 mL round bottom flask, add a PTFE stir bar, 2.0 g of anhydrous sodium carbonate, and 10 mL of methanol.</li>
	<li>Cool the flask containing the sodium carbonate mixture in an ice bath and vigorously stir it magnetically.</li>
	<li>Upon completion of the 30-min period (step 2.4), cease magnetic stirring. Two layers should form.</li>
	<li>Using a Pasteur pipette, transfer the viscous, brown lower layer to the rapidly stirring sodium carbonate suspension.</li>
	<li>Stir for ~5 min, and then carefully and slowly add 50 mL of deionized water. 
	CAUTION: Vigorous bubbling is involved in this step.</li>
	<li>Pour the mixture into a 250 mL separatory funnel and extract with methylene chloride (2x 50 mL).</li>
	<li>Sequentially wash the combined organic layers with water (50 mL) and brine (50 mL).</li>
	<li>Dry the organic layers over anhydrous magnesium sulfate.</li>
	<li>Remove the magnesium sulfate via gravity or vacuum filtration and concentrate the filtrate via rotary evaporation to obtain a red-brown oil. 
	NOTE: The protocol may be paused at this point.</li>
	<li>Add 3 mL of acetic anhydride to a 25 mL Erlenmeyer flask and cool it in an ice bath.</li>
	<li>Add 1 mL of 48% aqueous tetrafluoroboric acid to the cold acetic anhydride dropwise. 
	CAUTION: The addition is highly exothermic. However, the exotherm is readily contained by controlling the temperature and rate of addition.</li>
	<li>In a 100 mL round bottom flask submerged in an ice bath, add the mixture obtained from step 2.15 to the oil obtained in step 2.13.</li>
	<li>Agitate the mixture with a stainless steel spatula for 5 min. 
	NOTE: The mixture generally takes on a gummy consistency upon agitation and the color becomes lighter.</li>
	<li>Add 50 mL of diethyl ether to the mixture. Collect the resulting pale yellow solid via vacuum filtration using a Buchner funnel to obtain the cationic complex as its tetrafluoroborate salt.</li>
</ol>
3. Synthesis of aza-Michael adduct 4: Tricarbonyl[(2-5-h)-6-((2-phenylethyl)amino)cyclohepta-2,4-dien-1-one]iron
<ol>
	<li>Add a PTFE magnetic stir bar, 150 mg of tricarbonyl(tropone)iron (1), and 0.154 mL of phenethylamine to a 1-dram vial. Cap the vial under an air atmosphere and commence magnetic stirring. 
	NOTE: Phenethylamine will be oxidized by air upon prolonged storage resulting in a yellow-brown color. Phenethylamine should be distilled prior to use if it is not colorless.</li>
	<li>Monitor the reaction periodically by removing a small (~1 drop) aliquot from the reaction mixture, dissolving in CDCl3, and acquiring a 1H NMR spectrum. 
	NOTE: While this particular reaction is usually complete within 1 h, the reaction may be left to stir overnight.</li>
	<li>Upon disappearance of the signals for tricarbonyl(tropone)iron in the 1H NMR spectrum (see Representative Results and Figure 3 and Figure 4), purify the crude reaction mixture via chromatography on basic alumina (Activity II/III) as follows.
	<ol>
		<li>Pack a 30 mm diameter chromatography column with alumina (10-15 cm) and hexanes and apply the crude reaction mixture to the top of the column.</li>
		<li>Elute the column with 1:1 hexanes:diethyl either to remove the excess phenethylamine from the column. Monitor the elution via thin layer chromatography (TLC). 
		NOTE: The column was monitored using alumina TLC plates and a 1:1 diethyl ether:methylene chloride mixture as the mobile phase. If alumina TLC plates are not available, silica gel plates may be used (use 5% methanol in methylene chloride as the mobile phase).</li>
		<li>After the excess amine has finished eluting, change the eluting solvent to 1:1 diethyl ether:methylene chloride to elute the product. 
		NOTE: The title compound elutes as a yellow band.</li>
		<li>Combine the product-containing fractions (as judged by thin layer chromatography) and remove the solvent on a rotary evaporator to obtain the purified product as a dark yellow oil.</li>
	</ol>
	</li>
</ol>
4. Synthesis of tricarbonyl[(2-5-h)-6-(2-methylanilino)cyclohepta-2,4-dien-1-one]iron (3)
<ol>
	<li>Add a PTFE stir bar, 0.021 mL of o-toluidine, and 1.0 mL of diethyl ether to a 1-dram vial. Commence vigorous magnetic stirring.</li>
	<li>Carefully add 33 mg of the cationic complex to the mixture. Allow the suspension to stir for 12 h.</li>
	<li>Pour the reaction mixture into 5 mL of deionized water in a separatory funnel and extract the aqueous layter with 5 mL of ethyl acetate three times.</li>
	<li>Wash the combined organic layers with 10 mL of brine before drying over anhydrous sodium sulfate.</li>
	<li>Remove the sodium sulfate by gravity filtration and concentrate the filtrate via rotary evaporation to obtain the crude product.</li>
	<li>Purify the crude product via column chromatography on basic alumina using a gradient of 30-50% diethyl ether in hexanes to obtain the pure product as a yellow solid.</li>
</ol>
5. Protection of amine 4 as a tert-butyl carbamate
<ol>
	<li>Dissolve 76 mg of amine 4 in 2 mL of absolute ethanol in a 25 mL round bottom flask under air atmosphere.</li>
	<li>Add 104 mg of di-tert&#173;-butyl dicarbonate followed by 40 mg of solid sodium bicarbonate to the reaction mixture.</li>
	<li>Cap the flask with a rubber septum and sonicate the mixture for 1 h. 
	NOTE: This reaction may be allowed to run overnight.</li>
	<li>Filter the crude reaction mixture through a bed of diatomaceous earth using a Buchner funnel. Wash the diatomaceous earth with ethanol until no more brown-colored solution comes out the bottom of the funnel.</li>
	<li>Transfer the filtrate to a round bottom flask and concentrate on a rotary evaporator. Dissolve the resulting oil in ~2.5 mL of methylene chloride.</li>
	<li>Add ~1.3 g of silica gel to the solution and remove the methylene chloride on the rotary evaporator until a fine, free-flowing solid is obtained.</li>
	<li>Pack the silica gel into a 10 g silica cartridge for automated flash chromatography. 
	NOTE: An automated purification system was used in this protocol. However, conventional flash chromatography with silica gel may also be employed.</li>
	<li>Run the column using a gradient starting from 90:10 hexanes:ethylacetate and ending at 20:80 hexanes:ethyl acetate over a period of 20 min. Collect the fractions containing the product (as indicated by the major peak detected at 254 nm absorbance) in a round bottom flask. Evaporate the hexanes and ethyl acetate on a rotary evaporator to obtain the purified product as a yellow oil.</li>
</ol>
6. Synthesis of tert-butyl (6-oxocyclohepta-2,4-dien-1-yl)(2-phenylethyl) carbamate (6)
<ol>
	<li>In a 10 mL round bottom flask, dissolve 27 mg of iron complex 5 in 1 mL of methanol under air atmosphere and immerse the flask in an ice bath.</li>
	<li>Commence magnetic stirring and add 33 mg of cerium(IV) ammonium nitrate.</li>
	<li>After 30 min, add a second 33 mg portion of cerium(IV) ammonium nitrate, followed by a third 33 mg portion after an additional 30 min of stirring.</li>
	<li>After adding the third portion of cerium(IV) ammonium nitrate, dilute the reaction mixture with ethyl acetate (5 mL).</li>
	<li>Pour the mixture into a 30 mL separatory funnel containing 5 mL of saturated aqueous sodium bicarbonate. Separate the layers.</li>
	<li>Re-extract the aqueous layer with ethyl acetate (2x 5 mL). Dry the combined organic layers over anhydrous sodium sulfate.</li>
	<li>Remove the sodium sulfate via gravity or vacuum filtration and concentrate the filtrate on a rotary evaporator.</li>
	<li>Dissolve the crude product in ~2.5 mL of methylene chloride, add ~1.3 g of silica gel, and remove the solvent on a rotary evaporator.</li>
	<li>Pack the silica gel with the adsorbed crude product into a 10 g silica gel column for automated flash chromatography. 
	NOTE: An automated purification system was used in this protocol. However, conventional flash chromatography with silica gel may also be employed.</li>
	<li>Run the column using a gradient starting from 90:10 hexanes:ethylacetate and ending at 20:80 hexanes:ethyl acetate over a period of 20 min. Collect the fractions containing the product (as indicated by the major peak detected at 254 nm absorbance) in a round bottom flask. Evaporate the hexanes and ethyl acetate on a rotary evaporator to obtain the purified product as a pale brown oil.</li>
</ol>

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The authors have nothing to disclose.

Whether the solvent-free protocol involving direct addition to tricarbonyl(tropone)iron (Figure 2) or the indirect method utilizing the corresponding cationic complex as the electrophile (Figure 1) is to be employed depends on the amine substrate used. In general, the direct addition method is preferable since it requires fewer steps to generate the aza-Michael adducts from tropone and the overall yields are generally higher. However, this more direct m...

Structurally complex amines containing a seven-membered carbocyclic ring are common to a number of biologically active molecules. Notable examples include the tropane alkaloids1 and several members of the Lycopodium2, Daphniphyllum3, and monoterpenoid indole alkaloid4 families. However, such compounds are often more difficult to synthesize compared to compounds of similar complexity containing only five- or six-membered rings. Thus, we sought to develop a new avenue towards such compounds by attaching diverse amine nucleophiles to tropone5. The resulting adduct contains several functional handles for subsequent synthetic elaboration to diverse complex seven-membered ring-containing scaffolds that would be otherwise difficult to access.
While previous work with tropone6,7 suggests that it would not be suitable for such a transformation, the related organometallic complex tricarbonyl(tropone)iron8 (1, Figure 1) has proven to be a versatile synthetic building block that has been utilized in the synthesis of a number of natural products and complex molecules9,10,11,12,13. Furthermore, the uncomplexed double bond of tricarbonyl(tropone)iron has been shown to behave similar to an &#945;,&#946;-unsaturated ketone in reactions with, for example, dienes14,15, tetrazines16, nitrile oxides17, diazoalkanes8,10, and organocopper reagents11. Thus, we envisioned that an aza-Michael reaction of tricarbonyl(tropone)iron would provide an efficient entry to synthetically valuable aminated tropone derivatives.
Eisenstadt had previously reported that, following protonation of tricarbonyl(tropone)iron, the resulting cationic complex 2 (Figure 1) could undergo nucleophilic attack by aniline or tert-butylamine to produce aminated derivatives of the tropone iron complex.18 However, the synthetic potential of this method remains unrealized. Indeed, no additions of other amines had been reported, and the demetallation of those products was not explored in Eisenstadt&#8217;s report. We have adapted this protocol to demonstrate the addition of a wide variety of amine nucleophiles.
We also describe a method for direct aza-Michael additions to tricarbonyl(tropone)iron (Figure 2), which does not require synthesis of the cationic complex and generally proceeds in higher yields compared to the previously reported method. We also report herein a protocol for the demetallation of the resulting adducts. Overall, this protocol provides formal aza-Michael adducts of tropone in four steps from tropone (and three steps from the known iron complex).

<table border="0" cellpadding="0" cellspacing="0" style="width:676px;" width="676">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">10 g SNAP Ultra silica gel columns</td>
			<td style="width:145px;">Biotage</td>
			<td style="width:119px;"></td>
			<td style="width:197px;">for automated column chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Acetic anhydride</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">A10-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Acetone</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">A-16S-20</td>
			<td>for cooling baths</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Acetonitrile-D3</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">366544</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Benzene, anhydrous, 99.8%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">401765</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Biotage Isolera Prime</td>
			<td style="width:145px;">Biotage</td>
			<td style="width:119px;">ISO-PSF</td>
			<td>for automated chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Celite; 545 Filter Aid</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">C212-500</td>
			<td>diatomaceous earth</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">Cerium(IV) ammonium nitrate, ACS, 99+%</td>
			<td style="width:145px;">Alfa Aesar</td>
			<td align="right" style="width:119px;">33254</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Chloroform-D</td>
			<td style="width:145px;">Acros</td>
			<td align="right" style="width:119px;">209561000</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Di-tert-butyl dicarbonate, 99%</td>
			<td style="width:145px;">Acros</td>
			<td align="right" style="width:119px;">194670250</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Ethyl acetate</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">E145-4</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">Ethyl alcohol, absolute - 200 proof</td>
			<td style="width:145px;">Greenfield Global</td>
			<td style="width:119px;">111000200PL05</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Ethyl ether anhydrous</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">E138-1</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Hexanes</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">H302-4</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">iron nonacarbonyl 99%</td>
			<td style="width:145px;">Strem</td>
			<td style="width:119px;">26-2640</td>
			<td>air sensitive, synonymous with diiron nonacarbonyl</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Magnesium sulfate</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">M65-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Methanol</td>
			<td style="width:145px;">EMD Millipore</td>
			<td style="width:119px;">MX0475-1</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Methylene chloride</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">D37-4</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">MP alumina, Act. II-III acc. To Brockmann</td>
			<td style="width:145px;">MP Biomedicals</td>
			<td align="right" style="width:119px;">4691</td>
			<td>for column chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">o-toluidine 98%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">466190</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Phenethylamine 99%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">128945</td>
			<td>distill prior to use if not colorless</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium bicarbonate</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S233-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium carbonate anhydrous</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S263-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium chloride</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S271-500</td>
			<td>dissolved in deionized water to perpare a saturated aqueous solution</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sodium sulfate anhydrous</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">S415-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sonicator</td>
			<td style="width:145px;">Branson</td>
			<td style="width:119px;"></td>
			<td>model 2510</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Sulfuric acid</td>
			<td style="width:145px;">Fisher Scientific</td>
			<td style="width:119px;">A300C-212</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">Tetrafluoroboric acid solution, 48 wt.%</td>
			<td style="width:145px;">Sigma Aldrich</td>
			<td align="right" style="width:119px;">207934</td>
			<td>aqueous solution</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:215px;">TLC Aluminium oxide 60 F254, neutral</td>
			<td style="width:145px;">EMD Millipore</td>
			<td style="width:119px;">1.05581.0001</td>
			<td>for thin layer chromatography</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:215px;">Tropone 97%</td>
			<td style="width:145px;">Alfa Aesar</td>
			<td style="width:119px;">L004730-06</td>
			<td>Light sensitive</td>
		</tr>
	</tbody>
</table>

preparation of 6-aminocyclohepta-2,4-dien-1-one derivatives via tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate in a direct aza-Michael reaction with tricarbonyl(tropone)iron under solvent-free conditions. Less nucleophilic aniline derivatives and more hindered secondary amines add efficiently to the cationic tropone complex formed by protonation of tricarbonyl(tropone)iron. While the protocol utilizing the cationic complex is less efficient overall for accessing the aza-Michael adducts than the direct, solvent-free addition to the neutral complex, it allows the use of a broader range of amine nucleophiles. Following protection of the amine of the aza-Michael adduct as a tert-butyl carbamate, the diene is decomplexed from the iron tricarbonyl fragment upon treatment with cerium(IV) ammonium nitrate to provide derivatives of 6-aminocyclohepta-2,4-dien-1-one. These products can serve as precursors to diverse compounds containing a seven-membered carbocyclic ring. Because the demetallation requires protection of the amine as a carbamate, the aza-Michael adducts of secondary amines cannot be decomplexed using the protocol described here.

All novel compounds in this study were characterized by 1H and 13C NMR spectroscopy and high resolution mass spectrometry. Previously reported compounds were characterized by 1H NMR spectroscopy. NMR data for representative compounds are described in this section.
The 1H NMR spectrum of tricarbonyl(tropone)iron is shown in Figure 3. The protons of the &#951;4-diene ligand give rise to the signals at 6.39 ppm (...

Watch this Scientific Journal Video about Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron at JoVE.com

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Representative experimental procedures for the addition of amine nucleophiles to tricarbonyl(tropone)iron and subsequent demetallation of the resulting complexes are presented in detail.

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate ...

preparation-6-aminocyclohepta-24-dien-1-one-derivatives-via

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Organic Chemistry

Unit 1

Amines

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

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7.9K Views.  Lafayette College. פרוטוקול זה הוא שיטה יעילה לסינתזה של נגזרות טרופון ממין. תרכובות אלה יכולות לשמש מתווכים סינתטיים לסינתזה של אמינים מורכבים מבנית. היתרון של טכניקה זו היא כי תוספת aza-Micheal ניתן להשיג בתהליך ללא ממס עם מצעים אמין רבים.פעולה זו מפשטת את הגדרת התגובה ואת בידוד המוצר. הוסף מ...

Video: Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Preparation of Hydrophobic Metal-Organic Frameworks via Plasma Enhanced Chemical Vapor Deposition of Perfluoroalkanes for the Removal of Ammonia

Plasma enhanced chemical vapor deposition (PECVD) of perfluoroalkanes has long been studied for tuning the wetting properties of surfaces. For high surface area microporous materials, such as metal-organic frameworks (MOFs), unique challenges present themselves for PECVD treatments. Herein the protocol for development of a MOF that was previously unstable to humid conditions is presented. The protocol describes the synthesis of Cu-BTC (also known as HKUST-1), the treatment of Cu-BTC with PECVD of perfluoroalkanes, the aging of materials under humid conditions, and the subsequent ammonia microbreakthrough experiments on milligram quantities of microporous materials. Cu-BTC has an extremely high surface area (~1,800 m2/g) when compared to most materials or surfaces that have been previously treated by PECVD methods. Parameters such as chamber pressure and treatment time are extremely important to ensure the perfluoroalkane plasma penetrates to and reacts with the inner MOF surfaces. Furthermore, the protocol for ammonia microbreakthrough experiments set forth here can be utilized for a variety of test gases and microporous materials.

Herein the procedures for plasma enhanced chemical vapor deposition of perfluoroalkanes on microporous materials such as metal-organic frameworks to enhance their stability and hydrophobicity are described. Furthermore, breakthrough testing of milligram quantities of samples is described in detail.

הכנת מסגרות מתכת אורגנית הידרופובי באמצעות פלזמה משופרת שיקוע הכימי של Perfluoroalkanes להסרת אמוניה

Plasma enhanced chemical vapor deposition (PECVD) of perfluoroalkanes has long been studied for tuning the wetting properties of surfaces. For high ...

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

סינתזה של נגזרות אנטי Tetrahydrocarbazole ידי פוטו וFunctionalization CH זרז חומצה באמצעות חמצניים ביניים (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

Facile and Efficient Preparation of Tri-component Fluorescent Glycopolymers via RAFT-controlled Polymerization

Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and efficient synthesis of well-controlled fluorescent statistical glycopolymers using reversible addition-fragmentation chain-transfer (RAFT)-based polymerization is demonstrated. The synthesis starts with the preparation of &#946;-galactose-containing glycomonomer 2-lactobionamidoethyl methacrylamide obtained by reaction of lactobionolactone and N-(2-aminoethyl) methacrylamide (AEMA). 2-Gluconamidoethyl methacrylamide (GAEMA) is used as a structural analog lacking a terminal &#946;-galactoside. The following RAFT-mediated copolymerization reaction involves three different monomers: N-(2-hydroxyethyl) acrylamide as spacer, AEMA as target for further fluorescence labeling, and the glycomonomers. Tolerant of aqueous systems, the RAFT agent used in the reaction is (4-cyanopentanoic acid)-4-dithiobenzoate. Low dispersities (&#8804;1.32), predictable copolymer compositions, and high reproducibility of the polymerizations were observed among the products. Fluorescent polymers are obtained by modifying the glycopolymers with carboxyfluorescein succinimidyl ester targeting the primary amine functional groups on AEMA. Lectin-binding specificities of the resulting glycopolymers are verified by testing with corresponding agarose beads coated with specific glycoepitope recognizing lectins. Because of the ease of the synthesis, the tight control of the product compositions and the good reproducibility of the reaction, this protocol can be translated towards preparation of other RAFT-based glycopolymers with specific structures and compositions, as desired.

An efficient, three-step synthesis of RAFT-based fluorescent glycopolymers, consisting of glycomonomer preparation, copolymerization, and post-modification, is demonstrated. This protocol can be used to prepare RAFT-based statistical glycopolymers with desired structures.

הכנה קלילה ויעילה של Glycopolymers פלורסנט Tri-רכיב באמצעות פלמור שליטת רפסודה

Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and ...

Preparation of Carbon Nanosheets at Room Temperature

Amphiphilic molecules equipped with a reactive, carbon-rich "oligoyne" segment consisting of conjugated carbon-carbon triple bonds self-assemble into defined aggregates in aqueous media and at the air-water interface. In the aggregated state, the oligoynes can then be carbonized under mild conditions while preserving the morphology and the embedded chemical functionalization. This novel approach provides direct access to functionalized carbon nanomaterials. In this article, we present a synthetic approach that allows us to prepare hexayne carboxylate amphiphiles as carbon-rich siblings of typical fatty acid esters through a series of repeated bromination and Negishi-type cross-coupling reactions. The obtained compounds are designed to self-assemble into monolayers at the air-water interface, and we show how this can be achieved in a Langmuir trough. Thus, compression of the molecules at the air-water interface triggers the film formation and leads to a densely packed layer of the molecules. The complete carbonization of the films at the air-water interface is then accomplished by cross-linking of the hexayne layer at room temperature, using UV irradiation as a mild external stimulus. The changes in the layer during this process can be monitored with the help of infrared reflection-absorption spectroscopy and Brewster angle microscopy. Moreover, a transfer of the carbonized films onto solid substrates by the Langmuir-Blodgett technique has enabled us to prove that they were carbon nanosheets with lateral dimensions on the order of centimeters.

We present the synthesis of an amphiphilic hexayne and its use in the preparation of carbon nanosheets at the air-water interface from a self-assembled monolayer of these reactive, carbon-rich molecular precursors.

הכנת פחמן Nanosheets בטמפרטורת החדר

Amphiphilic molecules equipped with a reactive, carbon-rich "oligoyne" segment consisting of conjugated carbon-carbon triple bonds self-assemble into ...

Facile Preparation of 4-Substituted Quinazoline Derivatives

Reported in this paper is a very simple method for direct preparation of 4-substituted quinazoline derivatives from a reaction between substituted 2-aminobenzophenones and thiourea in the presence of dimethyl sulfoxide (DMSO). This is a unique complementary reaction system in which thiourea undergoes thermal decomposition to form carbodiimide and hydrogen sulfide, where the former reacts with 2-aminobenzophenone to form 4-phenylquinazolin-2(1H)-imine intermediate, whilst hydrogen sulfide reacts with DMSO to give methanethiol or other sulfur-containing molecule which then functions as a complementary reducing agent to reduce 4-phenylquinazolin-2(1H)-imine intermediate into 4-phenyl-1,2-dihydroquinazolin-2-amine. Subsequently, the elimination of ammonia from 4-phenyl-1,2-dihydroquinazolin-2-amine affords substituted quinazoline derivative. This reaction usually gives quinazoline derivative as a single product arising from 2-aminobenzophenone as monitored by GC/MS analysis, along with small amount of sulfur-containing molecules such as dimethyl disulfide, dimethyl trisulfide, etc. The reaction usually completes in 4-6 hr at 160 &#186;C in small scale but may last over 24 hr when carried out in large scale. The reaction product can be easily purified by means of washing off DMSO with water followed by column chromatography or thin layer chromatography.

A protocol for facile preparation of 4-substituted quinazoline derivatives from 2-aminobenzophenones, thiourea and dimethyl sulfoxide is presented.

הכנה קלילה של נגזרי Quinazoline 4-הוחלפו

Reported in this paper is a very simple method for direct preparation of 4-substituted quinazoline derivatives from a reaction between substituted ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

פרוטוקול לסינתזה של<em&gt; Ortho</em&gt; נגזרי אנילין -trifluoromethoxylated

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Preparation of Biopolymer Aerogels Using Green Solvents

Although the first reports on aerogels made by Kistler1 in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers (gelatin, agar, cellulose), only recently have biomasses been recognized as an abundant source of chemically diverse macromolecules for functional aerogel materials. Biopolymer aerogels (pectin, alginate, chitosan, cellulose, etc.) exhibit both specific inheritable functions of starting biopolymers and distinctive features of aerogels (80-99% porosity and specific surface up to 800 m2/g). This synergy of properties makes biopolymer aerogels promising candidates for a wide gamut of applications such as thermal insulation, tissue engineering and regenerative medicine, drug delivery systems, functional foods, catalysts, adsorbents and sensors. This work demonstrates the use of pressurized carbon dioxide (5 MPa) for the ionic cross linking of amidated pectin into hydrogels. Initially a biopolymer/salt dispersion is prepared in water. Under pressurized CO2 conditions, the pH of the biopolymer solution is lowered to 3 which releases the crosslinking cations from the salt to bind with the biopolymer yielding hydrogels. Solvent exchange to ethanol and further supercritical CO2 drying (10 - 12 MPa) yield aerogels. Obtained aerogels are ultra-porous with low density (as low as 0.02 g/cm3), high specific surface area (350 - 500 m2/g) and pore volume (3 - 7 cm3/g for pore sizes less than 150 nm).

A new way for the production of biopolymer-based aerogels by carbon dioxide (CO2) induced gelation is shown. The technique utilizes pressurized carbon dioxide (5 MPa) for the production of biopolymer hydrogels and supercritical CO2 (12 MPa) to convert gels into aerogels. The only solvents needed besides CO2 are water and ethanol.

הכנת Aerogels biopolymer בעזרת ממיסים גרין

Although the first reports on aerogels made by Kistler1 in the 1930s dealt with aerogels from both inorganic oxides (silica and others) and biopolymers ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

סינתזה של חלבון Bioconjugates<em&gt; דרך</em&gt; כימיה ציסטאין-maleimide

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

The Preparation and Properties of Thermo-reversibly Cross-linked Rubber Via Diels-Alder Chemistry

A method for using Diels Alder thermo-reversible chemistry as cross-linking tool for rubber products is demonstrated. In this work, a commercial ethylene-propylene rubber, grafted with maleic anhydride, is thermo-reversibly cross-linked in two steps. The pending anhydride moieties are first modified with furfurylamine to graft furan groups to the rubber backbone. These pendant furan groups are then cross-linked with a bis-maleimide via a Diels-Alder coupling reaction. Both reactions can be performed under a broad range of experimental conditions and can easily be applied on a large scale. The material properties of the resulting Diels-Alder cross-linked rubbers are similar to a peroxide-cured ethylene/propylene/diene rubber (EPDM) reference. The cross-links break at elevated temperatures (&#62; 150 &#176;C) via the retro-Diels-Alder reaction and can be reformed by thermal annealing at lower temperatures (50-70 &#176;C). Reversibility of the system was proven with infrared spectroscopy, solubility tests and mechanical properties. Recyclability of the material was also shown in a practical way, i.e., by cutting a cross-linked sample into small parts and compression molding them into new samples displaying comparable mechanical properties, which is not possible for conventionally cross-linked rubbers.

A simple two-step approach involving rubber modification and cross-linking yields fully reworkable, elastic rubber products.

הכנת המאפיינים של Thermo-הפיך צולב הגומי Via דילס-אלדר לכימיה

A method for using Diels Alder thermo-reversible chemistry as cross-linking tool for rubber products is demonstrated. In this work, a commercial ...

Self-assembling Morphologies Obtained from Helical Polycarbodiimide Copolymers and Their Triazole Derivatives

A facile method for the preparation of polycarbodiimide-based secondary structures (e.g., nano-rings, &#34;craters,&#34; fibers, looped fibers, fibrous networks, ribbons, worm-like aggregates, toroidal structures, and spherical particles) is described. These aggregates are morphologically influenced by extensive hydrophobic side chain-side chain interactions of the singular polycarbodiimide strands, as inferred by atomic force microscopy (AFM) and scanning electron microscopy (SEM) techniques. Polycarbodiimide-g-polystyrene copolymers (PS-PCDs) were prepared by a combination of synthetic methods, including coordination-insertion polymerization, copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) &#34;click&#34; chemistry, and atom transfer radical polymerization (ATRP). PS-PCDs were found to form specific toroidal architectures at low concentrations in CHCl3. To determine the influence of a more polar solvent medium (i.e., THF and THF/EtOH) on polymer aggregation behavior, a number of representative PS-PCD composites have been tested to show discrete concentration-dependent spherical particles. These fundamental studies are of practical interest to the development of experimental procedures for desirable architectures by directed self-assembly in thin film. These architectures may be exploited as drug carriers, whereas other morphological findings represent certain interest in the area of novel functional materials.

Here, we present a protocol to prepare and visualize secondary structures (e.g., fibers, toroidal architectures, and nano-spheres) derived from helical polycarbodiimides. The morphology characterized by both atomic force microscopy (AFM) and scanning electron microscopy (SEM) was shown to depend on molecular structure, concentration, and the solvent of choice.

מורפולוגיה הרכבה עצמיות המתקבלות סליל Polycarbodiimide קופולימרים ונגזר triazole שלהם

A facile method for the preparation of polycarbodiimide-based secondary structures (e.g., nano-rings, &#34;craters,&#34; fibers, looped fibers, fibrous ...